RESUMO
PROBLEM: Electronic Stability Control (ESC) is believed to be among the most efficient vehicle safety interventions with reported effects around 50% for fatal single and rollover crashes. However, such estimates have used sample data, which have not controlled for the possibilities of self-selection, behavioral adaptation, increased access to the technology by less safe drivers, and the calculation of effects on very specific categories of crashes. Effects of ESC in the population can therefore be expected to be smaller than is currently believed. METHOD: National U.S. data for fatal crashes, driving exposure and other control factors, and market penetration of ESC over 1991-2021 were used to calculate whether the trends in fatalities over time in crash rates for singles, rollovers, and fatal crashes in general matched projections from estimates of effectiveness. RESULTS: It was found that downward trends in the relevant crash types were generally present before ESC was introduced, and that the trends thereafter were weaker. Although some trends were consistent with effects of ESC, they were markedly smaller than the projected ones, and could be explained by other factors such as the number of vehicles per capita. At best, the effect for rollovers could be up to two-thirds of previous estimates, no effect was detected for singles, while for all fatal crashes results depended upon the type of analysis performed. These results conflict with conclusions in all published ESC crash sample studies, which have compared vehicles with and without ESC. This discrepancy can be explained by methodological errors in the previous studies using induced exposure methods and self-selected samples. PRACTICAL APPLICATIONS: Traffic safety may not be as much improved by technological interventions as believed. Alternative approaches to traffic safety are needed, which do not rely on technology that interferes with driver behavior.
Assuntos
Acidentes de Trânsito , Tecnologia , Humanos , Estados UnidosRESUMO
To avoid potentially fatal wrong-route neuraxial drug errors, international standard ISO 80369-6 specifying a non-Luer neuraxial connector design was published in 2016. We describe usability studies used in development of the design. Thirty-eight doctors and 17 nurses performed simulated procedures on manikins, using devices fitted with Luer connectors or draft ISO 80369-6 'non-Luer' connectors. The procedures included spinal anaesthesia; intrathecal chemotherapy; lumbar puncture, cerebrospinal fluid collection and pressure measurement; epidural catheter placement with bolus injection and critical care use. Participants attempted cross connection between neuraxial connectors and a range of other medical device connectors, including those from the ISO 80369 small-bore connector series. Video recording analysis was used for all assessments. Participants subjectively assessed performance of the draft non-Luer connector, including suitability for routine clinical use. Participants performed 198 procedures. The connector achieved easy, leak-free connections. The willingness of participants to use the non-Luer connectors were: spinal anaesthesia 100%; intrathecal chemotherapy 88%; lumbar puncture, cerebrospinal fluid collection and pressure measurement 93%; epidural catheter placement with bolus injection 78%; critical care use 100%. Concerns raised were generally device related, rather than connector related. Most cross-connection attempts failed, even using above clinical forces and, when successful, were judged of low clinical risk potential; the exception was a malaligned connection between the non-Luer slip and female Luer connectors. This led to revision of the dimensional tolerances of the non-Luer connector to reduce this risk, before publication of the final specification in 2016. We conclude that the ISO 80369-6 neuraxial non-Luer connector is suitable for clinical use.
