RESUMEN
The callipyge mutation causes postnatal muscle hypertrophy in heterozygous lambs that inherit a paternal callipyge allele (+/CLPG). Our hypothesis was that the up-regulation of one or both of the affected paternally expressed genes (DLK1 or PEG11) initiates changes in biochemical and physiological pathways in skeletal muscle to induce hypertrophy. The goal of this study was to identify changes in gene expression during the onset of muscle hypertrophy to identify the pathways that are involved in the expression of the callipyge phenotype. Gene expression was analysed in longissimus dorsi total RNA from lambs at 10, 20, and 30 days of age using the Affymetrix Bovine Expression Array. An average of 40.6% of probe sets on the array was detected in sheep muscle. Data were normalized and analysed using a two-way anova for genotype and age effects with a false discovery rate of 0.10. From the anova, 13 genes were significant for the effect of genotype and 13 were significant for effect of age (P < 0.10). No significant age-by-genotype interactions were detected (P > 0.10). Of the 13 genes indicating an effect of genotype, quantitative PCR assays were developed for all of them and tested on a larger group of animals from 10 to 200 days of age. Nine genes had significantly elevated transcript levels in callipyge lambs. These genes included phosphofructokinase, a putative methyltransferase protein, a cAMP phosphodiesterase, and the transcription factor DNTTIP1.
Asunto(s)
Músculos/patología , Enfermedades Musculares/veterinaria , ARN Mensajero/metabolismo , Enfermedades de las Ovejas/genética , Factores de Edad , Animales , Perfilación de la Expresión Génica , Genotipo , Hipertrofia/veterinaria , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Ovinos , Enfermedades de las Ovejas/patologíaRESUMEN
We investigate by lattice Boltzmann methods the effect of inertia on the deformation and breakdown of stability of a two-dimensional fluid droplet surrounded by fluid of equal viscosity (in a confined geometry) whose shear rate is increased very slowly. We give evidence that in two dimensions inertia is necessary for the loss of stability, so that at zero Reynolds number there is always a stable stationary droplet shape. We identify two different routes to breakdown, via two-lobed and three-lobed structures and give evidence for a sharp transition between these routes as parameters are varied.
RESUMEN
A 65 year old woman with history of ischaemic heart disease underwent standard adenosine stress test for myocardial perfusion imaging. She sustained inferior myocardial infarction during the final stages of the stress test. She was admitted to the coronary care unit and received thrombolytic treatment. The patient made an uneventful recovery. Adenosine is widely used for myocardial stress imaging tests and has a good safety profile. So far there has been only one other reported myocardial infarction during adenosine stress test, which was under special circumstances because three days before the test the patient had undergone percutaneous transluminal coronary angioplasty when a severe circumferential dissection was noted. The present patient's case highlights the need to be aware of rare but potentially serious complications of adenosine, even though it generally has an excellent safety record for use in myocardial stress testing.
Asunto(s)
Adenosina/efectos adversos , Infarto del Miocardio/inducido químicamente , Vasodilatadores/efectos adversos , Anciano , Ecocardiografía de Estrés/efectos adversos , Electrocardiografía/métodos , Femenino , HumanosRESUMEN
Association studies based on linkage disequilibrium (LD) can provide high resolution for identifying genes that may contribute to phenotypic variation. We report patterns of local and genome-wide LD in 102 maize inbred lines representing much of the worldwide genetic diversity used in maize breeding, and address its implications for association studies in maize. In a survey of six genes, we found that intragenic LD generally declined rapidly with distance (r(2) < 0.1 within 1500 bp), but rates of decline were highly variable among genes. This rapid decline probably reflects large effective population sizes in maize during its evolution and high levels of recombination within genes. A set of 47 simple sequence repeat (SSR) loci showed stronger evidence of genome-wide LD than did single-nucleotide polymorphisms (SNPs) in candidate genes. LD was greatly reduced but not eliminated by grouping lines into three empirically determined subpopulations. SSR data also supplied evidence that divergent artificial selection on flowering time may have played a role in generating population structure. Provided the effects of population structure are effectively controlled, this research suggests that association studies show great promise for identifying the genetic basis of important traits in maize with very high resolution.
