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1.
Br J Dermatol ; 175 Suppl 2: 30-34, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27667313

RESUMEN

Survival from melanoma is influenced by several, well-established clinical and histopathological factors, e.g. age, Breslow thickness and microscopic ulceration. We (the Section of Epidemiology and Biostatistics, University of Leeds) have carried out research to better understand the biological basis for these observations. Preliminary results indicated a protective role for vitamin D in melanoma relapse and that higher vitamin D was associated with thinner primary melanomas. Funding from the British Skin Foundation enabled JNB to establish a study of the effects of vitamin A in melanoma. The results suggested that vitamin A could reduce the protective effect of vitamin D in terms of overall survival. Therefore, we propose that vitamin D3 supplementation alone might be preferable to combined multivitamin preparations, where vitamin D supplementation is deemed to be appropriate. Proving a causal link between vitamin D and melanoma-specific survival is challenging. We have shown limited evidence of causation in a Mendelian randomization experiment (described in more detail later). Recent work in Leeds has also shown that higher vitamin D may be protective for microscopic ulceration. Taken together, vitamin D appears to be associated with less aggressive primary melanomas and may itself influence outcome. We continue to explore the role of vitamin D in melanoma survival and the optimum levels that might be crucial.

2.
Lasers Surg Med ; 44(5): 397-405, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22505339

RESUMEN

BACKGROUND: Light therapy is a common mode of treatment for musculoskeletal injuries but the depth of penetration of light radiation is controversial. Evidence exists for the efficacy of intense pulsed light (IPL) treatment for the rejuvenation of skin (superficial tissue) but it is not known if the IPL can penetrate deeper. If the IPL can penetrate to the depth of the Achilles tendon it may provide a potential management options in the treatment of a chronic mid-body Achilles tendinopathy. OBJECTIVES: To examine if any optical radiation produced by an IPL transmits to the depth of the Achilles tendon when applied cutaneously to excised samples of human Achilles tissue. A secondary aim was to establish the relative amount of optical radiation that was attenuated within the tendon. MATERIALS AND METHODS: Three samples of human Achilles tendon and surrounding tissue were harvested following elective lower limb amputation operations. Each sample was irradiated 2-6 cm above the insertion into the calcaneus (area of an Achilles tendinopathy) with IPL (model iPulse; Cyden Ltd, Wales, UK) set at a single pulse of 25 millisecond, wavelength range 530-1,110 nm and fluence of 13 J/cm(2). The transmission of light radiation was evaluated using (a) standard SLR digital camera, (b) spectrometer, and (c) an external energy meter. RESULTS: Light radiation was found to have transmitted through each of the three tissue samples by all three instruments. There were observable differences in the color of light detected for the control photo and the IPL irradiated tissue samples photographs. The percentage of fluence that was detected to have transmitted through the tissue samples by the energy meter was 4-8.1% and wavelengths between 645 and 843 nm were detected to have transmitted through the tissue by the spectrometer. In addition, the percentage of light radiation that attenuated with the tendon was 10.2-17.32%. CONCLUSION: The results of this study provides evidence that IPL penetrates to the depth of the Achilles tendon and attenuates with the tendon. IPL has potential to produce physiological effects in the treatment of patients with a chronic mid-body Achilles tendinopathy.


Asunto(s)
Tendón Calcáneo , Fenómenos Ópticos , Fototerapia/instrumentación , Adulto , Femenino , Tecnología de Fibra Óptica , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Fotograbar , Análisis Espectral
3.
Complement Ther Med ; 19(6): 303-10, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22036522

