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1.
Acta Paediatr ; 112(7): 1574-1585, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37129464

RESUMEN

AIM: Children often fall sick, which causes concern among parents. Online health information can be confusing and difficult to understand. We aimed to produce simple, informative video tutorials on the symptoms ill children present. METHODS: We used a modified Delphi method to produce video tutorials on the symptoms of fever, vomiting and diarrhoea, abdominal pain, breathing difficulties, sore throat, red eyes, earache and rash. We identified the most common symptoms in acutely ill children. During the first consensus round, experts rated statements on out-of-hospital management from existing health information. Video tutorials were produced from statements rated to be included. The second consensus round involved video showings and editing. Two videos were evaluated in focus groups by parents. RESULTS: During the first round, experts rated a median of 79 (40-154) statements for each symptom. Panels consisted of a median of seven (6-11) experts, primarily. Panels reached a consensus on inclusion, neutrality or exclusion in 83% of statements. The second round led to adjustments to the videos and final approval by experts. Most parents evaluated the videos as 'informative, easy to understand and calming'. CONCLUSION: We produced video tutorials on the common symptoms ill children present using a modified Delphi method. Feedback from parents in focus groups was positive.


Asunto(s)
Padres , Humanos , Niño , Técnica Delphi , Enfermedad Aguda , Consenso , Grupos Focales
2.
J Environ Manage ; 348: 119199, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37844396

RESUMEN

This study investigated methods for predicting the duration and impact on groundwater quality from persistent and mobile organic compounds (PMOCs) at a drinking water well field affected by multiple contaminant sources. The fungicide metabolite N,N-dimethylsulfamide (DMS), which frequently occurs above the Danish groundwater quality criterion (0.1 µg/L), was used as an example. By combining contaminant mass discharge (CMD) estimations, modeling, and groundwater dating, a number of important discoveries were made. The current center of contaminant mass was located near the source area. The CMD at the well field was predicted to peak in 2040, and an effect from the investigated sources on groundwater quality could be expected until the end of the 21st century. A discrepancy in the current CMD at the well field and the estimated arrival time from the studied source area suggested an additional pesticide source, which has not yet been thoroughly investigated. The presence of the unknown source was supported by model simulations, producing an improved mass balance after inclusion of a contaminant source closer to the well field. The approach applied here was capable of predicting the duration and impact of DMS contamination at a well field at catchment scale. It furthermore shows potential for identification and quantification of the contribution from individual sources, and is also applicable for other PMOCs. Predicting the duration of the release and impact of contaminant sources on abstraction wells is highly valuable for water resources management and authorities responsible for contaminant risk assessment, remediation, and long-term planning at water utilities.


Asunto(s)
Agua Subterránea , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Compuestos Orgánicos , Recursos Hídricos , Monitoreo del Ambiente
3.
Hum Reprod ; 37(7): 1594-1608, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35451014