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Genoma de Planta , Desequilibrio de Ligamiento , Fenotipo , Zea mays/genética , Mapeo Cromosómico , Datos de Secuencia Molecular , Polimorfismo Genético , Carácter Cuantitativo HeredableRESUMEN
GTP cyclohydrolase I feedback regulatory protein (GFRP) mediates the feedback inhibition of GTP cyclohydrolase I activity by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) through protein complex formation. Since guanine and BH4 have a common pyrimidine ring structure, we examined the inhibitory effect of guanine and its analogs on the enzyme activity. Guanine, 8-hydroxyguanine, 8-methylguanine, and 8-bromoguanine inhibited the enzyme activity in a GFRP-dependent and pH-dependent manner and induced complex formation between GTP cyclohydrolase I and GFRP. The type of inhibition by this group is a mixed type. All these properties were shared with BH4. In striking contrast, inhibition by 8-azaguanine and 8-mercaptoguanine was GFRP-independent and pH-independent. The type of inhibition by 8-azaguanine and 8-mercaptoguanine was a competitive type. The two compounds did not induce complex formation between the enzyme and GFRP. These results demonstrate that guanine compounds of the first group bind to the BH4-binding site of the GTP cyclohydrolase I/GFRP complex, whereas 8-azaguanine and 8-mercaptoguanine bind to the active site of the enzyme. Finally, the possible implications in Lesch-Nyhan syndrome and Parkinson diseases of the inhibition of GTP cyclohydrolase I by guanine and 8-hydroxyguanine are discussed.
Asunto(s)
GTP Ciclohidrolasa/química , GTP Ciclohidrolasa/metabolismo , Guanina/análogos & derivados , Guanosina/análogos & derivados , Adyuvantes Inmunológicos/farmacología , Animales , Antimetabolitos Antineoplásicos/farmacología , Azaguanina/farmacología , Sitios de Unión , Unión Competitiva , Cromatografía en Gel , Relación Dosis-Respuesta a Droga , Guanina/metabolismo , Guanina/farmacología , Guanosina/farmacología , Guanosina Trifosfato/metabolismo , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Cinética , Síndrome de Lesch-Nyhan/metabolismo , Modelos Químicos , Enfermedad de Parkinson/metabolismo , Ratas , Tionucleósidos/farmacologíaRESUMEN
The mechanism of arsine (AsH3) toxicity is not completely understood. In this investigation, the toxicity of AsH3 and AsH3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and in the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH3 exposure. The hypothesis was that unchanged AsH3 and AsH3-produced hemolysate that may contain arsenite (As(III)) as metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxa nilide inner salt (XTT) bioreduction, intracellular potassium (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the arsenic species. At 4 hours, the observed toxicity depended on the arsenic species and was generated by As(III). In the isolated cells, the As(III)-spiked hemolysate produced similar toxicities with regard to intracellular K and LDH. The AsH3-hemolysate only affected LDH at 1 hour. Unchanged AsH3 was very toxic to the isolated rat kidney. In this system, after 10 minutes exposure to AsH3, the effects of toxicity were observed mainly in the glomerular and peritubular endothelial cells. Tubular epithelial cells also presented early signs of toxicity. The AsH3-hemolysate was not toxic after a 1 -minute exposure. These data suggested that early cytotoxicity caused by unchanged AsH3 results in kidney dysfunction, produced by AsH3, and later by the formation of a hemolysate that may contain As(III). These data may be important in understanding the renal toxic effects after AsH3 intoxication.
