RESUMEN
OBJECTIVE: This study aimed to determine the awareness, otological symptoms and prevalence of external auditory canal exostoses in Irish cold-water athletes. METHOD: An online and in person cross-sectional survey was undertaken with Irish cold-water athletes to explore athletes' awareness, known prevalence of external auditory canal exostoses and attitudes towards preventive measures. RESULTS: Of the 926 participants surveyed, 67.5 per cent were aware of external auditory canal exostoses. Triathletes reported the lowest awareness (39.9 per cent) among water athletes. A total of 9.7 per cent (n = 90) had previously been diagnosed with external auditory canal exostoses and 46.7 per cent (n = 42) were non-surfers. Ear symptoms were reported in 76 per cent of athletes. Otoscopic examinations showed that 23.7 per cent had external auditory canal exostoses, 3.6 per cent of whom were aware of their diagnosis. CONCLUSION: The majority of Irish surfing athletes are aware of external auditory canal exostoses. There is less awareness with regard to Ireland's newly emerging sports such as open water swimming and triathlons. Over 90 per cent of athletes surveyed had no idea they had external auditory canal exostoses, which highlights the need to increase public awareness.
Asunto(s)
Conducto Auditivo Externo , Exostosis , Atletas , Estudios Transversales , Exostosis/epidemiología , Humanos , AguaRESUMEN
Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
Asunto(s)
Incendios , Incendios Forestales , Ecosistema , Bosques , Humanos , América del NorteRESUMEN
Introduction The purpose of this study was to compare obstetric and neonatal outcomes between women attending a specialised maternal medicine service and the general obstetric population. Methods Women attending from January 2011 to December 2016 were identified from the clinic database. Medical diagnosis, demographics, obstetric and neonatal outcomes were compared with data from hospital annual report 2014. Results 1873 women were compared with 8632 women who delivered at the hospital in 2014. Delivery before 34 weeks [82 (4.5%) vs 189 (2.2%)], induction of labour [761 (40.6%) vs 2664 (30.9%)] and delivery by Caesarean Section (CS) [664 (35%) vs 2479 (29%)] were higher p<0.001; but elective CS [334 (18%) vs 1425 (17%), p=0.18] did not differ between the two groups. Neonatal outcomes were similar. Conclusion Premature delivery, induction of labour and CS rates are higher in women with medical disorders in pregnancy. Encouragingly, 77% of women attempting vaginal birth in this group were successful.
Asunto(s)
Parto Obstétrico , Resultado del Embarazo , Parto Obstétrico/estadística & datos numéricos , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/epidemiologíaRESUMEN
STUDY QUESTION: Does neutralization of apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) improve sperm motility in men with spinal cord injury (SCI)? SUMMARY ANSWER: Neutralization of ASC improves sperm motility in men with SCI. WHAT IS KNOWN ALREADY: Semen of men with SCI contains normal sperm concentrations but abnormally low sperm motility. Inflammatory cytokines, activated via the inflammasome complex, are contributory. A key component of the inflammasome is ASC. STUDY DESIGN, SIZE, DURATION: This prospective study included semen samples collected from 32 men with SCI. PARTICIPANTS/MATERIALS, SETTING, METHODS: At a major university medical center, untreated semen was compared with semen treated with anti-ASC polyclonal antibody. Semen treated with IgG was used as a control. MAIN RESULTS AND THE ROLE OF CHANCE: Addition of anti-ASC polyclonal antibody to semen significantly increased mean sperm motility from 11.5% (95% CI, 6.3-16.7) to 18.3% (95% CI, 11.8-24.8). Improvements were most pronounced in the subgroup whose starting motility ranged between 6 and 40%. In this subgroup, the mean sperm motility improved from 13.3% (95% CI, 9.3-17.3) to 23.9% (95% CI, 14.7-23.0). Sperm motility did not improve after treatment with IgG. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the small sample size as this is a rare population. WIDER IMPLICATIONS OF THE FINDINGS: Blockade of the inflammasome via treatment with anti-ASC improved sperm motility in men with SCI. In doing so, this treatment significantly increased their total motile sperm count. This is the first study to demonstrate that interference with the inflammasome improves sperm motility in men with SCI. This treatment has potential as a therapeutic intervention. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Craig H. Neilsen Foundation, Grant # 224598, the University of Miami Miller School of Medicine and the Miami Project to Cure Paralysis, Miami, FL, USA. R.W.K. and J.P.d.R.V. hold a patent for the treatment of inflammation after central nervous system injury using antibodies against inflammasome proteins. The other authors have no conflicts of interest to declare.