RESUMEN

STUDY QUESTION: Is fetal exposure to lower-chlorinated polychlorinated biphenyls (LC-PCBs) in indoor air of private homes built with PCB-containing materials associated with semen characteristics and testicular volume in adult men? SUMMARY ANSWER: We observed only marginal and inconsistent associations between maternal exposure to PCBs in indoor air and semen quality, testicular size and reproductive hormones in the adult offspring. WHAT IS KNOWN ALREADY: Recent studies have shown LC-PCBs to exhibit endocrine-disrupting properties and increase the risk of cryptorchidism. Although exposure to LC-PCBs in indoor air is relatively common, the long-term impact of prenatal exposure on male reproductive health has not yet been investigated. STUDY DESIGN, SIZE, DURATION: In this cohort study, participants were men (18+ years) whose mothers carried them while living in one of two residential areas where indoor air had been contaminated by LC-PCB evaporating from building materials in subsets of the apartments. Men were considered prenatally exposed if their mother had lived in a PCB-contaminated apartment and unexposed if their mother had lived in an uncontaminated apartment for a minimum of 1 year during the 3.6 years before conception or during the first trimester. Mothers of prenatally unexposed men could not have lived in a contaminated apartment at any point. Recruitment lasted from 2017 to 2019. In total, 73 exposed and 111 unexposed men gave a blood and semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Percentage differences in semen volume, sperm concentration, total sperm count, morphologically normal spermatozoa, progressively motile spermatozoa and DNA fragmentation index (DFI) between prenatally exposed and unexposed men were estimated using negative binomial regression. Associations with total and calculated free testosterone (CFT), LH and FSH were modeled using the linear regression. Odds of small testicular volume was estimated with logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the results of this study were conflicting. No differences in semen volume, sperm concentration, testosterone and CFT were observed between the groups, but there were slight indications of lower total sperm count, increased FSH and risk of small testicles, alongside lower sperm DFI and a higher proportion of normal spermatozoa in men exposed to LCB-PCBs from indoor air during fetal life. There is no apparent biologically plausible explanation for the apparently improved measures of DNA fragmentation and morphology, and these findings may have occurred purely by chance. LIMITATIONS, REASONS FOR CAUTION: Owing to the indirect measure of exposure, lack of adjustment for paternal factors, the potential for self-selection due to known exposure status and fertility issues, inability to take time spent away from the residence, limited statistical power and lack of comparable literature, independent replication of the study in larger cohorts is warranted. WIDER IMPLICATIONS OF THE FINDINGS: While our findings may appear reassuring for the large number of people residing and/or working in buildings with indoor air contaminated with LC-PCBs, further efforts to understand the full range of health consequences of fetal LC-PCB exposure are needed. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Independent Research Fund Denmark (ref no. 6110-00085B), Bispebjerg Hospital, Landsbyggefonden, Realdania (ref. no. PRJ-2017-00176), Grundejernes Investeringsfond (ref. no. 18-58) and Helsefonden (ref. no. 16-B-01-22 and 21-B-0412). K.S.H. was supported by FFIKA, Focused Research Effort on Chemicals in the Working Environment, from the Danish Government. The authors declare that they have no financial, personal or professional competing interests. TRIAL REGISTRATION NUMBER: Not applicable.


Asunto(s)
Bifenilos Policlorados , Efectos Tardíos de la Exposición Prenatal , Adulto , Estudios de Cohortes , Femenino , Hormona Folículo Estimulante , Humanos , Masculino , Bifenilos Policlorados/toxicidad , Embarazo , Salud Reproductiva , Semen , Análisis de Semen , Recuento de Espermatozoides , Testosterona
4.
J Appl Microbiol ; 126(5): 1580-1593, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30614172

RESUMEN

AIMS: To obtain knowledge about (i) how to sample airborne methicillin-resistant Staphylococcus aureus (MRSA) and dust in the pig farm environment including effects of sampler on (a) measured exposure, (b) MRSA survival and (c) spatial and temporal variation in exposure, and (ii) the association between exposure to MRSA, dust and optical density OD. METHODS AND RESULTS: Airborne dust was sampled on five pig farms using five active and one passive samplers. Staphylococcus aureus and MRSA (as a subset of S. aureus) were quantified using selective agar media and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The Andersen sampler, electrostatic dust collectors (EDC), and Gesamtstaubprobenahme (GSP) and Institute of Occupational Medicine samplers with polycarbonate or Teflon filters were applicable for sampling airborne MRSA. The half-life of MRSA was not reduced by active sampling. A significant correlation was found between dust and S. aureus exposure within, but not between, farm section and farms. A significant spatial and temporal variation in dust and MRSA exposure was found within a stable. The dust sampling rate and the concentration of MRSA in the sampled dust decreased after 5 days of sampling. CONCLUSION: Sampling using the GSP can be performed for 1 h without affecting the following half-life of MRSA. Sampling for MRSA using the EDC should not exceed 3 days due to overloading and the die-off of MRSA. The measurement of OD may be used as a proxy measure for dust exposure. To obtain knowledge about potential exposure, samples should be taken repeatedly and in different areas within a stable section. SIGNIFICANCE AND IMPACT OF THE STUDY: Sampling method, sampling time and number of samples taken, but not force of airflow on the filter, influence the measured potential exposure to MRSA and dust.


