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1.
Pediatr Crit Care Med ; 20(3): 280-289, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30830016

RESUMO

OBJECTIVES: The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. METHODS AND MAIN RESULTS: This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, nine are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, three are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The purpose of publishing the algorithm as a separate document is to provide guidance for clinicians while maintaining a clear distinction between what is evidence based and what is consensus based. This approach allows, and is intended to encourage, continued creativity in treatment and research where evidence is lacking. Additionally, it allows for the use of the evidence-based recommendations as the foundation for other pathways, protocols, or algorithms specific to different organizations or environments. The complete guideline document and supplemental appendices are available electronically from this journal. These documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. CONCLUSIONS: New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

2.
Neurosurgery ; 84(6): 1169-1178, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30822776

RESUMO

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental appendices are available electronically (https://doi.org/10.1097/PCC.0000000000001735). The online documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

4.
Ann Intern Med ; 167(12): 867-875, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29181532

RESUMO

Background: Naloxone is effective for reversing opioid overdose, but optimal strategies for out-of-hospital use are uncertain. Purpose: To synthesize evidence on 1) the effects of naloxone route of administration and dosing for suspected opioid overdose in out-of-hospital settings on mortality, reversal of overdose, and harms, and 2) the need for transport to a health care facility after reversal of overdose with naloxone. Data Sources: Ovid MEDLINE (1946 through September 2017), PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, U.S. Food and Drug Administration (FDA) materials, and reference lists. Study Selection: English-language cohort studies and randomized trials that compared different doses of naloxone, administration routes, or transport versus nontransport after reversal of overdose with naloxone. Main outcomes were mortality, reversal of overdose, recurrence of overdose, and harms. Data Extraction: Dual extraction and quality assessment of individual studies; consensus assessment of overall strength of evidence (SOE). Data Synthesis: Of 13 eligible studies, 3 randomized controlled trials and 4 cohort studies compared different administration routes. At the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone, and 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation (low SOE). Evidence was insufficient to evaluate other comparisons of route of administration. Six uncontrolled studies reported low rates of death and serious adverse events (0% to 1.25%) in nontransported patients after successful naloxone treatment. Limitation: There were few studies, all had methodological limitations, and none evaluated FDA-approved autoinjectors or highly concentrated intranasal formulations. Conclusion: Higher-concentration intranasal naloxone (2 mg/mL) seems to have efficacy similar to that of intramuscular naloxone for reversal of opioid overdose, with no difference in adverse events. Nontransport after reversal of overdose with naloxone seems to be associated with a low rate of serious harms, but no study evaluated risks of transport versus nontransport. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42016053891).


Assuntos
Analgésicos Opioides/toxicidade , Serviços Médicos de Emergência/métodos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Administração Intranasal , Analgésicos Opioides/antagonistas & inibidores , Overdose de Drogas/tratamento farmacológico , Humanos , Injeções Intramusculares , Naloxona/administração & dosagem
5.
Int J Health Serv ; 47(3): 410-431, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28649927

RESUMO

This article builds on recent work that has explored how welfare regimes moderate social class inequalities in health. It extends research to date by using longitudinal data from the EU-SILC (2003-2010) and examines how the relationship between social class and self-reported health and chronic conditions varies across 23 countries, which are split into five welfare regimes (Nordic, Anglo-Saxon, Eastern, Southern, and Continental). Our analysis finds that health across all classes was only worse in Eastern Europe (compared with the Nordic countries). In contrast, we find evidence that the social class gradient in both measures of health was significantly wider in the Anglo-Saxon and Southern regimes. We suggest that this evidence supports the notion that welfare regimes continue to explain differences in health according to social class location. We therefore argue that although downward pressures from globalization and neoliberalism have blurred welfare regime typologies, the Nordic model may continue to have an important mediating effect on class-based inequalities in health.


