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1.
Nat Aging ; 3(2): 162-172, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-37118113

RESUMEN

Diminished insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates1-4; however, whether it is a feasible longevity target in mammals is less clear5-12. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females. While long-term PI3Ki treatment was well tolerated and led to greater strength and balance, negative impacts on common human aging markers, including reductions in bone mass and mild hyperglycemia, were also evident. These results suggest that while pharmacological suppression of insulin receptor (IR)/insulin-like growth factor receptor (IGFR) targets could represent a promising approach to delaying some aspects of aging, caution should be taken in translation to humans.


Asunto(s)
Longevidad , Fosfatidilinositol 3-Quinasas , Ratones , Animales , Masculino , Humanos , Femenino , Envejecimiento , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Mamíferos/metabolismo , Suplementos Dietéticos
2.
Colorectal Dis ; 13(3): e37-41, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21073645

RESUMEN

AIM: This study analysed trends in polypoid colorectal cancer (PCRC) diagnosed by colonoscopy during the period 1995-2008 and compared the patterns observed in the years 2005-2008 with 1995-1998. METHOD: In the period 1995-2008, 24,245 colonoscopies were performed and 1041 patients with PCRC were diagnosed: pediculated (n = 220) or sessile (n = 821). RESULTS: The mean age at diagnosis was 68.3 ± 11.6 years. Males were more likely to have PCRC (males 62.6%vs females 37.4%; P < 0.0001). Significantly more pediculated PCRCs were located in the distal colon (P < 0.001). In the 2005-2008 period the prevalence of PCRC among patients undergoing colonoscopy decreased, the number of polypectomies increased significantly (P < 0.0001) and the pediculated PCRC location changed, with a significant increase in right-sided lesions. CONCLUSION: The prevalence of PCRC in patients undergoing colonoscopy decreased, with a significant increase in the number of polypectomies in the last decade. Pediculated PCRCs were more often located in the left colon and sessile PCRCs in the right colon. From the period 1995-1998 to 2005-2008 the location of pediculated PCRCs changed, with an increase in right-sided lesions.


Asunto(s)
Colon/patología , Neoplasias Colorrectales/patología , Recto/patología , Distribución por Edad , Anciano , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , España
3.
Colorectal Dis ; 12(10 Online): e273-7, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19930145

RESUMEN

AIM: We aimed to determine the incidence of colonic perforation (CP) following colonoscopy and postpolypectomy bleeding (PPB) in a teaching hospital, assessing the influence of endoscopist experience as a risk factor. METHOD: All colonoscopies performed between 1995 and 2008 were reviewed. Demographic data, endoscopic procedure information, incidence of CP and PPB, and endoscopist experience were recorded. RESULTS: In the 14-year period, 25,214 endoscopic colonic procedures were performed, and 3991 patients underwent polypectomy. The overall CP risk was 0.51/1000 procedures; and PPB 14.7/1000. The relative risk (RR) ratio of complications was 2.8/1000 procedures. The RR rate was highest for endoscopists performing less than 591 procedures per year (4.0/1000 [95% CI, 3.7-4.3] vs 2.9/1000 [95% CI, 2.6-3.2]), P < 0.001). CONCLUSION: The complication rate after colonoscopy was comparable to that previously reported. Colonoscopy carried out by a low-volume endoscopist was independently associated with bleeding and perforation.


Asunto(s)
Competencia Clínica , Enfermedades del Colon/etiología , Pólipos del Colon/cirugía , Colonoscopía/efectos adversos , Gastroenterología , Perforación Intestinal/etiología , Hemorragia Posoperatoria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Colon/epidemiología , Pólipos del Colon/diagnóstico , Pólipos del Colon/patología , Femenino , Humanos , Perforación Intestinal/epidemiología , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/epidemiología , Estudios Retrospectivos , Factores de Riesgo
4.
Oncogene ; 25(47): 6304-18, 2006 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-16702956