Asunto(s)
Polvo , Microbiología Ambiental , Granjas , Staphylococcus aureus Resistente a Meticilina , Animales , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Porcinos
5.
Am J Transplant ; 14(10): 2391-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25135383

RESUMEN

In heart transplant (HTx) recipients, there has been reluctance to recommend high-intensity interval training (HIIT) due to denervation and chronotropic impairment of the heart. We compared the effects of 12 weeks' HIIT versus continued moderate exercise (CON) on exercise capacity and chronotropic response in stable HTx recipients >12 months after transplantation in a randomized crossover trial. The study was completed by 16 HTx recipients (mean age 52 years, 75% males). Baseline peak oxygen uptake (VO2peak ) was 22.9 mL/kg/min. HIIT increased VO2peak by 4.9 ± 2.7 mL/min/kg (17%) and CON by 2.6 ± 2.2 mL/kg/min (10%) (significantly higher in HIIT; p < 0.001). During HIIT, systolic blood pressure decreased significantly (p = 0.037) with no significant change in CON (p = 0.241; between group difference p = 0.027). Peak heart rate (HRpeak ) increased significantly by 4.3 beats per minute (p = 0.014) after HIIT with no significant change in CON (p = 0.34; between group difference p = 0.027). Heart rate recovery (HRrecovery ) improved in both groups with a trend toward greater improvement after HIIT. The 5-month washout showed a significant loss of improvement. HIIT was well tolerated, had a superior effect on oxygen uptake, and led to an unexpected increase in HRpeak accompanied by a faster HRrecovery . This indicates that the benefits of HIIT are partly a result of improved chronotropic response.


Asunto(s)
Ejercicio Físico , Trasplante de Corazón , Oxígeno/metabolismo , Adulto , Anciano , Presión Sanguínea , Estudios Cruzados , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad
6.
J Contam Hydrol ; 257: 104218, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37356422

RESUMEN

Environmental pollution with Persistent and Mobile Organic Compounds (PMOC) from anthropogenic activities is an increasing cause for concern. These compounds are readily leached to groundwater aquifers and are likely to resist degradation, putting pressure on groundwater resources. Pesticides can form PMOCs upon degradation in the environment. The PMOC N,N-dimethylsulfamide (DMS) was the most frequently detected pesticide metabolite in Danish drinking water wells in 2020, although the pesticidal use of the last parent compound (tolylfluanid) ended in 2007. This study aimed to improve the understanding of the leaching of the PMOC DMS from clayey tills by combining a review of compound properties, sources and use, comprehensive field observations and numerical flow and solute transport modeling. The modeling explored the mechanisms of DMS retention during vertical transport in clayey till and the fingerprint in the underlying aquifer. The results were supported by detailed field observations at an agricultural site with strawberry production. Porewater samples were collected from clayey till to a depth of 12 m bgs by a custom designed installation method of suction cups. Groundwater sampling (249 samples) was designed to provide vertical concentration profiles at various distances from the presumed sources. The review of properties showed that the parent compounds and intermediates degrade quickly in topsoil, releasing the highly persistent and mobile DMS. We tested the effect of fractures on transport with different hydraulic apertures and a scenario without fractures by numerical modeling. The results showed that the presence of fractures can smooth the breakthrough curve below the clayey till, leading to faster breakthrough, lower maximum concentration, and several decades of prolonged leaching in simulations with the largest aperture (20 µm). The fracture-matrix interaction is a possible explanation for the observed delay of leaching from clayey till. The vertical concentration profiles in groundwater were used for identifying the sources at the field site and testing source strengths. Assigning one point source (200 µg/L) and two diffuse sources (40-50 µg/L) to the model produced vertical concentration profiles that compared well with observed field data in clayey till and the aquifer. All results were integrated into a conceptual model for the environmental fate of PMOCs in soil and groundwater. The findings of this study imply that the presence of fractures in clayey till should be considered in conceptual site models, since they can substantially prolong the leaching of PMOCs to groundwater. The integration of comprehensive field investigations and numerical modeling is key to understand the fate of PMOCs in complex field systems with different source types. Together with widespread occurrences of PMOCs in groundwater systems, the results highlight the need for improved approval procedures for pesticides and biocides which considers their persistent and mobile metabolites.


