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1.
Appl Ergon ; 111: 103995, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37207523

RESUMEN

Previous studies suggest that performance in visual inspection and typical vigilance tasks depend on time on task and task load. European regulation mandates that security officers (screeners) take a break or change tasks after 20 min of X-ray baggage screening. However, longer screening durations could reduce staffing challenges. We investigated the effects of time on task and task load on visual inspection performance in a four-month field study with screeners. At an international airport, 22 screeners inspected X-ray images of cabin baggage for up to 60 min, while a control group (N = 19) screened for 20 min. Hit rate remained stable for low and average task loads. However, when the task load was high, the screeners compensated by speeding up X-ray image inspection at the expense of the hit rate over time on task. Our results support the dynamic-allocation resource theory. Moreover, extending the permitted screening duration to 30 or 40 min should be considered.


Asunto(s)
Aeropuertos , Medidas de Seguridad , Humanos , Rayos X , Radiografía , Factores de Tiempo
2.
Schmerz ; 33(1): 57-65, 2019 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-29951920

RESUMEN

BACKGROUND: Joint pain may be an early indicator of biomechanical stress. During adolescence the physical development, including the development of the musculoskeletal system, is still ongoing and joint pain requires special attention, especially among young athletes. OBJECTIVE: Young athletes from the highest national basketball leagues in Germany were questioned about prevalence, location, context and coping strategies concerning joint pain. MATERIAL AND METHODS: Data were derived from the German "Adolescents' and Childrens' Health in Elite Basketball study" (ACHE study). Analyses were based on an online survey of 182 elite basketball players between 13 and 19 years of age from 46 German teams, conducted between April 2016 and June 2016. RESULTS: In the highest German leagues 2 out of 3 players suffered from joint pain at the time of the survey (7-day prevalence 64.6%). Pain in the lower extremities occurred most frequently. The 7­day prevalence for knee and leg pain reached up to 40% and foot pain up to 21%. For 84% of all players, occasional consumption of analgesics was the norm and 40% took them frequently. The consumption of several medicinal substances, especially of cyclooxygenase inhibitors, such as ibuprofen and diclofenac, is widespread among adolescent elite basketball players as 1 out of 7 athletes (13%) used medicinal substances despite being pain-free and 5% used it prophylactically with the purpose of preventing pain. CONCLUSION: From the point of view of pain medicine, it is not only the high prevalence of pain that is remarkable but also the widespread use of analgesics without a prescription and the misguided conception of adolescent competitive athletes that such medications have preventive effects.


Asunto(s)
Artralgia , Baloncesto , Adolescente , Adulto , Analgésicos , Atletas , Traumatismos en Atletas , Alemania , Humanos , Adulto Joven
3.
Br J Surg ; 105(11): 1519-1529, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29744860

RESUMEN

BACKGROUND: It is not clear whether all patients with rectal cancer need chemoradiotherapy. A restrictive use of neoadjuvant chemoradiotherapy (nCRT) based on MRI findings for rectal cancer was investigated in this study. METHODS: This prospective multicentre observational study included patients with stage cT2-4 rectal cancer, with any cN and cM0 status. Carcinomas in the middle and lower third that were 1 mm or less from the mesorectal fascia, all cT4 tumours, and all cT3 tumours of the lower third were classified as high risk, and these patients received nCRT followed by total mesorectal excision (TME). All other carcinomas with a minimum distance of more than 1 mm from the mesorectal fascia and those in the upper third were classified as low risk; these patients underwent TME alone (no nCRT). Patients were followed for at least 3 years. Outcomes were the rates of local recurrence, distant metastasis and survival. RESULTS: Among 545 patients included, 428 were treated according to the study protocol: 254 (59·3 per cent) had TME alone and 174 (40·7 per cent) received nCRT and TME. Median follow-up was 60 months. The 3- and 5-year local recurrence rates were 1·3 and 2·7 per cent respectively, with no differences between the two treatment protocols. Patients with disease requiring nCRT had higher 3- and 5-year rates of distant metastasis (17·3 and 24·9 per cent respectively versus 8·9 and 14·4 per cent in patients who had TME alone; P = 0·005) and worse disease-free survival compared with that in patients who did not need nCRT (3- and 5-year rates 76·7 and 66·7 per cent, versus 84·9 and 76·0 per cent in the TME-alone group; P = 0·016). CONCLUSION: Restriction of nCRT to high-risk patients achieved good results.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Supervivencia sin Enfermedad , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/diagnóstico , Estudios Prospectivos , Neoplasias del Recto/diagnóstico , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento
4.
J Phys Chem B ; 122(2): 527-533, 2018 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-28621937

