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PURPOSE: Despite a lower risk of nausea and vomiting in patients receiving radiotherapy to the upper abdomen (UA-RINV) with prophylactic 5-HT3 antagonist therapy, patients can still experience UA-RINV. The aim of this multicenter phase II study was to assess effectiveness, safety, and tolerability of protracted dual NK1-receptor and 5-HT3 antagonist prophylaxis against UA-RINV. METHODS: Patients receiving fractionated radiotherapy with radiosensitizing chemotherapy received oral ondansetron 8 mg po q12 h and aprepitant 125/80/80 mg on a Monday, Wednesday, Friday schedules throughout radiotherapy. The primary outcome was complete response (CR) defined as no vomiting or rescue therapy during the entire observation period of radiotherapy (OP). Nausea, vomiting, and use of rescue medication were recorded in a modified version of the MASCC antiemesis tool completed twice weekly. RESULTS: Fifty-five patients were enrolled at 5 sites, 52 of whom were evaluable. 57.7% of patients (30/52, 95% CI 43.2-71.3%) achieved CR on study, with 73.1% (38/52, 95% CI 59.0-84.4%) who did not vomit, and 71.2% (37/52, 95% CI 56.9-82.9%) who did not use rescue medication during the OP. Overall, participants vomited or experienced significant nausea (SN) for an average of 6.8% (95% CI 11.4-21.0) and 8.4% (95% CI 4.2-12.7%) of time on study, respectively. Nausea was common with 32 (61.5%) reporting SN at any time during the OP. CONCLUSIONS: UA-RINV remains an important morbidity despite the advent of modern radiotherapy. Aprepitant and ondansetron as dosed in this trial was not superior to standard ondansetron monotherapy.
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Abdomen/efectos de la radiación , Antieméticos/uso terapéutico , Morfolinas/uso terapéutico , Náusea/prevención & control , Ondansetrón/uso terapéutico , Radioterapia/efectos adversos , Vómitos/prevención & control , Anciano , Antieméticos/administración & dosificación , Antieméticos/farmacología , Aprepitant , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/administración & dosificación , Morfolinas/farmacología , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Ondansetrón/administración & dosificación , Ondansetrón/farmacología , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológicoRESUMEN
PURPOSE: Bone pain is a common side effect of pegfilgrastim and can interfere with quality of life and treatment adherence. This study investigated the impact of antihistamine prophylaxis on pegfilgrastim-induced bone pain. METHODS: This is a two-stage enrichment trial design. Patients receiving an initial dose of pegfilgrastim after chemotherapy were enrolled into the observation (OBS) stage. Those who developed significant back or leg bone pain (SP) were enrolled into the treatment (TRT) stage and randomized to daily loratadine 10 mg or placebo for 7 days. SP was defined by Brief Pain Inventory as back or leg pain score ≥5 and a 2-point increase after pegfilgrastim. The primary end point of TRT was reduction of worst back or leg bone pain with loratadine, defined as a 2-point decrease after treatment compared to OBS. RESULTS: Two hundred thirteen patients were included in the final analysis. Incidence of SP was 30.5 %. The SP subset had a worse overall Functional Assessment of Cancer Therapy-Bone Pain score (33.9 vs. 51.7, p < 0.001) and a higher mean white blood cell count (15.4 vs. 8.4 K/cm(3), p = 0.013) following pegfilgrastim than those without SP. Forty-six patients were randomized in the TRT. Benefit was 77.3 % with loratadine and 62.5 % with placebo (p = 0.35). Baseline NSAID use was documented in four patients (18.2 %) in loratadine arm and two patients (8.3 %) in placebo arm, with baseline non-NSAID use documented in five (22.7 %) and six (25 %) patients, respectively. Eight additional patients used NSAIDS by day 8 compared to day 1 (six in the loratadine and two in the placebo arm). A total of six additional patients used non-NSAIDS by day 8 compared to day 1 (four in the loratadine and two in the placebo arm). CONCLUSIONS: Administration of prophylactic loratadine does not decrease the incidence of severe bone pain or improve quality of life in a high-risk patient population. ClinicalTrials.gov identifier: NCT01311336.