Asunto(s)
Agua Subterránea , Plaguicidas , Contaminantes Químicos del Agua , Arcilla , Plaguicidas/análisis , Sulfonamidas , Compuestos Orgánicos , Contaminantes Químicos del Agua/análisis
7.
BJOG ; 119(1): 7-19, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21895959

RESUMEN

BACKGROUND: If human papillomavirus (HPV) testing will replace cytology in primary cervical screening, the frequency of low-grade abnormal screening tests will double. Several available alternatives for the follow-up of low-grade abnormal screening tests have similar outcomes. In this situation, women's preferences have been proposed as a guide for management decisions. OBJECTIVES: To determine women's preferences for the follow-up of low-grade cervical screening abnormalities. SEARCH STRATEGY: Using Medical Subject Headings (MeSH) terms, PubMed was searched for articles published up to December 2010. The reference lists of the retrieved studies were consulted. SELECTION CRITERIA: Studies asking women to state a preference between active follow-up and observation for the management of low-grade abnormalities on screening cytology or HPV tests. DATA COLLECTION AND ANALYSIS: Information on study design, participants and outcomes was retrieved using a prespecified form. Studies were sorted by design. MAIN RESULTS: Thirteen studies were included in the review. In all five studies that surveyed women with abnormal tests before any management had started, two-thirds preferred active follow-up, predominantly as immediate colposcopy, to observation, predominantly as repeated Pap smears. In all but two studies testing other situations, women more often expressed a preference for active follow-up than for observation; however, women appeared to be somewhat more willing to accept observation if reassured of the low risk of cervical cancer. CONCLUSIONS: Even for low-grade abnormal cervical tests, women tend to prefer active management strategies. It may be a challenge to meet their expectations of optimal follow-up when HPV testing is used in primary screening.


Asunto(s)
Manejo de la Enfermedad , Tamizaje Masivo/psicología , Infecciones por Papillomavirus/prevención & control , Prioridad del Paciente/psicología , Neoplasias del Cuello Uterino/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Conducta de Elección , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/psicología , Proyectos de Investigación , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adulto Joven
8.
Food Chem Toxicol ; 164: 112999, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35427705

RESUMEN

Consumer spray products release aerosols that can potentially be inhaled and reach the deep parts of the lungs. A thin layer of liquid, containing a mixture of proteins and lipids known as lung surfactant, coats the alveoli. Inhibition of lung surfactant function can lead to acute loss of lung function. We focused on two groups of spray products; 8 cleaning and 13 impregnation products, and in the context of risk assessment, used an in vitro method for assessing inhibition of lung surfactant function. Original spray-cans were used to generate aerosols to measure aerodynamic particle size distribution. We recreated a real-life exposure scenario to estimate the alveolar deposited dose. Most impregnation products inhibited lung surfactant function at the lowest aerosolization rate, whereas only two cleaning products inhibited function at the highest rates. We used inhibitory dose and estimated alveolar deposition to calculate the margin of safety (MoS). The MoS for the inhibitory products was ≤1 for the impregnation products, while much larger for the cleaning products (>880). This risk assessment focused on the risk of lung surfactant function disruption and provides knowledge on an endpoint of lung toxicity that is not investigated by the currently available OECD test guidelines.


Asunto(s)
Exposición por Inhalación , Surfactantes Pulmonares , Aerosoles/toxicidad , Excipientes , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Pulmón/metabolismo , Tamaño de la Partícula , Surfactantes Pulmonares/metabolismo , Surfactantes Pulmonares/toxicidad , Medición de Riesgo , Tensoactivos/toxicidad
9.
J Anim Ecol ; 77(5): 1020-9, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18557956

