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1.
Rev. Soc. Esp. Dolor ; 21(4): 205-211, jul.-ago. 2014. tab, ilus
Article in Spanish | IBECS | ID: ibc-129913

ABSTRACT

Objetivo: conocer la prevalencia de dolor y su enfoque terapéutico en un servicio de urgencias. Material y métodos: estudio transversal llevado a cabo en el Servicio de Urgencias de un hospital universitario durante 7 días consecutivos. El médico de triaje interrogó sobre la presencia de dolor a los pacientes mayores de 15 años que acudían a urgencias. Se excluyeron los pacientes atendidos en el Servicio de Psiquiatría, Obstetricia-Ginecología y aquellos cuya gravedad no permitía la valoración del dolor en el triaje. Se revisó posteriormente el tratamiento analgésico previo a la visita, la evaluación del dolor, el tratamiento analgésico aplicado durante su estancia en urgencias y el tratamiento pautado al alta. Resultados: se analizaron 668 de los 2.287 pacientes que acudieron a urgencias durante el periodo del estudio. Presentaron dolor 501 pacientes (75 %), de los que 45 ingresaron y 456 fueron dados de alta a domicilio (240 pacientes procedentes de nivel 1 y 216 de nivel 2). El 24,5 % de los 501 pacientes que manifestaron tener dolor realizaba tratamiento analgésico previo. De los 216 pacientes atendidos en el nivel 2, el 41,7 % recibió tratamiento analgésico durante su estancia [paracetamol (80,2 %), antiinflamatorios no esteroideos (AINE) (50 %), coanalgésicos (1 %), opioides débiles (20,8 %), opioides fuertes (3,1 %)]. El 32,7 % de los 196 pacientes sin registro de evaluación del dolor recibió tratamiento analgésico a demanda. En un 69,4 % de los 456 pacientes que no precisaron ingreso, al alta se pautó analgesia o se modificó el tratamiento analgésico previo [paracetamol (55 %), AINE (67 %), co-analgésicos (10 %), opioides débiles (10 %), opioides fuertes (1,1 %)]. Conclusiones: se evidencia una elevada prevalencia de dolor (75 %) en los pacientes que acuden al servicio de urgencias. El 41,7 % de los pacientes que presentaban dolor recibió tratamiento analgésico durante su estancia y en el 69,4 % de los pacientes que no precisaron ingreso se pautó analgesia al alta. Destaca la baja prescripción de opioides (AU)


Aim: To know the prevalence of pain and the therapeutic approach in an emergency department (ED). Material and methods: Cross-sectional study in the ED of a university hospital during 7 consecutive days was performed. The presence of pain was asked by a physician to patients older than 15 years admitted at ED. Patients admitted at Psychiatry, Obstetrics-Gynecology Emergency Department and those whose serious condition would not allow pain assessment in triage were excluded. The previous analgesic treatment, pain assessment, analgesic treatment in the ED and also scheduled treatment at discharge were later reviewed. Results: Six hundred and sixty-eight from 2,287 patients who were admitted at ED were analyzed. Five hundred and one patients reported pain (75 %), of which 45 were admitted and 456 were discharged at home (240 patients in level 1, 216 at level 2). The 24.5 % of the 501 patients who reported pain at admission were previously treated with analgesics. The 41.7 % of the 216 patients treated at level 2 received analgesic treatment during their stay [paracetamol (80.2 %), nonsteroidal antiinflammatory drugs (NSAIDs) (50.0 %), co-analgesics (1.0 %), weak opioids (20.8 %), strong opioids (3.1 %)]. The 32.7 % of the 196 patients without documented pain assessment received analgesic treatment as required. In 69.4 % of the 456 patients who did not require hospitalization, analgesic treatment was prescribed or modified at discharge [paracetamol (55 %), nonsteroidal anti-inflammatory drugs (NSAIDs) (67 %), co-analgesics (10 %), weak opioids (10 %), strong opioids (1.1 %)]. Conclusions: A high prevalence of pain (75 %) was found in patients admitted at ED. The 41.7 % received analgesic treatment during their stay and in 69.4 % of patients analgesia was prescribed at discharge. Low opioid prescription was detected (AU)