Assuntos
Raquianestesia/instrumentação , Erros de Medicação/prevenção & controle , Antineoplásicos/administração & dosagem , Competência Clínica , Desenho de Equipamento , Segurança de Equipamentos , Humanos , Injeções Epidurais/instrumentação , Injeções Espinhais/instrumentação , Manequins , Segurança do Paciente , Punção Espinal/instrumentaçãoRESUMO
INTRODUCTION: The significance of cervical proprioception for human balance has thus far not been sufficiently elucidated. The aim of this study was to provoke selective cervico-vestibular stimulation using the trunk excursion test (TET) we ourselves constructed. This chair is designed to enable evaluation of cervico-ocular reactions during isolated trunk excursion and possible effects of aging. METHODS: The previously used head excursion test (HET) was statistically compared to the TET. In both methods, 100 healthy subjects of two age groups (group(26): median age = 26 years, n = 50; group(50): median age = 50 years, n = 50) were randomized for comparison of similar neck-to-trunk-positions. RESULTS: HET enabled detection of significant nystagmus modulation in horizontal and vertical dimensions; whereas in pure cervical stimulation using the new TET, this was only evident in the horizontal dimension and only during trunk torsion. Comparison of the two methods confirmed significantly stronger nystagmus modulation through head excursion. In terms of the HET, group(50) showed significantly more vertical nystagmus activity than group(26). However, no significant difference was found between the groups in terms of their reactions to trunk excursion in the TET. In a group-specific comparison of the methods, group(26) showed a significant increase in horizontal nystagmus in head compared to trunk excursion, whereas group(50) generally displayed a significantly greater response to provocation by head excursion in HET. Analysis of the significant vertical nystagmus modulation produced with the TET method showed predominance of upbeat- (UBN) over downbeat-nystagmus (DBN). Through head excursion with the HET, DBN was more frequently evoked in group(50) than in group(26). No significant age-dependent difference could be derived in UBN. CONCLUSION: The results of the pilot study indicate that head-to-trunk provocation is a suitable means of evaluating cervicotonic provocation nystagmus. Only by evaluation of adequate excursion limits and consistent analysis of patients with cervical deficiency can the effects of the method be further assessed.
Assuntos
Vértebras Cervicais/inervação , Movimentos da Cabeça/fisiologia , Nistagmo Fisiológico/fisiologia , Postura/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Testes de Função Vestibular/instrumentação , Adulto , Eletronistagmografia/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Estimulação Física/instrumentação , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Offering rapid HIV testing improves rates of testing in adults, but little is known about whether offering adolescents a choice of testing methods increases rates of testing. The aims of the study were to determine rates of HIV testing in adolescents when different testing methods were offered and explore factors associated with agreement to be tested for HIV. Participants (n= 200, sexually experienced 13-22 year olds) were recruited from an urban adolescent clinic, completed a 99-item theory-based survey and were offered their choice of venipuncture, rapid fingerstick or rapid oral fluid HIV testing. Approximately half (49.5%) agreed to HIV testing. Male gender, parental completion of high school, intention to test for HIV if offered by clinician and higher perceived likelihood of current HIV infection were independently associated with agreement to test. Combining new strategies, such as opt-out testing, with routine testing may be needed to improve rates of adolescent HIV testing.
Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por HIV/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Sangue/imunologia , Sangue/virologia , Estudos Transversais , Feminino , Humanos , Masculino , Saliva/imunologia , Saliva/virologia , Inquéritos e Questionários , Adulto JovemRESUMO
Contemporary research indicates that brain development occurs during childhood and into early adulthood, particularly in certain regions. A critical question is whether premature or atypical hormone exposures impact brain development (e.g., structure) or function (e.g., neuropsychological functioning). The current study enrolled 40 girls (aged 6-8 years) diagnosed with premature adrenarche (PA) and a comparison group of 36 girls with on-time maturation. It was hypothesized that girls with PA would demonstrate lower IQ and performance on several neuropsychological tasks. The potential for a sexually dimorphic neuropsychological profile in PA was also explored. No significant univariate or multivariate group differences emerged for any neuropsychological instrument. However, effect size confidence intervals contained medium-sized group differences at the subscale level. On-time girls performed better on verbal, working memory, and visuospatial tasks. Girls with PA showed improved attention, but not a sexually dimorphic profile. These results, though preliminary, suggest that premature maturation may influence neuropsychological functioning.