Asunto(s)
Anticuerpos Neutralizantes/farmacología , Proteínas del Citoesqueleto/metabolismo , Motilidad Espermática/efectos de los fármacos , Traumatismos de la Médula Espinal/fisiopatología , Adulto , Proteínas Adaptadoras de Señalización CARD , Humanos , Masculino , Estudios Prospectivos , Recuento de Espermatozoides , Motilidad Espermática/fisiología , Traumatismos de la Médula Espinal/metabolismoRESUMEN
Colonoscopic surveillance of hyperplastic polyps alone is controversial and may be inappropriate. The colonoscopy surveillance register at a university teaching hospital was audited to determine the extent of such hyperplastic polyp surveillance. The surveillance endoscopy records were reviewed, those patients with hyperplastic polyps were identified, their clinical records were examined and contact was made with each patient. Of the 483 patients undergoing surveillance for colonic polyps 113 (23%) had hyperplastic polyps alone on last colonoscopy. 104 patients remained after exclusion of those under appropriate surveillance. 87 of the 104 patients (84%) were successfully contacted. 37 patients (8%) were under appropriate colonoscopic surveillance for a significant family history of colorectal carcinoma. 50 (10%) patients with hyperplastic polyps alone and no other clinical indication for colonoscopic surveillance were booked for follow up colonoscopy. This represents not only a budgetary but more importantly a clinical opportunity cost the removal of which could liberate valuable colonoscopy time for more appropriate indications.
Asunto(s)
Pólipos del Colon/diagnóstico , Colonoscopía , Procedimientos Innecesarios , Pólipos del Colon/epidemiología , Pólipos del Colon/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The policy of redistributing surgical case volume toward designated high-volume hospitals to improve outcome in cancer is supported by an international literature on volume-outcome association. METHODS: All patients who underwent surgery for colorectal carcinoma under the care of one surgeon at a non-high-volume hospital 1995-2005 were identified. 5-year overall survival probability and 30-day operative mortality were measured. RESULTS: Two hundred and forty patients were identified. Mean annual surgeon caseload was 21.6 (SD 4.2). 5-year overall survival probability was 57.1% (95% confidence interval ±7.4%). 30-day operative mortality was 4.6%. CONCLUSION: Estimates of outcome were not different from publically available values from a high-volume unit in Ireland. These findings suggest that concentrating case volume per se may not improve outcome to the extent desired. Future improvement in colorectal cancer outcome is just as likely to derive from wider screening, better surgical training, and adequately powered clinical research, should these accompany centralisation.
Asunto(s)
Adenocarcinoma/mortalidad , Neoplasias Colorrectales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Colectomía/métodos , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Calidad de la Atención de SaludRESUMEN
The aim of this study was to determine whether hypoxic-ischemia from asphyxial cardiac arrest activates brain caspases-1 and -3, and the anti-apoptotic protein, XIAP. Asphyxial cardiac arrest in rats was used to induce hypoxic-ischemia. A pan-caspase inhibitor (zVAD) was given in the treatment group. At 72 h after reperfusion, caspase-3 and XIAP expression were present in multiple vulnerable brain regions, whereas caspase-1 was predominantly found in the CA1 hippocampus. zVAD significantly reduced expression of caspases and XIAP and the number of ischemic neurons in the CA1 hippocampus while neurological deficit scores were improved. We conclude that hypoxic-ischemia increases caspases-1 and-3, and XIAP expression. Treatment with zVAD significantly decreases caspase and XIAP expression in these brain regions and improves neurological outcome.
