RESUMO
Abstract: Introduction: The takotsubo syndrome is a rare clinical entity commonly associated with elderly women (ratio 6:1), easily confused with an acute ischemic syndrome, strangely associated with a myasthenic crisis. It is characterized with chest pain, elevated biomarkers, ST segment elevation, absence of coronary flow obstruction, and a characteristic deformity (anteroapical dyskinesia) of the left ventricle; these changes associated with a stressor. Case report: A woman of 69 years, diagnosed with myasthenia gravis six years ago, who entered in the intensive care unit with a suspected diagnosis of acute coronary syndrome and respiratory failure which required mechanical ventilation. Coronary angiography discarded a coronary disease. Ventriculography revealed a systolic anteroapical deformation. Treatment was initiated with acetylcholinesterase inhibitors and plasmapheresis with partial response, it required the use of vasoactive amines, with a suitable progressive cardiovascular and neurological outcome, with echocardiographic resolution. Conclusions: The takotsubo syndrome can be associated with myasthenia gravis and myasthenic crisis. The prognosis depends on early diagnosis, appropriate differential diagnosis, immediate treatment of myasthenic crisis, and management of the hemodynamic consequences of the takotsubo syndrome.
Resumen: Introducción: El síndrome de takotsubo es una entidad clínica poco frecuente asociada comúnmente con las mujeres de edad avanzada (relación 6:1), puede fácilmente confundirse con un síndrome isquémico agudo, extrañamente asociado con una crisis miasténica. Se caracteriza por dolor torácico, biomarcadores elevados, elevación del segmento ST, ausencia de obstrucción del flujo coronario, y una deformidad característica (discinesia anteroapical) del ventrículo izquierdo; estos cambios asociados con un factor de estrés. Caso clínico: Una mujer de 69 años, con diagnóstico de miastenia gravis hace seis años, que ingresó en la Unidad de Cuidados Intensivos con un diagnóstico de sospecha de síndrome coronario agudo e insuficiencia respiratoria que requirió de ventilación mecánica. La angiografía descartó una enfermedad coronaria. La ventriculografía reveló una deformación anteroapical sistólica. Se inició el tratamiento con inhibidores de la acetilcolinesterasa y plasmaféresis con respuesta parcial, se requirió el uso de aminas vasoactivas, con un resultado progresivo cardiovascular y neurológico adecuado, con resolución ecocardiográfica. Conclusiones: El síndrome de takotsubo puede estar asociada con miastenia gravis y la crisis miasténica. El pronóstico depende del diagnóstico precoz, el diagnóstico diferencial adecuado, el tratamiento inmediato de la crisis miasténica, y la gestión de las consecuencias hemodinámicas del síndrome takotsubo.
RESUMO
Selenium (Se) is a crucial element exerting antioxidant and neuroprotective effects in different toxic models. It has been suggested that Se acts through selenoproteins, of which thioredoxin reductase (TrxR) is relevant for reduction of harmful hydroperoxides and maintenance of thioredoxin (Trx) redox activity. Of note, the Trx/TrxR system remains poorly studied in toxic models of degenerative disorders. Despite previous reports of our group have demonstrated a protective role of Se in the excitotoxic/pro-oxidant model induced by quinolinic acid (QUIN) in the rat striatum (Santamaría et al., 2003, 2005), the precise mechanism(s) by which Se is inducing protection remains unclear. In this work, we characterized the time course of protective events elicited by Se as pretreatment (Na(2)SO(3), 0.625 mg/kg/day, i.p., administered for 5 consecutive days) in the toxic pattern produced by a single infusion of QUIN (240 nmol/µl) in the rat striatum, to further explore whether TrxR is involved in the Se-induced protection and how is regulated. Se attenuated the QUIN-induced early reactive oxygen species formation, lipid peroxidation, oxidative damage to DNA, loss of mitochondrial reductive capacity and morphological alterations in the striatum. Our results also revealed a novel pattern in which QUIN transiently stimulated an early TrxR cellular localization/distribution (at 30 min and 2 h post-lesion, evidenced by immunohistochemistry), to further stimulate a delayed protein activation (at 24 h) in a manner likely representing a compensatory response to the oxidative damage in course. In turn, Se induced an early stimulation of TrxR activity and expression in a time course that "matches" with the reduction of the QUIN-induced oxidative damage, suggesting that the Trx/TrxR system contributes to the resistance of nerve tissue to QUIN toxicity.