RESUMEN

Although the (111) surface of Fe3O4 (magnetite) has been investigated for more than 20 years, substantial controversy remains in the literature regarding the surface termination proposed based on structural and adsorption studies. The present article provides density functional theory results that allow to rationalize experimental results of infrared reflection-absorption spectroscopy and temperature-programmed desorption studies on CO adsorption, thus leading to a unified picture in which the Fe3O4(111) surface is terminated by a 1/4 monolayer of tetrahedrally coordinated Fe3+ ions on top of a close-packed oxygen layer as previously determined by low energy electron diffraction. However, surface defects play a crucial role in adsorption properties and may dominate chemical reactions on Fe3O4(111) when exposed to the ambient.

5.
Eur J Cardiovasc Nurs ; 16(5): 409-417, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28565966

RESUMEN

BACKGROUND: Vascular complications are still common in the catheterization laboratory setting. However, no risk scores for their prediction have been described. With a view to bridging this gap, the present study sought to develop and validate a score for prediction of vascular complications associated with arterial access in patients undergoing interventional cardiology procedures. METHODS: This prospective multicenter cohort study included adult patients who underwent cardiac catheterization via the femoral or radial route. The outcomes of interest were: access site hematoma; major and minor bleeding; and retroperitoneal hemorrhage, pseudoaneurysm, or arteriovenous fistula requiring surgical repair. Past medical history as well as pre-procedural, intra-procedural, and post-procedural variables were collected. Patients were randomly allocated to the derivation or validation cohorts at a 2:1 ratio. The following equation constituted the score: (>6F introducer sheath×4.0)+(percutaneous coronary intervention×2.5)+(history of vascular complication after prior interventional cardiology procedure×2.0)+(prior use of warfarin or phenprocoumon×2.0)+(female sex×1.5)+(age⩾60 years×1.5). The maximum score is 13.5 points. RESULTS: A score dichotomized at ⩾3 (best cutoff for balancing sensitivity and specificity) was moderately accurate (sensitivity=0.66 (95% confidence interval: 0.59-0.73); specificity=0.59 (95% confidence interval: 0.56-0.61)). Patients with a score ⩾3 were at increased risk of complications (odds ratio: 2.95; 95% confidence interval: 2.22-3.91). CONCLUSIONS: This study yielded a score that is capable of predicting vascular complications and easily applied in daily practice by providers working in the catheterization laboratory setting.


Asunto(s)
Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/normas , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/normas , Complicaciones Posoperatorias/etiología , Medición de Riesgo/normas , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Estudios Prospectivos
6.
J Gastrointest Surg ; 20(1): 25-32; discussion 32-3, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26556476

RESUMEN

INTRODUCTION: Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR. METHODS: Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup. RESULTS: TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR. CONCLUSIONS: Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.


Asunto(s)
Adenocarcinoma/terapia , Quimioradioterapia Adyuvante , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Selección de Paciente , Cuidados Preoperatorios/métodos , Neoplasias del Recto/terapia , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Recto/cirugía
7.
Bioresour Technol ; 200: 905-13, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26609947

RESUMEN

Experiments with a process development unit for fast pyrolysis of biomass residues of 10kgh(-1) have been performed to quantify the impact of two different product recovery options. Wheat straw, miscanthus and scrap wood have been used as feedstock. A separate recovery of char increases the organic oil yield as compared to a combined recovery of char and organic condensate (OC). Furthermore, it allows for an alternative use of the byproduct char which represents an important product fraction for the high ash biomass residues under consideration. The char produced shows little advantage over its biomass precursor when considered as energy carrier due to its high ash content. Significant value can be added by demineralizing and activating the char. The potential to increase the economic feasibility of fast pyrolysis is shown by an assessment of the bioliq® process chain.