Subject(s)
Humans , Male , Female , Pain/epidemiology , Pain Measurement/trends , Pain Measurement , Emergencies/epidemiology , Emergency Medicine/organization & administration , Emergency Medicine/standards , Hospitals, University/standards , Hospitals, University , Analgesia/methods , Analgesia , Cross-Sectional Studies/methods , Cross-Sectional Studies/trends , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Acetaminophen/therapeutic use , Receptors, Opioid, delta/therapeutic use
2.
SD, Rev. med. int. Síndr. Down (Ed. castell.) ; 16(1): 3-10, ene.-abr. 2012. tab, ilus
Article in Spanish | IBECS | ID: ibc-99892

ABSTRACT

La esperanza de vida está aumentando considerablemente en la población con síndrome de Down (SD), gracias a los avances sanitarios y a las condiciones de vida. Como consecuencia de este fenómeno, surgen necesidades específi cas para las personas con SD de edad avanzada, que requieren una atención sanitaria especializada. El presente artículo pretende dar una visión actualizada del envejecimiento y fi nal de vida en la población con SD, mediante tres apartados: a) defi nición de conceptos geriátricos; b) problemas médicos específi cos del envejecimiento en el SD, y c) fi nal de vida en el SD. En último lugar, se propone una guía de recomendaciones para detectar problemas específi cos en la atención de pacientes con SD de edad avanzada (AU)


Life expectancy is increasing considerably in the population with Down’s syndrome (DS), thanks to advances in health care and living conditions. As a result, older people with DS require specialized care. This article aims to give an updated view of ageing and end of life in people with DS, with three sections: 1. Defi nition of geriatric concepts, 2. Specifi c medical problems of ageing in DS, 3. End of life in DS. Finally, a set of guidelines for the detection of specifi c problems in the care of older patients with DS is proposed (AU)


Subject(s)
Humans , Male , Female , Down Syndrome/epidemiology , Down Syndrome/prevention & control , Down Syndrome/physiopathology , Aging/physiology , Obesity/complications , Life Expectancy/trends , Down Syndrome/mortality , Comorbidity , Dementia/complications , Dementia/psychology , Vision Disorders/complications , Hearing Disorders/complications , Musculoskeletal Abnormalities/complications , Mitral Valve/pathology
4.
Med. paliat ; 17(1): 13-16, ene.-feb. 2010. tab
Article in Spanish | IBECS | ID: ibc-137738

ABSTRACT

Introducción: la actividad de los voluntarios en cuidados paliativos es esencial para todo equipo asistencial de calidad. Es conveniente evaluar la actividad de los mismos del modo más objetivo posible. Sin embargo, esta valoración implica notables dificultades metodológicas. Objetivo: evaluar la efectividad de la actividad de un equipo de voluntarios en una unidad de cuidados paliativos. Método: estudio observacional prospectivo. Durante un año los voluntarios de una unidad de cuidados paliativos evaluaron los parámetros dolor, tristeza, ansiedad, aislamiento, enfado, resignación y tranquilidad, antes y después de su intervención, mediante una puntuación de O a 4 para cada parámetro. Se compararon los cambios en la puntuación de los parámetros antes y después de la actividad, globalmente y en función de si se han realizado sobre familiares o pacientes. Resultados: se realizaron un total de 659 actividades de voluntariado sobre pacientes (78,9%) y familiares (21,1%). Todos los parámetros analizados mejoraron globalmente, según los voluntarios, después de la intervención de los mismos, aunque desglosados por pacientes (resignación) o familiares (ansiedad, aislamiento, enfado) no obtuvieron significación estadística. Conclusiones: la actividad de los voluntarios parece efectiva según los resultados obtenidos. A pesar de la subjetividad de la valoración por parte de los voluntarios es necesario realizar evaluaciones sistemáticas de la actividad del voluntariado. Conviene diseñar estudios que superen esta dificultad y que confirmen el beneficio de la actividad de voluntariado (AU)


Introduction: volunteers take an active part in a Palliative Care Unit. Adequate methodology should be encouraged to evaluate their activity. Objective: to evaluate volunteer activity effectiveness in a Palliative Care Unit. Method: a prospective study. During a year, volunteers examined their task by evaluating their next items both before and after their activity (score 0-4): pain, sadness, anxiety, isolation/solitude, anger, resignation, serenity. Increased or decreased item scores were compared (before and after the activity, dealing with patients or families). Results: 659 volunteer activities were conducted (78.9% patients, 21.1% family members). All items analyzed improved after volunteer activity, and it was statistically significant except for resignation in patients and anxiety, isolation and anger in family members. Conclusion: voIunteer activity seems to be effective in patients and families despite the (act that their own evaluation may be subjective. There is a need to improve the methodology to evaluate their task (AU)