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Enfermedades Óseas/prevención & control , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Antagonistas de los Receptores Histamínicos H1 no Sedantes/uso terapéutico , Loratadina/uso terapéutico , Manejo del Dolor/métodos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas/inducido químicamente , Femenino , Filgrastim , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles , Calidad de Vida , Proteínas Recombinantes/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Patients with metastatic colon cancer (mCRC) are at increased risk of venous thromboembolism (VTE). Limited preclinical data suggest that the oncogene (KRAS) mutational status of the tumor represents a plausible clinical link to systemic hypercoagulability in cancer patients. OBJECTIVES: To determine if a tumor genetic characteristic, KRAS mutational status, is associated with an increased risk of VTE in patients with mCRC. PATIENTS/METHODS: A retrospective cohort study of patients with mCRC and KRAS test results was conducted at multiple practice sites across New England in the United States. The primary outcome was a VTE event, defined as deep venous thrombosis (DVT) and/or pulmonary embolism (PE), either 6 months before or at any time after the diagnosis of mCRC. KRAS status (mutated vs. wild type) and other relevant predictors of thrombosis were collected. RESULTS: Of 172 histologically confirmed patients with mCRC, 40 developed a VTE (23.3%). Sixty-five patients (37.8%) had a mutant KRAS status. The incidence of VTE and DVT among patients with mutated KRAS was 32.3 and 23.1%, respectively. The corresponding incidence among patients with wild-type KRAS was 17.8 and 9.4%. Odd ratios for the association were 2.21 (95% CI, 1.08-4.53) for VTE and 2.62 (95% CI, 1.12-6.12) for DVT, and remained significant despite adjustment for Khorana score and bevacizumab use. CONCLUSION: Tumor mutant KRAS status is associated with an increased risk of VTE in patients with mCRC. The tumor genetic profile may represent a novel and important risk factor for thrombosis in patients with cancer.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Embolia Pulmonar/epidemiología , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/epidemiología , Anciano , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , New England/epidemiología , Oportunidad Relativa , Fenotipo , Valor Predictivo de las Pruebas , Embolia Pulmonar/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tromboembolia Venosa/diagnóstico , Trombosis de la Vena/diagnósticoRESUMEN
BACKGROUND: Surveys are important research tools that permit the accumulation of information from large samples that would otherwise be impractical to collect. Resident surveys have been used frequently to monitor the quality of postgraduate training. Low response rates threaten the utility of this research tool. The purpose of this study was to determine the standard response rate of surveys administered to surgery residents and identify characteristics associated with achieving greater response rates. METHODS: A search of peer-reviewed literature published between September 2003 and June 2011 was performed with the use of PubMed with Medical Subject Headings: "internship and residency," "surgery," "data collection," and "questionnaires." For inclusion, articles must have described a survey given to active surgery residents within the United States. Surveys were evaluated based on the following criteria: population size, response rate, incentive use, follow-up use, survey format (online vs paper), and institution versus national. RESULTS: Of 433 initial results, 47 met inclusion criteria with a mean response rate of 65.3%. Surveys administered in paper format had a greater response rate compared with those given electronically (mean 78.6% vs 36.4%, respectively, P < .001). Greatest mean response rates were seen for institutional surveys compared with those given nationally (83.1% vs 42% respectively, P < .001). CONCLUSION: Our review demonstrated that paper surveys administered at the institutional level and during assemblies integrated into residents' schedules demonstrated enhanced response rates. The validity and generalizability of data collected through such surveys will improve as the aspects which dictate response rate are better understood and implemented.