RESUMEN

Indirubin, an isomer of indigo, is a reported inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3) as well as an agonist of the aryl hydrocarbon receptor (AhR). Indirubin is the active ingredient of a traditional Chinese medicinal recipe used against chronic myelocytic leukemia. Numerous indirubin analogs have been synthesized to optimize this promising kinase inhibitor scaffold. We report here on the cellular effects of 7-bromoindirubin-3'-oxime (7BIO). In contrast to its 5-bromo- and 6-bromo- isomers, and to indirubin-3'-oxime, 7BIO has only a marginal inhibitory activity towards CDKs and GSK-3. Unexpectedly, 7BIO triggers a rapid cell death process distinct from apoptosis. 7-Bromoindirubin-3'-oxime induces the appearance of large pycnotic nuclei, without classical features of apoptosis such as chromatin condensation and nuclear fragmentation. 7-Bromoindirubin-3'-oxime-induced cell death is not accompanied by cytochrome c release neither by any measurable effector caspase activation. Furthermore, the death process is not altered either by the presence of Q-VD-OPh, a broad-spectrum caspase inhibitor, or the overexpression of Bcl-2 and Bcl-XL proteins. Neither AhR nor p53 is required during 7BIO-induced cell death. Thus, in contrast to previously described indirubins, 7BIO triggers the activation of non-apoptotic cell death, possibly through necroptosis or autophagy. Although their molecular targets remain to be identified, 7-substituted indirubins may constitute a new class of potential antitumor compounds that would retain their activity in cells refractory to apoptosis.


Asunto(s)
Muerte Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Indoles/farmacología , Oximas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Animales , Proteína Quinasa CDC2/antagonistas & inhibidores , Caspasas/fisiología , Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral/efectos de los fármacos , Línea Celular Tumoral/enzimología , Núcleo Celular/ultraestructura , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Femenino , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Humanos , Indoles/síntesis química , Indoles/química , Masculino , Ratones , Oximas/síntesis química , Oximas/química , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Quinolinas/farmacología , Proteínas Recombinantes de Fusión/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Spodoptera , Estrellas de Mar , Relación Estructura-Actividad , Porcinos , Proteína p53 Supresora de Tumor/fisiología , Proteína bcl-X/fisiología
6.
Clin Transl Oncol ; 9(3): 177-82, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17403629

RESUMEN

INTRODUCTION: To evaluate the efficacy and tolerability of weekly docetaxel concurrent with radiotherapy in inoperable oesophageal cancer patients. MATERIAL AND METHODS: Thirty-four oesophageal cancer patients with co-morbid medical conditions, locally advanced tumours (T4) or advanced age (older than 75 years) received docetaxel (20 mg/m2 weekly) plus concurrent radiotherapy (2 Gy daily, to a total dose of 66 Gy). Twenty-two patients (64%) were stage III, 19 of whom had T4 tumours. RESULTS: Twenty-seven patients (79%) completed the planned chemoradiotherapy treatment. Nine patients (26%) achieved a complete response and 8 (24%) achieved a partial response, for an overall response rate of 50%. Median survival was 6 months, and 1-year survival was 35%. Patients with T4 tumours had significantly shorter survival than other patients: 5 months for T4 tumours vs. 11 months for T1-3 (p=0.04). Grade 3-4 oesophagitis occurred in 6 patients (17%). There were two treatment-related deaths due to radiation pneumonitis. CONCLUSIONS: Docetaxel plus concurrent radiotherapy is active in poor-prognosis oesophageal cancer patients, with a lower incidence of severe oesophagitis than with cisplatin-based chemoradiotherapy regimens. This schedule can be considered, especially in patients with non-T4 tumours who are not candidates for oesophageal resection.


Asunto(s)
Adenocarcinoma/terapia , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Radioterapia de Alta Energía , Taxoides/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Comorbilidad , Docetaxel , Esquema de Medicación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/radioterapia , Esofagitis/etiología , Femenino , Enfermedades Hematológicas/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Neumonitis por Radiación/etiología , Radioterapia de Alta Energía/efectos adversos , Inducción de Remisión , Análisis de Supervivencia , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del Tratamiento
7.
Clin Transl Oncol ; 18(11): 1106-1113, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26856597

RESUMEN

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUVmax shows promise as a potential prognostic factor.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia Adyuvante/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Terapia Neoadyuvante/métodos , Adulto , Anciano , Carcinoma de Células Escamosas/cirugía , Quimioradioterapia Adyuvante/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Tomografía de Emisión de Positrones
8.
Int J Dev Biol ; 35(1): 43-8, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1867999