RESUMEN

OBJECTIVES: To report the frequency of Complementary and Alternative Medicine (CAM) use by a population of pregnant women in the UK. DESIGN: Four postal self-completion questionnaires completed at 8, 12, 18 and 32 weeks' gestation provided the source of CAMs used. Questions asked for written descriptions about the use of any treatments, pills, medicines, ointments, homeopathic medicines, herbal medicines, supplements, drinks and herbal teas. SETTING: An observational, population-based, cohort study of parents and children of 14,541 pregnant women residing within the former county of Avon in south-west England. Data was available for 14,115 women. RESULTS: Over a quarter (26.7%; n=3774) of women had used a CAM at least once in pregnancy, the use rising from 6% in the 1st trimester to 12.4% in the 2nd to 26.3% in the 3rd. Herbal teas were the most commonly reported CAM at any time in pregnancy (17.7%; n=2499) followed by homeopathic medicine (14.4%; n=2038) and then herbal medicine (5.8%; n=813). The most commonly used herbal product was chamomile used by 14.6% of women, the most commonly used homeopathic product was Arnica used by 3.1% of women. Other CAMs (osteopathy, aromatherapy, acupuncture/acupressure, Chinese herbal medicine, chiropractic, cranial sacral therapy, hypnosis, non-specific massage and reflexology) accounted for less than 1% of users. CONCLUSIONS: CAM use in pregnancy, where a wide range of CAMs has been assessed, has not been widely reported. Studies that have been conducted report varying results to this study (26.7%) by between 13.3% and 87% of pregnant women. Survey results will be affected by a number of factors namely the inclusion/exclusion of vitamins and minerals, the timing of data collection, the country of source, the number of women surveyed, and the different selection criteria of either recruiting women to the study or of categorising and identifying a CAM treatment or product.


Asunto(s)
Terapias Complementarias/estadística & datos numéricos , Extractos Vegetales/uso terapéutico , Complicaciones del Embarazo/terapia , Arnica , Bebidas/estadística & datos numéricos , Manzanilla , Femenino , Homeopatía/estadística & datos numéricos , Humanos , Materia Medica/uso terapéutico , Fitoterapia/estadística & datos numéricos , Embarazo , Trimestres del Embarazo , Reino Unido
4.
Minerva Pediatr ; 60(1): 103-14, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18277369

RESUMEN

The increasing number and availability of various complementary and alternative medicines (CAM) has resulted in an exponentially growing utilization of these products for everything from minor aches and pains to the treatment of mental illness. Difficulties in treating mental illnesses in children, averseness to having children take psychiatric medications, and stigma all drive patients and their families to research alternative treatments. As a result, there has been an increased utilization of CAM in psychiatry, particularly for hard to treat conditions like pediatric BD. It is important for the health care providers to be aware of the alternative treatments by some of their patients. A review of studies investigating the utility of complementary and alternative medicines in bipolar patients was conducted and selected studies were included. Omega-3 fatty acids and lecithin/ choline have preliminary data indicating potential utility in the CAM treatment for bipolar disorder while S-adenosyl methionine (SAM-e) and inositol have some data supporting their efficacy in the treatment of depressive symptoms. Some data for CAM suggest they may be useful adjunctive treatments but only little data are available to support their use as stand-alone therapy. Thus, the conventional medicines remain the first choice in pediatric bipolar management. Healthcare providers need to routinely inquire about the utilization of these treatments by their patients and become familiar with the risks and benefits involved with their use in children.


Asunto(s)
Trastorno Bipolar/tratamiento farmacológico , Terapias Complementarias , Nootrópicos/uso terapéutico , Adolescente , Niño , Colina/uso terapéutico , Quimioterapia Combinada , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Inositol/uso terapéutico , Lecitinas/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , S-Adenosilmetionina/uso terapéutico , Tensoactivos/uso terapéutico , Resultado del Tratamiento , Complejo Vitamínico B/uso terapéutico
6.
Science ; 303(5660): 971-5, 2004 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-14963320

RESUMEN

The life cycles of sexually reproducing animals and flowering plants begin with male and female gametes and their fusion to form a zygote. Selection at this earliest stage is crucial for offspring quality and raises similar evolutionary issues, yet zoology and botany use dissimilar approaches. There are striking parallels in the role of prezygotic competition for sexual selection on males, cryptic female choice, sexual conflict, and against selfish genetic elements and genetic incompatibility. In both groups, understanding the evolution of sex-specific and reproductive traits will require an appreciation of the effects of prezygotic competition on fitness.