Subject(s)
Humans , Palliative Care/organization & administration , Hospital Volunteers/organization & administration , Terminally Ill/psychology , Affective Symptoms/epidemiology , Prospective Studies , Evaluation of the Efficacy-Effectiveness of Interventions
5.
Med. paliat ; 16(5): 261-264, sept.-oct. 2009. tab, ilus
Article in Spanish | IBECS | ID: ibc-84461

ABSTRACT

La elevada prevalencia de la oclusión intestinal en pacientes oncológicos avanzados hace que esta complicación sea frecuente en unidades de cuidados paliativos. En el diagnóstico diferencial se incluyen las causas adinámicas, y entre ellas el síndrome de Ogilvie o seudo obstrucción intestinal aguda colónica (SOAC). Dicha entidad consiste en una obstrucción aguda que afecta exclusivamente al intestino grueso sin una causa mecánica.Es de interés reconocer el SOAC porque su manejo difiere radicalmente de otras entidades si no se resuelve con medidas de soporte habituales. En estos casos el tratamiento indicado es la neostigmina (inhibidor de la colinesterasa). Como última opción, se debe recurrir a la colonoscopiades compresiva o la cirugía. Presentamos el caso de una mujer afecta de carcinoma escamoso de glotis, que tras cirugía radical ingresó en una unidad de cuidados paliativos para control sintomático. Durante el ingreso presentó un cuadro de SOAC, que se resolvió con neostigmina (AU)


Intestinal obstruction is a prevalent complication of advanced cancer. There is often clinical obstruction in the absence of a mechanical lesion(functional obstruction). Ogilvie’s syndrome or acute colonic pseudo obstruction is a cause of functional obstruction whose management differs from that used for other etiologies in the absence of response to conservative measures. In these cases the recommended treatment is the cholinesterase inhibitor neostigmine. When neostigmine is ineffective, colonoscopic tube decompression or surgery are indicated. We report a case of a woman who was admitted to a palliative care unit after glottis cancer surgery. She developed acute colonic pseudo obstruction, which responded to neostigmine treatment (AU)


Subject(s)
Humans , Female , Middle Aged , Colonic Pseudo-Obstruction/diagnosis , Laryngeal Neoplasms/complications , Glottis/pathology , Diagnosis, Differential
6.
Mol Ecol ; 18(19): 3980-91, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19735449

ABSTRACT

Assessing how genes flow across populations is a key component of conservation genetics. Gene flow in a natural population depends on ecological traits and the local environment, whereas for a livestock population, gene flow is driven by human activities. Spatial organization, relationships between farmers and their husbandry practices will define the farmer's network and so determine farmer connectivity. It is thus assumed that farmer connectivity will affect the genetic structure of their livestock. To test this hypothesis, goats reared by four different ethnic groups in a Vietnamese province were genotyped using 16 microsatellites. A Bayesian approach and spatial multivariate analysis (spatial principal component analysis, sPCA) were used to identify subpopulations and spatial organization. Ethnic group frequencies, husbandry practices and altitude were used to create cost maps that were implemented in a least-cost path approach. Genetic diversity in the Vietnamese goat population was low (0.508) compared to other local Asian breeds. Using a Bayesian approach, three clusters were identified. sPCA confirmed these three clusters and also that the genetic structure showed a significant spatial pattern. The least-cost path analysis showed that genetic differentiation was significantly correlated (0.131-0.207) to ethnic frequencies and husbandry practices. In brief, the spatial pattern observed in the goat population was the result of complex gene flow governed by the spatial distribution of ethnic groups, ethnicity and husbandry practices. In this study, we clearly linked the livestock genetic pattern to farmer connectivity and showed the importance of taking into account spatial information in genetic studies.