RESUMEN

The relative proportions of four major chicken histone H1 subtypes (referred to as H1a, H1b, H1c and H1d) change markedly in different chicken tissues. The relative amount of H1c is higher in nonreplicating somatic tissues, such as liver, than in replicating immature testis. The proportion of H1c sharply decreases as spermatogenesis proceeds, being much lower in mature than in immature testis. It has been proposed that the relative increment of H1c correlates with low rates of cell division in chicken tissues. It was assumed that the sharp decrease in H1c observed during maturation of chicken testis was a consequence of the intensification of proliferative activity in spermatogonia (Berdnikov et al., 1976). Our results, however, clearly show that the decrease of H1c during maturation is due to the low levels of this protein in postreplicative stages of spermatogenesis, where H1c is barely detectable. These results suggest that the presence of the arginine-rich H1c subtype would neither be compatible with the relaxed structure of acetylated chromatin present in active replicating cells nor with the hyperacetylated chromatin characteristic of postreplicative late spermatids undergoing the nucleohistone nucleoprotamine transition.


Asunto(s)
Histonas/metabolismo , Espermatogénesis , Espermatogonias/fisiología , Secuencia de Aminoácidos , Animales , Anticuerpos/inmunología , Pollos , Eritrocitos/metabolismo , Histonas/química , Histonas/inmunología , Hígado/metabolismo , Masculino , Datos de Secuencia Molecular , Espermatogonias/metabolismo , Testículo/fisiología
9.
FEBS Lett ; 272(1-2): 213-6, 1990 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-2146160

RESUMEN

The organization of the U1snRNP-specific A protein (34 kDa) has been analyzed by 12 and 16 A thiol-reversible chemical cross-linking and Western blotting. A-containing cross-linked complexes had molecular masses of 43, 47, 56, 62, 67, 105 and 125 kDa. None of these complexes could be cross-linked following ribonuclease digestion, suggesting that UsnRNA may play important roles in the spatial organization of A and other proteins. Moreover, the data suggest that A is proximal to, and may have interactions with, UsnRNP-specific proteins C and 70 kDa as well as with UsnRNP-common proteins B, E and G.


Asunto(s)
Reactivos de Enlaces Cruzados , Ribonucleoproteínas/química , Western Blotting , Electroforesis en Gel de Poliacrilamida , Células HeLa , Humanos , Imidoésteres , Peso Molecular , Ribonucleasa T1/metabolismo , Ribonucleasa Pancreática/metabolismo , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas Nucleares Pequeñas , Compuestos de Sulfhidrilo/farmacología
10.
Eur J Cancer ; 30A(6): 827-31, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7522496

RESUMEN

Recent cloning of the t(11;22) region has led to the detection of a number of sequences involved in the breakpoints by substituting a sequence which encodes a putative RNA binding domain for that of the DNA binding domain of the human homologue of murine FLI-1. Several tumours display consistent translocation at t(11;22) (q24;q12), a finding that suggests these fusion transcripts could be expressed and detected by reverse transcriptase polymerase chain reaction amplification. To date, only a small number of Ewing's sarcomas (Es) and peripheral neuroectodermal tumours (pPNET) of bone have been tested with this novel molecular biology approach. In this study, we confirmed the presence of the three putative chimaeric transcripts on 7 cases of Es and pPNET sarcomas of bone and soft tissue, providing 100% positivity for the tested tumours. For comparative purposes, a number of other neuroectodermal tumours were analysed with negative results: esthesioneuroblastoma, retinoblastoma, Schwannoma. A primitive soft tissue sarcoma (ectomesenchymoma) with a 22 chromosome rearrangement did not express any transcript, nor did a number of non-neuroectodermal small round cell sarcomas of soft tissue (rhabdomyosarcomas) and bone (microcellular osteosarcoma), conventional bone sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and synovial sarcomas. These results reinforce the value of molecular biology techniques for the correct assessment of histology difficult evaluable neoplasms, such as the group of small round cell tumours within the Es family.