RESUMEN

1. Most scenarios for future climate change predict increased variability and thus increased frequency of extreme weather events. To predict impacts of climate change on wild populations, we need to understand whether this translates into increased variability in demographic parameters, which would lead to reduced population growth rates even without a change in mean parameter values. This requires robust estimates of temporal process variance, for example in survival, and identification of weather covariates linked to interannual variability. 2. The European shag Phalacrocorax aristotelis (L.) shows unusually large variability in population size, and large-scale mortality events have been linked to winter gales. We estimated first-year, second-year and adult survival based on 43 years of ringing and dead recovery data from the Isle of May, Scotland, using recent methods to quantify temporal process variance and identify aspects of winter weather linked to survival. 3. Survival was highly variable for all age groups, and for second-year and adult birds process variance declined strongly when the most extreme year was excluded. Survival in these age groups was low in winters with strong onshore winds and high rainfall. Variation in first-year survival was not related to winter weather, and process variance, although high, was less affected by extreme years. A stochastic population model showed that increasing process variance in survival would lead to reduced population growth rate and increasing probability of extinction. 4. As in other cormorants, shag plumage is only partially waterproof, presumably an adaptation to highly efficient underwater foraging. We speculate that this adaptation may make individuals vulnerable to rough winter weather, leading to boom-and-bust dynamics, where rapid population growth under favourable conditions allows recovery from periodic large-scale weather-related mortality. 5. Given that extreme weather events are predicted to become more frequent, species such as shags that are vulnerable to such events are likely to exhibit stronger reductions in population growth than would be expected from changes in mean climate. Vulnerability to extreme events thus needs to be accounted for when predicting the ecological impacts of climate change.


Asunto(s)
Aves/fisiología , Tiempo (Meteorología) , Animales , Femenino , Masculino , Modelos Biológicos , Dinámica Poblacional , Análisis de Supervivencia
11.
Trends Pharmacol Sci ; 12(3): 96-101, 1991 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2053193

RESUMEN

Although most pharmacokinetic studies are conducted in normal subjects, their clinical utility depends on the reliability with which the results can be extrapolated to patients. This reliability can be improved by increased understanding of how drug absorption and disposition mechanisms are affected by physiological changes or by disease. In recent years, important insight has been gained regarding the effects of altered renal function on drug elimination by the kidneys. There has also been considerable progress in defining the interaction of hemodynamic and metabolic factors that affect the hepatic elimination of drugs. Although comparatively little progress has been made in elucidating the underlying basis of changes in the rate and extent of drug distribution, Arthur Atkinson and colleagues analyse methods of compartmental pharmacokinetic analysis that may provide physiological insight into the factors affecting drug distribution.


Asunto(s)
Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Distribución Tisular , Animales , Humanos , Modelos Biológicos
12.
Clin Pharmacol Ther ; 53(3): 324-8, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8453851

RESUMEN

Prednisolone transfer to breast milk was studied in three nursing women who required oral steroid therapy for asthma. Each patient received a 50 mg intravenous dose of prednisolone phosphate, and blood and breast milk were sampled for 6 hours. Concentrations of prednisolone in milk declined more rapidly than in serum but were similar to expected unbound serum concentrations, suggesting that exchange between unbound prednisolone in serum and breast milk is relatively rapid and bidirectional. Because an average of 0.025% (range, 0.010% to 0.049%) of the prednisolone dose was recovered in milk, prednisolone transfer to breast milk does not appear to pose a clinically significant risk to nursing infants.


Asunto(s)
Leche Humana/metabolismo , Prednisolona/farmacocinética , Adulto , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Prednisolona/sangre
13.
Clin Pharmacol Ther ; 40(3): 321-8, 1986 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-3742937

RESUMEN

Theophylline pharmacokinetics were studied serially in five women during and after pregnancy. Theophylline protein binding was reduced to 11.1% +/- 4.7% (P less than 0.01) and 13.0% +/- 5.9% (P less than 0.01) during the second and third trimesters of pregnancy, respectively, compared with 28.1% +/- 2.8% when the patients were more than 6 months postpartum. Similar comparisons indicate that theophylline distribution volume and elimination t1/2 were increased from 30.7 +/- 4.4 L and 262 +/- 57 minutes to 36.8 +/- 4.2 L (P less than 0.05) and 389 +/- 73 minutes (P less than 0.01) in the third trimester of pregnancy. In the second and third trimesters, intrinsic nonrenal clearance was reduced to 0.82 +/- 0.25 ml/min X kg (P less than 0.05) and 0.67 +/- 0.18 ml/min X kg (P less than 0.01) compared with a remote postpartum value of 1.25 +/- 0.37 ml/min X kg. However, these reductions were offset by increases in theophylline intrinsic renal clearance so that apparent reductions in the overall unbound clearance of this drug did not reach statistical significance either during pregnancy or in the early postpartum period.