Asunto(s)
Evolución Biológica , Magnoliopsida/fisiología , Polen/fisiología , Reproducción , Conducta Sexual Animal , Espermatozoides/fisiología , Animales , Conducta Competitiva , Copulación , Femenino , Expresión Génica , Masculino , Selección Genética , Caracteres Sexuales
7.
Eur J Cancer ; 40(3): 429-35, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14746862

RESUMEN

Migration, latitude and case-control studies have clearly established a link between melanoma and sun exposure. This case-control study of melanoma was set up to examine the role of sun exposure and sunbeds in the pathogenesis of melanoma in the United Kingdom (UK), a country with low levels of ultraviolet radiation. The study included 413 cases and 416 controls. More than 10 severe sunburns compared with less than 10 sunburns was associated with an Odds Ratio (OR) of 1.98 (95% Confidence Interval (CI) 1.02-3.86) (P=0.04) when adjusted for age, gender and skin type. Sunburns before the age of 15 years were not associated with melanoma once adjustments for age, gender and skin were made. 31% of women and 16% of the men had used sunbeds. Sunbed users were younger than non-users (40 years versus 51 years, P<0.0001). Ever use of sunbeds gave an adjusted OR of 1.19 (95% CI 0.84-1.68) (P=0.33). The risk of melanoma did not increase with increasing hours or years of sunbed exposure. The risk associated with sunbed use was only significant for young individuals with fair skin for whom there was a significant OR of 2.66 (95% CI 1.66-6.09) (P=0.02) after adjustment for the sun exposure variables. Outdoor occupation and residence in hot countries were not associated with an increased risk of melanoma. The only significant associations in this study were with 10 or more sunburns and the use of a sunbed in young subjects with fair skin. Sunbed use is now becoming more prevalent in Caucasian populations and the results of this study suggest that sunbed usage may moderately affect individuals with sun-sensitive skin types. However, the magnitude of melanoma risk in association with natural and artificial sun exposure is small compared with phenotypic risk factors such as skin type and naevus counts. However, it is possible that the mean lag time of 7 years between exposure to sunbed and melanoma in this study may have led to an under-estimation of the long-term melanoma risk.


Asunto(s)
Helioterapia/efectos adversos , Melanoma/etiología , Neoplasias Cutáneas/etiología , Luz Solar/efectos adversos , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Vacaciones y Feriados , Humanos , Lactante , Recién Nacido , Londres/epidemiología , Masculino , Melanoma/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Factores de Tiempo
8.
Arch Dis Child Fetal Neonatal Ed ; 88(4): F302-7, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12819162

RESUMEN

OBJECTIVE: To assess the effect on growth and iron status in preterm infants of a specially devised weaning strategy compared with current best practices in infant feeding. The preterm weaning strategy recommended the early onset of weaning and the use of foods with a higher energy and protein content than standard milk formula, and foods that are rich sources of iron and zinc. SUBJECTS AND DESIGN: In a blinded, controlled study, 68 preterm infants (mean (SD) birth weight 1470 (430) g and mean (SD) gestational age 31.3 (2.9) weeks) were randomised to either the preterm weaning strategy group (n = 37) or a current best practice control group (n = 31), from hospital discharge until 1 year gestation corrected age (GCA). MAIN OUTCOME MEASURES: Weight, supine length, occipitofrontal head circumference, and intakes of energy, protein, and minerals were determined at 0, 6, and 12 months GCA. Levels of haemoglobin, serum iron, and serum ferritin were assayed at 0 and 6 months GCA. RESULTS: Significant positive effects of treatment included: greater increase in standard deviation length scores and length growth velocity; increased intake of energy, protein, and carbohydrate at 6 months GCA and iron at 12 months GCA; increased haemoglobin and serum iron levels at 6 months GCA. CONCLUSIONS: The preterm weaning strategy significantly influenced dietary intakes with consequent beneficial effects on growth in length and iron status. This strategy should be adopted as the basis of feeding guidelines for preterm infants after hospital discharge.


Asunto(s)
Fenómenos Fisiológicos Nutricionales del Lactante , Recien Nacido Prematuro/crecimiento & desarrollo , Destete , Factores de Edad , Estatura , Peso Corporal , Cefalometría , Distribución de Chi-Cuadrado , Dieta , Proteínas en la Dieta/administración & dosificación , Adhesión a Directriz , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro/sangre , Hierro/sangre , Estado Nutricional , Método Simple Ciego
9.
Proc Natl Acad Sci U S A ; 99(8): 5442-7, 2002 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-11960000