Assuntos
Antioxidantes/farmacologia , Neostriado/enzimologia , Neurotoxinas/toxicidade , Oxidantes/toxicidade , Compostos de Selênio/farmacologia , Tiorredoxina Dissulfeto Redutase/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Animais , Western Blotting , Contagem de Células , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/farmacologia , Imuno-Histoquímica , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neostriado/patologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Quinolínico/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Research into ancient societies frequently faces a major challenge in accessing the lives of those who made up the majority of their populations, since the available evidence so often concerns only the ruling elite. Our excavations at the ancient Maya site of Calakmul, Mexico, have uncovered a "painted pyramid:" a structure decorated with murals depicting scenes of its inhabitants giving, receiving, and consuming diverse foods, as well as displaying and transporting other goods. Many are accompanied by hieroglyphic captions that describe the participants, and include spellings of key subsistence items. Collectively, they offer insights into the social mechanisms by which goods were circulated within major Maya centers.
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Atividades Cotidianas , Arqueologia , Civilização/história , Pinturas/história , Feminino , História Antiga , Humanos , Masculino , MéxicoRESUMO
BACKGROUND: The relationship between psychiatric morbidity and characteristics of the work environment has been well-documented, and one of the professional groups in which psychiatric symptoms are most common is schoolteachers. AIMS: The present study was designed to evaluate the association between psychiatric morbidity [measured with General Health Questionnaire (GHQ)-28 score] and workplace-, sociodemographic- and personality-related variables in schoolteachers. METHODS: A sample of 498 non-university teachers in the city of Granada (southern Spain) were studied with a questionnaire comprising items that covered work-related variables (work and professional variables, as well as job perceptions), sociodemographic characteristics of the teachers and personality, evaluated with the Temperament and Character Inventory (TCI-125). The dependent variable was psychiatric morbidity, measured as scores >6 on the GHQ-28. Crude and adjusted odds ratios between each independent variable and psychiatric morbidity were obtained. RESULTS: In the adjusted analysis, psychiatric morbidity was associated with heavy workload, physical assault from pupils, low appraisal by superiors, low job satisfaction, high stress, female gender and (regarding personal characteristics) high scores for harm avoidance and novelty seeking and low scores for self-directedness. CONCLUSIONS: When personality characteristics are taken into account, the effect of workplace and sociodemographic variables was limited, although workload, poor job satisfaction and female sex remained associated with psychiatric morbidity.
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Docentes , Transtornos Mentais/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Distribuição por Idade , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/psicologia , Personalidade , Distribuição por Sexo , Espanha/epidemiologia , Violência , Carga de TrabalhoRESUMO
BACKGROUND AND OBJECTIVE: Cation-containing drugs have the potential to affect the absorption of quinolones. The current study was conducted to assess whether the bioavailability of garenoxacin was affected by administration as crushed tablets with and without concomitant enteral nutrition. METHODS: This was a randomised, open-label, three-period, single-dose, crossover study carried out in healthy male volunteers who received study treatments at a clinical facility. The study included 18 subjects (mean age 30 +/- 6 years) who were treatment-naive to garenoxacin and had a body mass index of > or =18 kg/m(2) and < or =30 kg/m(2). Subjects received garenoxacin 600 mg orally in three treatments: (A) intact tablets; (B) crushed tablets suspended in water delivered via a nasogastric (NG) tube; and (C) treatment B plus concomitant enteral feeding (Osmolite; 600 mL at 100 mL/h). Serial plasma samples were collected post-dose for pharmacokinetic analysis. Pharmacokinetic parameters were determined by noncompartmental methods. Geometric mean ratio with 90% CI for area under the concentration-time curve from time 0 extrapolated to infinity (AUC(infinity)) and maximum observed plasma concentration (C(max)) were used to assess potential effects of the different conditions of administration. Absence of an effect was concluded if the 90% CIs for the ratio of geometric means for C(max) and AUC(infinity) were within 0.7-1.43 and 0.8-1.25, respectively. The pharmacokinetics (AUC(infinity)and C(max)) and safety of garenoxacin were assessed. RESULTS: Geometric means for C(max) were 8.3, 8.5 and 8.3 microg/mL and for AUC(infinity) were 103.3, 97.2 and 93.4 microg.h/mL for treatments A, B and C, respectively. The 90% CIs for geometric mean ratios for AUC(infinity) and C(max) of garenoxacin administered as crushed tablets and crushed tablets with Osmolite via NG tube relative to intact tablets administered orally were within 0.80-1.25, suggesting that the bioavailability of garenoxacin was not affected by delivery of crushed tablets via NG tube, regardless of concomitant enteral feeding, compared with oral delivery of intact tablets. Half-life (mean range 12-13 hours) was similar for all three groups. CONCLUSIONS: The relative bioavailability of garenoxacin was not affected by administration as crushed tablets, regardless of enteral feeding. Garenoxacin can be administered as crushed tablets in the presence or absence of concomitant Osmolite.