Subject(s)
Animals, Domestic/genetics , Breeding , Gene Flow , Genetics, Population , Goats/genetics , Animal Husbandry , Animals , Animals, Domestic/classification , Cluster Analysis , Genotype , Goats/classification , Microsatellite Repeats , Multivariate Analysis , Principal Component Analysis , Sequence Analysis, DNA , Vietnam
7.
Med. paliat ; 16(4): 222-228, jul.-ago. 2009. graf, tab
Article in Spanish | IBECS | ID: ibc-76817

ABSTRACT

Objetivo: analizar la producción científica en el ámbito de los cuidados paliativos basándose en las comunicaciones presentadas en los III, IV,V y VI congresos de la SECPAL. Material y método: se han presentado un total de 1.069 comunicaciones orales o póster. Para cada comunicación se han analizado los siguientes parámetros: comunidad de origen, número de autores, principales centros investigadores, lugar de trabajo, áreas temáticas y tipo de estudio. Las comunicaciones presentadas en los V y VI Congresos se han puntuado en función de 6 parámetros: importancia, interés, relación entre título y contenido, adecuación del diseño y metodología, solidez y relevancia de los resultados y solidez de las conclusiones. Resultados: las comunidades autónomas más activas han sido Cataluña,Valencia, Canarias y Andalucía. El equipo más productivo ha sido el Hospital Dr. Negrín de Las Palmas de Gran Canaria (90 comunicaciones). La mayoría de comunicaciones corresponden a trabajos realizados en unidades de cuidados paliativos (434), seguidas por las efectuadas en equipos de soporte domiciliarios (175). Los temas de organización, otros síntomas excepto dolor, tratamiento complementario y farmacología son las áreas temáticas preponderantes. El 21% son estudios prospectivos. Sobre un máximo de 18 puntos por comunicación, la media ha sido de 7,66 para el V Congreso y de 7,36 para el VI. Conclusiones: el mayor número de aportaciones a los congresos de la SECPAL corresponde a las unidades de cuidados paliativos. El nivel científico es mejorable y es necesario un esfuerzo para la mejora de la calidad de los trabajos presentados (AU)


Objective: to describe the scientific activity in palliative care research in Spain, as measured by the abstracts submitted to four national congresses of the Spanish Society of Palliative Care (SECPAL) (3th-6th, from 2000 to 2006). Material and method: 1,069 abstracts accepted in the four congresses were analyzed. Data collected: autonomic administration source, number of authors, work center, issues, study design. The quality of the abstracts presented to the 5th and 6th congresses was evaluated. Assessments included six items: study importance, interest, connection between title and contents, study design, result and conclusion significance. Results: the most productive autonomic administrations were Catalonia, Valencia, Canary Islands and Andalusia. Mean authors: 5.4 (1-19). Setting: 175 (16%) Home Palliative Care Team, 434 (41%) Palliative CareUnit, 129 (12%) Medical Oncology Department, 154 (14%) other hospital departments, and 179 (17%) others. Topic areas: 234 (22%) organization, 69 (6%) pain, 186 (17%) other symptoms, 106 (10%) complementary therapies/treatment, 101 (9%) pharmacology, 51 (5%) family, 322 (31%) others. Study design: 452 (42%) descriptive, 224 (21%) retrospective, 224 (21%) prospective, 22 (2%) others. Mean total score obtained was 7.66 (5th congress) and 7.36 (6th congress) (range: 0-18). Conclusions: Palliative Care Units presented most of the abstracts. Organization and health system issues were common topics. The mean total score obtained was low. Prospective and multicenter studies should be encouraged to improve research in palliative care, and more stringent criteria for abstract acceptance should be implemented (AU)


Subject(s)
Humans , Scientific and Technical Publications , Palliative Care/statistics & numerical data , Congresses as Topic , Societies, Medical , Bibliometrics , Spain
8.
Diagn Microbiol Infect Dis ; 46(4): 259-64, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12944017

ABSTRACT

The frequency of isolation and antifungal susceptibility patterns to established and two new antifungal agents were determined for 218 Candida spp isolates causing bloodstream infection from 1996 to 2001. Overall, 41.7% of the candidemias were due to C. albicans, followed by C. parapsilosis (22%), C. tropicalis (16.1%), C. glabrata (11.9%), C. krusei (6%) and miscellaneous Candida spp (2.3%). Isolates of C. albicans C. parapsilosis and C. tropicalis (80% of isolates) were highly susceptible to fluconazole (94 to 100% at /= 32 microg/ml).


