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1.
Birth ; 50(1): 99-108, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36625522

RESUMO

BACKGROUND: Women with prenatal substance use have been identified as at-risk for the lack of engagement in perinatal services, such as medical care and home visitation programs. This issue is of particular concern in Florida (United States) where rates of fetal substance exposure have been steadily increasing. METHODS: To identify pathways of and barriers to perinatal system and service engagement, journey mapping was used to compile various personas of perinatal women with substance use. A structured guide was developed to elicit maternal personas, system and service touchpoints, and system strengths and weaknesses from focus group participants with statewide stakeholders, including perinatal service administrators and community coalition members within three Florida communities. Workshop transcripts, debriefing, and member-checking sessions were transcribed verbatim and analyzed manually. RESULTS: Six journey-mapping workshops and two member-checking meetings with mothers in-recovery were conducted with a total of 109 participants. Four personas were identified: women who (1) have substance use on a recreational basis, (2) have prescription drug use/misuse, (3) have chronic substance dependence, and (4) are in-recovery from substance dependence. Pathways that promote and barriers that prevent perinatal women with substance use from being identified, referred, or willing to accept and engage in medical care and social services were identified. CONCLUSIONS: While these personas shed light on differential pathways experienced by women with OUD, they were not intended as fixed-member groups but rather fluid descriptions of circumstances in which individuals could shift over time. These personas are beneficial to understand differences in circumstances, as well as variations in pathways and barriers to service engagement. Additionally, personas may be used to identify approaches to optimize service engagement by perinatal women with substance use and to support system improvements and integrations.


Assuntos
Poder Familiar , Transtornos Relacionados ao Uso de Substâncias , Gravidez , Feminino , Humanos , Parto , Mães , Grupos Focais
2.
Public Health Nutr ; 26(1): 12-22, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36345562

RESUMO

OBJECTIVE: The COVID-19 pandemic changed early care and education (ECE) mealtimes. Feeding practices that support children's emerging autonomy may support children's healthy eating, but it is unknown whether and how COVID-19 changed feeding practices. This paper describes caregiver feeding practices in ECE centres in Florida during COVID-19. DESIGN: A mixed-methods design was used to understand mealtime feeding practices. Survey and interview questions were developed based on the Trust Model. More than 7000 surveys were sent to ECE centres. Analysis included descriptive statistics for survey data and thematic analysis for interview data. SETTING: This statewide study included teachers in all licensed and license-exempt ECE centres. PARTICIPANTS: Four hundred and thirty-one teachers completed a survey, and twenty-nine participated in follow-up interviews. RESULTS: Surveys showed most teachers engaged in autonomy-supportive behaviours, such as letting children eat until they were finished (90 %). The most common controlling behaviour was praising children for cleaning their plates (70 %). The most common responses about changes to mealtimes were keeping physical distance and serving healthy food. Interview themes were Autonomy Support, Controlling Feeding Practices, Interactions are the Same, Interactions are Different, Physical Distancing and Healthy Eating. CONCLUSIONS: Mealtimes are a central part of the day for young children and teachers in ECE environments. COVID-19 continues to influence ECE routines as behaviour change remains the primary method of reducing the risk of COVID-19 in the absence of a vaccine for young children. Understanding teachers' practices and perspectives is important for reducing the risk of COVID-19 and supporting children's autonomy and healthy eating.


Assuntos
COVID-19 , Cuidadores , Criança , Humanos , Pré-Escolar , Pandemias , COVID-19/epidemiologia , Comportamento Alimentar , Dieta Saudável
3.
Health Promot Pract ; 24(5): 944-949, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35574594

RESUMO

BACKGROUND: New federal health guidance was issued for early childhood education (ECE) programs to reduce the risk of COVID-19 in March 2020. The Centers for Disease Control and Prevention recommended mask-wearing for adults and children aged 2 years and older. Wearing masks was a new practice for teachers and children, and this study investigated when and how masks were worn in ECE centers in Florida. METHODS: This study was part of a larger assessment of the impact of COVID-19 on mealtime routines in ECE centers. Two statewide surveys based on the Trust Model were sent to directors and teachers via Florida Department of Children and Families. Only teachers were interviewed. Data were collected from August to October 2020. The analysis included survey results and interview responses related to mask-wearing. RESULTS: Surveys were completed by 759 directors and 431 teachers, and 29 teachers were interviewed. Survey results indicated that more teachers than children wore masks during pre- and postmeal activities. Interviews revealed three models that explain mask-wearing: (1) teachers only, in which teachers were required to wear a mask, but children were not; (2) teachers and children, in which teachers and children were required to wear a mask; and (3) masks optional, in which teachers and children could choose to wear a mask. CONCLUSION: Understanding how decisions about mask-wearing were made at the center level can inform training and support health and safety in ECE. Use of personal protective equipment (such as masks) is effective for reducing risk of pathogen transmission for children and adults in ECE settings.