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Arsenicales/farmacología , Riñón/efectos de los fármacos , Animales , Células Cultivadas , Riñón/patología , Riñón/ultraestructura , Masculino , Microscopía Electrónica , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Mental stress has been shown to produce intestinal disease, but the effects of a mild environmental stress on intestinal physiology have not been elucidated. This study was performed to determine the effects of environmental stress on the ultrastructure of the intestinal mucosa, using the rat as an experimental model. METHODS: One group of rats (group A, n = 3) was examined immediately upon arrival at the animal care facility. Groups B (n = 6) and C (n = 6) were housed in rooms with high and low personnel activity, respectively, for up to 4 wk. Group D (n = 8) was housed in the high activity room for 3 to 4 wk followed by 1, 2, or 3 in the low activity room. RESULTS: Rats in group B had the greatest number of degranulated intestinal mucosal mast cells, and activated goblet cells. Intestinal villi were edematous and epithelial cells were detaching from the basement membrane at villus tips. Changes were observed in capillary endothelial ultrastructure. In group B there were greater numbers of vesicles and multilamellar fenestral diaphragms compared to group C. Rats in groups A and C had the lowest numbers of degranulated mast cells and activated goblet cells. Intestinal villi showed normal ultrastructure. Group D was in a recovery phase and the condition of the intestinal mucosa was improved relative to group B, but the number of degranulated mast cells was not significantly reduced. CONCLUSIONS: This study demonstrates that environmentally induced stress causes pathological changes in the rat intestinal mucosa that compromise the epithelial-endothelial exchange barrier. These results emphasize the importance of closely monitoring the environment of experimental animals and provide evidence to stimulate further research into the mechanisms linking mental stress to gastrointestinal dysfunction in humans.
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Edema/etiología , Endotelio Vascular/patología , Ambiente , Células Epiteliales/patología , Enfermedades Intestinales/etiología , Mucosa Intestinal/patología , Mastocitos/citología , Estrés Psicológico/patología , Animales , Permeabilidad Capilar , Recuento de Células , Degranulación de la Célula , Células Epiteliales/ultraestructura , Células Caliciformes/metabolismo , Intestinos/citología , Masculino , Microcirculación/fisiología , RatasRESUMEN
An understanding of public health and its impact on the health of the nation is vital to anyone involved in implementing change in healthcare. The Healthy People Initiatives are the basis for change in an extraordinarily large segment of the healthcare population. These visions of public health are not simply an idea of the perfect health services, but are a very detailed plan of desired outcomes and the means to reach them. Availability of healthcare services to all segments of our population is an ethical obligation to anyone with a true vocation in healthcare. This article presents a brief overview of the Healthy People Initiative.
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Directrices para la Planificación en Salud , Política de Salud , Prioridades en Salud/organización & administración , Promoción de la Salud/organización & administración , Salud Pública/tendencias , Predicción , Humanos , Recién Nacido , Innovación Organizacional , Objetivos Organizacionales , Estados UnidosRESUMEN
OBJECTIVE: This study was performed to determine the effects of environmental stress on the leakage to albumin and architecture of microvessels in the rat mesentery. METHODS: One group of rats (Group A, n = 6) were examined immediately upon arrival at the animal care facility. Groups B (n = 24) and C (n = 32) were housed in rooms with high and low personnel activity, respectively, for up to 7 weeks. Group D (n = 18) was housed in the high activity room for 2, 3, or 4 weeks followed by the low activity room. RESULTS: Rats in the low activity room for 3-4 weeks showed robust microvascular networks within 25% to 50% of the mesenteric windows (each window consisting of the tissue extending between two adjacent feeding arterioles in the mesentery), whereas rats in Group B only showed fragile vessels at the edges of the mesenteric windows within fat deposits. Groups A and C demonstrated little mesenteric fat and few fragile vessels, in contrast to group B. Group D showed increased mesenteric networks and decreased mesenteric fat as recovery progressed. The microvascular networks of 6 rats, randomly selected from Group C, showed few venular leaks following perfusion with fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). Such leaks were abundant in the mesenteric microvasculature of 3 rats randomly selected from Group B. CONCLUSIONS: This study demonstrates that environmentally induced stress alters the architecture and leakage to albumin of the rat mesenteric microvasculature, and emphasizes the importance of closely monitoring the environment of experimental animals.