Asunto(s)
Asfixia/complicaciones , Encéfalo/enzimología , Caspasas/metabolismo , Muerte Celular/fisiología , Paro Cardíaco/complicaciones , Hipoxia-Isquemia Encefálica/enzimología , Proteínas/metabolismo , Clorometilcetonas de Aminoácidos/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Caspasa 1/metabolismo , Caspasa 3 , Inhibidores de Caspasas , Muerte Celular/efectos de los fármacos , Inhibidores de Cisteína Proteinasa/farmacología , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/fisiología , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Hipocampo/patología , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/etiología , Inmunohistoquímica , Masculino , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Proteínas/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Proteína Inhibidora de la Apoptosis Ligada a XRESUMEN
Caspase and inhibitor of apoptosis (IAP) expression was examined in rats subjected to moderate traumatic brain injury (TBI) using a parasagittal fluid-percussion brain insult (1.7 to 2.2 atm). Within 1 hour after injury, caspase-8 and -9, two initiators of apoptosis, were predominantly expressed in superficial cortical areas adjacent to the impact site and in the thalamus. Caspase-3, an effector caspase, was evident at 6 hours throughout the traumatized cerebral cortex and hippocampus. Moreover, the authors observed that XIAP, cIAP-1, and cIAP-2, members of the IAP family, were constitutively expressed in the brain. Colocalization of XIAP-immunolabled cells with cell-specific markers indicated that XIAP is expressed within neurons and a subpopulation of oligodendrocytes. Immunoblots of brain extracts revealed that the processed forms of caspase-8, -9, and -3 are present as early as 1 hour after trauma. The appearance of activated caspases corresponded with the detection of cleavage of XIAP into fragments after injury and a concomitant increase in the levels of cIAP-1 and cIAP-2 in the traumatized hemispheres. The current data are consistent with the hypotheses that caspases in both the extrinsic and intrinsic apoptotic pathways are activated after moderate TBI and that IAPs may have a protective role within the brain with alterations in levels and cleavage of IAPs that contribute to cell death in this setting.
Asunto(s)
Proteínas Bacterianas/metabolismo , Lesiones Encefálicas/patología , Caspasas/metabolismo , Corteza Cerebral/patología , Proteínas de Insectos , Proteínas , Animales , Apoptosis , Lesiones Encefálicas/enzimología , Caspasa 3 , Caspasa 8 , Caspasa 9 , Corteza Cerebral/enzimología , Hipocampo/enzimología , Hipocampo/patología , Inmunohistoquímica , Proteínas Inhibidoras de la Apoptosis , Cinética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Ellipticine derivatives have potential as anticancer drugs. Their clinical use has been limited, however, by poor solubility and host toxicity. As N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anticancer conjugates are showing promise in early clinical trials, a series of novel HPMA copolymer conjugates have been prepared containing the 6-(3-aminopropyl)-ellipticine derivative (APE, NSC176328). Drug was linked to the polymer via GFLG or GG peptide side chains. To optimize biological behavior, HPMA copolymer-GFLG-APE conjugates with different drug loading (total APE: 2.3-7% w/w; free APE: <0.1% w/w) were synthesized. Conjugation of APE to HPMA copolymers considerably increased its aqueous solubility (>10-fold). HPMA copolymer-GG-APE did not liberate drug in the presence of isolated lysosomal enzymes (tritosomes), but HPMA copolymer-GFLG-APE released APE to a maximum of 60% after 5 h. The rate of drug release was influenced by drug loading; lower loading led to greater release. Whereas free APE (35 microg/mL) caused significant hemolysis (50% after 1 h), HPMA copolymer-APE conjugates were not hemolytic up to 300 microg/mL (APE-equiv). As would be expected from its cellular pharmacokinetics, HPMA copolymer-GFLG-APE was >75 times less cytotoxic than free drug (IC(50) approximately 0.4 microg/mL) against B16F10 melanoma in vitro. However, in vivo when tested in mice bearing s.c. B16F10 melanoma, HPMA copolymer-GFLG-APE (1-10 mg/kg single dose, APE-equiv) given i.p. was somewhat more active (highest T/C value of 143%) than free APE (1 mg/kg) (T/C =127%). HPMA copolymer-APE conjugates warrant further evaluation as potential anticancer agents.