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Cirugía General/educación , Internado y Residencia , Recolección de Datos/estadística & datos numéricos , HumanosRESUMEN
The sensitizing potential of chemicals is usually identified and characterized using one of the available animal test methods, such as the mouse local lymph node assay. Due to the increasing public and political concerns regarding the use of animals for the screening of new chemicals, the Colipa Skin Tolerance Task Force collaborates with and/or funds research groups to increase and apply our understanding of the events occurring during the acquisition of skin sensitization. Knowledge gained from this research is used to support the development and evaluation of novel alternative approaches for the identification and characterization of skin sensitizing chemicals. At present one in chemico (direct peptide reactivity assay (DPRA)) and two in vitro test methods (cell based assays (MUSST and h-CLAT)) have been evaluated within Colipa inter-laboratory ring trials and accepted by the European Centre for the Validation of Alternative Methods (ECVAM) for pre-validation. Data from all three test methods will be used to support the development of testing strategy approaches for skin sensitizer potency prediction. The replacement of the need for animal testing for skin sensitization risk assessment is viewed as ultimately achievable and the next couple of years should set the timeline for this milestone.
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Alérgenos/toxicidad , Alternativas a las Pruebas en Animales , Haptenos/efectos de los fármacos , Pruebas de Irritación de la Piel/métodos , Piel/efectos de los fármacos , Alérgenos/clasificación , Alérgenos/farmacocinética , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Biología Computacional , Haptenos/análisis , Humanos , Medición de Riesgo , Piel/metabolismo , Células U937RESUMEN
Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen/non-allergen, especially using THP-1 cells. These results suggest that our method, human Cell Line Activation Test (h-CLAT), using human cell lines THP-1 and U-937, but especially THP-1 cells at 24h treatment, may be a useful in vitro skin sensitization model to predict various contact allergens.
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Alérgenos/toxicidad , Piel/efectos de los fármacos , Antígeno B7-2/análisis , Antígenos CD4/análisis , Línea Celular , Supervivencia Celular , Humanos , Laboratorios , Fenotipo , Piel/inmunología , Pruebas Cutáneas , Factores de Tiempo , Células U937RESUMEN
The aim of this study is to optimize the experimental conditions for an in vitro skin sensitization test using the human cell lines THP-1 and U-937. As regards pre-culturing time, the expression of CD86 on DNCB-treated THP-1 cells tended to be higher after 48h and 72h pre-culture compared with other time points evaluated. Next, we investigated the effect of chemical treatment time, and found that induction of CD86 expression on THP-1 cells by DNCB reached a plateau after 24h. Augmentation of CD86 expression is often observed when cells are treated with a subtoxic dose of allergens. To determine the appropriate dose of test samples, the cytotoxicity of test samples to THP-1 and U-937 cells was assessed with MTT assay, and the 50% inhibitory concentration (IC50) of each test sample was calculated. Based on the cytotoxicity assay data, four concentrations in the range between toxic and non-toxic were selected (0.1x, 0.5x, 1x and 2x IC50). Several kinds of antibodies were tested for staining THP-1 and U-937 cells treated with allergens/non-allergens (e.g., DNCB, Ni/SLS), and suitable antibodies for staining CD86 and CD54 were selected. We confirmed that the working dilutions of the selected CD86 and CD54 antibodies were appropriate for use in our method. The effect of an FcR blocking procedure was also evaluated. The mean fluorescence intensity (MFI value) was decreased by the FcR blocking procedure, which indicated that non-specific staining was blocked. Therefore, this procedure should be included in the method. Based on our findings, the protocol for this assay was optimized and the experimental conditions to be used in a future validation study were identified. We propose to call this kind of in vitro skin sensitization test h-CLAT, which is short for human Cell Line Activation Test.