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Mesenterio/irrigación sanguínea , Estrés Fisiológico/fisiopatología , Animales , Presión Sanguínea , Bovinos , Difusión , Ambiente , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Vivienda para Animales , Masculino , Mastocitos/metabolismo , Mesenterio/fisiología , Microcirculación , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Bovina/farmacocinética , Vénulas/fisiología , Aumento de PesoRESUMEN
BACKGROUND: The assessment of the psychosocial health of pregnant women and their families, although recommended, is not carried out by most practitioners. One reason is the lack of a practical and evidence-based tool. In response, a multidisciplinary group created the Antenatal Psychosocial Health Assessment (ALPHA) form. This article describes the development of this tool and experience with it in an initial field trial. METHODS: A systematic literature review revealed 15 antenatal psychosocial risk factors associated with poor postpartum family outcomes of woman abuse, child abuse, postpartum depression, marital/couple dysfunction and increased physical illness. The ALPHA form, incorporating these risk factors, was developed and refined through several focus groups. It was then used by 5 obstetricians, 10 family physicians, 7 midwives and 4 antenatal clinic nurses in various urban, rural and culturally diverse locations across Ontario. After 3 months, these health care providers met in focus groups to discuss their experiences. A sample of pregnant women assessed using the ALPHA form were interviewed about their experience as well. Results were analysed according to qualitative methods. RESULTS: The final version of the ALPHA form grouped the 15 risk factors into 4 categories--family factors, maternal factors, substance abuse and family violence--with suggested questions for each area of enquiry. The health care providers uniformly reported that the form helped them to uncover new and often surprising information, even when the women were well known to them. Incorporating the form into practice was usually accomplished after a period of familiarization. Most of the providers said the form was useful and would continue to use it if it became part of standard care. The pregnant women in the sample said they valued the enquiry and felt comfortable with the process, unless there were large cultural barriers. INTERPRETATION: The ALPHA form appears to be an important tool in assessing psychosocial health in pregnancy and to be readily integrated into practice. More study is required to quantify the number of risks identified and resources used, to determine the form's reliability and validity and, ultimately, to assess the effect of its use on postpartum outcomes.
Asunto(s)
Indicadores de Salud , Salud Mental , Periodo Posparto/psicología , Embarazo/psicología , Violencia Doméstica , Familia/psicología , Femenino , Humanos , Conducta Materna , Apoyo Social , Estrés Psicológico/etiologíaRESUMEN
Polyethylene glycol (PEG)-conjugated Hb (PEG-Hb) is being considered as a blood substitute. Previously, we showed that PEG-Hb extravasates rapidly from the intestinal mucosa and causes transient epithelial sloughing, resulting in temporary unimpeded passage of material between the intestinal lumen and the microcirculation. The present study quantifies the time course of factors related to this disturbance. Anesthetized Sprague-Dawley rats (350-450 g) were injected with a bolus of PEG-Hb (10 mg/ml) in saline. Control animals received saline, alone or with Dextran 70 (5 mg/ml). After 2, 8, 15, 60, or 90 min, the small intestine was perfusion fixed for microscopy (4 animals for each time point). Epithelial cell detachment and mucosal mast cell degranulation peaked at 2 and 8-15 min, respectively, but by 90 min were back to normal. Goblet cell secretion increased with time up to 8-15 min, after which it leveled off. Mean interstitial width was significantly greater 8 min after injection than for controls and continued to increase with time. In capillaries, endothelial fenestral diaphragms were replaced by thick, amorphous structures. Mesenteric mast cell degranulation was significantly greater 60-90 min after injection compared with controls. We propose that these results are consistent with intravascular injection of PEG-Hb invoking a transient inflammatory response in the intestine.
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Sustitutos Sanguíneos/farmacología , Hemoglobinas/farmacología , Mucosa Intestinal/efectos de los fármacos , Polietilenglicoles/farmacología , Animales , Sustitutos Sanguíneos/administración & dosificación , Sustitutos Sanguíneos/farmacocinética , Capilares/citología , Capilares/efectos de los fármacos , Capilares/ultraestructura , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/ultraestructura , Hemoglobinas/administración & dosificación , Hemoglobinas/farmacocinética , Inyecciones Intravenosas , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/citología , Mucosa Intestinal/ultraestructura , Intestino Delgado , Masculino , Mastocitos/citología , Mastocitos/efectos de los fármacos , Mastocitos/ultraestructura , Microscopía Electrónica , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Ratas , Ratas Sprague-Dawley , Circulación Esplácnica , Factores de TiempoRESUMEN
The management of 38 consecutive patients with differentiated thyroid carcinoma in the period 1991-1996, who each received at least one therapy dose of iodine-131, was reviewed, looking in particular at those in whom anterior mediastinal uptake was demonstrated on scans taken 3 and 7 days post-therapy. Such activity was noted in ten patients. On the basis of clinical follow-up, thyroglobulin measurement and radiological and other scintigraphic imaging, in nine of the ten patients the anterior mediastinal activity was attributed to physiological thymic uptake. Of those nine, all were under 50 years of age; seven were considered disease free, one had residual disease in the neck and one had distant metastases. Physiological uptake by the thymus was more prominent on the 7-day scans and in patients with low tumour volumes. For appropriate patient management it is essential to recognise that physiological uptake of 131I by the thymus in patients under 50 years of age is a potential cause of false-positive therapy scans.