Asunto(s)
Acrilamidas/farmacocinética , Antineoplásicos Fitogénicos/farmacocinética , Elipticinas/farmacocinética , Polímeros/farmacocinética , Acrilamidas/administración & dosificación , Acrilamidas/síntesis química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/síntesis química , División Celular/efectos de los fármacos , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Portadores de Fármacos/farmacocinética , Evaluación Preclínica de Medicamentos , Elipticinas/administración & dosificación , Elipticinas/síntesis química , Hemólisis/efectos de los fármacos , Masculino , Metacrilatos/administración & dosificación , Metacrilatos/síntesis química , Metacrilatos/farmacocinética , Ratones , Ratones Endogámicos C57BL , Neoplasias Experimentales/tratamiento farmacológico , Polímeros/administración & dosificación , Polímeros/síntesis química , Solubilidad , Equivalencia Terapéutica , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/trasplanteRESUMEN
There are now at least seven polymer-drug conjugates that have entered phase I/II clinical trial as anticancer agents. These include N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1, FCE28068), HPMA copolymer-paclitaxel (PNU 166945), HPMA copolymer-camptothecin, PEG-camptothecin, polyglutamic acid-paclitaxel, an HPMA copolymer-platinate (AP5280) and also an HPMA copolymer-doxorubicin conjugate bearing additionally galactosamine (PK2, FCE28069). The galactosamine is used as a means to target the conjugate to liver for the treatment of primary and secondary liver cancer. Promising early clinical results with lysosomotropic conjugates has stimulated significant interest in this field. Ongoing research is developing (1) conjugates containing drugs that could otherwise not progress due to poor solubility or uncontrollable toxicity; (2) conjugates of agents directed against novel targets; and (3) two-step combinations such as polymer-directed enzyme prodrug therapy (PDEPT) and polymer-enzyme liposome therapy (PELT) that can cause explosive liberation of drug from either polymeric prodrugs or liposomes within the tumour interstitium. Moreover, bioresponsive polymer-based constructs able to promote endosomal escape and thus intracytoplasmic delivery of macromolecular drugs (peptides, proteins and oligonucleotides) are also under study.
Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos , Polímeros/química , Profármacos/administración & dosificación , Acrilamidas/administración & dosificación , Acrilamidas/farmacología , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Portadores de Fármacos , Excipientes , Galactosamina/administración & dosificación , Galactosamina/farmacología , Liposomas , Metacrilatos , Ratones , Neoplasias Experimentales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/farmacologíaRESUMEN
OBJECTIVES: To evaluate a South Australian campaign to promote and implement knowledge that taking adequate folate/folic acid in the periconceptional period can reduce the risk of having a baby with a neural tube defect. DESIGN AND SETTING: The campaign, conducted in October 1994--August 1995, targeted women of reproductive age and health professionals. Evaluation was by computer-assisted telephone interviews undertaken by random dialling throughout the State before and after the campaign, and by self-administered questionnaires to health professionals and women in the postnatal period. PARTICIPANTS: Women of reproductive age and four groups of health professionals. MAIN OUTCOME MEASURES: Knowledge about folate, folate-rich foods and the periconceptional period; participation of health professionals in advising women about folate; use of periconceptional folic acid supplements; sales of folic acid tablets; and prevalence of neural tube defects. RESULTS: Significant increases in knowledge about folate followed the campaign. Health professionals and women in the postnatal period had higher initial levels of knowledge about folate, which also increased significantly. The proportions of women taking periconceptional folic acid supplements, and of health professionals advising women planning a pregnancy about folate, also increased significantly, and folic acid tablet sales doubled. Total prevalence of neural tube defects declined between 1966 and 1999 from a baseline of 2.0 per 1,000 births to 1.1 per 1,000 births (Poisson regression, P= 0.03; average decline of 1.0% per year). CONCLUSIONS: A short educational campaign with a limited budget ($40,000) can promote folate successfully, but alternative strategies such as food fortification are likely to be needed to achieve adequate periconceptional folate intake for a very high proportion of women.