Asunto(s)
Neoplasias Óseas/genética , Proteínas de Unión al ADN/genética , Proteínas Proto-Oncogénicas , Sarcoma de Células Pequeñas/genética , Neoplasias de los Tejidos Blandos/genética , Transactivadores/genética , Translocación Genética , Animales , Secuencia de Bases , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 22 , Humanos , Ratones , Ratones Desnudos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Proteína Proto-Oncogénica c-fli-1 , ADN Polimerasa Dirigida por ARN/genética , Sarcoma de Ewing/genética , Trasplante Heterólogo
11.
Neuropharmacology ; 36(6): 811-21, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9225309

RESUMEN

Staurosporine is a potent and non-specific inhibitor of protein kinases. There is also evidence of staurosporine being a potent inducer of apoptosis. In several human neuroblastoma cell lines (SH-SY5Y, NB69, IMR-5 and IMR-32) we have found 100 nM staurosporine to induce cell death in half the population (EC50). Electron microscopy of these cells, fluorescence microscopy after Hoechst-33258 staining of chromatin and agarose-electrophoresis of DNA, show two different types of cell death. SH-SY5Y and NB69 die by apoptosis and display all the characteristic features of it. IMR-5 and IMR-32 lack some of these features and a ladder pattern of DNA degradation is not found. Different morphological types of apoptosis have been described during the development of vertebrates; the possibility of finding a similar diversity in cell culture is suggested. On the other hand, staurosporine is a potent promoter of neurite outgrowth. In all the neuroblastoma cell lines we have tested, neurite-promoting and cell death-inducing staurosporine concentrations mostly overlap. This fact has not been reported before, probably because of an early versus late timing of these two different phenomena. The neuritogenic effect has prompted the suggestion that staurosporine could be a prototype of drugs for neurodegenerative diseases; the present study raises several concerns about such a proposal.


Asunto(s)
Muerte Celular/efectos de los fármacos , Neuroblastoma/patología , Estaurosporina/farmacología , Fragmentación del ADN , ADN de Neoplasias/metabolismo , Humanos , Técnicas In Vitro , Microscopía Electrónica , Neuritas/efectos de los fármacos , Neuritas/ultraestructura , Concentración Osmolar , Células Tumorales Cultivadas
12.
Aliment Pharmacol Ther ; 16(12): 2061-5, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12452938

RESUMEN

BACKGROUND: Intravenous ciclosporin is considered to be the only alternative to avoid surgery in severe, steroid-refractory ulcerative colitis. In responders, some authors recommend a switch to oral ciclosporin to act as a 'bridge' until the therapeutic action of azathioprine is achieved for maintenance treatment. AIM: To report the short- and long-term outcome of intravenous ciclosporin-responsive ulcerative colitis patients treated with oral azathioprine without oral ciclosporin. METHODS: The records of all patients treated with intravenous ciclosporin for severe, steroid-refractory ulcerative colitis were reviewed. Responders following treatment with azathioprine but without oral ciclosporin as maintenance therapy were included. Patients with colonic cytomegalovirus infection and/or follow-up of less than 1 year were excluded. RESULTS: Twenty-seven patients were included. Steroids were discontinued in 24 (89%). The median follow-up was 36 months. Eighteen (75%) patients presented mild or moderate relapses, which were easily managed with salicylates or steroids. Cumulative probabilities of relapse were 42%, 72% and 77% at 1, 3 and 5 years, respectively. Eleven (40.7%) patients underwent elective colectomy. Cumulative probabilities of colectomy were 29%, 35% and 42% at 1, 3 and 5 years, respectively. No opportunistic infections were observed. CONCLUSIONS: Oral azathioprine seems to be enough to maintain long-term remission induced by intravenous ciclosporin in patients with steroid-refractory ulcerative colitis. The 'bridging step' with oral ciclosporin may not be necessary in this subset of patients, although a randomized controlled trial is warranted to confirm this hypothesis.


Asunto(s)
Azatioprina/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Ciclosporina/uso terapéutico , Administración Oral , Adulto , Colectomía , Colitis Ulcerosa/cirugía , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Recurrencia , Inducción de Remisión , Resultado del Tratamiento
13.
Chest ; 100(6): 1488-92, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1959388