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Radioisótopos de Yodo/uso terapéutico , Timo/diagnóstico por imagen , Neoplasias de la Tiroides/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Radioisótopos de Yodo/farmacocinética , Masculino , Persona de Mediana Edad , Cintigrafía , Estudios Retrospectivos , Timo/metabolismo , Tiroglobulina/metabolismo , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Factores de TiempoRESUMEN
Temporary blood flow stoppage occurs in a greater percentage of the capillaries when blood flow to organs is reduced. Previous studies on the small intestine have suggested that acute blood stasis (< or = 10 min) results in expression of negative charge, not present when blood flow is brisk, on the luminal surface of mucosal capillaries. Negative surface charge would tend to reduce transcapillary passage of albumin from blood to interstitium, since albumin is also negatively charged. Here we test the hypothesis that acute blood stasis reduces the interstitial uptake of albumin from mucosal capillary networks in rat small intestine in situ. Animals were subjected to two treatments, which included intestinal blood flow and acute stasis. After each treatment, fluorescent albumins were perfused into the intestinal circulation, and then interstitial fluorescence was recorded using fluorescence microscopy. Images were later quantified by computer analysis. After brisk blood flow, but not after acute blood stasis, fluorescence rapidly appeared in the interstitium and resulted in higher interstitial fluorescence intensity values. These results may have relevance to the mechanisms by which albumin flux in the small intestine is synchronized with digestion and fasting, which are associated with high and low intestinal blood flow, respectively.
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Capilares/metabolismo , Intestinos/irrigación sanguínea , Isquemia/metabolismo , Albúmina Sérica/metabolismo , Animales , Velocidad del Flujo Sanguíneo , Electroquímica , Fluoresceína-5-Isotiocianato/análogos & derivados , Colorantes Fluorescentes , Mucosa Intestinal/irrigación sanguínea , Masculino , Microscopía Fluorescente , Ratas , Ratas Sprague-Dawley , Albúmina Sérica BovinaRESUMEN
A "porohyperelastic" (PHE) material model is described and the theoretical framework presented that allows identification of the necessary material properties functions for soft arterial tissues. A generalized Fung form is proposed for the PHE constitutive law in which the two fundamental Lagrangian material properties are the effective strain energy density function, W(e), and the hydraulic permeability, kij. The PHE model is based on isotropic forms using W(e) = Ue (phi) = 1/2C0(e phi - 1) and the radial component of permeability, kRR = kRR(phi), with phi = C1'(I1 - 3) + C2'(I2 - 3) + K'(J - 1)2. The methods for determination of these material properties are illustrated using experimental data from in situ rabbit aortas. Three experiments are described to determine parameters in Ue and kRR for the intima and media of the aortas, i.e., (1) undrained tests to determine C0, C1', and C2'; (2) drained tests to determine K'; and (3) steady-state pressurization tests of intact and de-endothelialized vessels to determine intimal and medial permeability (adventitia removed in these models). Data-reduction procedures are presented that allow determination of kRR for the intima and media and Ue for the media using experimental data. The effectiveness and accuracy of these procedures are studied using input "data" from finite element models generated with the ABAQUS program. The isotropic theory and data-reduction methods give good approximations for the PHE properties of in situ aortas. These methods can be extended to include arterial tissue remodeling and anisotropic behavior when appropriate experimental data are available.