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Candidiasis/blood , Fungemia/blood , Peptides, Cyclic/pharmacology , Pyrimidines/pharmacology , Triazoles/pharmacology , Anidulafungin , Candida/classification , Drug Resistance, Fungal , Echinocandins , Female , Hospitals, University , Humans , Male , Microbial Sensitivity Tests/statistics & numerical data , Microbial Sensitivity Tests/trends , Retrospective Studies , Sensitivity and Specificity , Spain , Voriconazole
9.
Mol Cell Biol ; 21(18): 6254-69, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11509668

ABSTRACT

Cyclin E is a G(1) cyclin essential for S-phase entry and has a profound role in oncogenesis. Previously this laboratory found that cyclin E is overexpressed and present in lower-molecular-weight (LMW) isoforms in breast cancer cells and tumor tissues compared to normal cells and tissues. Such alteration of cyclin E is linked to poor patient outcome. Here we report that the LMW forms of cyclin E are hyperactive biochemically and they can more readily induce G(1)-to-S progression in transfected normal cells than the full-length form of the protein can. Through biochemical and mutational analyses we have identified two proteolytically sensitive sites in the amino terminus of human cyclin E that are cleaved to generate the LMW isoforms found in tumor cells. Not only are the LMW forms of cyclin E functional, as they phosphorylate substrates such as histone H1 and GST-Rb, but also their activities are higher than the full-length cyclin E. These nuclear localized LMW forms of cyclin E are also biologically functional, as their overexpression in normal cells increases the ability of these cells to enter S and G(2)/M. Lastly, we show that cyclin E is selectively cleaved in vitro by the elastase class of serine proteases to generate LMW forms similar to those observed in tumor cells. These studies suggest that the defective entry into and exit from S phase by tumor cells is in part due to the proteolytic processing of cyclin E, which generates hyperactive LMW isoforms whose activities have been modified from that of the full-length protein.


Subject(s)
Cyclin E/metabolism , Neoplasms/metabolism , Amino Acid Sequence , Cyclin E/genetics , Humans , Molecular Sequence Data , Neoplasms/genetics , Neoplasms/pathology , S Phase , Structure-Activity Relationship , Tumor Cells, Cultured
10.
J Acquir Immune Defic Syndr ; 27(1): 35-43, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11404518

ABSTRACT

OBJECTIVE: To study the incidence, etiology, and outcome of pulmonary infiltrates (PIs) in HIV-infected patients and to evaluate the yield of diagnostic procedures. DESIGN: Prospective observational study of consecutive hospital admissions. SETTING: Tertiary hospital. PATIENTS: HIV-infected patients with new-onset radiologic PIs from April 1998 to March 1999. METHODS: The study protocol included chest radiography, blood and sputum cultures, serologic testing for "atypical" causes of pneumonia, testing for Legionella urinary antigen, testing for cytomegalovirus antigenemia, and bronchoscopy in case of diffuse or progressive PIs. RESULTS: One hundred two episodes in 92 patients were recorded. The incidence of PIs was 18 episodes per 100 hospital admission-years (95% confidence interval [CI]: 15-21). An etiologic diagnosis was achieved in 62 cases (61%). Bacterial pneumonia (BP), Pneumocystis carinii pneumonia (PCP), and mycobacteriosis were the main diagnoses. The incidences of BP and mycobacteriosis were not statistically different in highly active antiretroviral therapy (HAART) versus non-HAART patients. The incidence of PCP was lower in those receiving HAART (p =.011), however. Nine patients died (10%). Independent factors associated with higher mortality were mechanical ventilation (odds ratio [OR] = 83; CI: 4.2-1,682), age >50 years (OR = 23; CI: 2-283), and not having an etiologic diagnosis (OR = 22; CI: 1.6-293). CONCLUSIONS: Pulmonary infiltrates are still a frequent cause of hospital admission in the HAART era, and BP is the main etiology. There was no difference in the rate of BP and mycobacteriosis in HAART and non-HAART patients. Not having an etiologic diagnosis is an independent factor associated with mortality.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/complications , HIV Infections/drug therapy , Lung Diseases , Adult , Aged , CD4 Lymphocyte Count , Female , HIV-1/physiology , Humans , Incidence , Lung Diseases/diagnosis , Lung Diseases/epidemiology , Lung Diseases/etiology , Lung Diseases/mortality , Male , Middle Aged , Prospective Studies , Viral Load
11.
Thorax ; 56(5): 379-87, 2001 May.
Article in English | MEDLINE | ID: mdl-11312407