Asunto(s)
Biomasa , Biotecnología/métodos , Carbón Orgánico/química , Temperatura , Carbono/análisis , Simulación por Computador , Triticum/química , Residuos , Madera/química
8.
Chirurg ; 86(12): 1138-44, 2015 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-26347011

RESUMEN

BACKGROUND: In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI). OBJECTIVE: Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations. PATIENTS AND METHODS: Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells. RESULTS AND DISCUSSION: In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate (> 30 %) treated significantly more patients with very low lying carcinomas (< 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.


Asunto(s)
Canal Anal/cirugía , Quimioradioterapia Adyuvante , Preservación de Órganos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/patología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Factores de Riesgo
9.
Eur J Phys Rehabil Med ; 51(2): 149-54, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24755776

RESUMEN

BACKGROUND: Fibromyalgia (FM) is a rheumatic disease characterized by chronic widespread pain and symptoms such as fatigue, sleep disturbances, cognitive difficulties, and depression. Postural instability is a debilitating disorder increasingly recognized as part of FM. OBJECTIVE: To assess and compare postural control and balance self-efficacy in women with and without FM and verify the association of these variables with pain, symptom severity, and strength. DESIGN: Case-control study SETTING: Physiotherapeutic Clinical Research and Electromyography Laboratory Department of Physical Therapy, Speech Therapy, and Occupational Therapy, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. POPULATION: Case-control study of 117 women ranging from age 35 to 60 years. Of these, 67 had FM. METHODS: Posture control was assessed with the modified clinical test of sensory interaction on balance with patients in forceplates, balance self-efficacy with the Activities-specific Balance Confidence Scale, pain severity with the Visual Analog Scale, tender point pain threshold with digital algometry, symptom severity with the fibromyalgia impact questionnaire, and lower limb strength with a dynamometer. RESULTS: Individuals with FM had impaired postural control showing increased speed of oscillation of the center of gravity (P=0.004) and decreased balance self-efficacy (P<0.001). They had moderate to excellent correlations of balance self-efficacy with pain (r=0.7, P<0.01), muscle strength (r=0.52, P<0.01), and symptom severity (r=0.78, P<0.10) compared with the control group. Correlation of postural control with the same variables was weak. CONCLUSIONS: Patients with FM have impaired postural control and low balance self-efficacy that are associated with pain, muscle strength, and symptom severity. CLINICAL REHABILITATION IMPACT: Postural control and balance self-efficacy needs to be assessed in patients with FM and the treatment goals should be the improvement of postural control and balance self-efficacy.


Asunto(s)
Fibromialgia/terapia , Debilidad Muscular/etiología , Dolor/etiología , Equilibrio Postural/fisiología , Trastornos de la Sensación/etiología , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Fibromialgia/complicaciones , Fibromialgia/psicología , Humanos , Persona de Mediana Edad , Debilidad Muscular/psicología , Dolor/psicología , Dimensión del Dolor , Umbral del Dolor , Resistencia Física , Músculo Cuádriceps/fisiopatología , Autoeficacia , Trastornos de la Sensación/psicología , Índice de Severidad de la Enfermedad , Perfil de Impacto de Enfermedad
10.
J Clin Pharmacol ; 52(3): 388-403, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21543662

RESUMEN

Atomoxetine is a cytochrome P4502D6 (CYP2D6) substrate. The reduced-activity CYP2D6*10 allele is particularly prevalent in the Japanese population and may contribute to known ethnic differences in CYP2D6 metabolic capacity. The purpose of this study was to examine atomoxetine pharmacokinetics, safety, tolerability, and the effect of the CYP2D6*10/*10 genotype after single-stepped dosing (10, 40, 90, or 120 mg) and at steady state (40 or 60 mg twice a day for 7 days) in 49 healthy Japanese adult men. Dose proportionality was shown and tolerability confirmed at all doses studied. Comparison of pharmacokinetics, safety, and tolerability between Japanese and US subjects showed no clinically meaningful ethnic differences. The CYP2D6*10/*10 subjects had 2.1- to 2.2-fold and 1.8-fold higher area under the plasma concentration-time curve values relative to the CYP2D6*1/*1 and *1/*2 subjects and the CYP2D6*1/*10 and *2/*10 subjects, respectively. The adverse events reported by CYP2D6*10/*10 subjects were indistinguishable from those of other Japanese participants. The higher mean exposure in CYP2D6*10/*10 subjects is not expected to be clinically significant.