Assuntos
COVID-19 , Adulto , Criança , Humanos , Pré-Escolar , COVID-19/prevenção & controle , Máscaras , Florida , Inquéritos e Questionários , Refeições
4.
FEMS Microbiol Ecol ; 98(10)2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36007932

RESUMO

The human gut microbiota protects the host from invading pathogens and the overgrowth of indigenous opportunistic species via a process called colonization resistance. Here, we investigated the antagonistic activity of human gut bacteria towards Candida albicans, an opportunistic fungal pathogen that can cause severe infections in susceptible individuals. Coculture batch incubations of C. albicans in the presence of faecal microbiota from six healthy individuals revealed varying levels of inhibitory activity against C. albicans. 16S rRNA gene amplicon profiling of these faecal coculture bacterial communities showed that the Bifidobacteriaceae family, and Bifidobacterium adolescentis in particular, were most correlated with antagonistic activity against C. albicans. Follow-up mechanistic studies performed under anaerobic conditions confirmed that culture supernatants of Bifidobacterium species, particularly B. adolescentis, inhibited C. albicans in vitro. Fermentation acids (FA), including acetate and lactate, present in the bifidobacterial supernatants were important contributors to inhibitory activity. However, increasing the pH of both bacterial supernatants and mixtures of FA reduced their anti-Candida effects, indicating a combinatorial effect of prevailing pH and FA. This work, therefore, demonstrates potential mechanisms underpinning gut microbiome-mediated colonization resistance against C. albicans, and identifies particularly inhibitory components such as bifidobacteria and FA as targets for further study.


Assuntos
Candida albicans , Microbioma Gastrointestinal , Bactérias , Bifidobacterium , Humanos , Lactatos/farmacologia , RNA Ribossômico 16S/genética
5.
Ecol Food Nutr ; 61(5): 559-575, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35575781

RESUMO

Most young children in the United States attend early care and education (ECE) programs, in which they eat 3-4 times daily. 'Division of responsibility' between adult and child means the adults are responsible for what, when and where, and the child is responsible for whether, what and how much to eat. A balanced division of responsibility can support children's development of healthy eating competency. This paper aims to describe division of responsibility during mealtimes during COVID-19 in Florida using a cross-sectional, mixed methods design. Questions were developed based on Trust Model and Social Cognitive Theory. A survey was completed by 759 ECE directors and 431 teachers, and 29 teachers completed in-depth interviews. COVID-19 increased teacher mealtime responsibilities. Most (95%+) ECE teachers provided meals at the same time and place daily (when and where). Children determined what and how much they ate, but did not serve or handle food. Implications include modifying mealtime routines to minimize the risk of COVID-19 and support healthy eating with a balanced division of responsibility.


Assuntos
COVID-19 , Adulto , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Dieta Saudável , Comportamento Alimentar/psicologia , Florida/epidemiologia , Humanos , Refeições/psicologia , Estados Unidos/epidemiologia
6.
Child Care Health Dev ; 48(6): 990-1000, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35102591

RESUMO

BACKGROUND: Most young children in the United States attend early care and education (ECE) programmes, where they consume the majority of daily calories. Best practices to support children's healthy eating include teachers sitting together with children, eating the same food, and appropriately supporting children in serving and feeding themselves. To understand how the COVID-19 pandemic changed mealtime practices in ECE, this study (1) describes what adaptations ECE directors and teachers made to mealtimes to include best practices, and (2) identifies common adaptations made to comply with COVID-19 infection control guidelines. METHODS: This cross-sectional, mixed-methods study utilized survey and interview questions based on the trust model and social cognitive theory. More than 7000 surveys were distributed to ECE directors and teachers in Florida. Surveys were completed by 759 directors and 431 teachers. Also, 29 follow-up interviews with teachers were completed. Participants were asked to describe their mealtimes before and during COVID-19. Descriptive statistics and frequencies were used to analyse survey data, and thematic analysis was applied to interview data. RESULTS: Less than 5% of survey respondents reported children serving themselves, a pre-COVID best practice. Interviews identified three common adaptations: (1) modification-best practices were incorporated into new routines, such as eating together but sitting farther away, (2) elimination-routines changed so that best practices were no longer possible, such as teachers wearing masks and standing during meals, and (3) minimal change-minimal changes due to COVID-19 occurred and consequently mealtime practices did not change. CONCLUSIONS: Current recommendations do not allow children to self-serve, which previously was a key best practice. ECE centres that have successfully integrated COVID-19 modifications and maintained mealtime best practices-perhaps in a new form-can serve as examples for others. These findings are generalizable to ECE centres in Florida and could be compared with other states.


Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Comportamento Alimentar/psicologia , Humanos , Controle de Infecções , Refeições/psicologia , Pandemias/prevenção & controle , Estados Unidos/epidemiologia
7.
Child Abuse Negl ; 104: 104476, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251877

RESUMO

BACKGROUND: Child maltreatment, removal from the home and foster care placement are all associated with poor physical and developmental outcomes for children. Early Childhood Court (ECC) is a specialized, trauma-informed, team-based approach designed to meet the unique needs of young children and their families in the dependency court system. OBJECTIVE: The objective of the study was to evaluate the ECC program in 20 Florida circuits. PARTICIPANTS AND SETTING: Participants in the evaluation were 53 ECC professionals (e.g., judges, attorneys, mental health providers, caseworkers, etc.) and 9 parents and caregivers. Focus groups were conducted in person, and interviews were conducted either in person or on the phone. METHODS: Interviews and focus groups were transcribed verbatim and analyzed with a hybrid deductive/inductive process using MAX QDA. Two coders (trained doctoral student researchers) established inter-coder reliability with a Kappa greater than 0.80 and used an iterative process to discuss, refine, and describe each theme throughout the analysis. RESULTS: Participants described who is involved in ECC and most discussions focused on professional versus parent/caregiver team members. Participants also described how ECC is different from traditional dependency court and several themes, such as Child and Family Friendly, Judicial Leadership, and a Team-Based Approach, aligned with the national model. Emergent themes were Relationships and Success. CONCLUSIONS: Future research could explore the selection of parents into ECC.


Assuntos
Direito Penal , Cuidados no Lar de Adoção , Criança , Maus-Tratos Infantis , Pré-Escolar , Feminino , Florida , Grupos Focais , Cuidados no Lar de Adoção/legislação & jurisprudência , Humanos , Lactente , Entrevistas como Assunto , Masculino , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Reprodutibilidade dos Testes , Participação dos Interessados
8.
FEBS Lett ; 592(20): 3399-3413, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30194685

RESUMO

Glutamate racemases (GR) catalyze the racemization of d- and l-glutamate and are targets for the development of antibiotics. We demonstrate that GR from the periodontal pathogen Fusobacterium nucleatum (FnGR) catalyzes the racemization of d-homocysteic acid (d-HCA), while l-HCA is a poor substrate. This enantioselectivity arises because l-HCA perturbs FnGR's monomer-dimer equilibrium toward inactive monomer. The inhibitory effect of l-HCA may be overcome by increasing the total FnGR concentration or by adding glutamate, but not by blocking access to the active site through site-directed mutagenesis, suggesting that l-HCA binds at an allosteric site. This phenomenon is also exhibited by GR from Bacillus subtilis, suggesting that enantiospecific, "substrate"-induced dissociation of oligomers to form inactive monomers may furnish a new inhibition strategy.


Assuntos
Isomerases de Aminoácido/química , Proteínas de Bactérias/química , Homocisteína/análogos & derivados , Estrutura Quaternária de Proteína , Sítio Alostérico , Isomerases de Aminoácido/metabolismo , Bacillus subtilis/enzimologia , Proteínas de Bactérias/metabolismo , Biocatálise , Domínio Catalítico , Fusobacterium nucleatum/enzimologia , Homocisteína/química , Homocisteína/metabolismo , Cinética , Estereoisomerismo , Especificidade por Substrato
9.
Nat Microbiol ; 2: 16238, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27941860

RESUMO

As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We report that the exposure of ß-glucan, a key pathogen-associated molecular pattern (PAMP) located at the cell surface of C. albicans and other pathogenic Candida species, is modulated in response to changes in the carbon source. Exposure to lactate induces ß-glucan masking in C. albicans via a signalling pathway that has recruited an evolutionarily conserved receptor (Gpr1) and transcriptional factor (Crz1) from other well-characterized pathways. In response to lactate, these regulators control the expression of cell-wall-related genes that contribute to ß-glucan masking. This represents the first description of active PAMP masking by a Candida species, a process that reduces the visibility of the fungus to the immune system.


Assuntos
Candida albicans/imunologia , Candida albicans/metabolismo , Evasão da Resposta Imune , Ácido Láctico/metabolismo , Proteínas de Membrana/metabolismo , beta-Glucanas/metabolismo , Glicosilação
10.
PLoS One ; 11(6): e0158683, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27362522

RESUMO

Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits-metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease.