RESUMEN

The prime complication of heparin therapy is bleeding, and the gastrointestinal tract is the most common site of bleeding in patients treated with heparin. We recently reported that gastroduodenal lesions are common in patients admitted because of acute venous thromboembolism, and now we present our experience in a larger series of patients. The aims of the study were to try to validate our previous findings and to identify clinical factors that could increase the likelihood of having an acute, potential bleeding lesion in the gastroduodenal tract. Upper gastrointestinal endoscopy was performed on admission in 155 consecutive patients with acute venous thromboembolism (118 with deep vein thrombosis, 37 with pulmonary embolism). Acute lesions (both peptic ulcers and diffuse erosions) were found in 19 of 118 patients (16 percent) with venous thrombosis, and in 14 of 37 patients (38 percent) with pulmonary embolism (p = 0.005). When only patients with pulmonary embolism were considered, lesions were more commonly found in men, and in patients with severe hypoxemia on admission. When considered overall, only the timing of endoscopy was statistically significant; acute lesions were more commonly found when endoscopy was performed early after admission. No significant differences were found in terms of age, sex, smoking habits, alcohol intake, concomitant drug ingestion, comorbid diseases, or previous history of ulcer. The very high incidence of upper GI tract lesions in these patients will have long-term diagnostic/therapeutic implications which cannot be ignored. Who should receive prophylactic H2 blockers and for how long remains to be determined.


Asunto(s)
Úlcera Péptica/complicaciones , Embolia Pulmonar/complicaciones , Tromboflebitis/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/diagnóstico , Úlcera Péptica Hemorrágica/complicaciones , Factores de Riesgo
14.
Chest ; 111(5): 1322-5, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9149589

RESUMEN

STUDY OBJECTIVE: To assess whether pressure support ventilation (PSV) could be used as an alternative ventilatory mode to assist-control (A/C) ventilation in the treatment of respiratory failure. DESIGN: A short-term (4-h) prospective study in which the beneficial effect of PSV on respiratory mechanics, gas exchange, arterial oxygenation, cardiovascular hemodynamics, and oxygen consumption was compared with A/C ventilation. SETTING: ICU of a community hospital. PATIENTS: Forty-five patients (mean age, 62.8 [11.8] years) with respiratory failure secondary to COPD, restrictive disorders, or neuromuscular disease requiring mechanical ventilatory support in the ICU were selected for study. INTERVENTIONS: The mean duration of mechanical ventilation before the study was 7.16 (8.64) days. Patients were switched to the PSV mode of the mechanical ventilator for a period of 4 h after which conventional A/C ventilation was resumed. RESULTS: Patients supported with PSV compared with A/C ventilation showed significantly higher tidal volume, minute ventilation, and inspiratory time in association with significantly lower pressure in the airway and I:E ratio. With regard to gas exchange data, an increase in dead space/tidal volume ratio (VD/VT), decrease in PaO2, and statistically but not clinically significant alteration of arterial oxygenation indexes were noted. However, when patients with COPD, restrictive disorders, and neuromuscular disease were compared, significant changes in arterial oxygenation parameters were found only in patients with restrictive disorders. There were significant decreases in heart rate, systolic pulmonary artery pressure, and pulmonary capillary wedge pressure when PSV was applied. Oxygen transport and oxygen consumption were unchanged. CONCLUSIONS: PSV could be a possible alternative to A/C ventilation in patients with respiratory failure. PSV caused an increase in VD/VT in association with a significantly lower pressure in the airway and I:E ratio. Randomized studies are needed to define the long-term benefits of both respiratory modes and the conditions in which PSV may be a valuable alternative to A/C ventilation.


Asunto(s)
Respiración Artificial/métodos , Insuficiencia Respiratoria/terapia , Adulto , Presión Sanguínea , Cuidados Críticos , Femenino , Corazón/fisiología , Frecuencia Cardíaca , Hemodinámica/fisiología , Humanos , Inhalación/fisiología , Enfermedades Pulmonares Obstructivas/complicaciones , Masculino , Persona de Mediana Edad , Enfermedades Neuromusculares/complicaciones , Oxígeno/sangre , Consumo de Oxígeno/fisiología , Estudios Prospectivos , Edema Pulmonar/complicaciones , Intercambio Gaseoso Pulmonar/fisiología , Presión Esfenoidal Pulmonar , Respiración/fisiología , Espacio Muerto Respiratorio/fisiología , Síndrome de Dificultad Respiratoria/complicaciones , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Mecánica Respiratoria/fisiología , Volumen de Ventilación Pulmonar/fisiología , Factores de Tiempo
15.
Chest ; 103(3): 816-9, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8449074