Assuntos
Disparidades nos Níveis de Saúde , Classe Social , Seguridade Social , Doença Crônica/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino
6.
J Ethnopharmacol ; 192: 74-89, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27377341

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hidden in the documents of the dark past of the trans-Atlantic slavery are gems of ethnomedicinal observations, supported by herbarium specimens, which tell of the traditional medicine of a by-gone slave society in the Caribbean. In the context of the former Danish West Indies (now US Virgin Islands), we identify pre-1900 medicinal plants and their historical uses, and trace their status in the traditional medicine of St. Croix today (2014). By a combined historical and ethnobotanical approach we assess the scale of loss and preservation of traditional medicinal knowledge on St. Croix, and explore the drivers involved in the disappearance of knowledge in the oral tradition of medicine. MATERIALS AND METHODS: Names, uses and identities of 18th and 19th century medicinal plant uses in the Danish West Indies were derived from manuscripts and publications of Von Rohr (1757/58), Oldendorp (1777), West (1793), Benzon (1822), Riise (1853), Eggers (1876;1879) and Berg and Eggers (1888). The presence of the plant species in the pre-1900 Danish West Indies was confirmed by review of herbarium specimens in the University of Copenhagen Herbarium (C). The same species were collected on St. Croix in 2014 or their ecological status discussed with local specialists. Semi-structured interviews supported by photographs and specimens were conducted with six medicinal plant specialist on St. Croix, to document and compare contemporary names and uses of the historically used medicinal plants. RESULTS AND DISCUSSION: The historic ethnomedicinal sources revealed 102 medicinal uses of 64 plant species. Thirty-eight (37%) of the pre-1900 medicinal uses were traced in interviews, while sixty-four uses (63%) appear to be forgotten, discontinued or otherwise lost. Thirteen species appear to have entirely lost their status as medicinal plants on St. Croix, while 32 species (50%) have lost uses while retaining or gaining others. While 20% of the lost medicinal plant uses can be explained by biodiversity loss, and others likely have become obsolete due to advances in public health and scientific medicine, 33 of the 64 lost medicinal uses of non-rare species uses fall in the same categories as the preserved uses (fever, stomach, wound, laxative, pulmonary, intestinal, pain, anthelmintic, blood purifier, eye-inflammation). We therefore argue that at least half of the known pre-1900 medicinal plant uses have become culturally extinct for other reasons than to biodiversity loss or modern obsoleteness. CONCLUSIONS: The present study utilized knowledge from an oral medicinal tradition, documented in the context of a colonial society. Without doubt, basis for further similar studies exists in the more or less accessible archives, herbaria and collections of former colonial powers. Such studies could directly benefit the descendants of the original intellectual property holders culturally and economically, or serve as stepping stones to integrate, or re-integrate, lost medicinal plant uses in both local and wider evidence-based contexts.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Medicina Tradicional/história , Extratos Vegetais/história , Plantas Medicinais , Características Culturais , Etnobotânica/história , Etnofarmacologia/história , Conhecimentos, Atitudes e Prática em Saúde/etnologia , História do Século XVIII , História do Século XIX , História do Século XXI , Humanos , Disseminação de Informação , Entrevistas como Assunto , Medicina Tradicional/tendências , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Plantas Medicinais/classificação , Ilhas Virgens Americanas
8.
Hum Genet ; 134(6): 539-51, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25515860

RESUMO

Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h(2) ≤ 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r(g) = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h(2)(Meta) ≤ 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10(-5)) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence.


Assuntos
Transtorno Autístico/genética , Síndrome de Adaptação Geral/genética , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Reino Unido
9.
Mol Psychiatry ; 19(2): 253-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23358156

RESUMO

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.


Assuntos
Proteínas de Transporte/genética , Inteligência/genética , Herança Multifatorial , Adolescente , Criança , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Técnicas de Genotipagem , Humanos , Testes de Inteligência , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Característica Quantitativa Herdável , Software
10.
Transl Psychiatry ; 3: e229, 2013 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-23423138

RESUMO

The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities (P(comb) = 7.71 × 10(-10), n = 699), with an effect size of 4.87%. This association was also found in a sample from the general population (P = 0.048, n = 1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.


Assuntos
Discalculia/genética , Dislexia/genética , Variação Genética , Miosinas/genética , Lobo Parietal/anatomia & histologia , Proteínas Supressoras de Tumor/genética , Adulto , Envelhecimento/genética , Criança , Discalculia/fisiopatologia , Dislexia/fisiopatologia , Feminino , Marcadores Genéticos , Alemanha , Humanos , Masculino , Testes Neuropsicológicos , Lobo Parietal/fisiopatologia , Risco
11.
Mol Psychiatry ; 17(9): 867-74, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22688189

RESUMO

Twin studies allow us to estimate the relative contributions of nature and nurture to human phenotypes by comparing the resemblance of identical and fraternal twins. Variation in complex traits is a balance of genetic and environmental influences; these influences are typically estimated at a population level. However, what if the balance of nature and nurture varies depending on where we grow up? Here we use statistical and visual analysis of geocoded data from over 6700 families to show that genetic and environmental contributions to 45 childhood cognitive and behavioral phenotypes vary geographically in the United Kingdom. This has implications for detecting environmental exposures that may interact with the genetic influences on complex traits, and for the statistical power of samples recruited for genetic association studies. More broadly, our experience demonstrates the potential for collaborative exploratory visualization to act as a lingua franca for large-scale interdisciplinary research.