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Nutrição Enteral/métodos , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/farmacocinética , Administração Oral , Adolescente , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Índice de Massa Corporal , Cromatografia Líquida , Estudos Cross-Over , Fluoroquinolonas/sangue , Meia-Vida , Cefaleia/induzido quimicamente , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pós , Análise de Regressão , Comprimidos , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
BACKGROUND: AST-120 is an orally administered adsorbent used in Japan for prolonging time to initiation of hemodialysis and improving uremic symptoms in patients with chronic kidney disease (CKD). As AST-120 is suspected to reduce the progression of CKD by adsorbing renal toxins in the gastrointestinal tract, the objective of the current study was to determine whether binding of AST-120 to creatinine in the intestines could acutely alter creatinine balance, thereby limiting the utility of serum creatinine (sCr) as a measure of progression of renal function. Such information may be critical for the design of future studies to assess the efficacy of AST-120 in CKD patients. METHODS: Patients with CKD (n = 20) received oral doses of AST-120(3 g t.i.d.) and placebo in a two-way crossover study. Blood and urine were collected for determination of sCr, 24-hour urinary creatinine (UcrV), creatinine clearance (Ccr), and urea nitrogen clearance (URCL). Differences between treatments were assessed using an ANCOVA model. RESULTS: Following AST-120 and placebo treatments, mean sCr (1.73 and 1.79 mg/dl, respectively) and UcrV (1,264.73 and 1,286.05 mg) values were not significantly different. No significant differences were observed for Ccr and URCL. CONCLUSION: These results indicate that AST-120 has no acute impact on creatinine balance in patients with CKD. Consequently, sCr and other markers of renal function are acceptable measures for assessing changes in renal function following AST-120 treatment.
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Carbono/administração & dosagem , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Óxidos/administração & dosagem , Análise de Variância , Biomarcadores/sangue , Biomarcadores/urina , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Estudos Cross-Over , Método Duplo-Cego , Humanos , Falência Renal Crônica/sangue , Pessoa de Meia-Idade , Modelos Biológicos , Resultado do TratamentoRESUMO
The effect of pentosan polysulfate sodium on warfarin pharmacokinetics and pharmacodynamics was investigated in healthy subjects. Warfarin was titrated to an international normalized ratio between 1.4 and 1.8. Subjects continued their titrated dose of warfarin and received pentosan polysulfate sodium 100 mg or placebo every 8 hours for 7 days. The Cmax of R- and S-warfarin was approximately 840 to 890 ng/mL and 680 to 730 ng/mL, respectively, and was similar in the absence and presence of pentosan polysulfate sodium. The half-life for R- and S-warfarin was 52 to 56 hours and 36 to 40 hours, respectively. Prothrombin time, partial thromboplastin time, and the international normalized ratio for warfarin + placebo and warfarin + pentosan polysulfate sodium were comparable. The AUC(INR) indicated no treatment effect (P = .772); however, there was a period effect. Analysis of variance for the treatments by period indicated no treatment effect (P > .1). Adverse events were mild and included headache, epistaxis, and rash. Most adverse events were unrelated to treatment and were seen during warfarin titration. Pentosan polysulfate sodium did not affect warfarin pharmacokinetics or pharmacodynamics.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anticoagulantes/farmacocinética , Poliéster Sulfúrico de Pentosana/farmacologia , Varfarina/farmacocinética , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Área Sob a Curva , Coagulação Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Feminino , Meia-Vida , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Poliéster Sulfúrico de Pentosana/administração & dosagem , Tempo de Protrombina , Varfarina/administração & dosagem , Varfarina/farmacologiaRESUMO