ABSTRACT

BACKGROUND: The development of pulmonary infiltrates is a frequent life threatening complication in immunocompromised patients, requiring early diagnosis and specific treatment. In the present study non-invasive and bronchoscopic diagnostic techniques were applied in patients with different non-HIV immunocompromised conditions to determine the aetiology of the pulmonary infiltrates and to evaluate the impact of these methods on therapeutic decisions and outcome in this population. METHODS: The non-invasive diagnostic methods included serological tests, blood antigen detection, and blood, nasopharyngeal wash (NPW), sputum and tracheobronchial aspirate (TBAS) cultures. Bronchoscopic techniques included fibrobronchial aspirate (FBAS), protected specimen brush (PSB), and bronchoalveolar lavage (BAL). Two hundred consecutive episodes of pulmonary infiltrates were prospectively evaluated during a 30 month period in 52 solid organ transplant recipients, 53 haematopoietic stem cell transplant (HSCT) recipients, 68 patients with haematological malignancies, and 27 patients requiring chronic treatment with corticosteroids and/or immunosuppressive drugs. RESULTS: An aetiological diagnosis was obtained in 162 (81%) of the 200 patients. The aetiology of the pulmonary infiltrates was infectious in 125 (77%) and non-infectious in 37 (23%); 38 (19%) remained undiagnosed. The main infectious aetiologies were bacterial (48/125, 24%), fungal (33/125, 17%), and viral (20/125, 10%), and the most frequent pathogens were Aspergillus fumigatus (n=29), Staphylococcus aureus (n=17), and Pseudomonas aeruginosa (n=12). Among the non-infectious aetiologies, pulmonary oedema (16/37, 43%) and diffuse alveolar haemorrhage (10/37, 27%) were the most common causes. Non-invasive techniques led to the diagnosis of pulmonary infiltrates in 41% of the cases in which they were used; specifically, the diagnostic yield of blood cultures was 30/191 (16%); sputum cultures 27/88 (31%); NPW 9/50 (18%); and TBAS 35/55 (65%). Bronchoscopic techniques led to the diagnosis of pulmonary infiltrates in 59% of the cases in which they were used: FBAS 16/28 (57%), BAL 68/135 (51%), and PSB 30/125 (24%). The results obtained with the different techniques led to a change in antibiotic treatment in 93 cases (46%). Although changes in treatment did not have an impact on the overall mortality, patients with pulmonary infiltrates of an infectious aetiology in whom the change was made during the first 7 days had a better outcome (29% mortality) than those in whom treatment was changed later (71% mortality; p=0.001). CONCLUSIONS: Non-invasive and bronchoscopic procedures are useful techniques for the diagnosis of pulmonary infiltrates in immunocompromised patients. Bronchial aspirates (FBAS and TBAS) and BAL have the highest diagnostic yield and impact on therapeutic decisions.


Subject(s)
AIDS-Related Opportunistic Infections/complications , HIV Infections/complications , Immunocompromised Host , Lung Diseases/diagnosis , AIDS-Related Opportunistic Infections/diagnosis , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Antiviral Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Bronchoalveolar Lavage Fluid/microbiology , Bronchoscopy/methods , Female , Humans , Lung Diseases/drug therapy , Lung Diseases/microbiology , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Male , Prognosis , Prospective Studies
12.
J Natl Cancer Inst ; 92(24): 1999-2008, 2000 Dec 20.
Article in English | MEDLINE | ID: mdl-11121462