Assuntos
Adrenarca , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Deficiências do Desenvolvimento/fisiopatologia , Testes Neuropsicológicos , Puberdade Precoce/complicações , Nível de Alerta , Criança , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Inteligência , Análise Multivariada , Aprendizagem VerbalRESUMO
BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) has been suspected of involvement in Crohn's disease (CD). We investigated this potential association by testing whole blood from CD patients and healthy controls for the presence of MAP by culture and molecular methods. In addition, each blood sample was analyzed for polymorphisms in the NOD2/CARD15 gene previously associated with CD. METHODS: Four 4-mL K(2)-EDTA tubes of whole blood were drawn from each subject (n = 260, 130 CD patients and 130 healthy controls). Two tubes of blood were cultured for MAP by the following methods: Mycobacterial Growth Indicator Tube, Herrold's Egg Yolk Agar, BACTEC 460, and Hungate. The remaining 2 tubes of blood were tested for MAP DNA and polymorphisms in the NOD2/CARD15 gene by polymerase chain reaction (PCR). RESULTS: One healthy control patient was positive for MAP via PCR; however, no viable MAP was cultured from this individual. All blood cultures were negative for MAP. One CD patient's blood was culture-positive for M. tuberculosis complex. CD patients exhibited a higher rate of polymorphism in the NOD2/CARD15 gene than healthy control patients. CONCLUSIONS: In this study MAP was not recovered from the blood of CD patients or healthy controls. However, CD patients showed higher mutation rates in the NOD2/CARD15 gene, compared with healthy controls, supporting the findings of other investigators. No correlation between these polymorphisms and MAP bacteremia in CD patients could be identified in this study.
Assuntos
Bacteriemia/complicações , Doença de Crohn/complicações , Doença de Crohn/microbiologia , Mycobacterium avium subsp. paratuberculosis/genética , Paratuberculose/complicações , Doença de Crohn/genética , DNA Bacteriano/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Proteína Adaptadora de Sinalização NOD2/genética , Reação em Cadeia da Polimerase/normas , Polimorfismo Genético , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: It is often implicitly or explicitly assumed in traffic accident research that drivers with accidents designated as non-culpable are a random sample from the population. However, this assumption is dependent upon differences in the criterion used for culpability. If drivers are erroneously categorized by assuming randomness, results could be grossly misleading. METHOD: The assumption of randomness leads to two predictions: first, no correlation should exist between culpable and non-culpable crashes; and second, the accident groups should differ on the variables known to be associated with accidents, such as amount of driving experience. These predictions were tested in two samples of bus drivers. RESULTS: It was found that in a sample with a harsh criterion (70% culpable accidents) for crash responsibility, the drivers with non-culpable accidents had the features expected, namely, they were more experienced for example, while in a sample with a lenient criterion (50 % culpable), this was not so. DISCUSSION: It was concluded that similar studies to the present one would need to be undertaken to establish exactly what percentage of drivers in a given population should be assigned culpable accidents, and construct a criterion that yields this ratio. Otherwise, the theoretical assumptions of randomness and non-responsibility will probably be violated to some degree. IMPACT ON INDUSTRY: Many estimates of risk of crash involvement may have been wrong. Given the potential for erroneous criteria, a number of studies may make invalid assumptions from their data.
Assuntos
Acidentes de Trânsito , Condução de Veículo , Comportamentos Relacionados com a Saúde , Veículos Automotores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Segurança , Suécia/epidemiologia , Reino Unido/epidemiologiaRESUMO
The presence of Mycobacterium avium subsp. paratuberculosis (MAP) in non-ruminant wildlife has raised questions regarding the role of these species in Johne's disease transmission. In this study we tested 472 tissues from 212 animals of six different species of scavenging mammals. All animals were taken from within a 210-square-mile area in Dane and Iowa counties of south central Wisconsin from September to May in 2003-04 and tested for the presence of MAP. We detected MAP-specific DNA in 81 of 212 (38%) scavenging mammals, in 98 of the 472 (21%) tissues; viable MAP was cultured from one coyote's ileum and lymph node tissue. Despite the low numbers of viable MAP isolated in this study, our data adds to the increasing evidence demonstrating the potential for transmission and infection of MAP in nonruminant species and provides possible evidence of interspecies transmission. The apparently high exposure of nonruminant wildlife provides potential evidence of a spill-over of MAP to wildlife species and raises the question of spillback to domestic and wild ruminants. These results demonstrate the importance of understanding the role of wildlife species in developing management strategies for Johne's disease in domestic livestock.