Asunto(s)
Actitud del Personal de Salud , Actitud Frente a la Salud , Planificación en Salud Comunitaria/organización & administración , Ácido Fólico/uso terapéutico , Educación en Salud/organización & administración , Promoción de la Salud/organización & administración , Defectos del Tubo Neural/prevención & control , Salud de la Mujer , Adolescente , Adulto , Femenino , Alimentos Fortificados , Conocimientos, Actitudes y Práctica en Salud , Humanos , Defectos del Tubo Neural/epidemiología , Comunicación Persuasiva , Prevalencia , Evaluación de Programas y Proyectos de Salud , Análisis de Regresión , Australia del Sur/epidemiología , Encuestas y CuestionariosRESUMEN
In subalpine forests of the northern Rocky Mountains, fire exclusion has contributed to large-scale shifts from early-successional whitebark pine (Pinus albicaulis Engelm.) to late-successional subalpine fir (Abies lasiocarpa (Hook.) Nutt.), a species assumed to be more shade tolerant than whitebark pine and with leaf to sapwood area ratios (A(L):A(S)) over twice as high. Potential consequences of high A(L):A(S) for subalpine fir include reduced light availability and, if hydraulic sufficiency is maintained, increased whole-tree water use. We measured instantaneous gas exchange, carbon isotope ratios and sap flow of whitebark pine and subalpine fir trees of different sizes in the Sapphire Mountains of western Montana to determine: (1) whether species-specific differences in gas exchange are related to their assumed relative shade tolerance and (2) how differences in A(L):A(S) affect leaf- and whole-tree water use. Whitebark pine exhibited higher photosynthetic rates (A = 10.9 micromol x m(-2) x s(-1) +/- 1.1 SE), transpiration rates (E = 3.8 mmol x m(-2) x s(-1) +/- 0.7 SE), stomatal conductance (g(s) = 166.4 mmol x m(-2) x s(-1) +/- 5.3 SE) and carbon isotope ratios (delta13C = -25.5 per thousand +/- 0.2 SE) than subalpine fir (A = 5.7 micromol x m(-2) x s(-1) +/- 0.9 SE; E = 1.4 mmol x m(-2) x s(-1) +/- 0.3 SE; g(s) = 63.4 mmol x m(-2) x s(-1) +/- 1.2 SE, delta13C = -26.2 per thousand +/- 0.2 SE; P < 0.01 in all cases). Because subalpine fir had lower leaf-area-based sap flow than whitebark pine (QL = 0.33 kgx m(-2) x day(-1) +/- 0.03 SE and 0.76 kg x m(-2) x day(-1) +/- 0.06 SE, respectively; P < 0.001), the higher A(L):A(S) in subalpine fir did not result in direct proportional increases in whole-tree water use, although large subalpine firs used more water than large whitebark pines. The linear relationships between tree size and daily water use (r2 = 0.94 and 0.97 for whitebark pine and subalpine fir, respectively) developed at the Sapphire Mountains site were applied to trees of known size classes measured in 12 natural subalpine stands in the Bob Marshall Wilderness Complex (western Montana) ranging from 67 to 458 years old. Results indicated that the potential for subalpine forests to lose water by transpiration increases as succession proceeds and subalpine fir recruits into whitebark pine stands.