Asunto(s)
Complicaciones del Embarazo/sangre , Teofilina/sangre , Asma/tratamiento farmacológico , Proteínas Sanguíneas/metabolismo , Femenino , Humanos , Cinética , Matemática , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Teofilina/uso terapéutico
14.
Clin Pharmacol Ther ; 47(1): 68-72, 1990 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2295221

RESUMEN

Sera from 10 subjects in the third trimester of pregnancy and from 10 nonpregnant women were studied to elucidate the mechanism underlying decreased theophylline protein binding during pregnancy. Consistent with the physiologic hypoalbuminemia of pregnancy, serum albumin concentrations averaged only 3.2 +/- 0.3 gm/dl (+/- SD) in pregnant subjects, compared with 4.4 +/- 0.3 gm/dl in control subjects (p less than 1 x 10(-6], and this was the main cause of decreased theophylline binding. Saturation binding studies indicated a single class of theophylline binding sites. Theophylline binding capacity (N) was greater in pregnant (N = 4.3 +/- 1.0) than in nonpregnant (N = 3.3 +/- 0.4) subjects, but binding affinity (ka) averaged only 227 +/- 69 (mol/L)-1 in pregnant subjects, compared with 303 +/- 44 (mol/L)-1 in control subjects (F2,17 = 4.26; p = 0.032). At a theophylline plasma concentration of 10 micrograms/ml, the combined effects of hypoalbuminemia and lowered ka would reduce theophylline binding to 31% +/- 3% in pregnant women, compared to 39% +/- 3% in nonpregnant control subjects (p less than 1 x 10(-5]. Nonesterified fatty acid concentrations were similar in both subject groups and did not contribute to the pregnancy-associated decrease in theophylline binding.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Embarazo/metabolismo , Teofilina/metabolismo , Adulto , Ácidos Grasos no Esterificados/sangre , Femenino , Polarización de Fluorescencia , Humanos , Inmunoensayo , Monitoreo Fisiológico , Embarazo/sangre , Tercer Trimestre del Embarazo , Unión Proteica , Albúmina Sérica/análisis , Teofilina/sangre
15.
Clin Pharmacol Ther ; 40(2): 187-94, 1986 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3731681

RESUMEN

The effects of low- and high-protein diets on theophylline kinetics and the time course of changes in 13C-labeled caffeine and aminopyrine CO2 breath tests were examined in six young men. With a low-protein diet, mean theophylline clearance fell 21% (P less than 0.04) and the t1/2 rose from 8.0 to 10.6 hours (P less than 0.02). With a high-protein diet, mean theophylline clearance rose 26% (P less than 0.004) and the t1/2 shortened to 7.4 hours (P less than 0.03). Theophylline volume of distribution and protein binding did not change. Renal clearance of theophylline was lowered during the low-protein diet. Theophylline clearance correlated with caffeine breath test values during the low- (r = 0.73) and high- (r = 0.70) protein diets. Theophylline clearance correlated less well with the aminopyrine breath test values during the low- (r = 0.47) and high- (r = 0.55) protein diets. Thus dietary protein significantly influenced theophylline clearance, but the caffeine and aminopyrine breath tests showed a differential response to this important environmental factor.