AIMS: To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), tolerability and safety of donepezil HCl 5 mg following oral doses for 1 and 24 days in hepatically impaired patients compared with healthy controls under steady-state, multiple-dose conditions. METHODS: In this single-centre, multiple-dose, open-label study, patients with impaired hepatic function (Child-Pugh grade A or B) and healthy controls (matched by gender, age and weight to the hepatically impaired patients) received a single 5 mg dose of donepezil on day 1 and then donepezil HCl 5 mg once daily from days 6 to 29. PK and PD (determination of erythrocyte acetylcholinesterase inhibition) parameters were evaluated on days 1 and 29. Treatment-emergent adverse events (AEs), vital signs, physical examination and clinical laboratory test parameters were monitored throughout the study. RESULTS: A total of 35 subjects (18 patients with hepatic impairment and 17 healthy controls) were enrolled and 32 subjects (16 in each group) completed the study. On day 1 (following a single dose) hepatically impaired patients showed a significant decrease in T(max), while t((1/2)) and AUC(0-infinity) were significantly increased compared with the healthy controls. On day 29 (following multiple doses), AUC(0-24 h), C(max), t((1/2)), C(SS), and R(A) were significantly increased in hepatically impaired patients compared with healthy controls. AUC(0-24 h) increased by 47.6% in the patients with hepatic impairment compared with the healthy controls. There were no significant differences in PD between the groups, although at steady state, the mean AChE inhibition was 16.2% higher in the hepatically impaired patients. No serious AEs were reported and no subject withdrew from the study due to AEs. The most common AEs in both groups were headache and diarrhoea. No clinically significant changes from baseline were observed in vital signs, physical examination findings or electrocardiograms. There was a significant difference in the number of hepatically impaired subjects with abnormalities in serum glucose compared with healthy subjects. However, these elevations were not associated with AEs. CONCLUSIONS: The results of this study suggest that patients with AD and mild to moderate hepatic impairment (Child-Pugh grade A or B) can be safely given donepezil 5 mg once daily and that this dose is associated with a nonsignificantly higher AChE inhibition than age-matched volunteers.
Assuntos
Inibidores da Colinesterase/farmacocinética , Indanos/farmacocinética , Hepatopatias/metabolismo , Piperidinas/farmacocinética , Administração Oral , Adolescente , Adulto , Idoso , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacologia , Donepezila , Relação Dose-Resposta a Droga , Feminino , Humanos , Indanos/efeitos adversos , Indanos/farmacologia , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Piperidinas/farmacologiaRESUMO
OBJECTIVE: To assess the separate effects of age, sex, and experience on the risk of drivers aged 18-24 years being actively involved in a car collision in Spain from 1990 to 1999. METHODS: For this matched case-control study, data were obtained from the Spanish Register of Traffic Crashes with Victims held by the General Directorate of Transport. The study population comprised all drivers involved in car collisions in which only one of the drivers committed a traffic infraction. Drivers who committed infractions constituted the case group while non-infracting drivers involved in the same collision were their corresponding matched controls. Drivers with incomplete or inconsistent data were excluded and a total of 123,586 cases and 140,482 controls was studied. Crude and adjusted (for the effect of potential confounders) odds ratio (OR) were obtained for each combination of driver age (from 18 to 24 years old), sex and years in possession of a driving license (from 0 to 7). RESULTS: For each category of age and years in possession of a driving license, OR estimates for men were usually higher than those for women. In men, crude and adjusted OR significantly decreased with increasing number of years in possession of a driving license for each age group. A similar but less clear trend was also observed for female drivers. After adjustment for the effect of the number of years in possession of a driving license, driver age did not seem to be strongly associated with the risk of being actively involved in a car collision. CONCLUSIONS: Our results suggest that the effect of inexperience is more important than that of age in explaining the higher risk of being involved in a traffic crash in the youngest drivers.