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Alérgenos/toxicidad , Piel/efectos de los fármacos , Antígenos de Superficie/análisis , Antígeno B7-2/análisis , Línea Celular , Dinitroclorobenceno/toxicidad , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Receptores Fc/fisiología , Piel/inmunología , Pruebas Cutáneas , Factores de TiempoRESUMEN
Most fungicide sprays applied to apple orchards in the New England states are targeted at the management of apple scab. Researchers have developed action thresholds that aid in decision-making on whether early spring fungicide applications could be eliminated without a significant increase in the incidence of fruit scab at harvest. To facilitate grower adoption of these thresholds, a simplified, sequential sampling technique in autumn to determine the "scab risk" of an orchard for the following spring was proposed in the scientific literature. However, this technique had not been evaluated in the field. In autumn 1999, 2000, and 2001, orchards were evaluated using the new sequential sampling technique to determine scab risk. Risk ratings were compared with those obtained by the original, nonsequential procedure in each orchard. Data also were examined using a simulation sequential sampling computer program to determine whether or not risk ratings would change if different trees or shoots were used. In two of the assessed orchards, "delayed-spray" experiments involving two treatments (a delayed-spray and full-spray treatment) were conducted in 2000 and 2001. Delayed-spray replicates were to receive no fungicide sprays until after the third primary infection period (but before the fourth) or until the pink stage of bud development, whichever came first; full-spray replicates received fungicide sprays starting at the green-tip stage of bud development. The sequential sampling technique provided scab-risk ratings consistent with the original, nonsequential procedure, at potentially significant time savings. Also, following the delayed-spray strategy in low-risk orchards did not result in significant differences in fruit scab at harvest compared with initiating spraying at the green-tip phenological bud stage.
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BACKGROUND: New therapeutic approaches have to be considered in the treatment of irritant contact dermatitis (ICD). Recently, phosphodiesterase 4 (PDE-4) inhibitors have been introduced as nonsteroidal, antiinflammatory agents. These agents inhibit the secretion of the cytokines thought to be involved in the pathogenesis of ICD. We investigated the effect of a new selective PDE-4 inhibitor (cipamfylline) in human models using single and repeated exposures to an irritant in a blind, randomized pilot study with healthy volunteers. We compared the effect of cipamfylline ointment with a strong corticosteroid (betamethasone-17-valerate) and with a placebo ointment. METHODS: Ten volunteers were patch tested at four investigation sites with sodium dodecyl sulphate (1%) for 24 h. In a model that simulates chronic damage, 11 volunteers were patch tested with sodium dodecyl sulphate (0.2%) for 4 h daily for four consecutive days. The investigation sites were treated once a day with the above-mentioned agents. One site was left untreated. We used erythema scoring, measurements of transepidermal water loss (TEWL) and several immunohistochemical markers for epidermal proliferation and differentiation. RESULTS: Repeated application revealed that betamethasone-17-valerate caused a statistically significant reduction in erythema and TEWL compared to cipamfylline and placebo. We also observed a significant suppression of proliferating cells and cytokeratin 16 expression at sites treated with betamethasone compared to the other sites. In the model for acute ICD, no significant differences were seen between the investigated sites. CONCLUSIONS: Our results show that betamethasone-17-valerate may modulate the response in ICD. In this human model of ICD we could not confirm the efficacy of cipamfylline. Clinical studies are needed before the effect of PDE-4 inhibitors in ICD can be refuted with certainty.