RESUMEN

The Suppressor of Fused [Su(fu)] protein plays a conserved role in the regulation of Gli transcription factors of the hedgehog (Hh) signaling pathway that controls cell fate and tissue patterning during development. In both Drosophila and mammals, Su(fu) represses Gli-mediated transcription, but the mode of its action is not completely understood. Recent evidence suggests that Su(fu) physically interacts with the Gli proteins and, when overexpressed, sequesters Gli in the cytoplasm. However, Su(fu) also traverses into the nucleus under the influence of a serine-threonine kinase, Fused (Fu), and has the ability to form a DNA-binding complex with Gli, suggesting that it has a nuclear function. Here we report that the mouse homolog of Su(fu) [mSu(fu)] specifically interacts with SAP18, a component of the mSin3 and histone deacetylase complex. In addition, we demonstrate that mSu(fu) functionally cooperates with SAP18 to repress transcription by recruiting the SAP18-mSin3 complex to promoters containing the Gli-binding element. These results provide biochemical evidence that Su(fu) directly participates in modulating the transcriptional activity of Gli.


Asunto(s)
Proteínas Portadoras , Proteínas de Drosophila , Proteínas Oncogénicas/metabolismo , Proteínas Represoras/fisiología , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/metabolismo , Transcripción Genética , Animales , Western Blotting , Núcleo Celular/metabolismo , Proteínas Co-Represoras , Citoplasma/metabolismo , ADN Complementario/metabolismo , Relación Dosis-Respuesta a Droga , Drosophila , Biblioteca de Genes , Glutatión Transferasa/metabolismo , Histona Desacetilasas/metabolismo , Humanos , Plásmidos/metabolismo , Pruebas de Precipitina , Unión Proteica , Proteínas de Unión al ARN , Proteínas Represoras/metabolismo , Transactivadores , Transfección , Técnicas del Sistema de Dos Híbridos , Proteína con Dedos de Zinc GLI1
10.
Cancer Gene Ther ; 7(8): 1165-71, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10975677

RESUMEN

Using a novel cationic lipid delivery system consisting of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride and cholesterol, we delivered murine interleukin-2 (IL-2) cDNA directly into an established murine renal cell carcinoma (Renca). Production of IL-2 within the tumor induced rejection of established tumors (62% on average), whereas control plasmid had little or no effect (17% on average). Surviving animals treated with IL-2:lipid were highly resistant to Renca rechallenge, but not to cross-challenge with a syngeneic mammary adenocarcinoma. Experiments on selectively immunosuppressed animals indicated a requirement for CD8+ T, natural killer, and polymorphonuclear cells. By contrast, depletion of CD4+ T cells did not disrupt the ability of IL-2:lipid to induce tumor rejection. A combination of IL-2 gene therapy with 5-fluorouracil treatment increased the antitumoral efficacy and survival of mice bearing primary and metastatic Renca tumors (42% survival with IL-2:lipid compared with 94% survival with IL-2:lipid plus 5-fluorouracil). These data indicate that rejection of primary and metastatic tumors can be achieved after intratumoral delivery of a nonviral IL-2 gene therapy, and is increased in combination with systemic delivery of a conventional chemotherapeutic agent.


Asunto(s)
Carcinoma de Células Renales/terapia , Fluorouracilo/uso terapéutico , Terapia Genética , Interleucina-2/genética , Neoplasias Renales/terapia , Animales , Terapia Combinada , ADN Complementario/administración & dosificación , Femenino , Interleucina-2/biosíntesis , Interleucina-2/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Compuestos de Amonio Cuaternario/administración & dosificación
11.
Hum Mol Genet ; 9(11): 1709-15, 2000 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10861298

RESUMEN

The PDS gene encodes a transmembrane protein, known as pendrin, which functions as a transporter of iodide and chloride. Mutations in this gene are responsible for Pendred syndrome and autosomal recessive non-syndromic hearing loss at the DFNB4 locus on chromosome 7q31. A screen of 20 individuals from the midwestern USA with non-syndromic hearing loss and dilated vestibular aqueducts identified three people (15%) with PDS mutations. To determine whether PDS mutations in individuals with Pendred syndrome differ functionally from PDS mutations in individuals with non-syndromic hearing loss, we compared three common Pendred syndrome allele variants (L236P, T416P and E384G), with three PDS mutations reported only in individuals with non-syndromic hearing loss (V480D, V653A and I490L/G497S). The mutations associated with Pendred syndrome have complete loss of pendrin-induced chloride and iodide transport, while alleles unique to people with DFNB4 are able to transport both iodide and chloride, albeit at a much lower level than wild-type pendrin. We hypothesize that this residual level of anion transport is sufficient to eliminate or postpone the onset of goiter in individuals with DFNB4. We propose a model for pendrin function in the thyroid in which pendrin transports iodide across the apical membrane of the thyrocyte into the colloid space.