Assuntos
Animais Selvagens/microbiologia , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Paratuberculose/epidemiologia , Paratuberculose/transmissão , Animais , Animais Domésticos , DNA Bacteriano/isolamento & purificação , Feminino , Masculino , Fatores de Risco , Especificidade da Espécie , Wisconsin/epidemiologiaRESUMO
Research has been focused on the detection of Mycobacterium avium subspecies paratuberculosis (MAP) in pasteurized milk; however, pasteurized milk is a key ingredient in a variety of food products. Therefore, MAP contamination in milk-derived products must be investigated. We undertook a six-month study to investigate the presence of viable MAP and MAP genetic components in cheese curds purchased from retail outlets in the northern and southern regions of Wisconsin and Minnesota. A total of 98 retail cheese curd samples were tested for MAP by PCR prescreen, culture on Herrold's egg yolk agar slants with mycobactin J and amphoteracin B, naladixic acid, and vancomycin, and slant rinse PCR using IS900 and hspX primer sets. Although no viable MAP were able to be cultured, 5% of the samples were PCR positive with both the IS900 and hspX primer sets (MAP-specific DNA) when prescreened and 1% of the samples were PCR positive with both the IS900 and hspX primer sets when culture slants were rinsed and tested.
Assuntos
Queijo/microbiologia , Contaminação de Alimentos/análise , Mycobacterium avium subsp. paratuberculosis/genética , Reação em Cadeia da Polimerase/métodos , Animais , Bovinos , Contagem de Colônia Microbiana , Primers do DNA/genética , DNA Bacteriano/genética , Microbiologia de Alimentos , Minnesota , Mycobacterium avium subsp. paratuberculosis/crescimento & desenvolvimento , Mycobacterium avium subsp. paratuberculosis/isolamento & purificação , Esterilização , WisconsinRESUMO
Mycobacterium avium subspecies paratuberculosis (MAP) is the etiological agent of Johne's disease in ruminants. The hspX gene and insertion sequence IS900 can be used to diagnose Johne's with PCR. Generally, a single PCR tube containing the DNA sequence of interest is run as a positive control with each set of reactions. Single reactions within a PCR run can fail while the positive control does not. Thus, a single positive control tube does not determine if all PCR reactions worked properly. Our objective was to construct a plasmid to use as an internal control in each reaction. A plasmid containing an insert of M. bovis-hspX-M. bovis DNA was modified to remove a portion of the hspX insert used by the reverse hspX primer. The remaining insert was ligated back together and transformed into competent cells. Sequencing confirmed removal of 71 bp. PCR reactions using three primers (TB/M. bovis reverse, hspX forward and reverse) for hspX gene detection and four primers (IS900 forward and reverse, hspX forward, and TB/M. bovis reverse) for IS900 detection were optimized by titrating various amounts of plasmid against varied amounts of MAP genomic DNA. Plasmid insert amplification confirms a successful PCR reaction and identifies true positives and negatives within each individual reaction. The optimal plasmid amounts are 10 fg/reaction (hspX detection) and 1 fg/reaction (IS900 detection).