Asunto(s)
Abies/fisiología , Pinus/fisiología , Árboles/fisiología , Ecosistema , Incendios , Montana , Hojas de la Planta/fisiología , Brotes de la Planta/fisiología , AguaRESUMEN
Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.
Asunto(s)
Alopecia/enzimología , Caspasas/metabolismo , Folículo Piloso/enzimología , Cabello/crecimiento & desarrollo , Péptidos y Proteínas de Señalización Intracelular , Proteínas/metabolismo , Inhibidores de 5-alfa-Reductasa , Adolescente , Adulto , Alopecia/genética , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Estudios de Casos y Controles , Caspasas/efectos de los fármacos , Caspasas/genética , Inhibidores Enzimáticos/farmacología , Finasterida/farmacología , Humanos , Inmunohistoquímica , Masculino , Proteínas/efectos de los fármacos , Proteína Inhibidora de la Apoptosis Ligada a XRESUMEN
A number of studies have provided evidence that cell death from moderate traumatic spinal cord injury (SCI) is regulated, in part, by apoptosis that involves the caspase family of cysteine proteases. However, little or no information is available about anti-apoptotic mechanisms mediated by the inhibitors of apoptosis (IAP) family of proteins that inhibit cell death pathways. In the present study, we examined caspase and IAP expression in spinal cords of rats subjected to moderate traumatic injury. Within 6 h after injury, caspase-8 and-9 (2 initiators of apoptosis) were predominantly present in gray matter neurons within the lesion epicenter. By 3 days following spinal cord injury (SCI), caspase-8 and-9 immunoreactivity was localized to gray and white matter cells, and by 7 days following SCI, both upstream caspases were expressed in cells within white matter or within foamy macrophages in gray matter. Caspase-3, an effector caspase, was evident in a few fragmented cells in gray matter at 24 h following injury and then localized to white matter in later stages. Thus, distinct patterns of caspase expression can be found in the spinal cord following injury. XIAP, cIAP-1, and cIAP-2, members of the IAP family, were constitutively expressed in the cord. Immunoblots of spinal cord extracts revealed that the processed forms of caspases-8 and-9 and cleavage of PARP are present as early as 6 h following trauma. The expression of caspases corresponded with the detection of cleavage of XIAP into 2 fragments following injury. cIAP-1 and cIAP-2 expression remained constant during early periods following SCI but demonstrated alterations by 7 days following SCI. Our data are consistent with the idea that XIAP may have a protective role within the spinal cord, and that alteration in cleavage of XIAP may regulate cell death following SCI.
Asunto(s)
Apoptosis , Traumatismos de la Médula Espinal/fisiopatología , Animales , Caspasa 8 , Caspasa 9 , Caspasas/metabolismo , Femenino , Proteínas Inhibidoras de la Apoptosis , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína Inhibidora de la Apoptosis Ligada a XRESUMEN
OBJECTIVES: To determine the contribution of maternal smoking to preterm birth (< 37 weeks' gestation), small for gestational age (SGA, birthweight < 10th percentile for gestational age) and low birthweight (< 2500 g) among Aboriginal and non-Aboriginal births in South Australia. DESIGN: Retrospective cohort analysis of population-based perinatal data. SETTING: The State of South Australia, population 1.5 million. PARTICIPANTS: 36059 women (of whom 851 were Aboriginal women) who had singleton births in 1998-1999. MAIN OUTCOME MEASURES: Relative risks and population-attributable risks of preterm birth, SGA and low birthweight from smoking in the second half of pregnancy, by age and Aboriginality. RESULTS: Aboriginal women had a higher rate of smoking in pregnancy than non-Aboriginal women (57.8% v 24.0% at the first antenatal visit) and high rates for all age groups, while the rates decreased with age among non-Aboriginal women. Heavy smoking increased with age, and Aboriginal women were heavier smokers. Women who smoked had elevated relative risks of preterm birth (1.64), SGA (2.28) and low birthweight (2.52), and all these showed a dose-response relationship. Among Aboriginal (versus non-Aboriginal) births, population-attributable risks were significantly higher for SGA (48% v 21%, and 59% for births to Aboriginal teenagers), low birthweight (35% v 23%) and preterm birth (20% v 11%). CONCLUSIONS: Health promotion programs, with a focus on smoking cessation and reducing uptake of smoking, need to be implemented in an appropriate cultural context, especially among young Aboriginal women. Such a program is being developed in South Australia.