Assuntos
Doenças em Gêmeos/epidemiologia , Interação Gene-Ambiente , Mapeamento Geográfico , Modelos Estatísticos , Estudos em Gêmeos como Assunto/estatística & dados numéricos , Criança , Doenças em Gêmeos/genética , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Reino Unido/epidemiologia
12.
Genes Brain Behav ; 9(2): 234-47, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-20039944

RESUMO

Numeracy is as important as literacy and exhibits a similar frequency of disability. Although its etiology is relatively poorly understood, quantitative genetic research has demonstrated mathematical ability to be moderately heritable. In this first genome-wide association study (GWAS) of mathematical ability and disability, 10 out of 43 single nucleotide polymorphism (SNP) associations nominated from two high- vs. low-ability (n = 600 10-year-olds each) scans of pooled DNA were validated (P < 0.05) in an individually genotyped sample of (*)2356 individuals spanning the entire distribution of mathematical ability, as assessed by teacher reports and online tests. Although the effects are of the modest sizes now expected for complex traits and require further replication, interesting candidate genes are implicated such as NRCAM which encodes a neuronal cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The association is linear across the distribution consistent with a quantitative trait locus (QTL) hypothesis; the third of children in our sample who harbour 10 or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96; df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution. Our results correspond with those of quantitative genetic research in indicating that mathematical ability and disability are influenced by many genes generating small effects across the entire spectrum of ability, implying that more highly powered studies will be needed to detect and replicate these QTL associations.


Assuntos
Mapeamento Cromossômico , Estudo de Associação Genômica Ampla , Transtornos de Aprendizagem/genética , Matemática , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Criança , Currículo , DNA/genética , Genoma Humano , Genótipo , Humanos , Internet , Aprendizagem/fisiologia , Funções Verossimilhança , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo
13.
Mol Psychiatry ; 15(11): 1112-20, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19488046

RESUMO

Although common sense suggests that environmental influences increasingly account for individual differences in behavior as experiences accumulate during the course of life, this hypothesis has not previously been tested, in part because of the large sample sizes needed for an adequately powered analysis. Here we show for general cognitive ability that, to the contrary, genetic influence increases with age. The heritability of general cognitive ability increases significantly and linearly from 41% in childhood (9 years) to 55% in adolescence (12 years) and to 66% in young adulthood (17 years) in a sample of 11 000 pairs of twins from four countries, a larger sample than all previous studies combined. In addition to its far-reaching implications for neuroscience and molecular genetics, this finding suggests new ways of thinking about the interface between nature and nurture during the school years. Why, despite life's 'slings and arrows of outrageous fortune', do genetically driven differences increasingly account for differences in general cognitive ability? We suggest that the answer lies with genotype-environment correlation: as children grow up, they increasingly select, modify and even create their own experiences in part based on their genetic propensities.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Envelhecimento/genética , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Característica Quantitativa Herdável , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Testes de Inteligência , Masculino , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Estados Unidos
14.
Genes Brain Behav ; 7(4): 455-62, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17983460

RESUMO

A key translational issue for neuroscience is to understand how genes affect individual differences in brain function. Although it is reasonable to suppose that genetic effects on specific learning abilities, such as reading and mathematics, as well as general cognitive ability (g), will overlap very little, the counterintuitive finding emerging from multivariate genetic studies is that the same genes affect these diverse learning abilities: a Generalist Genes hypothesis. To conclusively test this hypothesis, we exploited the widespread access to inexpensive and fast Internet connections in the UK to assess 2541 pairs of 10-year-old twins for reading, mathematics and g, using a web-based test battery. Heritabilities were 0.38 for reading, 0.49 for mathematics and 0.44 for g. Multivariate genetic analysis showed substantial genetic correlations between learning abilities: 0.57 between reading and mathematics, 0.61 between reading and g, and 0.75 between mathematics and g, providing strong support for the Generalist Genes hypothesis. If genetic effects on cognition are so general, the effects of these genes on the brain are also likely to be general. In this way, generalist genes may prove invaluable in integrating top-down and bottom-up approaches to the systems biology of the brain.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Testes de Inteligência/normas , Inteligência/genética , Internet , Aprendizagem/fisiologia , Característica Quantitativa Herdável , Fatores Etários , Criança , Cognição/fisiologia , Estudos de Coortes , Feminino , Variação Genética/genética , Genoma Humano/genética , Humanos , Padrões de Herança/genética , Transtornos de Aprendizagem/genética , Masculino , Matemática , Modelos Estatísticos , Análise Multivariada , Leitura , Comportamento Verbal/fisiologia
15.
Genes Brain Behav ; 7(4): 435-46, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18067574