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Aorta Torácica/fisiología , Animales , Aorta Torácica/anatomía & histología , Fenómenos Biomecánicos , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Simulación por Computador , Elasticidad , Endotelio Vascular/anatomía & histología , Endotelio Vascular/fisiología , Análisis de Elementos Finitos , Hemorreología , Modelos Cardiovasculares , Permeabilidad , Porosidad , Conejos , Estrés Mecánico , Túnica Íntima/anatomía & histología , Túnica Íntima/fisiología , Túnica Media/anatomía & histología , Túnica Media/fisiología , AguaAsunto(s)
Instituciones Asociadas de Salud , Hospitales Comunitarios/organización & administración , Hospitales con Fines de Lucro/organización & administración , Hospitales Filantrópicos/organización & administración , Arkansas , Servicios Hospitalarios Compartidos/organización & administración , HumanosRESUMEN
Local infusion of agents through perforated catheters may reduce neointimal formation following vascular angioplasty. Such treatment will succeed only if the drug is retained within the arterial intima long enough to promote repair. Drugs will be dispersed throughout the wall predominantly by transmural convection instead of diffusion if the Peclet number, Pe = J (1-delta f)/P, is greater than unity, where J is the transmural fluid flow per unit surface area and delta(f) and P are the reflection and permeability coefficients to the drug, respectively. Although the targets of local drug delivery will be atherosclerotic vessels, little is known about the transport properties of these vessels. Accordingly, we evaluated the effects of hypercholesterolemia and atherosclerosis on J per unit pressure (hydraulic conductance, Lp) and on ultrastructure in femoral arteries. Measurements were made at 30, 60, and 90 mm Hg in anesthetized New Zealand white rabbits fed a normal diet (n = 6) and after 3 weeks of lipid feeding (n = 19). Atherosclerosis was induced in six lipid-fed animals by air desiccation of a femoral artery. Hydraulic conductance was significantly greater in vessels from hypercholesterolemic than from normal animals and decreased with pressure only in hypercholesterolemic arteries. Atherosclerosis did not augment hydraulic conductance compared with hypercholesterolemia alone. Electron microscopic examination demonstrated damaged endothelium in hypercholesterolemic arteries and both altered endothelium and less tightly packed medial tissue, compared with controls, in atherosclerotic vessels, at least at lower pressures. Peclet numbers for macromolecules exceeded unity for all three groups of arteries and reached 0.3 to 0.4 for molecules as small as heparin. Thus, convection plays a dominant role in the distribution of macromolecular agents following local delivery and may result in their rapid transport to the adventitia in the femoral artery.
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Angioplastia de Balón/métodos , Arterias/ultraestructura , Arteriosclerosis/fisiopatología , Angioplastia de Balón/efectos adversos , Animales , Arterias/lesiones , Arteriosclerosis/patología , Presión Sanguínea , Colchicina/administración & dosificación , Endotelio Vascular/ultraestructura , Inhibidores de Crecimiento/administración & dosificación , Heparina/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Microscopía Electrónica , Músculo Liso Vascular/ultraestructura , Conejos , ReologíaRESUMEN
BACKGROUND: Individuals who had cancer in childhood are at higher risk of developing bone cancer than any other type of second primary cancer. PURPOSE: Using the population-based National Registry of Childhood Tumours in Britain, we investigated the incidence and etiology of second primary bone cancer after childhood cancer in a cohort study and in a case-control study. METHODS: A cohort study of 13,175 3-year survivors of childhood cancer diagnosed in Britain between 1940 and 1983 revealed 55 subsequent bone cancers. A largely nested case-control study comprised 59 case subjects developing second primary bone cancer, and 220 control subjects were selected and matched for sex, type of first cancer, age at first cancer, and interval between diagnosis of first cancer and subsequent bone cancer. Outcome measures were the incidence of bone cancer after childhood cancer, the cumulative dose of radiation received at the site of the second cancer in the case subject and at the corresponding anatomic site in the matched control subjects, and the cumulative dose of alkylating agents and vinca alkaloids received by case and control subjects. RESULTS: The percentage of 3-year survivors developing bone cancer within 20 years did not exceed 0.9%, except following heritable retinoblastoma (7.2%), Ewing's sarcoma (5.4%), and other malignant bone tumors (2.4%). The risk of bone cancer increased substantially with increased cumulative dose of radiation to the bone (P< .001, linear trend). At the highest levels of exposure, however, the risk appeared to decline somewhat (P=.065, nonlinearity). Exposure to less than 10 Gy was at worst, associated with only a small increased relative risk (RR) of bone cancer (RR= 0.7; 95% confidence interval = 0.2-2.2). The risk of bone cancer increased linearly (P= .04, one-tailed test) with increased cumulative dose of alkylating agents. IMPLICATIONS: This population-based study provides grounds for reassurance of the majority of survivors in that their risk of developing bone cancer within 20 years of 3-year survival did not exceed 0.9%. The higher risks found for bone cancer following the other specific rare types of childhood cancer provide a rational basis for surveillance. The RRs reported for bone cancer after specified levels of exposure to radiation should help in making decisions concerning future treatment protocols.