RESUMEN

We prospectively studied 78 consecutive patients with acute pulmonary embolism (PE) to determine the most appropriate workup study for searching for hidden cancer. After a careful physical examination, the following tests were performed: erythrocyte sedimentation rate (ESR), complete blood cell counts, biochemistry, carcinoembryonic antigen levels, chest radiograph, upper gastrointestinal endoscopy, and abdominal ultrasound. If a malignant lesion was suspected, further appropriate tests were performed. After hospital discharge, periodic follow-up was performed on all patients in our outpatient clinic. A malignant lesion was detected in 9 of 78 patients: in 7 of them, cancer was diagnosed during the hospital admission because of acute PE. All but one of these 7 patients were asymptomatic, except for PE symptoms. In three of them some abnormalities on physical examination led to the diagnosis of cancer; in the remaining three patients the diagnosis was suspected from abnormal results of blood tests. Cancer was detected several months after hospital discharge in two additional patients: an esophageal cancer was diagnosed 5 months later in one of the 23 patients who refused endoscopy; and a colonic carcinoma was detected 21 months after hospital discharge in a patient in whom colonoscopy was not performed at the time of hospital admission. When considered overall, cancer was more commonly found in patients with "idiopathic" PE as compared with patients with known risk factors for PE development (6 of 21 patients vs 3 of 51 patients; p < 0.05). On the other hand, one patient died because of massive recurrent PE after a biopsy sample was obtained because of a prostatic node. Gross hematuria had developed shortly after biopsy, and any attempt to increase heparin doses was followed by recurrent hematuria. According to our experience, any decision about procedures that potentially involve bleeding should be carefully individualized in patients with acute PE.


Asunto(s)
Neoplasias Primarias Desconocidas/epidemiología , Embolia Pulmonar/epidemiología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/diagnóstico , Estudios Prospectivos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Reproducibilidad de los Resultados , España/epidemiología
16.
Virchows Arch ; 435(6): 596-605, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10628802

RESUMEN

TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation. Immunohistochemical and Western-blot techniques were used to study nuclear accumulation of p53 and mdm2 proteins: 11 cases (40.7%) with p53 protein expression and thirteen cases (48.1%) with mdm2 protein expression were detected. We confirmed overexpression of mdm2 protein in eight of ten cases (80%) with p53 protein expression without TP53 gene mutation. Statistical analysis shows that simultaneous co-expression of p53 and mdm2 in malignant fibrous histiocytoma is significantly correlated with survival in absence of gene alteration in contrast to the lack of statistical correlation with survival of p53 protein expression alone.


Asunto(s)
Histiocitoma Fibroso Benigno/química , Proteínas de Neoplasias/análisis , Proteínas Nucleares , Proteínas Proto-Oncogénicas/análisis , Neoplasias de los Tejidos Blandos/química , Proteína p53 Supresora de Tumor/análisis , Animales , Southern Blotting , Western Blotting , Núcleo Celular/metabolismo , Núcleo Celular/patología , ADN de Neoplasias/análisis , Histiocitoma Fibroso Benigno/genética , Histiocitoma Fibroso Benigno/mortalidad , Histiocitoma Fibroso Benigno/patología , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Endogámicos BALB C , Mutación , Proteínas de Neoplasias/genética , Recurrencia Local de Neoplasia , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-mdm2 , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genética
17.
Intensive Care Med ; 13(4): 273-7, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-3611499

RESUMEN

To examine the clinical course of patients with acute myocardial infarction complicated by "extension", we studied prospectively 141 patients who had been diagnosed as having acute myocardial infarction. The serum CKMB level of these patients was determined at 8-h intervals during the first 5 days following admission. The patients were classified into 3 groups. Group A (early extension): patients who showed CKMB re-elevation before the CKMB values reached normal levels (28%). Group B (late extension): patients who showed CKMB re-elevation after the normalization of serum CKMB levels (21%). Group C (control group): patients without CKMB re-elevation (51%). Patients in group A showed the most unfavourable clinical course with a greater rate of haemodynamic deterioration compared with patients in the B or C groups, and a higher rate of recurrent ischemic pain. We found no significant differences in these parameters between the B and C groups. We were unable to find any risk factor associated with the development of extension. The pattern of the serum CKMB curve may allow a separation of two different subgroups of patients with acute myocardial infarct extension: patients with early extension, who show a high prevalence of haemodynamic deterioration, and patients with late extension, characterized by small infarcts and a benign clinical course.