RESUMO

General cognitive ability (g), which refers to what cognitive abilities have in common, is an important target for molecular genetic research because multivariate quantitative genetic analyses have shown that the same set of genes affects diverse cognitive abilities as well as learning disabilities. In this first autosomal genome-wide association scan of g, we used a two-stage quantitative trait locus (QTL) design with pooled DNA to screen more than 500,000 single nucleotide polymorphisms (SNPs) on microarrays, selecting from a sample of 7000 7-year-old children. In stage 1, we screened for allele frequency differences between groups pooled for low and high g. In stage 2, 47 SNPs nominated in stage 1 were tested by individually genotyping an independent sample of 3195 individuals, representative of the entire distribution of g scores in the full 7000 7-year-old children. Six SNPs yielded significant associations across the normal distribution of g, although only one SNP remained significant after a false discovery rate of 0.05 was imposed. However, none of these SNPs accounted for more than 0.4% of the variance of g, despite 95% power to detect associations of that size. It is likely that QTL effect sizes, even for highly heritable traits such as cognitive abilities and disabilities, are much smaller than previously assumed. Nonetheless, an aggregated 'SNP set' of the six SNPs correlated 0.11 (P < 0.00000003) with g. This shows that future SNP sets that will incorporate many more SNPs could be useful for predicting genetic risk and for investigating functional systems of effects from genes to brain to behavior.


Assuntos
Cognição/fisiologia , DNA/genética , Genoma Humano/genética , Inteligência/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Adolescente , Criança , DNA/análise , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Humanos , Padrões de Herança/genética , Estudos Longitudinais , Masculino , Herança Multifatorial/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Característica Quantitativa Herdável
17.
J Assist Reprod Genet ; 23(4): 185-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16758349

RESUMO

PURPOSE: To analyze the success of autologous endometrial coculture (AECC) in improving embryo quality and pregnancy outcome based on the histologic characteristic of the biopsy. METHODS: Prospective study of 86 consecutive patients undergoing IVF utilizing AECC. RESULTS: The patients were on average 37.4+/-4.0 years with a history of 2.6+/-1.8 failed previous attempts. An overall clinical pregnancy rate of 45.3% per ET was found. The embryos grown in AECC were of an improved quality in comparison to those grown in conventional media. 33.7% (29/86) of the biopsies were out of phase (>3 days). In-phase (IP) and OOP (out of phase) specimens both demonstrated an improvement in embryo quality. However, OOP endometrial biopsies that displayed significant retarded endometrial development (< cycle day 19) did not demonstrate an improvement in embryos grown on AECC as compared to IP endometrial biopsies or OOP endometrial biopsies that demonstrated at least an endometrial development of cycle day 19. CONCLUSIONS: We have demonstrated a significant improvement in embryo quality with AECC. We have also demonstrated that histologic dating of the endometrium is predictive of IVF outcome when utilizing AECC.


Assuntos
Técnicas de Cocultura/métodos , Técnicas de Cultura Embrionária/métodos , Endométrio/anatomia & histologia , Fertilização In Vitro/métodos , Adulto , Endométrio/citologia , Feminino , Previsões , Humanos , Gravidez , Taxa de Gravidez , Falha de Tratamento
18.
Afr J Med Med Sci ; 34(2): 167-72, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16749342