Assuntos
Acidentes de Trânsito , Condução de Veículo , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Razão de Chances , Fatores de Risco , Fatores Sexuais , Espanha , Fatores de TempoRESUMO
Objetivo: Cuantificar el efecto independiente de la edad, el sexo y la experiencia de los conductores de 18 a 24 años sobre el riesgo de verse activamente involucrados en una colisión entre turismos en España, en un estudio realizado entre 1990 y 1999.Métodos: Se ha realizado un estudio de casos y controles emparejados a partir de la información contenida en el Registro de accidentes de tráfico con víctimas de la Dirección General de Tráfico. La población de estudio estuvo constituida por los conductores involucrados en aquellas colisiones entre turismos en las que sólo uno de los conductores implicados cometió alguna infracción. Los conductores infractores constituyeron el grupo de casos, y los no infractores implicados en la misma colisión, sus controles emparejados. Tras excluir los casos con información faltante o inconsistente, se dispuso de un total de 123.586 casos y 140.482 controles. Se calculó la odds ratio (OR) cruda y ajustada para cada combinación de la edad del conductor (entre 18 y 24 años), el sexo y los años de antigüedad del permiso (entre 0 y 7).Resultados: En general, las estimaciones de la OR de los varones fueron superiores a las de las mujeres de igual edad y antigüedad. En los varones se observa que, para cualquier edad, las OR crudas y ajustadas disminuyen significativamente a medida que aumenta el número de años de antigüedad del permiso. En las mujeres se apreció una tendencia similar, aunque con menor claridad. Tras ajustar por el efecto de la experiencia, la edad del conductor no parece estar asociada con el riesgo de verse activamente implicado en la colisión. Conclusiones: El presente estudio confirma la importancia que tiene la inexperiencia como factor responsable del exceso de accidentalidad en los conductores jóvenes, por encima del efecto atribuible a la edad en sí misma (AU)
Assuntos
Masculino , Feminino , Humanos , Adolescente , Adulto , Condução de Veículo , Acidentes de Trânsito , Estudos de Casos e Controles , Espanha , Fatores Sexuais , Fatores de Risco , Razão de Chances , Fatores Etários , Fatores de TempoRESUMO
The pharmacokinetics and safety of the ketolide telithromycin were evaluated in two separate studies after single and repeat oral dosing in patients with varying degrees of renal impairment and in subjects with normal renal function. The single-dose study was an open-label, nonrandomized, parallel-group design in which all 40 patients received a single oral dose of telithromycin 800 mg. The repeat-dose study was an open-label study with a randomized, balanced, incomplete three-block treatment crossover design. In this study, each of the 36 patients received two of three telithromycin regimens (400, 600, or 800 mg once daily for 5 days), with a washout period of >/= 7 days between treatments. Telithromycin was well tolerated. Adverse events were generally mild in severity, and no serious drug-related adverse events were reported. Plasma exposure to telithromycin (C(max), AUC) showed a tendency to increase with increasing severity of renal impairment in both studies. In patients with severe renal impairment (CL(CR) < 30 mL/min) receiving telithromycin 800 mg in the repeat-dose study, C(max,ss) and AUC((0-24 h)ss) increased 1.5-fold (p < 0.05) to 2.0-fold (p = 0.0005), respectively, compared with healthy subjects. The percentage of dose excreted in urine and renal clearance (CL(R)) of telithromycin was found to decrease significantly with increasing severity of renal impairment in both studies, and CL(R) was found to be independent of telithromycin dose in the repeat-dose study. In conclusion, telithromycin dosage adjustment is not necessary in patients with mild to moderate renal impairment (CL(CR) >/= 30 mL/min). In patients with severe renal impairment (CL(CR) < 30 mL/min), dosage adjustment could be considered.
Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Cetolídeos , Nefropatias/metabolismo , Macrolídeos/efeitos adversos , Macrolídeos/farmacocinética , Administração Oral , Adolescente , Adulto , Fatores Etários , Idoso , Antibacterianos/sangue , Área Sob a Curva , Estudos Cross-Over , Eletrocardiografia , Feminino , Meia-Vida , Humanos , Macrolídeos/sangue , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fatores de TempoRESUMO
OBJECTIVE: To assess the differences between patients with hepatic insufficiency and healthy subjects with regard to the pharmacokinetics, cardiac safety and overall safety of ebastine and its active metabolite carebastine. DESIGN: Open-label parallel-group study. PARTICIPANTS: 24 patients with varying degrees of hepatic insufficiency, as categorised by the Child-Pugh classification, and 12 healthy volunteers. METHODS: Healthy subjects and patients with Child-Pugh class A (n = 8) or B (n = 8) received ebastine 20 mg once daily for 7 days. Patients with Child-Pugh class C (n = 8) [single or repeated dose] received ebastine 10 mg. Plasma concentrations of ebastine and carebastine were determined for 23.5 hours following the initial dose on day 1 and for 96 hours following the dose on day 7 by using a sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 microg/L for ebastine and 1.00 microg/L for carebastine. Hepatic function was assessed by blood clearance of indocyanine green 0.5 mg/kg administered intravenously on day 2. Cardiac and overall safety parameters were monitored. RESULTS: Overall, the pharmacokinetics of ebastine were not modified by hepatic impairment. No correlation between ebastine pharmacokinetics and hepatic function, as expressed by indocyanine green clearance, was observed. Comparison of the effective half-life of ebastine and carebastine between groups did not show relevant differences. Therefore, no apparent accumulation of ebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics both in healthy subjects and in hepatically impaired patients. Finally, no apparent difference was noted in the safety of ebastine between patients with hepatic insufficiency and healthy subjects as assessed by evaluation of adverse events, vital signs and laboratory parameters. CONCLUSION: Ebastine can be safely administered to patients with impaired hepatic function, as no clinically important differences can be anticipated from the pharmacokinetics and safety profile of ebastine/carebastine as compared with healthy subjects. Nevertheless, the dosage used in severely impaired patients (10mg daily) was half that used in patients with mild to moderate impairment, and any comedication did not include drugs affecting liver function; in clinical practice, both these factors should be taken into account.