Asunto(s)
Aminopirina/análisis , Cafeína/metabolismo , Proteínas en la Dieta/farmacología , Teofilina/metabolismo , Adulto , Aminopirina N-Demetilasa/metabolismo , Pruebas Respiratorias , Humanos , Infusiones Parenterales , Cinética , Masculino
16.
Clin Pharmacol Ther ; 53(4): 419-25, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8477557

RESUMEN

To elucidate the physiologic basis of multicompartmental systems used to model drug distribution, we studied inulin and 15N2-urea kinetics after simultaneous intravenous injection in five normal subjects. Distribution of both compounds was characterized by three-compartment models in which the central compartment corresponded to intravascular space. The mean distribution volumes of 0.164 +/- 0.009 L/kg (+/- SD) for inulin and of 0.670 +/- 0.143 L/kg for urea were similar to expected values for extracellular space and total body water, respectively. Distribution from intravascular space was kinetically heterogeneous, presumably reflecting differences in vascular beds supplied by either fenestrated and discontinuous capillaries or capillaries with a continuous basement membrane. Intercompartmental clearances of inulin and urea and the ratio of their free water diffusion coefficients were used to estimate blood flows and permeability coefficient-surface area products for the peripheral compartments. The sum of compartmental blood flows averaged 5.39 +/- 0.49 L/min and was similar to dual-beam Doppler measurements of cardiac output (5.47 +/- 0.40 L/min).


Asunto(s)
Inulina/farmacocinética , Urea/farmacocinética , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Gasto Cardíaco , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Femenino , Humanos , Inulina/sangre , Inulina/orina , Masculino , Persona de Mediana Edad , Distribución Tisular , Urea/sangre
17.
Clin Pharmacol Ther ; 35(3): 387-93, 1984 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-6697646

RESUMEN

The kinetics of epsilon-aminocaproic acid (EACA) distribution and elimination were studied in six normal subjects after a single 10-gm iv dose. Steady-state distribution volume averaged 30.01 or 0.39 l/kg. Mean elimination t 1/2 was 294 min and the elimination clearance was 0.19 l/min. Renal excretion of unchanged EACA accounted for 68% of its elimination and renal EACA clearance averaged 115% of creatinine clearance. EACA antifibrinolytic effect kinetics were also characterized in five of the subjects by the monitoring of clot lysis times in whole blood and platelet-rich plasma. Peak antifibrinolytic effects were observed 15 to 60 min after peak EACA plasma concentrations were attained. A model of maximal fibrinolysis inhibition (Emax) was used to estimate a half-maximal inhibition (IC50) of 63 +/- 19.7 microgram/ml. This agrees with the value of 0.55 mM or 72 microgram/ml that has been reported for the dissociation constant of the EACA-plasminogen complex and is consistent with the proposed biochemical mechanism of EACA action.


Asunto(s)
Aminocaproatos/metabolismo , Ácido Aminocaproico/metabolismo , Fibrinólisis/efectos de los fármacos , Adulto , Ácido Aminocaproico/farmacología , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Infusiones Parenterales , Cinética , Masculino
18.
Proc Biol Sci ; 268(1475): 1519-26, 2001 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-11454297

RESUMEN

Few studies have addressed the proximate factors affecting the age at which individuals of long-lived bird species are recruited into the breeding population. We use capture-recapture analysis of resightings of 16 birth cohorts of colour-ringed great cormorants, Phalacrocorax carbo sinensis, in a Danish colony to assess the evidence for two hypotheses: conspecific attraction (earlier recruitment when the colony is large) and conspecific reproductive success (earlier recruitment following years of high breeding success). For both males and females, conspecific reproductive success was the most important covariate explaining the interannual variation in age of recruitment; colony size was also important for females. These covariates explained nearly 60% of the year-to-year variation for both sexes. The age of recruitment increased for cohorts born after 1990, and this increase was correlated with a decline in breeding success in the colony; we interpret this as an indirect and delayed density-dependent effect. Females were recruited earlier than males (mean age of recruitment for cohorts born before 1990: 2.98 years versus 3.53 years); the most plausible reason for this is a skewed sex ratio in favour of males in the adult population. Recruitment of males may thus, to some extent, be constrained by the availability of females. This study provides the first evidence that conspecific reproductive success can affect the age at which individual birds start to breed.