RESUMO

The effects of honey (Hoc) and aqueous suspensions of garlic (Allium sativum) (Ga) and bitter kola (Garcina kola seed) (Bi) on the toxicities induced by 2-acetylaminofluorene (2-AAF) a model carcinogen, were investigated in mice. The animals were dosed for seven consecutive days with Ho, Ga and Bi as dietary supplements. They were then challenged with a single intraperitoneal (i.p.) dose of 2-AAF at 50 mg/kg bd. wt on the seventh day. The degree of clastogenicity was assessed using the mouse micronucleus assay while liver damage was monitored by measuring the level of gamma glutamyltransferase (gamma-GT) in serum and liver homogenates respectively. The results revealed that 2-AAF induced micronuclei formation in the polychromatic erythrocytes (PCEs) of the bone marrow by about five fold in comparison to the PCEs formed in control mice. Ho, Ga, and Bi also induced micronucleus formation on their own. However. feeding of any of Ho, Ga or Bi and the administration (i.p) of 2-AAF reduced significantly, the ability of 2-AAF to induce micronuclei formation in the order Ho>Ga>Bi. Furthermore, 2-AAF induced gamma-GT activity in the serum and liver homogenate by about two and a half and three folds respectively. A combination of 2-AAF and any of Ga or Bi or Ho significantly decreased 2-AAF-induced activity of gamma-GT in the order Ho>Bi>Ga (serum) and Bi>Ga=Ho (liver). These findings suggest that honey, garlic and bitter kola protect against 2-AAF-induced gamma-GTactivity and micronuleated PCEs formation.


Assuntos
2-Acetilaminofluoreno/toxicidade , Suplementos Nutricionais , Exposição Ambiental/prevenção & controle , Garcinia kola , Alho , Mel , Fígado/efeitos dos fármacos , Fígado/enzimologia , gama-Glutamiltransferase/efeitos dos fármacos , Animais , Masculino , Camundongos
19.
Semin Reprod Med ; 21(1): 65-71, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12806561

RESUMO

Ovarian cancer is the fifth most common cancer in the Western world. Infertility and nulliparity are independent risk factors for this disease. The possible link between fertility drugs and ovarian cancer remains controversial. Despite concern regarding increasing use of fertility therapy, the incidence of ovarian cancer in the Western world has remained stable for several decades. Evaluation of the literature requires assessment of the validity, importance, and applicability of the study to your particular patient. The following article demonstrates how to conduct such an assessment. The data to date do not support a causal relationship between fertility drugs and ovarian cancer. In fact, infertility therapy may confer protection for those patients who conceive. Further prospective, long-term data are needed to further delineate this relationship.


Assuntos
Fármacos para a Fertilidade Feminina/efeitos adversos , Infertilidade Feminina/tratamento farmacológico , Neoplasias Ovarianas/induzido quimicamente , Indução da Ovulação/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Humanos
20.
Hum Reprod ; 18(1): 90-5, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12525446

RESUMO

BACKGROUND: Breast cancer chemotherapy commonly causes premature ovarian failure and infertility. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, natural cycle IVF (NCIVF) has been used to preserve fertility and treat infertility in these women. METHODS: Twelve women with breast cancer received 40-60 mg tamoxifen for 6.9 +/- 0.6 days beginning on days 2-3 of their menstrual cycle (15 cycles), and had IVF (TamIVF) with either fresh embryo transfer (six cycles) or cryopreservation (nine cycles). They were compared to a retrospective control group (n = 5) who had natural cycle IVF (NCIVF, nine cycles). RESULTS: Cycle cancellation was significantly less frequent in TamIVF, compared with NCIVF (1/15 versus 4/9, P < 0.05). Compared with NCIVF, TamIVF patients had a greater number of mature oocytes (1.6 +/- 0.3 versus 0.7 +/- 0.2, P = 0.03) and embryos (1.6 +/- 0.3 versus 0.6 +/- 0.2, P = 0.02) per initiated cycle. TamIVF resulted in the generation of embryo(s) in every patient (12/12) while only three out of five patients had an embryo following NCIVF. Two out of six patients in TamIVF, and 2/5 in NCIVF conceived. One patient in the TamIVF group delivered a set of twins. After a mean follow up of 15 +/- 3.6 months (range 3-54), none of the patients had a recurrence of cancer. CONCLUSIONS: Tamoxifen stimulation appears to result in a higher number of embryos and may provide a safe method of IVF and fertility preservation in breast cancer patients.


Assuntos
Neoplasias da Mama/fisiopatologia , Criopreservação , Embrião de Mamíferos , Antagonistas de Estrogênios/administração & dosagem , Fertilidade , Fertilização In Vitro , Indução da Ovulação , Tamoxifeno/administração & dosagem , Adulto , Contagem de Células , Senescência Celular , Relação Dose-Resposta a Droga , Esquema de Medicação , Transferência Embrionária , Feminino , Humanos , Oócitos/patologia , Oócitos/fisiologia , Gravidez , Gravidez Múltipla , Estudos Prospectivos , Gêmeos
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