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Antineoplásicos Alquilantes/efectos adversos , Neoplasias Óseas/etiología , Neoplasias Primarias Secundarias/etiología , Radioterapia/efectos adversos , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Retinoblastoma/terapia , Riesgo , Sarcoma de Ewing/terapiaRESUMEN
OBJECTIVE: To determine the strength of the association between antenatal psychosocial risk factors and adverse postpartum outcomes in the family, such as assault of women by their partner, child abuse, postpartum depression, marital dysfunction and physical illness. DATA SOURCES: MEDLINE, Cinahl, Famli, Psych Abstracts and the Oxford Database of Perinatal Trials were searched from relevant articles published from Jan. 1, 1980, to Dec. 31, 1993, with the use of MeSH terms "depression, involutional," "child abuse," "child neglect," "domestic violence," "family," "marital adjustment," "family health," "newborn health," "child health," "physical illness," "social support," "psychosocial risk," "prediction," "risk factors," "obstetrics" and "prenatal care." Further articles were identified from bibliographies. STUDY SELECTION: Of the 370 articles identified through the search, 118 were included for review. Studies were included if they examined the association between psychosocial risk factors and the outcomes of interest. Articles were excluded if they were reviews of poor quality or they had one or more of the following features: insufficient description of the sample, a high attrition rate, a lack of standardized outcome measures, outcomes other than the ones of interest or results that had already been reported in a previous study. DATA EXTRACTION: The strength of evidence of each study was evaluated. On the basis of the evidence, each risk factor was assigned a rating of the strength of its association with each of the postpartum outcomes. The ratings were class A (good evidence of association), class B (fair evidence) and class C (no clear evidence). Of the 129 antenatal psychosocial risk factors studied, 15 were found to have a class A association with at least one of the postpartum outcomes. DATA SYNTHESIS: Child abuse and abuse of the mother by her partner were most strongly correlated (class A evidence) with a history of lack of social support, recent life stressors, psychiatric disturbance in the mother and an unwanted pregnancy. Child abuse was also strongly associated with a history of childhood violence in the mother or her partner, previous child abuse by the mother's partner, a poor relationship between the mother and her parents, low self-esteem in the mother and lack of attendance at prenatal classes. Postpartum abuse of the mother was also associated with a history of abuse of the mother, prenatal care not started until the third trimester and alcohol or drug abuse by the mother or her partner (class A evidence). Child abuse had a fair (class B) association with poor marital adjustment or satisfaction, current or past abuse of the mother and alcohol or drug abuse by the mother or her partner. There was class B evidence supporting an association between abuse of the mother and poor marital adjustment, traditional sex-role expectations, a history of childhood violence in the mother or her partner and low self-esteem in the mother. Postpartum depression was most strongly associated with poor marital adjustment, recent life stressors, antepartum depression (class A evidence), but was also associated with lack of social support, abuse of the mother and a history of psychiatric disorder in the mother (class B evidence). Marital dysfunction was associated with poor marital adjustment before the birth and traditional sex-role expectations (class A evidence), and physical illness was correlated with recent life stressors (class B evidence). CONCLUSIONS: Psychosocial risk factors during the antenatal period may herald postpartum morbidity. Research is required to determine whether detection of these risk factors may lead to interventions that improve postpartum family outcomes.