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3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Dermatitis Irritante/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Xantinas/uso terapéutico , Adulto , Anciano , Valerato de Betametasona/uso terapéutico , División Celular/efectos de los fármacos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4 , Dermatitis Irritante/complicaciones , Dermatitis Irritante/metabolismo , Dermatitis Irritante/patología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Eritema/etiología , Eritema/patología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Queratinas/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Proyectos Piloto , Dodecil Sulfato de Sodio/administración & dosificación , Tensoactivos/administración & dosificación , Pérdida Insensible de Agua/efectos de los fármacosRESUMEN
The aim of this study was to explore the usefulness of a human monocyte cell line in the development of in vitro models for predictive testing of contact sensitizers. Several studies have shown that contact sensitizers induce CD86 expression and enhanced internalization of MHC class II molecules in dendritic cells (DCs). We used THP-1, a human monocyte cell line, as a replacement for DCs for evaluation of these phenotypical alterations as predictive endpoints for contact sensitizers. Known sensitizers and irritants were evaluated. After 24-h exposure to samples, the expression of CD86 on THP-1 cells was measured by flow cytometry. Sensitizers such as dinitrochlorobenzene (DNCB), 2-mercaptobenzothiazole (MBT), eugenol, p-phenylenediamine (PPDA) and ammonium tetrachloroplatinate (Pt) enhanced CD86 expression on THP-1 cells, while nickel sulfate, cobalt sulfate and irritants such as methylsalicylate (MS), sodium dodecyl sulfate (SDS) and dimethyl sulfoxide (DMSO) did not augment CD86 expression. A synergistic effect was observed when DNCB and IFN-alpha were added simultaneously to a culture of THP-1 cells. Furthermore, internalization of MHC class II molecules was observed when the cells were treated with some of sensitizers for 2 h. The inducing effects of chemicals on the two phenotypical alterations were the same. These results suggest that these test systems can be used to predict contact-sensitizing ability of chemicals as an in vitro sensitization assay.
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Antígenos CD/biosíntesis , Dermatitis por Contacto/inmunología , Regulación de la Expresión Génica , Genes MHC Clase II , Glicoproteínas de Membrana/biosíntesis , Alternativas a las Pruebas en Animales , Antígeno B7-2 , Técnicas de Cultivo de Célula , Dermatitis por Contacto/fisiopatología , Evaluación Preclínica de Medicamentos , Determinación de Punto Final , Humanos , Irritantes/efectos adversos , Monocitos , Fenotipo , Valor Predictivo de las PruebasRESUMEN
We present a patient with nonischemic cardiomyopathy who had ventricular tachycardia (VT) with QRS morphology alternans. VTs of two QRS morphologies (VT1 and VT2) exhibiting a right bundle branch block pattern with inferior axis was induced by ventricular pacing. The morphology of the QRS complex during VT1 exhibited more distinctively inferior axis than those during VT2. Induced VTs had similar morphologies to clinically the documented VTs. Pacemapping at anterolateral site of the left ventricle during sinus rhythm produced the same QRS complex of VT1 in a surface 12-lead electrocardiogram. A mapping study was performed with an electrode catheter located at the same site of LV during sustained VT1. The analysis of the local electrograms and postpacing interval during concealed entrainment at the catheter mapping revealed this pacing site was at the inner loop of the reentry circuit. Radiofrequency catheter ablation was performed at this site. The morphology of VT1 changed to different QRS morphology (VT2) during the first delivery of radiofrequency energy and was terminated after 20 seconds of the application. Then VT with alternans of QRS morphology and cycle length of VT1 and VT2 was induced by ventricular pacing, and was abolished by the second application of radiofrequency energy at this same site, suggesting that this site was located in the exit site close to inner loop of the reentry circuit and the alternans of QRS morphology was linked to the change of exit site.
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Cardiomiopatía Dilatada/complicaciones , Cardiomiopatía Dilatada/cirugía , Ablación por Catéter , Taquicardia Ventricular/complicaciones , Taquicardia Ventricular/cirugía , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Sistema de Conducción Cardíaco/cirugía , Humanos , Persona de Mediana EdadRESUMEN
Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.