Assuntos
Butirofenonas/farmacocinética , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Hepatopatias/tratamento farmacológico , Piperidinas/farmacocinética , Adulto , Área Sob a Curva , Butirofenonas/efeitos adversos , Butirofenonas/metabolismo , Butirofenonas/uso terapêutico , Estudos de Casos e Controles , Feminino , Meia-Vida , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Absorção Intestinal , Hepatopatias/classificação , Hepatopatias/metabolismo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Piperidinas/metabolismo , Piperidinas/uso terapêuticoRESUMO
E5564 (alpha-D-glucopyranose) is a synthetic antagonist of bacterial endotoxin that has been shown to completely block human endotoxin response. Low doses of E5564 (0.35-3.5 mg) have a long pharmacokinetic half-life, but a surprisingly short ex vivo and in vivo pharmacodynamic half-life (generally less than several hours). To determine whether extended antagonistic activity can be achieved in vivo, this study assesses the pharmacodynamic activity of 4- and 72-h infusions of E5564 into normal volunteers. Administration of 3.5 mg of E5564/h x 72 h completely blocked effects of endotoxin challenge at the end of dosing (72 h), and at 48 and 72 h postdosing. Similarly, a 4-h infusion of E5564, 3 mg/h completely blocked endotoxin administered 8 h postdosing. A lower dose of E5564, 0.5 mg/h x 4 h, ameliorated but did not block most effects of endotoxin 8 h postdosing (p <0.05). Finally, the effect of varying plasma lipoprotein content on E5564 activity was studied in subjects having high or low cholesterol levels (>180 or <140 mg/dl) after 72-h infusion of 252 mg of E5564. No differences were observed. These results demonstrate that E5564 blocks the effects of endotoxin in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis.
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Endotoxemia/prevenção & controle , Lipídeo A/análogos & derivados , Lipídeo A/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Citocinas/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxinas , Humanos , Leucócitos/efeitos dos fármacos , Lipídeo A/efeitos adversos , Lipídeo A/farmacocinética , Masculino , Pessoa de Meia-Idade , Taquicardia/induzido quimicamenteRESUMO
E5564 is a second-generation synthetic analogue of the lipid A component of endotoxin (lipopolysaccharide [LPS]). The ability of E5564 to block the toxic activity of LPS was assessed in a double-blind, placebo-controlled study. A bolus infusion of endotoxin (4 ng/kg) was administered to healthy subjects to induce a mild transient syndrome similar to clinical sepsis. Single E5564 doses of 50-250 microg ameliorated or blocked all of the effects of LPS in a dose-dependent manner. All E5564 dose groups had statistically significant reductions in elevated temperature, heart rate, C-reactive protein levels, white blood cell count, and cytokine levels (tumor necrosis factor-alpha and interleukin-6), compared with placebo (P<.01). In doses of > or = 100 microg, E5564 acted as an LPS antagonist and completely eliminated these signs. E5564 also blocked or ameliorated LPS-induced fever, chills, headache, myalgia, and tachycardia (P<.01). These results demonstrate that E5564 blocks the effects of LPS in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis.