Assuntos
Mycobacterium avium subsp. paratuberculosis/genética , Plasmídeos/genética , Reação em Cadeia da Polimerase/métodos , Animais , Sequência de Bases , Bovinos , Dados de Sequência Molecular , Paratuberculose/diagnóstico , Paratuberculose/genética , Paratuberculose/microbiologia , Plasmídeos/metabolismoRESUMO
Objetivo: El propósito de este trabajo es informar sobre los efectos de los trabajos de construcción en las tasas de infección de herida en hernioplastia y artroplastia de cadera, la evolución de las tasas y las medidas de intervención para prevenir la ocurrencia de brotes de infección de herida operatoria, durante las obras en el Hopital de Coquimbo durante los años 2001-2002. Finalmente, se proponen recomendaciones sobre medidas de protección para pacientes en riesgo de infecciones cuando se realizan obras dentro de un hospital. Método: Estudio prospectivo, longitudinal, descriptivo y analítico, desarrollado entre enero de 2001 y marzo de 2003. Se midió el material particulado en suspensión dentro de los pabellones quirúrgicos, antes y durante los trabajos de remodelación. El indicador de resultado fue la tasa de infección trimestral de herida operatoria de hernia inguinal con malla y artroplastia de cadera con implante de prótesis. La medida de efecto se midió mediante riesgo relativo (RR). Resultados: La norma sobre el valor máximo de polvo para el funcionamiento de los pabellones es 180 mcg/m³ aire. Antes de los trabajos el valor fue de 60 mcg/m³. Durante los trabajos los valores subieron hasta 1.000 mcg/m³. Luego de instalar filtros HEPA el material particulado disminuyó bajo 100 mcg/m³. Hernioplastia: La tasa de infección antes de los trabajos fue 0,7 y 2,2 durante las obras (p= 0,22); el RR asociado a las obras fue de 3,1. La tasa de infección antes de aire ultra filtrado fue 1,5 y con el uso de aire filtrado en pabellones quirúrgicos fue de 1,8 (p= 0,56). El RR asociado a usar aire filtrado fue de 1,2. Artroplastia de cadera: La tasa de infección antes de los trabajos fue 0,7 y 2,7 durante las obras (p= 0,18), con RR asociado a las obras de 3,8. La tasa de infección antes de aire ultra filtrado fue 2,1 y con el uso de aire filtrado en pabellones quirúrgicos fue de 2,4 (p= 0,61). El RR asociado a usar aire filtrado fue de 1,1. La ausencia de diferencia estadística de los resultados se puede atribuir a tamaño de muestra. Conclusiones: El aumento del material particulado en suspensión y sedimentable se asocian a un aumento de la morbilidad infecciosa de la herida operatoria de hernioplastia inguinal y de artroplastia de cadera. El uso de aire filtrado redujo la polución de material particulado, sin embargo no resultó suficiente para reducir las tasas de infección.
Assuntos
Humanos , Microbiologia do Ar , Infecção Hospitalar , Arquitetura Hospitalar , Controle de Infecções , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Chile , Estudos Prospectivos , Fatores de RiscoRESUMO
Environmental variation in temperature can have dramatic effects on plant morphology, phenology, and fitness, and for this reason it is important to understand the evolutionary dynamics of phenotypic plasticity in response to temperature. We investigated constraints on the evolution of phenotypic plasticity in response to a temperature gradient in the model plant Arabidopsis thaliana by applying modern analytical tools to the classic data of Westerman & Lawrence (1970). We found significant evidence for two types of constraints. First, we detected numerous significant genetic correlations between plastic responses to temperature and the mean value of a trait across all environments, which differed qualitatively in pattern between the set of ecotypes and the set of mutant lines in the original sample. Secondly, we detected significant costs of flowering time plasticity in two of the three experimental environments, and a net pattern of selection against flowering time plasticity in the experiment overall. Thus, when explored with contemporary methods, the prescient work of Westerman & Lawrence (1970) provides new insights about evolutionary constraints on the evolution of plasticity.
Assuntos
Arabidopsis/fisiologia , Evolução Biológica , Flores/fisiologia , Fenótipo , Temperatura , Arabidopsis/genética , Seleção Genética , Estatística como Assunto , Fatores de TempoRESUMO
Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.
Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/psicologia , Adulto , Anemia Falciforme/mortalidade , Anemia Falciforme/psicologia , Transplante de Medula Óssea/mortalidade , Transplante de Medula Óssea/psicologia , Coleta de Dados , Tomada de Decisões , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Medição de Risco , Transplante Homólogo/mortalidade , Transplante Homólogo/psicologiaRESUMO
The maternal photoperiod at the time of seed maturation can predict the seasonal conditions of newly dispersed seeds. We investigated the effects of maternal photoperiod on seasonal dormancy in Arabidopsis thaliana using a set of F6 recombinant inbred lines derived from a cross between individuals from two natural populations (Cal-0 and Tac-0) differing in cold requirements for germination. We grew 40 Cal × Tac lines in a long-day photoperiod (8 h of full spectrum light plus 8 h of low-fluence incandescent light) and a short-day photoperiod (8 h full spectrum light). We then exposed seeds from each family and maternal photoperiod to either a cold stratification treatment (4°C, 21 d) or no cold stratification. Both maternal photoperiod and progeny stratification influenced the percentage of seeds that germinated and the speed of germination. The short-day photoperiod caused increased responsiveness to stratification, with higher germination percentages and speeds in stratified seeds. Stratification influenced the expression of maternal photoperiod effects, such that short days increased germination percentage and speed in stratified seeds but inhibited germination in unstratified seeds. Families differed significantly in their plasticity to maternal photoperiod and stratification, but genetic variation for plasticity to maternal photoperiod was expressed only in unstratified seeds. Because the expression of maternal photoperiod effects and genetic variation for photoperiod effects depended on progeny stratification, the evolution of these maternal effects will depend on the seasonal environment experienced by progeny.
RESUMO
Premature adrenarche is a condition characterized by precocious development of pubic and/or axillary hair, due to early onset of adrenal androgen secretion. Girls with premature adrenarche may later develop menstrual irregularities, hyperandrogenism, and the classic polycystic ovary syndrome. As leptin is thought to modulate the onset of pubertal development, we measured plasma leptin levels in 7 girls with premature adrenarche, and 8 age-matched comparison girls. Because leptin, the hypothalamic-pituitary-adrenal (HPA), the hypothalamic-pituitary-gonadal axes are functionally interrelated, we also determined salivary and plasma cortisol, dehydroepiandrosterone (DHEA), DHEA-sulfate, androstenedione, estradiol, and estrone. Finally, since IGF-I may play a role in adrenocortical function, we determined plasma levels of IGF-1, and IGF-BP1. Plasma was collected by an intravenous catheter at times 0, 20, and 40 min, starting at 1.30 p.m. Girls with premature adrenarche had a higher body mass index (BMI) and an over two-fold elevation of their plasma leptin than comparison girls. This group also had elevated levels of salivary and plasma cortisol, and increased levels of DHEA, DHEA-S, androstenedione, estradiol and estrone. Plasma IGF-1 and the ratio of IGF-1/IGF-BP1 were elevated. We propose that girls with premature adrenarche may represent an overlapping group characterized by both features of increased adiposity and HPA axis activity, which together, and depending on the genetic/constitutional background of the individual, may account for the development of adrenal hyperandrogenism, and, later, the polycystic ovary syndrome.
Assuntos
Glândulas Suprarrenais/metabolismo , Androgênios/metabolismo , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Proteínas de Transporte/sangue , Criança , Estudos Transversais , Desidroepiandrosterona/sangue , Estrogênios/sangue , Feminino , Glicodelina , Humanos , Hidrocortisona/sangue , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas da Gravidez/sangue , Maturidade SexualRESUMO
BACKGROUND: This study examined growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in a large sample of depressed children compared with normal control children. Within-subject comparisons were also performed in control subjects to examine test-retest reliability and in depressed children comparing episode versus clinical recovery. METHODS: The sample included depressed children (n = 82) and normal control children (n = 55) group-matched for age, gender, and pubertal status; the mean ages were 11.2 +/- 1.7 and 11.2 +/- 1.8 years, respectively. We gave GHRH (0.1 mcg/Kg) at 9 AM, and serum GH levels were determined every 15 min from -30 min through +90 min of the GHRH infusion. A subgroup of normal control subjects (n = 11) repeated the protocol for test-retest reliability within a 2-month interval. A subgroup of depressed children (n = 20) were restudied off all medications following full clinical remission from depression. RESULTS: The mean GH response to GHRH was significantly lower in the depressed group (8.7 ng/mL +/- SEM 0.9) compared with normal control children [12.2 ng/mL +/- SEM 1.3; t(135) = 2.59, p =.01 effect size 0.44]. The test-retest reliability of GH response to GHRH was stable (intraclass correlation =.93 for mean post-GH). The GH response to GHRH remained low in subjects restudied during clinical remission from depression. CONCLUSIONS: Depressed children show low GH response to GHRH. The measure appears to be reliable, and the low GH response continues following clinical remission. Further studies are needed to explore the mechanism and relative specificity of this finding.