Asunto(s)
Maltrato a los Niños , Depresión/etiología , Violencia Doméstica , Familia/psicología , Matrimonio , Embarazo/psicología , Trastornos Puerperales/etiología , Niño , Maltrato a los Niños/psicología , Preescolar , Violencia Doméstica/psicología , Etanol/envenenamiento , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Matrimonio/psicología , Trastornos Mentales/complicaciones , Relaciones Madre-Hijo , Evaluación de Resultado en la Atención de Salud , Relaciones Padres-Hijo , Embarazo no Deseado/psicología , Atención Prenatal , Factores de Riesgo , Autoimagen , Ajuste Social , Apoyo Social , Maltrato Conyugal/psicología , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
The purpose of the present study was to compare the endothelial actin cytoskeleton at sites of inflammation-induced macromolecular leakage with that of intact endothelium. The circulation of a selected mesenteric window of anesthetized rats was perfused for 3 min with histamine (100 microM) plus fluorescein isothiocyanate (FITC)-albumin, or FITC-albumin alone, and was fixed at physiological pressure. The vasculature was then perfusion stained with rhodamine phalloidin to label filamentous actin (F-actin) and examined with a confocal microscope. The leakage sites were divided into three categories based on the extent of FITC-albumin leakage: 1) focal leaks, 2) mid leaks, and 3) extended leaks. The leaks were identifiable with a particular endothelial cell(s), and the structure of the endothelial actin cytoskeleton was characterized at these sites. Focal leaks occurred along a small region of endothelial cell-cell contact and in most observed cases were located at a region of specific disruption of the endothelial peripheral actin rim (PAR). Mid leaks involved the disruption of one endothelial cell, and the affected cell was observed to have extended disruption of the PAR as well as increased diffuse F-actin staining throughout the cell (1.9-fold increase relative to adjacent cells). Extended leaks involved the disruption of two or more adjacent endothelial cells, and each cell exhibited an actin pattern similar to that seen at mid leaks. These results show that histamine-induced macromolecular leakage in situ is associated with significant changes in the endothelial actin cytoskeleton.
Asunto(s)
Actinas/metabolismo , Citoesqueleto/ultraestructura , Endotelio Vascular/ultraestructura , Microcirculación/fisiología , Circulación Esplácnica , Actinas/ultraestructura , Animales , Arteriolas/fisiología , Endotelio Vascular/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Masculino , Microscopía Confocal , Microscopía Fluorescente , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Rodaminas , Albúmina Sérica Bovina , Vénulas/fisiologíaRESUMEN
OBJECTIVE: To determine whether physician characteristics affect attitudes or practices regarding assessment of psychosocial risk factors during pregnancy, and to evaluate whether an antenatal psychosocial risk factor assessment form would help family physicians. DESIGN AND SETTING: A questionnaire asking physicians to rate the importance of information on a scale of one to five was mailed to all active members of the University of Toronto Department of Family and Community Medicine's Survey Network of Attitudes and Practice (SNAP). PARTICIPANTS: A volunteer sample of physicians doing prenatal and intrapartum obstetrics who are active members of SNAP. The network is made up of full-time faculty in the University of Toronto's family practice units and teaching practice physicians (rural, suburban, and urban) who are interested in participating in research projects. MAIN OUTCOME MEASURES: Response rate was 78%. Responses of the 45 SNAP members who did not practise obstetrics were excluded; 125 of 218 questionnaires mailed were analyzed. RESULTS: Women family physicians rated the form potentially helpful more frequently than their male colleagues. Urban and suburban physicians' concerns differed from those of rural physicians. Alcohol and drug abuse, abuse in the relationship, and acceptance of the pregnancy were rated highly important by physicians. Of the physicians surveyed, 77% thought that an antenatal psychosocial risk assessment form would be of some benefit or very helpful. Only 15% indicated it would be useless or not helpful. CONCLUSION: The importance respondents accorded to risk factors showed little correspondence to the frequency of inquiry about them. The survey confirmed our plan to design an antenatal psychosocial risk factor assessment form.