Asunto(s)
Proteínas Portadoras/genética , Bocio/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de Transporte de Membrana , Alelos , Sustitución de Aminoácidos , Animales , Femenino , Variación Genética , Bocio/patología , Pérdida Auditiva Sensorineural/patología , Humanos , Yodo/farmacocinética , Mutación , Oocitos/citología , Oocitos/metabolismo , Fenotipo , ARN Complementario/administración & dosificación , Transportadores de Sulfato , Xenopus laevis
12.
Cardiovasc Res ; 47(1): 57-67, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10869530

RESUMEN

OBJECTIVES: Elevated systemic arterial blood pressure is associated with left ventricular hypertrophy and fibrosis. It has been suggested that both circulating and local myocardial renin-angiotensin systems play a role in mediating these responses. Here we describe the natural history of ventricular hypertrophy and fibrosis in the transgenic (mRen2)27 rat--a monogenetic model--which has a high tissue expression of the murine renin transgene, and suffers severe hypertension. We further explored the relative contribution of both hypertensive burden and circulating and tissue renin-angiotensin systems to the fibrotic process. METHODS: The transgenic rats were treated from 28 days old with (1) a hypotensive dose of the ACE inhibitor ramipril which inhibited both tissue and circulating ACE activity, (2) the calcium antagonist amlodipine, or (3) a non-hypotensive dose of ramipril which inhibited about 60% of tissue ACE activity with little effect on circulating ACE. Normotensive Sprague-Dawley rats were used as controls. RESULTS: The transgenics developed left ventricular hypertrophy along with perivascular and interstitial fibrosis which became progressively worse up to 24 weeks of age. Both the high dose of ramipril and amlodipine prevented the hypertrophy and fibrosis, whereas tissue ACE inhibition without lowering blood pressure had no effect, and actually led to a worsening of the fibrosis by 24 weeks. CONCLUSIONS: These results suggest that the development of left ventricular hypertrophy and fibrosis in the transgenic (mRen2)27 rat are regulated by blood pressure and not activity of the renin-angiotensin systems and that progression of fibrosis at 24 weeks involves a mechanism unrelated to local renin-angiotensin activity.


Asunto(s)
Hipertensión/complicaciones , Miocardio/patología , Sistema Renina-Angiotensina , Amlodipino/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Animales Modificados Genéticamente , Antihipertensivos/uso terapéutico , Colágeno/análisis , Fibrosis , Hipertensión/metabolismo , Hipertensión/patología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/patología , Masculino , Ratones , Miocardio/química , Peptidil-Dipeptidasa A/sangre , Ramipril/uso terapéutico , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
13.
Clin Cancer Res ; 5(6): 1551-6, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10389944

RESUMEN

We have developed a novel nonviral interleukin 2 (IL-2) gene therapy that demonstrates significant treatment-specific, antitumor efficacy in combination with subtotal surgical resection in a head and neck cancer murine model. Treatment of established head and neck tumors in immunocompetent mice was performed via direct injection with a cationic liposome composed of DOTMA and cholesterol formulation carrying DNA plasmid for human IL-2 (hIL-2) gene expression. ELISA assays of tumor extracts 24 h after treatment of hIL-2 gene therapy revealed increased local hIL-2 production as well as a formulation-specific secondary induction of murine IFN-gamma and IL-12. We hypothesize that the paracrine production of multiple cytokines after IL-2 single gene transfer is important for generating a therapeutic effect, and that this strategy will be well tolerated and effective in combination with surgery for head and neck cancer. In animal experiments where surgery was performed in conjunction with an operative site injection of hIL-2 plasmid formulation, no pre-, intra-, or postoperative toxicity or compromise to wound healing was identified. In murine experiments combining partial surgical resection with the nonviral gene therapy, significant antitumor efficacy was demonstrated in the hIL-2 plasmid formulation group compared with empty plasmid formulation and lactose-injected controls. In a separate experiment using smaller tumor sizes, we also demonstrated that treatment outcomes were dependent on the technical aspect of the actual treatment injection as well as visualization with surgical access. The hIL-2 plasmid formulation gene therapy induces local expression of multiple cytokines, results in treatment-specific antitumor effects, and circumvents many of the concerns and toxicity encountered with viral gene transfer. These data support the need for continued preclinical investigation and the consideration of human clinical trials for combination nonviral hIL-2 gene therapy and surgery for head and neck cancer.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Terapia Genética , Neoplasias de Cabeza y Cuello/terapia , Interleucina-2/administración & dosificación , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Modelos Animales de Enfermedad , Portadores de Fármacos , Evaluación Preclínica de Medicamentos , Ensayo de Inmunoadsorción Enzimática , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-2/genética , Liposomas , Ratones , Ratones Endogámicos C3H , Plásmidos/administración & dosificación
14.
Undersea Hyperb Med ; 26(2): 93-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10372428