Assuntos
Transtorno Depressivo/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/sangue , Criança , Transtorno Depressivo/psicologia , Feminino , Seguimentos , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Caracteres SexuaisRESUMO
Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.
Assuntos
Anemia Falciforme/tratamento farmacológico , Azacitidina/análogos & derivados , Azacitidina/uso terapêutico , Hemoglobina Fetal/biossíntese , Adolescente , Adulto , Anemia Falciforme/sangue , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Contagem de Células Sanguíneas , Estudos de Coortes , Decitabina , Contagem de Eritrócitos , Feminino , Hemoglobina Fetal/análise , Globinas/biossíntese , Humanos , Hidroxiureia/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neutrófilos , Contagem de Plaquetas , Reticulócitos/químicaRESUMO
BACKGROUND: Decreased growth hormone (GH) response to pharmacologic stimulation has been found in children and adolescents during an episode of major depressive disorder and after recovery. In this study, we sought to determine whether GH secretion is similarly altered in children and adolescents who had never experienced depression but were at high risk of developing depression. METHODS: Subjects were 8 through 16 years of age and selected for high- and low-risk status according to familial loading for mood disorders. Sixty-four high-risk and 55 low-risk healthy subjects participated in the study, which assessed the following GH measures: (1) GH before growth hormone-releasing hormone (GHRH) infusion, every 15 minutes for 30 minutes; (2) GH response after intravenous infusion of GHRH (0.1 microg/kg), every 15 minutes for 90 minutes; and (3) nocturnal GH every 20 minutes from 9 PM until morning awakening. RESULTS: After stimulation with GHRH, the high-risk subjects secreted significantly less GH compared with the low-risk healthy controls (effect sizes for mean and peak GH, 0.52 [P =.007] and 0.40 [P =.04], respectively). In contrast, there were no between-group differences in the pre-GHRH and nocturnal GH secretion levels. Exposure to recent stressors was not associated with GH secretion. CONCLUSIONS: Taken together with previous evidence of decreased GH after GHRH infusion in acutely depressed and recovered children, these results indicate that the decreased GH response found in high-risk subjects may represent a trait marker for depression in children and adolescents.
Assuntos
Transtorno Depressivo/diagnóstico , Hormônio Liberador de Hormônio do Crescimento , Hormônio do Crescimento Humano/sangue , Adolescente , Biomarcadores , Criança , Transtorno Depressivo/sangue , Transtorno Depressivo/epidemiologia , Família , Feminino , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/metabolismo , Humanos , Infusões Intravenosas , Acontecimentos que Mudam a Vida , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de Risco , Sono/fisiologiaRESUMO
The purposes of this study were to examine the level of improvement of cognitive function 12 months posttreatment in adult patients with Cushing syndrome (CS), the relationships of cognitive function to duration of CS or recovery of the hypothalamic pituitary adrenal (HPA) axis, and depression and improved cognitive functioning. Thirty-three patients with CS and a matched comparison group were enrolled. IQ, depression, and endocrine factors were measured during the active phase of CS and at 12 months posttreatment for CS. Results show no group differences in cognitive function across time but a trend for CS patients to have lower IQ scores at baseline. Individual differences in performance were striking. For some subscales of IQ there was a positive relationship with recovery of the HPA axis and a negative relationship with duration of CS as well as an improvement if depression had decreased. Limitations of the study are cited along with clinical implications and directions for future research.