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Células Sanguíneas/efectos de los fármacos , Vasos Sanguíneos/efectos de los fármacos , Fibrinolíticos/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Piridinas/farmacología , Animales , Trastornos Cerebrovasculares/tratamiento farmacológico , Ensayos Clínicos como Asunto , Fibrinolíticos/química , Fibrinolíticos/uso terapéutico , Humanos , Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/uso terapéutico , Piridinas/química , Piridinas/uso terapéuticoRESUMEN
Autoimmune hepatitis is associated with genes located in the major histocompatibility complex. The search for genes at other loci that may play a role in disease susceptibility and/or severity is an area of active investigation in autoimmune liver diseases. Genes for glutathione-S-transferases, enzymes that are widely distributed and collectively metabolize carcinogens, pollutants, drugs, and a broad spectrum of harmful, foreign compounds have been associated with liver disease. The objective of this study was to search for a relationship between the glutathione-S-transferase Ml null genotype and autoimmune hepatitis using polymerase chain reaction analysis. The findings indicate that the frequency of the null genotype is not increased in patients with autoimmune hepatitis when compared to control subjects. These results coupled with similar ones in primary biliary cirrhosis do not support a role for this mutation in autoimmune liver disease.
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Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Hepatitis Autoinmune/enzimología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Hepatitis Autoinmune/genética , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Platelet activation is pivotal in the pathogenesis of complications after percutaneous coronary interventions (PCI). We previously reported substantial interindividual variability in activation of glycoprotein (GP) IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa activation prospectively to determine whether this could differentiate patients at low risk from those at high risk for complications early and late after PCI. Methods and Results-- A total of 112 patients undergoing PCI were studied. Platelet reactivity was determined with the use of flow cytometry. Patients were classified into high and low platelet reactivity groups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 micromol/L ADP. The median value was used for differentiation. The incidence during 90-day follow-up interval of a composite end point (myocardial infarction, urgent revascularization, or repeat revascularization) was determined in each group. Follow up was completed in all 112 patients. The 2 groups were similar with respect to diverse clinical characteristics. Nevertheless, the incidence of the composite end point occurred in 26.8% of the high and 7.1% in the low platelet reactivity group (P=0.01). The difference in the composite end point was most striking during the 30- to 90-day interval after PCI (16.7% versus 1.9%; P=0.02). Repeat revascularization was more frequent in those with increased platelet reactivity (17.9% versus with 3.6%, P=0.029). CONCLUSIONS: Prospective assessment of platelet GP IIb/IIIa activation permits stratification of patients into low- and high-risk groups with respect to adverse events after PCI.
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Angioplastia Coronaria con Balón , Enfermedad Coronaria/metabolismo , Enfermedad Coronaria/terapia , Activación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Angioplastia Coronaria con Balón/efectos adversos , Determinación de Punto Final , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reoperación , Medición de Riesgo , Resultado del TratamientoRESUMEN
There have been few clinical studies exploring the characteristics of spontaneous polymorphic ventricular tachycardia (VT) during a vasospastic angina attack. During a 4-year recruitment period, Holter ECG recordings were monitored for 42+/-24 h during a drug-free period in 60 consecutive patients with vasospastic angina (VSA) and of these, 8 patients had at least one episode of polymorphic VT during monitoring. Ischemic ST segment elevation was immediately preceded the spontaneous polymorphic VT in all 8 patients, 4 of whom had silent coronary vasospasm. Immediately before the onset of polymorphic VT, both R-on-T and long-short sequences were observed in 4 of the 8 patients and ST wave alternans were recorded in 2 patients. VT exhibited a pattern of torsade de pointes in 4 of the 8 patients. Five patients underwent electrophysiologic testing during a drug-free asymptomatic phase, and polymorphic VT was induced in 2 of the 5 patients, with one developing ventricular fibrillation. During a follow-up period of 73+/-17 months, there was a significant difference in the incidence of sudden death between patients with and without VT (2/8 cases [25%] vs 0/52 [0%]; p<0.01). Thus, vasospastic attacks, even if asymptomatic, that immediately precede the development of polymorphic VT may be associated with a repolarization abnormality and an increased risk of sudden death.