RESUMEN

Ten men were exposed to hyperbaric oxygen (HBO2), and their tissue oxygen levels were monitored after they drank either placebo or caffeine beverages. Transcutaneous tissue oxygen (PtcO2) monitor measurements in a normobaric air environment were initially obtained from transducers on the subject's chest and foot. The subjects then consumed either the caffeine (3 mg.kg-1) or the placebo beverage, and after 20 min the subjects were pressurized in a hyperbaric chamber to 2.36 atm abs (1 atm = 101.3250 kPa). The test subjects began breathing 100% oxygen at 2.36 atm abs, 30 min after administration of the experimental beverage, and continued for 30 min, after which the final chest and foot PtcO2 measurements were recorded (1 h after ingestion of the test drink). Each subject underwent a second hyperbaric exposure during which the alternate drink was administered (either the placebo or the caffeine), and PtcO2 measurements were again obtained. The increase in right foot PtcO2 values during HBO2 exposure was significantly smaller after caffeine consumption than after placebo (P = 0.0018).


Asunto(s)
Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Oxigenoterapia Hiperbárica , Consumo de Oxígeno/efectos de los fármacos , Adulto , Monitoreo de Gas Sanguíneo Transcutáneo , Cafeína/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Humanos , Pierna , Masculino , Persona de Mediana Edad
15.
J Clin Oncol ; 16(5): 1948-53, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9586914

RESUMEN

PURPOSE: Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS: A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION: Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Taxoides , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Progresión de la Enfermedad , Docetaxel , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Tasa de Supervivencia
16.
Mod Pathol ; 11(12): 1247-51, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9872658

RESUMEN

During a study of eosinophil-predominant gallbladder disease, an image analysis (IA) technique was developed for quantification of eosinophils and lymphocytes in routine formalin-fixed tissue sections. Alternating sections were stained with hematoxylin and eosin for eosinophils and with monoclonal CD45 antibody visualized with diaminobenzidine by an avidin-biotin procedure for lymphocytes. A protocol was then developed using a commercially available image analyzer and two well-defined macro routines. The system was validated with cell block sections prepared from peripheral blood samples with known eosinophil and lymphocyte counts. The eosinophil counts obtained by this IA technique showed excellent correlation with the absolute counts from a peripheral blood analyzer (r2 = 0.987). The lymphocyte counts obtained by IA showed good correlation with the absolute counts (r2 = 0.820). This IA-based technique provides a sensitive, reproducible, and substantiated means of quantifying inflammatory cells in tissue sections. This rapid and easily learned technique adds quantification as a complementary dimension to the subjective assessment of tissue morphology.


Asunto(s)
Eosinófilos/patología , Procesamiento de Imagen Asistido por Computador/métodos , Recuento de Leucocitos/métodos , Linfocitos/patología , Enfermedades de la Vesícula Biliar/patología , Humanos , Citometría de Imagen/métodos , Técnicas para Inmunoenzimas , Antígenos Comunes de Leucocito/análisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
17.
Br J Cancer ; 75(5): 690-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9043026