Asunto(s)
Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Trabajo de Parto Prematuro/etiología , Fumar/efectos adversos , Adulto , Femenino , Humanos , Recién Nacido , Trabajo de Parto Prematuro/etnología , Embarazo , Factores de Riesgo , Fumar/etnología , Australia del Sur/epidemiologíaRESUMEN
The objective of this study was to determine whether women who have experienced an unexplained stillbirth have a higher risk of adverse perinatal outcomes in subsequent births. We compared 316 subsequent births to women with a previous unexplained stillbirth, with 3160 births to women with no previous history of stillbirth, matched by year of birth, in the period 1987-1997, from the South Australian perinatal database, using logistic regression analysis. There was no increase in the rate of stillbirth and no statistically significant increase in the rate of perinatal death (OR 1.62 [95%CI 0.63-4.20]) or neonatal death, although larger studies are needed to confirm this. However, after adjusting for age, parity, and hospital category of birth, women who had a previous stillbirth had increased incidences in subsequent births of abnormal glucose tolerance or gestational diabetes (a fourfold increase); induction of labour and elective Caesarean section; fetal distress and postpartum haemorrhage; and forceps and emergency Caesarean delivery and preterm birth, which were independent of induction of labour. Gestational age at birth and birthweight were also significantly reduced, suggesting a need for close monitoring of their future pregnancies.
Asunto(s)
Muerte Fetal/epidemiología , Resultado del Embarazo/epidemiología , Adulto , Análisis de Varianza , Peso al Nacer , Estudios de Cohortes , Parto Obstétrico/métodos , Parto Obstétrico/estadística & datos numéricos , Femenino , Muerte Fetal/prevención & control , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Modelos Logísticos , Evaluación de Necesidades , Paridad , Vigilancia de la Población , Embarazo , Embarazo de Alto Riesgo , Atención Prenatal , Estudios Retrospectivos , Factores de Riesgo , Australia del Sur/epidemiologíaRESUMEN
OBJECTIVES: To describe the impact of maternal serum screening on the birth prevalence of Down's syndrome and on the use of amniocentesis and chorionic villus sampling in South Australia. DESIGN: A descriptive population-based study. SETTING: South Australia (population 1.48 million persons; approximately 20,000 births per year). PARTICIPANTS: Women who had births or terminations of pregnancy with Down's syndrome in 1982-1996, women who had maternal serum screening in 1991-1996, amniocentesis or chorionic villus sampling in 1986-1996. METHODS: Analysis of data from multiple sources on maternal serum screening, amniocentesis and chorionic villus sampling, births and terminations of pregnancy. MAIN OUTCOME MEASURES: Total prevalence and birth prevalence of Down's syndrome each year in 1982-1996; proportion of pregnant women using maternal serum screening in 1991-1996, and proportion using amniocentesis and chorionic villus sampling by indication in 1986-1996, by age group. RESULTS: Use of maternal serum screening for Down's syndrome increased from 17% when introduced in 1991 to 76% of women who gave birth in 1996. Between 1982 and 1986 and 1996, terminations of pregnancy for fetal Down's syndrome increased from 7.1 % to 75% and the birth prevalence of Down's syndrome fell by 60% from 1.05 to 0.42 per 1,000 births, against the background of an increase in total prevalence due to increasing maternal age. The use of amniocentesis increased from 5.8% in 1991 to 10.1% in 1996 mainly due to the increase among women younger than 35 years with maternal serum screening as the main reason. The increasing chorionic villus sampling rate among younger women stabilised at 0.4%, while the rate among older women decreased from 11.0% to 7.4%. CONCLUSIONS: The introduction of maternal serum screening in South Australia has resulted in increased use of any prenatal testing for Down's syndrome from about 7% (mainly older women having amniocentesis or chorionic villus sampling) to 84% of women (about 8% having direct amniocentesis or chorionic villus sampling and 76% having maternal serum screening first). This has resulted in a significant fall in the birth prevalence of Down's syndrome. maternal serum screening was the first indication of Down's syndrome for about half the terminations of pregnancy for Down's syndrome in 1993-1996, including three quarters of those in younger women.