Asunto(s)
Pueblo Asiatico/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Propilaminas/efectos adversos , Propilaminas/farmacocinética , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/farmacocinética , Adulto , Área Bajo la Curva , Clorhidrato de Atomoxetina , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Regulación Enzimológica de la Expresión Génica , Genotipo , Semivida , Humanos , Masculino , Adulto Joven
11.
Cancer Gene Ther ; 18(7): 457-66, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21436868

RESUMEN

Motile bacteria can overcome diffusion resistances that substantially reduce the efficacy of standard cancer therapies. Many reports have also recently described the ability of Salmonella to deliver therapeutic molecules to tumors. Despite this potential, little is known about the spatiotemporal dynamics of bacterial accumulation in solid tumors. Ultimately this timing will affect how these microbes are used therapeutically. To determine how bacteria localize, we intravenously injected Salmonella typhimurium into BALB/c mice with 4T1 mammary carcinoma and measured the average bacterial content as a function of time. Immunohistochemistry was used to measure the extent of apoptosis, the average distance of bacteria from tumor vasculature and the location of bacteria in four different regions: the core, transition, body and edge. Bacteria accumulation was also measured in pulmonary and hepatic metastases. The doubling time of bacterial colonies in tumors was measured to be 16.8 h, and colonization was determined to delay tumor growth by 48 h. From 12 and 48 h after injection, the average distance between bacterial colonies and functional vasculature significantly increased from 130 to 310 µm. After 48 h, bacteria migrated away from the tumor edge toward the central core and induced apoptosis. After 96 h, bacteria began to marginate to the tumor transition zone. All observed metastases contained Salmonella and the extent of bacterial colocalization with metastatic tissue was 44% compared with 0.5% with normal liver parenchyma. These results demonstrate that Salmonella can penetrate tumor tissue and can selectively target metastases, two critical characteristics of a targeted cancer therapeutic.


Asunto(s)
Neoplasias Mamarias Animales/microbiología , Neoplasias Mamarias Animales/terapia , Neoplasias/microbiología , Salmonella/fisiología , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Neoplasias/metabolismo , Salmonella typhimurium/fisiología
12.
Clin Exp Dermatol ; 36 Suppl 2: 4-11, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21443598

RESUMEN

BACKGROUND: Alitretinoin (9-cis retinoic acid) is currently registered in many European countries and in Canada as the only licensed treatment for severe chronic hand eczema unresponsive to potent topical corticosteroids. Alitretinoin, like all retinoids, is teratogenic, and women of child-bearing potential must strictly adhere to pregnancy-prevention measures. AIM: To investigate the influence of alitretinoin on the pharmacokinetics (PK) of ethinyl estradiol/norgestimate (Ortho Tri-Cyclen 28(®)), a commonly prescribed combination oral contraceptive. METHODS: In total, 16 healthy premenopausal women received three consecutive cycles of the triphasic contraceptive ethinyl estradiol/norgestimate together with concomitant oral alitretinoin 40 mg once daily during cycle 2. Steady-state PK (noncompartmental analysis) of ethinyl estradiol, 17-deacetyl norgestimate, alitretinoin and its main metabolite 4-oxo-alitretinoin were assessed alone and in combination. RESULTS: The PK profiles of ethinyl estradiol and 17-deacetyl norgestimate were similar when contraceptives were given alone or with alitretinoin, and the area under the plasma concentration vs. time curve and the maximum concentration met the conventional criteria for PK equivalence. Similarly, the influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin was not clinically relevant. Alitretinoin was well tolerated when given either alone or with ethinyl estradiol/norgestimate. CONCLUSIONS: There was no clinically relevant influence of alitretinoin on the PK of ethinyl estradiol/norgestimate, and no influence of ethinyl estradiol/norgestimate on systemic exposure to alitretinoin and 4-oxo-alitretinoin. Consequently, oral contraception with ethinyl estradiol/norgestimate is an appropriate primary method of birth control during alitretinoin treatment for women of childbearing potential.