Assuntos
Endotoxemia/tratamento farmacológico , Lipídeo A/análogos & derivados , Lipídeo A/uso terapêutico , Adolescente , Adulto , Citocinas/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Endotoxemia/sangue , Endotoxemia/induzido quimicamente , Humanos , Infusões Intravenosas , Lipídeo A/administração & dosagem , Lipopolissacarídeos/antagonistas & inibidores , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVE: This study aimed to assess the protective effect of helmet use by cyclists on risk of suffering head injury or dying as a consequence of a traffic crash. SUBJECTS AND METHOD: 26,832 cyclists involved in traffic crashes with victims registered in the Dirección General de Tráfico database from 1990 to 1999 in Spain were studied. From this database, variables relating to each cyclist (i.e., age, sex, presence of head trauma, severity of lesions) and those related with the crash (i.e., place, date, type of crash), were collected. The odds ratio and the proportion of the population attributable risk for non-use of a helmet by cyclist were estimated. RESULTS: An adjusted odds ratio of 2.45 (2.19-2.73) for the association between non-use of a helmet and the risk of head injury was obtained. As death of the cyclist as the outcome, the corresponding odds ratio was 1.35 (1.09-1.67). The values of proportion of the population attributable risk were 0.51 (0.47-0.55) and 0.22 (0.07-0.36), for head injury and death, respectively. CONCLUSIONS: This study confirms that helmet use among cyclists significantly decreased the risk of head injury and, to a lesser extent, death. These results constitute a strong argument for increasing in the frequency of helmet use among cyclists in Spain.
Assuntos
Acidentes de Trânsito/prevenção & controle , Ciclismo/lesões , Traumatismos Craniocerebrais/prevenção & controle , Dispositivos de Proteção da Cabeça , Adolescente , Adulto , Idoso , Criança , Traumatismos Craniocerebrais/epidemiologia , Dispositivos de Proteção da Cabeça/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Sistema de Registros , Fatores de Risco , Espanha/epidemiologiaRESUMO
FUNDAMENTO Y OBJETIVO: El objetivo del presente estudio es cuantificar el efecto protector del uso de casco entre los ciclistas sobre el riesgo de sufrir una lesión en la cabeza y de morir tras un accidente de tráfico. SUJETOS Y MÉTODO: Se ha estudiado la serie de casos constituida por los 26.832 ciclistas implicados en accidentes de tráfico con víctimas, recogidos en la base de datos de accidentes de tráfico de la Dirección General de Tráfico en España, entre 1990 y 1999. Se han recogido variables del ciclista (lesividad, presencia de lesiones en la cabeza, edad, sexo, entre otras), y del accidente (lugar, momento del día, tipo de accidente, entre otras). Se han estimado la odds ratio y la proporción del riesgo atribuible poblacional para el no uso de casco. RESULTADOS: Las odds ratio ajustadas (intervalo de confianza del 95 per cent) de no usar casco para el riesgo de sufrir una lesión en la cabeza y de morir han sido, respectivamente, de 2,45 (2,192,73) y 1,35 (1,09-1,67). Las correspondientes proporciones de riesgos atribuibles poblacionales han sido de 0,51 (0,47-0,55) y 0,22 (0,07-0,36). CONCLUSIONES: El presente estudio confirma que el uso de casco entre los ciclistas accidentados reduce significativamente su riesgo de sufrir lesiones en la cabeza y, en menor medida, de morir. Estos resultados constituyen un sólido argumento a favor de la generalización del uso de casco entre los ciclistas en España (AU)
Assuntos
Pessoa de Meia-Idade , Criança , Adolescente , Idoso , Adulto , Humanos , Dispositivos de Proteção da Cabeça , Fatores de Risco , Espanha , Razão de Chances , Análise Multivariada , Sistema de Registros , Ciclismo , Acidentes de Trânsito , Traumatismos CraniocerebraisRESUMO
This retrospective, paired case-control study was designed to estimate crude and adjusted effects of age and sex on the risk of causing collisions between vehicles with four or more wheels in Spain during the period from 1990 to 1999. We selected all 220284 collisions registered from 1990 to 1999 in the Spanish Dirección General de Tráfico (DGT) traffic crash database in which only one driver committed any infraction. Information was collected about age, sex and several confounding factors for both the responsible and paired-by-collision nonresponsible drivers. Crude and adjusted odds ratios (aORs) were calculated for each age and sex category. For men, the lowest risk was seen for drivers aged 25-49 years. Below the age of 35 years the crude odds ratio (cOR) was highest in the 18-24-year-old group (1.61; CI: 1.57-1.65). The risk increased significantly and exponentially after the age of 50 years, to a maximum odds ratio of 3.71 (3.43-4.00) for drivers aged >74 years. In women, the lowest risk values were found for the 25-44-year-old age group. In older women the risk increased significantly with age to a maximum odds ratio of 3.02 (2.31-3.97) in the oldest age group. aOR estimates tended to be lower than crude estimates for drivers younger than 40 years of age, but the opposite was seen for drivers 40 years old and older. Regarding sex differences, among younger drivers crude and aORs for men were higher than for women. Our results suggest that the risk of causing a collision between vehicles with four or more wheels is directly dependent on the driver's age.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Acidentes de Trânsito/prevenção & controle , Adolescente , Adulto , Distribuição por Idade , Idoso , Causalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Assunção de Riscos , Distribuição por Sexo , EspanhaRESUMO
Celecoxib is a novel cyclooxygenase-2-specific inhibitor for the management of acute pain, primary dysmenorrhea, and the signs and symptoms of arthritis. This double-blind, placebo-controlled study in 16 healthy volunteers evaluated whether celecoxib alters the effect of concomitant aspirin on platelet function. Volunteers received celecoxib (400 mg/day) or placebo for 4 days. On day 5, they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo. Thromboxane and platelet aggregation response to adenosine 5'-diphosphate (ADP), collagen, and arachidonic acid were measured before the first dose of celecoxib or placebo (baseline) and before dosing and 2 and 8 hours post dose on day 5. There was no significant difference in thromboxane inhibition between the two groups (percent inhibition: placebo 99.4%, celecoxib 99.0%; p = 0.555). There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP, collagen, or arachidonic acid between the groups. Therefore, these data indicate that celecoxib does not alter the effects of aspirin on platelet function.