Asunto(s)
Pruebas Enzimáticas Clínicas , Creatina Quinasa/sangre , Infarto del Miocardio/diagnóstico , Anciano , Femenino , Humanos , Isoenzimas , Masculino , Persona de Mediana Edad , Pronóstico
18.
Arch Surg ; 133(2): 189-93, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9484733

RESUMEN

OBJECTIVES: To study the incidence of band erosion in patients who have undergone vertical banded gastroplasty and to describe the reparative techniques used. DESIGN: A retrospective review case series. SETTING: A university hospital-based tertiary referral center. PATIENTS: Two hundred fifty consecutive morbidly obese patients who underwent vertical banded gastroplasty between 1987 and 1995. MAIN OUTCOME MEASURES: The development of band erosion into the stomach, reparative surgical techniques, and long-term weight loss control. RESULTS: Band erosion developed in 7 (2.8%) of the patients. Two patients had symptoms 1 month after undergoing forced endoscopy. Six patients required reoperation. The operative findings included 2 cases of "external" band erosion through the lesser curvature into the stomach and 4 cases of "internal" band erosion through the circular staple line. The surgical techniques used for repair depended on the radiological and endoscopic data and on the operative findings; the techniques included conversion into a gastric bypass, band replacement after the creation of a new stoma, and gastroplasty plus distal gastric bypass. There were no complications, and adequate long-term weight loss was achieved in all but 1 of the patients who underwent reoperation. CONCLUSION: Band erosion may be corrected using appropriate surgical techniques to allow for adequate long-term weight loss in patients who have undergone vertical banded gastroplasty.


Asunto(s)
Gastroplastia/métodos , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
19.
Neurosci Lett ; 223(3): 141-4, 1997 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-9080452

RESUMEN

Cytosine arabinoside (1-beta-D-arabinofuranosylcytosine, AraC) is a commonly used antimitotic agent that kills proliferating cells by inhibiting DNA synthesis. We report that AraC is toxic to cultured chick embryo spinal cord motoneurons (MTNs) in a concentration-dependent fashion with an EC50 of about 2 microM. Interestingly, this type of MTN death is specific, resembles that occurring upon muscle extract (MEX) trophic deprivation regarding its morphological and temporal characteristics, and has apoptotic features, as judged by observation of nuclear morphology. The death of AraC-treated MTNs can be blocked by 2'-deoxycytidine (dC), a pyrimidine metabolite AraC is structurally related to. Overall, these findings suggest that dC may participate in a pathway, different from inhibition of DNA synthesis, that is necessary for cultured MTNs to respond to the trophic activities present in MEX.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Citarabina/farmacología , Neuronas Motoras/efectos de los fármacos , Neurotoxinas/farmacología , Médula Espinal/efectos de los fármacos , Animales , Células Cultivadas , Embrión de Pollo , Citarabina/antagonistas & inhibidores , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Concentración Osmolar , Médula Espinal/citología
20.
Clin Nutr ; 16(4): 177-83, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16844596

RESUMEN

BACKGROUND AND AIMS: Plasma polyunsaturated fatty acid profile in patients with inflammatory bowel disease is abnormal. We aimed to assess the mucosal fatty acid pattern in patients with ulcerative colitis and Crohn's disease, and in rats with trinitrobenzene-sulfonic acid (TNB) induced colitis. METHODS: Fatty acids were measured in colonic mucosa of patients with ulcerative colitis (n = 30), Crohn's disease (n = 21), and healthy controls (n = 13). Likewise, they were assessed in the colonic mucosa of rats with TNB- and sham-colitis. RESULTS: There was an increase of the end-products (C22:5n3, C22:6n3, C20:4n6, C22:5n6) and a decrease of the precursors (C18:3n3, C18:2n6) of both n3 and n6 polyunsaturated fatty acids in the mucosa of active ulcerative colitis and TNB-colitis. Also, high values of saturated (C16:0, C18:0) and low values of monounsaturated fatty acids (C18:1n9) were observed. Furthermore, the mucosa of active Crohn's disease showed substantial changes in saturated, monounsaturated and essential fatty acids, but not in polyunsaturated fatty acids. Mucosa of patients with inactive disease showed intermediate fatty acid values between the mucosa of active patients and healthy controls. CONCLUSIONS: Colonic inflammation causes a characteristic modification of the mucosal fatty acid profile which appears to be common to different aetiologies and seems to be related to the degree of inflammation.

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