ABSTRACT

BACKGROUND: A major limiting factor in human cancer chemotherapy is toxicity in normal tissues. Our goal was to determine whether normal proliferating cells could be protected from chemotherapeutic agents by taking advantage of the differential drug sensitivity of cell cycle G(1) checkpoint in normal and cancer cells. METHODS: Normal mammary epithelial cells and mammary cancer cells were initially treated with staurosporine at a cytostatic (i.e., nonlethal) concentration, which preferentially arrests normal cells in the G(0)/G(1) phase of the cell cycle without affecting the proliferation of tumor cells. After the selective arrest of normal cells in G(0)/G(1), both normal and tumor cells were treated with doxorubicin or camptothecin, two cytotoxic (i.e., lethal) chemotherapeutic agents. Cells were then allowed to recover in drug-free medium for 12 days. RESULTS: After pretreatment of both normal and tumor cells with staurosporine followed by treatment with doxorubicin or camptothecin, tumor cells were selectively killed by chemotherapeutic agents, whereas normal cells resumed proliferation after the drugs were removed. Pretreatment with staurosporine also protected normal circulating lymphocytes that had been induced to proliferate in vitro with phytohemagglutinin from chemotherapeutic agents. Staurosporine-induced arrest of normal cells in G(0)/G(1) phase was reversible, and arrested cells tolerated doses of camptothecin that were more than 100-fold higher than necessary to eradicate all tumor cells in culture. Staurosporine-mediated G(0)/G(1) arrest targets the retinoblastoma protein (pRb) pathway and was accompanied by a rapid decrease in cyclin-dependent kinase (CDK) 4 protein levels, increased binding of CDK inhibitors p21 and p27 to CDK2, and inhibition of CDK2 activity in normal cells. CONCLUSIONS: Breast cancer cells with defective checkpoints regulated by the pRb pathway can be targeted specifically with chemotherapeutic agents, following staurosporine-mediated, selective and reversible G(0)/G(1) arrest in normal cells.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast/drug effects , Cyclin-Dependent Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Epithelial Cells/drug effects , Interphase/drug effects , Lymphocytes/drug effects , Staurosporine/pharmacology , Blotting, Western , Breast/cytology , Breast/enzymology , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Camptothecin/adverse effects , Cells, Cultured/drug effects , Cytoprotection/drug effects , Doxorubicin/adverse effects , Feasibility Studies , Female , Flow Cytometry , Humans , Precipitin Tests , Time Factors , Tumor Cells, Cultured/drug effects
13.
Enferm Infecc Microbiol Clin ; 18(6): 274-8, 2000.
Article in Spanish | MEDLINE | ID: mdl-11075484

ABSTRACT

BACKGROUND: To study the usefulness of IgG and IgM titration, and avidity of IgG to date IgM anti-Toxoplasma gondii. METHODS: VIDAS Toxo IgG, VIDAS Toxo IgM and VIDAS Toxo IgG Avidity tests were used. 64 sera containing both IgM and IgG T. gondii antibodies were analyzed, 32 from 12 individuals infected 40 weeks previously (group I), and the remainder from 17 individuals with an infection of more than 40 weeks (group II). RESULTS: An IgM index < 1.05 was associated with an infection > 12 weeks. An avidity index > 0.164 excluded 100% infections of < or = 12 weeks. Avidity indexes > 0.26 and 0.45 excluded infections of < or = 20 and < or = 40 weeks, respectively. CONCLUSIONS: The serology methods used in this study can adequately identify residual IgM anti-T. gondii, often avoiding the need of a new blood extraction to analyze IgG kinetics in pregnant women.


Subject(s)
Antibodies, Protozoan/blood , Fluorescent Antibody Technique, Indirect , Immunoglobulin M/blood , Pregnancy Complications, Parasitic/immunology , Toxoplasmosis/immunology , Adolescent , Adult , Antibodies, Protozoan/biosynthesis , Antibody Affinity , Female , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin M/biosynthesis , Middle Aged , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Parasitic/blood , Pregnancy Complications, Parasitic/parasitology , Pregnancy Trimesters , ROC Curve , Reagent Kits, Diagnostic , Time Factors , Toxoplasmosis/blood , Toxoplasmosis/parasitology
14.
J Natl Cancer Inst ; 92(17): 1403-13, 2000 Sep 06.
Article in English | MEDLINE | ID: mdl-10974076

ABSTRACT

BACKGROUND: Estrogen stimulates the proliferation of cells in normal mammary glands and most estrogen receptor (ER)-positive mammary carcinomas by binding to the ER and promoting the transcription of ER-responsive genes. In cells with functional ERs, estrogen mediates the transition of cells from the G(1) to S phase of the cell cycle. Several cell cycle regulatory proteins have been implicated in the ER-signaling pathway involved in estrogen-mediated growth stimulation and antiestrogen-mediated growth arrest. We sought to determine whether p21, a cyclin-dependent kinase inhibitor, is a component of this pathway and, if so, whether it can mediate estrogen's action in ER-negative breast cancer cells. METHODS: We overexpressed p21 with a tetracycline-inducible system in ER-negative, p21-negative breast cancer cells. Activity of the ER-signaling pathway was monitored in transient transfection assays by using constructs in which the ER promoter or the estrogen-response element (ERE) controls Luciferase expression. The growth-modulating effects of estradiol and antiestrogens on p21-overexpressing clones were assessed. All P: values are from two-sided tests. RESULTS: A strong positive association was found between the expression of p21 and ER in nine breast cancer cell lines and in tumor samples from 60 patients with breast cancer (P:<. 001). Overexpression of p21 in a p21-negative, ER-negative cell line induced both the ER and ERE promoters in an estrogen-responsive manner. Last, stable p21 clones that also lack the expression of wild-type ER were responsive to the growth-inhibitory effects of ICI 182,780, a potent antiestrogen, and the growth-stimulatory effects of 17beta-estradiol. CONCLUSION: The ability of p21 to mediate the activation of the estrogen-signaling pathway in ER-negative tumor cells suggests that p21 plays a novel role in this pathway, a finding that also has important clinical implications.