Asunto(s)
Amniocentesis/estadística & datos numéricos , Muestra de la Vellosidad Coriónica/estadística & datos numéricos , Síndrome de Down/epidemiología , Adulto , Gonadotropina Coriónica/sangre , Síndrome de Down/sangre , Síndrome de Down/diagnóstico , Estradiol/sangre , Femenino , Humanos , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Edad Materna , Embarazo , Resultado del Embarazo , Embarazo de Alto Riesgo , Prevalencia , Australia del Sur/epidemiología , alfa-Fetoproteínas/análisisRESUMEN
Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stake-holders seems difficult to achieve.
Asunto(s)
Medicina de la Conducta/organización & administración , Programas Controlados de Atención en Salud/organización & administración , Medicaid/organización & administración , Trastornos Mentales/rehabilitación , Trastornos Relacionados con Sustancias/rehabilitación , Actitud del Personal de Salud , Medicina de la Conducta/tendencias , Comportamiento del Consumidor/estadística & datos numéricos , Servicios Contratados/organización & administración , Encuestas de Atención de la Salud , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Programas Controlados de Atención en Salud/normas , Programas Controlados de Atención en Salud/estadística & datos numéricos , Massachusetts , Desarrollo de Programa , Calidad de la Atención de Salud/estadística & datos numéricos , Estados UnidosRESUMEN
BACKGROUND: The Medical Research Council Working Party on Congenital Dislocation of the Hip have reported an ascertainment-adjusted incidence of a first operative procedure for congenital dislocation of the hip (CDH) of 0.78 per 1000 livebirths, which is similar to the incidence of CDH before the start of the UK screening programme. The report showed that CDH had not been detected by routine screening before age 3 months in 70% of children reported to the national orthopaedic surveillance scheme. This report raised concerns about the merit of screening at birth for CDH. We aimed to find out the incidence of an operative procedure for CDH in the first 5 years of life among children born in South Australia between 1988 and 1993, and the proportion of these patients that were detected at age 3 months or older. METHODS: The state's database for inpatient separations between January, 1988, and April, 1998 was searched. Case records were examined for the age and circumstances of diagnosis, and type of operative procedures. Prevalence rates of CDH were obtained from the South Australian Birth Defects Register, which receives notifications from a statutory perinatal data collection of birth defects detected at birth and subsequent voluntary notifications for children up to age 5 years. FINDINGS: Of the 55 children born in South Australia between 1988 and 1993 identified as having non-teratological CDH and operative procedures, only 22 (40%) had been diagnosed at age 3 months or older. 18 had an open reduction of the hip joint or osteotomy, or both, and the remainder had arthrograms, closed reductions, and/or tenotomy. The prevalence of non-teratological CDH in children was 7.74 per 1000 livebirths. The incidence of surgery for CDH in the first 5 years of life was 0.46 per 1000 livebirths (95% CI 0.34-0.59) and only 0.19 per 1000 livebirths (0.11-0.26) for those diagnosed late (age 3 months or older). These children diagnosed late represented 2.4% of all known cases of CDH. INTERPRETATION: Only 2.4% of known cases of CDH in children born in South Australia had been detected late and required surgery. These results show that a screening programme for CDH can be successful, contrary to the findings of the UK Medical Research Council Working Party.