Asunto(s)
Anticonceptivos Orales Combinados/sangre , Fármacos Dermatológicos/farmacología , Etinilestradiol/sangre , Norgestrel/análogos & derivados , Tretinoina/farmacología , Administración Oral , Adolescente , Adulto , Alitretinoína , Niño , Anticonceptivos Orales Combinados/administración & dosificación , Anticonceptivos Orales Combinados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/sangre , Esquema de Medicación , Combinación de Medicamentos , Interacciones Farmacológicas , Etinilestradiol/administración & dosificación , Etinilestradiol/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Norgestrel/administración & dosificación , Norgestrel/efectos adversos , Norgestrel/sangre , Progesterona/sangre , Tretinoina/efectos adversos , Tretinoina/sangre , Adulto Joven
13.
Clin Exp Dermatol ; 36 Suppl 2: 12-7, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21443599

RESUMEN

BACKGROUND: Alitretinoin, like all retinoids, is teratogenic, and can only be given to women of childbearing potential if pregnancy is excluded and a strict contraceptive programme is followed. AIM: This study was designed to determine whether alitretinoin in the semen of men treated with alitretinoin poses a teratogenic risk to their female partners. METHODS: In total, 24 healthy men aged 18-45 years received alitretinoin 20 mg (n = 12) or 40 mg (n = 12), once daily for 14 days. Subjects in the 40 mg dose group provided ejaculate at baseline, on day 1, before and approximately 4 h after dosing on day 2, and at follow-up on study day 21 (± 2). RESULTS: Alitretinoin and 4-oxo-alitretinoin were detected in 11 of the 12 semen samples. The highest level of alitretinoin in semen was 7.92 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be about 80 ng, 1/375,000 of a single 30 mg capsule. Complete absorption of 80 ng of alitretinoin from semen, presuming a volume of distribution confined to 5 L of circulating blood in the partner, would lead to an increase in plasma alitretinoin concentration of 0.016 ng/mL, which appears to be negligible compared with measured endogenous plasma levels. Increases in plasma levels of related retinoids are also negligible. CONCLUSIONS: Alitretinoin in the semen of men receiving up to 40 mg of oral alitretinoin per day is unlikely to be associated with teratogenic risk in their female partners. Barrier contraception is therefore not required for men taking alitretinoin.


Asunto(s)
Fármacos Dermatológicos/farmacocinética , Semen/metabolismo , Tretinoina/farmacocinética , Anomalías Inducidas por Medicamentos/etiología , Administración Oral , Adolescente , Adulto , Alitretinoína , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Tretinoina/administración & dosificación , Tretinoina/efectos adversos , Adulto Joven
14.
Clin Exp Dermatol ; 36 Suppl 2: 18-23, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21443600

RESUMEN

BACKGROUND: Previous studies have shown that concomitant administration of food may enhance the bioavailability of oral retinoids. AIM: To assess the influence of food on the pharmacokinetics (PK) of alitretinoin after a single oral dose. METHODS: This was a single-dose, open-label, randomized, crossover study, which enrolled 30 healthy men, aged 18-44 years. Subjects received sequential doses of alitretinoin 40 mg either after fasting (treatment A) or 5 min after completion of a standard breakfast (treatment B), with the dosing sequence randomized (A/B or B/A). The washout period between the two doses was 1 week. Plasma concentrations over time were plotted and standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)) and elimination half-life (t(1/2)] were determined. RESULTS: Drug exposure was markedly increased when alitretinoin was taken with food compared with fasting, and there were significant increases in mean C(max) (82.8 vs.25.4 ng/mL, respectively) and AUC (220.2 vs. 55.7 ng · h/mL). The delaying effect of food on t(max) was less marked (median of 3.0 vs. 2.0 h). Administration with food also increased exposure to drug metabolites. Variability in exposure was markedly reduced if alitretinoin was taken with vs. without food (percentage coefficient of variation 40% vs. 74% for AUC; 49% vs. 85% for C(max)). Alitretinoin was generally well tolerated, with typical retinoid adverse reactions, mostly comprising headache. CONCLUSIONS: Intake of alitretinoin with food substantially increased the bioavailability of alitretinoin, but variability in exposure was reduced. Consequently, oral alitretinoin should be taken with food as outlined in the manufacturer's summary of product characteristics.