Asunto(s)
Aves/fisiología , Reproducción , Conducta Sexual Animal , Envejecimiento , Animales , Aves/crecimiento & desarrollo , Femenino , Masculino , Modelos Estadísticos , Especificidad de la Especie
19.
Obstet Gynecol ; 91(4): 546-50, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9540938

RESUMEN

OBJECTIVE: To report the clinical features, management, and outcome of twin pregnancies consisting of a complete hydatidiform mole and a coexisting normal fetus. METHODS: Between 1966 and 1997, seven women with complete hydatidiform mole and coexisting normal fetus were treated at the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School. Clinical features, including presenting symptoms, gestational dates, hCG levels, and complications, as well as route of delivery or evacuation, pregnancy outcome, genetic analysis, and need for chemotherapy were assessed. RESULTS: Four women required uterine evacuation before 20 weeks' gestation because of vaginal bleeding or medical complications, one woman required an emergency hysterotomy because of hemorrhage at 24 weeks, and two women delivered normal, viable infants at 26 and 34 weeks. The pathologic diagnosis of complete hydatidiform mole was confirmed in each case and the chromosome complement was 46,XX in all molar gestations. Four of seven women required chemotherapy for treatment of nonmetastatic gestational trophoblastic tumors, including both women who delivered viable infants and two of the five women whose pregnancies were evacuated before 24 weeks' gestation. All four patients were treated with five to seven cycles of a 5-day methotrexate regimen and achieved complete remission. CONCLUSION: Patients with a twin pregnancy consisting of a complete mole and a normal fetus are at increased risk for hemorrhage and medical complications, as well as the development of persistent gestational trophoblastic tumor.


Asunto(s)
Enfermedades en Gemelos , Mola Hidatiforme/terapia , Resultado del Embarazo , Gemelos , Neoplasias Uterinas/terapia , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Parto Obstétrico , Femenino , Edad Gestacional , Humanos , Mola Hidatiforme/tratamiento farmacológico , Mola Hidatiforme/patología , Metotrexato/uso terapéutico , Embarazo , Estudios Retrospectivos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología
20.
Obstet Gynecol ; 87(6): 994-1000, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8649712

RESUMEN

OBJECTIVE: To evaluate whether once-daily gentamicin dosing is as effective as the traditional 8-hour regimen for the treatment of postpartum endometritis. METHODS: Postpartum women with endometritis were randomized to receive gentamicin 5 mg/kg as a single daily dose or 1.75 mg/kg every 8 hours. All subjects also received clindamycin. Each participant had a peak serum gentamicin level of at least 5.0 micrograms/mL within the first 24 hours. The dosing regimens were compared by analyzing the number of hours that patients were febrile, the length of hospital stay, occurrence of complications, pharmacy costs, and nursing time required to administer the regimens. RESULTS: The study group (n = 62) and the control group (n = 65) were similar in demographic characteristics and the presence of endometritis risk factors. No differences were found between the groups in the number of patients who completed therapy without complications, required changes in antibiotics, or required readmission for endometritis. The groups did not differ in the number of hours that patients remained febrile after the start of therapy or in the length of hospital stay. No patient in the study group had an initial peak serum concentration less than 5.0 micrograms/mL, whereas 24 patients in the control group had initial peak serum concentrations less than 5.0 micrograms/mL and required dose adjustment, a statistically significant difference (P < .001). Pharmacy costs averaged $16.12 +/- 5.68 for the study group and $41.75 +/- 17.41 for the control group, also a significant difference (P < .001). Nurse tasking time averaged 13.62 +/- 2.56 minutes for the study group and 28.06 +/- 8.77 minutes for the control group (P < .001). CONCLUSION: In patients with postpartum endometritis, once-daily gentamicin dosing provides consistently high peak serum levels of gentamicin, requires less nurse tasking time, costs less, and is as effective as the 8-hour dosing regimen.


Asunto(s)
Antibacterianos/administración & dosificación , Endometritis/tratamiento farmacológico , Gentamicinas/administración & dosificación , Infección Puerperal/tratamiento farmacológico , Adulto , Antibacterianos/farmacocinética , Clindamicina/administración & dosificación , Costos y Análisis de Costo , Método Doble Ciego , Esquema de Medicación , Femenino , Gentamicinas/economía , Gentamicinas/farmacocinética , Humanos
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