Subject(s)
Breast Neoplasms/metabolism , Cyclins/metabolism , Enzyme Inhibitors/metabolism , Estradiol/analogs & derivatives , Estrogens/metabolism , Antineoplastic Agents, Hormonal/pharmacology , Blotting, Western , Breast Neoplasms/drug therapy , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/drug effects , Estradiol/metabolism , Estradiol/pharmacology , Estrogen Receptor Modulators/pharmacology , Flow Cytometry , Fulvestrant , Humans , Luciferases/analysis , Receptors, Estrogen/metabolism , Signal Transduction/drug effects , Transfection , Tumor Cells, Cultured , Up-Regulation/drug effects
15.
Cancer Res ; 60(2): 481-9, 2000 Jan 15.
Article in English | MEDLINE | ID: mdl-10667604

ABSTRACT

Cyclin E is a G1 cyclin essential for G1 to S-phase transition of the cell cycle with a profound role in oncogenesis. In tumor cells and tissues, cyclin E is overexpressed and present in its lower molecular weight (LMW) isoforms, and it can be used as a prognosticator for poor patient outcome. In this study, we have examined differences in the processing of cyclin E between normal mammary epithelial and breast cancer cell lines. Five NH2-terminally deleted epitope-tagged (FLAG) cyclin E vectors were constructed spanning the range of LMW forms observed in tumor cells. These constructs were transfected into normal and tumor cells and analyzed for the production of cyclin E-FLAG protein products by Western blot analysis with FLAG and cyclin E antibodies. Our results show that only tumor cells had the machinery to process these cyclin E-FLAG constructs to their LMW forms, whereas normal cells mainly expressed the full-length unprocessed form of each protein. Tumor and normal cells always process the cyclin E-FLAG protein in the same way as endogenously expressed cyclin E. This phenomenon is consistent with all of the cell lines used, regardless of transfection efficiency, time of processing posttransfection, or method of transfection. Furthermore, measurement of FLAG-associated kinase activity in the transfectants revealed that the protein products of the cyclin E-FLAG constructs are 10 times more active in tumor cells than in normal cells. These studies suggest that the LMW forms of cyclin E detected at a much higher level in tumor cells arise from posttranslational action of a protease.


Subject(s)
Cyclin E/genetics , Gene Expression Regulation, Neoplastic , Gene Expression Regulation , Blotting, Western , Breast , Breast Neoplasms , Cell Line , Cyclin E/metabolism , Female , Genetic Vectors , Humans , Kinetics , Molecular Weight , Protein Biosynthesis , Protein Processing, Post-Translational , Recombinant Proteins/biosynthesis , Transcription, Genetic , Transfection , Tumor Cells, Cultured
16.
Med Clin (Barc) ; 115(10): 375-6, 2000 Sep 30.
Article in English, Spanish | MEDLINE | ID: mdl-11262353

ABSTRACT

UNLABELLED: To determine the need of prenatal screening for toxoplasmosis in our hospital from a seroepidemiological point of view. PATIENTS AND METHODS: The prevalence of IgG anti-T. gondii was retrospectively analyzed in 7.090 women of childbearing age attended in the Hospital Clínic of Barcelona from February 1992 to April 1999. The association among the seroprevalence and the variables year, age, birthplace (province of Barcelona/other provinces) and place of residence (urban/rural) was analyzed. A decreasing trend was observed in the prevalence (p < 0.001), currently being < 40% in the average women between 15 and 45 years. Infection was also directly related to age of women (p < 0.001) and birthplace out of the province of Barcelona (p = 0.001). Habitat (rural or urban) was not associated with seroprevalence. Prenatal screening for toxoplasmosis is necessary due to the high rate of seronegative women exposed to infection and the evidence of a high number of primoinfections in the childbearing period.


Subject(s)
Toxoplasmosis/epidemiology , Adolescent , Adult , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Prevalence , Retrospective Studies , Seroepidemiologic Studies , Spain/epidemiology , Toxoplasmosis/prevention & control
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