Asunto(s)
Fármacos Dermatológicos/sangre , Interacciones Alimento-Droga , Tretinoina/sangre , Administración Oral , Adolescente , Adulto , Alitretinoína , Disponibilidad Biológica , Estudios Cruzados , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Ayuno/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tretinoina/administración & dosificación , Tretinoina/efectos adversos , Adulto Joven
15.
Clin Exp Dermatol ; 36 Suppl 2: 24-8, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21443601

RESUMEN

BACKGROUND: Based on in vitro data with isolated cytochrome P450 (CYP) isoenzymes, alitretinoin interacts only with CYP3A4, and the potential for drug-drug interactions is considered negligible. AIM: To confirm in humans the lack of potential interactions between CYP3A4 and alitretinoin in vivo. METHODS: This was a multiple-dose, open-label, parallel-group, single-centre study, which enrolled 54 healthy male volunteers aged 18-45 years. Subjects were divided into three groups, with 18 in each group: group 1 received either alitretinoin 30 mg and ketoconazole 200 mg, group 2 alitretinoin 30 mg and simvastatin 40 mg, and group 3 alitretinoin 30 mg and ciclosporin A 300-mg. RESULTS: At the highest therapeutic dose of 30 mg, alitretinoin had no significant effect on the pharmacokinetics (PK) of ketoconazole and ciclosporin A. There was a significant but not clinically relevant effect of simvastatin on the area under the curve (AUC) of plasma concentration vs. time and on maximum plasma concentration (C(max)) after repeated administration of alitretinoin. Exposure to simvastatin concomitantly with alitretinoin was decreased by 16% for AUC and 23% for C(max). The CYP3A4 ± PgP substrates of simvastatin and ciclosporin A did not affect the single or repeated dose PK of alitretinoin. The strong CYP3A4/PgP inhibitor ketoconazole led to significant increases in both AUC and C(max) values for alitretinoin. CONCLUSIONS: Single and repeated doses of alitretinoin do not alter the PK of ciclosporin A and ketoconazole. Simvastatin levels were slightly but significantly reduced by co-administration of alitretinoin. Substrates of CYP3A4 did not affect the PK of alitretinoin. However, ketoconazole significantly increased the plasma levels of alitretinoin, therefore, co-administration with CYP3A4 inhibitors such as ketoconazole may require a dose reduction of alitretinoin.


Asunto(s)
Ciclosporina/sangre , Fármacos Dermatológicos/farmacología , Cetoconazol/sangre , Simvastatina/sangre , Tretinoina/farmacología , Adolescente , Adulto , Alitretinoína , Antifúngicos/sangre , Estudios Cruzados , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/sangre , Esquema de Medicación , Interacciones Farmacológicas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/sangre , Inmunosupresores/sangre , Masculino , Persona de Mediana Edad , Tretinoina/administración & dosificación , Tretinoina/sangre , Adulto Joven
16.
Clin Exp Dermatol ; 36 Suppl 2: 29-34, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21443602

RESUMEN

BACKGROUND: Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids. AIMS: To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily. METHODS: This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale. RESULTS: Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated. CONCLUSIONS: Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.


Asunto(s)
Fármacos Dermatológicos/sangre , Dermatosis de la Mano/sangre , Tretinoina/sangre , Adolescente , Adulto , Anciano , Alitretinoína , Enfermedad Crónica , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Dermatosis de la Mano/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Tretinoina/efectos adversos , Tretinoina/uso terapéutico , Adulto Joven
17.
Pathologe ; 32(2): 165-7, 2011 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-21046106

RESUMEN

Tailgut cysts are unusual benign cystic retrorectal malformations arising from persistent remnants of the postanal gut. Malignant transformation within this dysontogenetic lesion is very uncommon. We report the rare occurrence of a neuroendocrine tumor arising in a tailgut cyst with primary liver and lymph node metastases in a 55-year-old woman. The neuroendocrine differentiation of the tumor determines the therapeutic approach and prognosis.