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Angina de Pecho/complicaciones , Vasoespasmo Coronario/complicaciones , Taquicardia Ventricular/etiología , Acetilcolina/administración & dosificación , Acetilcolina/farmacología , Adulto , Anciano , Angina de Pecho/mortalidad , Angiografía Coronaria , Vasoespasmo Coronario/inducido químicamente , Vasoespasmo Coronario/mortalidad , Muerte Súbita Cardíaca/etiología , Electrocardiografía Ambulatoria , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Taquicardia Ventricular/mortalidad , Taquicardia Ventricular/fisiopatología , Resultado del TratamientoRESUMEN
The objective of this study was to maximize the success rate of sentinel node (SN) localization in breast cancer patients with the tracer that demonstrated the highest initial success during a preliminary evaluation. Altogether, 145 patients with operable invasive breast cancer and clinically negative lymph nodes were studied. Technetium 99m (99mTc)-sulfur colloid was injected into the breast parenchyma surrounding the invasive cancer or the biopsy cavity. Variable volumes of tracer, amounts of 99mTc, and duration of time between injection and surgery were evaluated. A hand-held gamma detector was used at surgery to locate and guide resection of all radioactive sentinel nodes (SNs), including those that were extraaxillary. A conventional lymphadenectomy was then performed in all cases. Based on previous studies, unfiltered sulfur colloid provided a higher success rate of SN identification than the other tracer types. Further evaluation with 99mTc-sulfur colloid demonstrated that increased volume increased the success rate of SN identification. An injection volume of 8 ml resulted in a success rate of 98%. SNs were not exclusively located in the axilla: In 8.6% of cases SNs were removed from an internal mammary location. The overall accuracy of patients with SNs resected was 98.4%, and the false-negative rate was 4.4%. It was concluded that (1) unfiltered 99mTc-sulfur colloid at a volume of 8 ml resulted in a high success rate for SN identification; (2) a significant number of the SNs were extraaxillary in location; and (3) the accuracy of the SNs for determining whether regional metastases had occurred was high. The U.S. National Cancer Institute is funding a randomized phase III clinical trial to evaluate SN resection compared to conventional axillary lymphadenectomy in clinical node-negative breast cancer patients. Major endpoints of this trial include long-term regional control and survival.
Asunto(s)
Neoplasias de la Mama/patología , Ganglios Linfáticos/diagnóstico por imagen , Radiofármacos , Biopsia del Ganglio Linfático Centinela , Azufre Coloidal Tecnecio Tc 99m , Ensayos Clínicos como Asunto , Femenino , Humanos , Ganglios Linfáticos/patología , Valor Predictivo de las Pruebas , Pronóstico , Cintigrafía , Apoyo a la Investigación como Asunto , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
An adaptation of Andersen's behavioral model of health services utilization is used to examine the psychosocial and socio-demographic factors that directly and indirectly influence the likelihood of undergoing genetic susceptibility testing for cancer, and the amount of money that individuals would be willing to pay out-of-pocket for such a test. Apart from willingness and likelihood, the model also included perceived benefits and barriers, perceived susceptibility, dispositional optimism, information seeking, family history of cancer, socioeconomic status (SES), and age, and explained 30.3% of the variation in willingness. We found as hypothesized that likelihood of undergoing such tests was central to understanding willingness to pay. Being aware of genetic susceptibility testing for cancer, and talking and seeking information about it was directly associated with an increased chance of being willing to pay more, independent of other indirect associations (effects). Interventions targeting those with a family history of cancer and those with a higher SES should generate more awareness about the potential positive and negative consequences to one's family of testing, and the interface between family history of cancer and perceived susceptibility. Interventions should also motivate people to talk and seek more information about genetic testing for cancer risk to enable them take well-informed decisions.
Asunto(s)
Actitud Frente a la Salud , Financiación Personal , Pruebas Genéticas/economía , Neoplasias/genética , Neoplasias/prevención & control , Adulto , Anciano , Análisis Factorial , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Modelos Teóricos , New York , Factores SocioeconómicosRESUMEN
Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.