RESUMEN

This study assesses the effect of adding continuous-infusion fluorouracil to palliative thoracic radiation therapy (RT) on the rate and duration of symptom relief in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred eligible patients with NSCLC were randomized to receive either 20 Gy in five daily fractions as palliation for intrathoracic disease or the same RT with concurrent continuous infusion of 1 g m(-2) day(-1) fluorouracil for 5 days. Survival, response and rates of symptom relief in the two groups were compared according to treatment intent, and toxicities were compared according to treatment received. The overall response rate was higher in patients randomized to the combination (29%) than in patients randomized to RT alone (16%) (P = 0.035). However, there were no significant differences between the treatment arms in terms of overall or progression-free survival or in palliation of symptoms. Patients treated with RT plus fluorouracil had significantly more acute toxicity, including nausea and vomiting (P = 0.01), oesophagitis (P = 0.0003), stomatitis (P = 0.0005) and skin reaction (P = 0.003). This study suggests for the first time an interaction between RT and infusional fluorouracil in NSCLC. Although RT plus fluorouracil resulted in a significantly higher response rate than achieved with RT alone, this did not translate into more effective palliation. Because the combination produced significantly more toxicity than RT alone, it is not recommended for the palliative treatment of NSCLC. Nevertheless, these results suggest that opportunities may exist for exploitation of the observed enhancement of antitumour effect in the setting of high-dose radical RT for NSCLC.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Fluorouracilo/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Terapia Combinada , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Radioterapia/efectos adversos
18.
AJR Am J Roentgenol ; 163(3): 671-9, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8079866

RESUMEN

OBJECTIVE: Pituitary microadenomas may not be detected on conventional MR images. We supplemented conventional unenhanced and contrast-enhanced MR imaging with a dynamic keyhole fast spin-echo (kFSE) method in order to compare how frequently a microadenoma could be detected with the three different methods. SUBJECTS AND METHODS: Eighteen consecutive patients with clinical and laboratory evidence of pituitary microadenomas had unenhanced, dynamic kFSE, and conventional contrast-enhanced MR imaging of the pituitary gland. A control group of 13 subjects without pituitary disease also had dynamic kFSE MR imaging. Hard copies of all the studies were obtained in an identical fashion, and then the MR images of the patients and control subjects were randomly mixed. The studies were reviewed by a neuroradiologist who had no knowledge of the clinical status of the subjects. The presence or absence of any pituitary focal hypointensity consistent with the appearance of a microadenoma was noted. RESULTS: A pituitary lesion consistent in appearance with a microadenoma was detected on dynamic kFSE images in 13 of the 18 patients, on unenhanced images in nine patients, and on conventional contrast-enhanced images in 10 patients. In four patients, a microadenoma was detected on dynamic kFSE images only. Dynamic kFSE images showed a lesion in four of the 13 control subjects. CONCLUSION: Dynamic kFSE MR imaging is a useful supplemental sequence in patients undergoing MR imaging because of pituitary endocrinopathy. It may show lesions that would otherwise escape detection.


Asunto(s)
Adenoma/diagnóstico , Imagen por Resonancia Magnética/métodos , Hipófisis/patología , Neoplasias Hipofisarias/diagnóstico , Prolactinoma/diagnóstico , Medios de Contraste , Combinación de Medicamentos , Femenino , Gadolinio , Gadolinio DTPA , Humanos , Masculino , Meglumina , Compuestos Organometálicos , Ácido Pentético/análogos & derivados
19.
J Pharmacol Exp Ther ; 268(2): 922-9, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8114006

RESUMEN

Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.


Asunto(s)
Indoles/farmacología , Activación de Linfocitos/efectos de los fármacos , Proteína Quinasa C/antagonistas & inhibidores , Pirroles/farmacología , Linfocitos T/efectos de los fármacos , Administración Oral , Secuencia de Aminoácidos , Animales , Artritis Experimental/prevención & control , Femenino , Masculino , Ratones , Datos de Secuencia Molecular , Forbol 12,13-Dibutirato/farmacología , Ratas , Ratas Endogámicas Lew , Linfocitos T/inmunología
20.
J Emerg Med ; 11(4): 485-90, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8228115

RESUMEN

Objectives for Emergency Medicine residents on Hyperbaric Medicine rotations is the 22nd article in this continuing series of "off-service" goals and objectives. The role of the emergency medicine physician in hyperbaric treatment is evolving as part of a multidisciplinary approach to patients with widely divergent disease states who may benefit from serum hyperoxia and compression. Therefore, emergency residents with interests in this area will benefit from clear goals and objectives during a 2 to 4-week Hyperbaric Medicine Elective.


Asunto(s)
Medicina Aeroespacial/educación , Curriculum , Medicina de Emergencia/educación , Oxigenoterapia Hiperbárica , Internado y Residencia , Humanos
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