Asunto(s)
Quistes/congénito , Quistes/patología , Hamartoma/congénito , Hamartoma/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/secundario , Enfermedades del Recto/congénito , Enfermedades del Recto/patología , Neoplasias del Recto/patología , Región Sacrococcígea/patología , Biomarcadores de Tumor/análisis , División Celular/fisiología , Transformación Celular Neoplásica/patología , Quistes/cirugía , Diagnóstico Diferencial , Femenino , Hamartoma/cirugía , Humanos , Queratina-7/análisis , Antígeno Ki-67/análisis , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Enfermedades del Recto/cirugía , Neoplasias del Recto/cirugía , Región Sacrococcígea/cirugía , Sinaptofisina/análisis
18.
Clin Exp Rheumatol ; 28(6 Suppl 63): S57-63, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21176422

RESUMEN

OBJECTIVES: The aim of this study was to assess the relationship between variables of physical assessment - muscular strength, flexibility and dynamic balance - with pain, pain threshold, and fibromyalgia symptoms (FM). METHODS: Our sample consists of 55 women, with age ranging from 30 to 55 years (mean of 46.5, (standard deviation, SD=6.6)), mean body mass index (BMI) of 28.7 (3.8) and diagnosed for FM according to the American College of Rheumatology criteria. Pain intensity was measured using a visual analogue scale (VAS) and pain threshold (PT) using Fisher's dolorimeter. FM symptoms were assessed by the Fibromyalgia Impact Questionnaire (FIQ); flexibility by the third finger to floor test (3FF); the muscular strength index (MSI) by the maximum volunteer isometric contraction at flexion and extension of right knee and elbow using a force transducer, dynamic balance by the time to get up and go (TUG) test and the functional reach test (FRT). Data were analysed using Pearson's correlation, as well as simple and multivariate regression tests, with significance level of 5%. RESULTS: PT and FIQ were weakly but significantly correlated with the TUG, MSI and 3FF as well as VAS with the TUG and MSI (p<0.05). VAS, PT and FIQ was not correlated with FRT. Simple regression suggests that, alone, TUG, FR, MSI and 3FF are low predictors of VAS, PT and FIQ. For the VAS, the best predictive model includes TUG and MSI, explaining 12.6% of pain variability. For TP and total symptoms, as obtained by the FIQ, most predictive model includes 3FF and MSI, which respectively respond by 30% and 21% of the variability. CONCLUSIONS: Muscular strength, flexibility and balance are associated with pain, pain threshold, and symptoms in FM patients.


Asunto(s)
Fibromialgia/fisiopatología , Fuerza Muscular/fisiología , Umbral del Dolor/fisiología , Dolor/fisiopatología , Equilibrio Postural/fisiología , Rango del Movimiento Articular/fisiología , Adulto , Femenino , Fibromialgia/rehabilitación , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Dimensión del Dolor , Análisis de Regresión
19.
Ergonomics ; 53(11): 1311-24, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20967655

RESUMEN

The article proposes a multi-level approach for evaluating communication skills training (CST) as an important element of crew resource management (CRM) training. Within this methodological framework, the present work examined the effectiveness of CST in matching or mismatching team compositions with regard to hierarchical status and competence. There is little experimental research that evaluated the effectiveness of CRM training at multiple levels (i.e. reaction, learning, behaviour) and in teams composed of members of different status and competence. An experiment with a two (CST: with vs. without) by two (competence/hierarchical status: congruent vs. incongruent) design was carried out. A total of 64 participants were trained for 2.5 h on a simulated process control environment, with the experimental group being given 45 min of training on receptiveness and influencing skills. Prior to the 1-h experimental session, participants were assigned to two-person teams. The results showed overall support for the use of such a multi-level approach of training evaluation. Stronger positive effects of CST were found for subjective measures than for objective performance measures. STATEMENT OF RELEVANCE: This work provides some guidance for the use of a multi-level evaluation of CRM training. It also emphasises the need to collect objective performance data for training evaluation in addition to subjective measures with a view to gain a more accurate picture of the benefits of such training approaches.


Asunto(s)
Comunicación , Capacitación en Servicio , Aprendizaje , Análisis y Desempeño de Tareas , Adolescente , Adulto , Conducta Cooperativa , Humanos , Masculino , Competencia Profesional , Evaluación de Programas y Proyectos de Salud , Adulto Joven
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