Assuntos
Aspirina/farmacologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Isoenzimas/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Sulfonamidas/efeitos adversos , Difosfato de Adenosina/farmacologia , Adolescente , Adulto , Ácido Araquidônico/farmacologia , Celecoxib , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Método Duplo-Cego , Interações Medicamentosas , Feminino , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Pirazóis , Tromboxano B2/sangueRESUMO
OBJECTIVE: To compare the influence of different levels of carbohydrate intolerance on neonatal outcomes. STUDY DESIGN: The cohort constituted by the 1962 pregnant women screened for gestational diabetes who gave birth at the University Hospital of Granada (Spain) in the year 1995 was followed retrospectively. Women were classified into three groups: diagnosis of gestational diabetes, positive screen but non-gestational diabetes, and negative screen. Frequency of adverse newborn outcomes were quantified for each group and compared for statistical significance. RESULTS: Gestational diabetes was associated with a greater incidence of high birth weight, hypoglycemia and hypocalcemia. Adequate metabolic control of the illness reduced the risk of adverse outcomes. Birth weight traced a positive slope with respect to the degree of carbohydrate intolerance. Regardless of carbohydrate intolerance, macrosomia was always higher among gravidae with gestational diabetes risk factors than among women without them. CONCLUSION: Both maternal gestational diabetes risk factors and greater carbohydrate intolerance in gravidae are associated with an increase in adverse newborn outcomes.
Assuntos
Diabetes Gestacional/complicações , Intolerância à Glucose/complicações , Resultado da Gravidez , Adulto , Peso ao Nascer , Índice de Massa Corporal , Estudos de Coortes , Feminino , Macrossomia Fetal/etiologia , Teste de Tolerância a Glucose , Humanos , Hipocalcemia/etiologia , Hipoglicemia/etiologia , Recém-Nascido , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To determine the prevalence of gestational diabetes mellitus in a large general obstetric population and its variations depending on the presence of risk factors, and to evaluate how the gestational diabetes screening strategies applied might modify the observed prevalence in the population. DESIGN: A retrospective cohort study. METHODS: The study population was a total of 2574 pregnant women. Information about risk factors, screening and diagnosis of gestational diabetes was obtained. Frequency of risk factors under the American College of Obstetrics and Gynecologists (ACOG) and the American Diabetes Association (ADA) criteria, and observed and expected prevalence of gestational diabetes mellitus were calculated and compared for statistical significance. RESULTS: Age > or = 30 years, family history of diabetes, obesity and previous fetal macrosomia were the most frequent risk factors. Under ACOG recommendations, 45% of our general obstetric population would have been exempt from gestational diabetes mellitus screening, as compared with only 15.5% under ADA guidelines. Sixty-five patients were diagnosed as having gestational diabetes mellitus, giving an overall prevalence of 2.5% (confidence interval 2.0-3.2). Among the low-risk women, prevalence values were 0.6% and 0.5% respectively under ACOG and ADA criteria, whereas for those presenting one or more risk factors rates were 4% and 2.9% respectively. CONCLUSIONS: In our general obstetric population, gestational diabetes mellitus prevalence was found to be approximately six times lower among low-risk gravidae than among the high-risk subjects, suggesting that selective screening might be beneficial. Nevertheless, selective gestational diabetes mellitus screening under ADA criteria seems to entail the same disadvantages as the selective screening strategies without any apparent benefits.