Assuntos
Candidíase/microbiologia , Cobre/metabolismo , Cobre/intoxicação , Rim/metabolismo , Fígado/metabolismo , Baço/metabolismo , Animais , Candida albicans/genética , Modelos Animais de Doenças , Progressão da Doença , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Homeostase , Espectrometria de Massas , Camundongos , Estresse Oxidativo , Virulência
11.
PLoS Pathog ; 12(4): e1005566, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27073846

RESUMO

Efficient carbon assimilation is critical for microbial growth and pathogenesis. The environmental yeast Saccharomyces cerevisiae is "Crabtree positive", displaying a rapid metabolic switch from the assimilation of alternative carbon sources to sugars. Following exposure to sugars, this switch is mediated by the transcriptional repression of genes (carbon catabolite repression) and the turnover (catabolite inactivation) of enzymes involved in the assimilation of alternative carbon sources. The pathogenic yeast Candida albicans is Crabtree negative. It has retained carbon catabolite repression mechanisms, but has undergone posttranscriptional rewiring such that gluconeogenic and glyoxylate cycle enzymes are not subject to ubiquitin-mediated catabolite inactivation. Consequently, when glucose becomes available, C. albicans can continue to assimilate alternative carbon sources alongside the glucose. We show that this metabolic flexibility promotes host colonization and virulence. The glyoxylate cycle enzyme isocitrate lyase (CaIcl1) was rendered sensitive to ubiquitin-mediated catabolite inactivation in C. albicans by addition of a ubiquitination site. This mutation, which inhibits lactate assimilation in the presence of glucose, reduces the ability of C. albicans cells to withstand macrophage killing, colonize the gastrointestinal tract and cause systemic infections in mice. Interestingly, most S. cerevisiae clinical isolates we examined (67%) have acquired the ability to assimilate lactate in the presence of glucose (i.e. they have become Crabtree negative). These S. cerevisiae strains are more resistant to macrophage killing than Crabtree positive clinical isolates. Moreover, Crabtree negative S. cerevisiae mutants that lack Gid8, a key component of the Glucose-Induced Degradation complex, are more resistant to macrophage killing and display increased virulence in immunocompromised mice. Thus, while Crabtree positivity might impart a fitness advantage for yeasts in environmental niches, the more flexible carbon assimilation strategies offered by Crabtree negativity enhance the ability of yeasts to colonize and infect the mammalian host.


Assuntos
Candida albicans/metabolismo , Candida albicans/patogenicidade , Candidíase/metabolismo , Macrófagos/microbiologia , Saccharomyces cerevisiae/metabolismo , Virulência/fisiologia , Animais , Western Blotting , Metabolismo dos Carboidratos , Linhagem Celular , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Ubiquitinação
12.
Public Health Nurs ; 27(1): 3-16, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20055963

RESUMO

OBJECTIVE: To identify the overlapping and unique health and safety needs and concerns identified by early care and education (ECE) directors, health records, and observed compliance with national health and safety (NHS) standards. DESIGN AND SAMPLE: Cross-sectional study. 127 ECE programs from 5 California counties participated in the study, including 118 directors and 2,498 children's health records. MEASURES: Qualitative data were collected using standardized ECE directors' interviews to identify their health and safety concerns; and objective, quantitative data were collected using child health record reviews to assess regular health care, immunizations, health insurance, special health care needs, and screening tests and an observation Checklist of 66 key NHS standards collected by research assistants. RESULTS: The overlapping health and safety needs and concerns identified by the directors and through observations were hygiene and handwashing, sanitation and disinfection, supervision, and the safety of indoor and outdoor equipment. Some of the health and safety needs identified by only one assessment method were health and safety staff training, medical plans for children with special health care needs and follow-up on positive screening tests. CONCLUSIONS: Comprehensive, multimethod assessments are useful to identify health and safety needs and develop public health nursing interventions for ECE programs.


Assuntos
Creches/organização & administração , Proteção da Criança , Necessidades e Demandas de Serviços de Saúde/organização & administração , Gestão da Segurança/organização & administração , Pessoal Administrativo/psicologia , Atitude Frente a Saúde , California , Proteção da Criança/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Segurança de Equipamentos , Guias como Assunto , Registros de Saúde Pessoal , Humanos , Lactente , Controle de Infecções , Pesquisa Metodológica em Enfermagem , Enfermagem em Saúde Pública , Pesquisa Qualitativa , Inquéritos e Questionários
13.
Acad Pediatr ; 9(5): 366-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19640823

RESUMO

OBJECTIVE: To evaluate the effects of county-level child care health consultation intervention programs on child care centers' health and safety policies and practices. METHODS: A 3-year experimental study was conducted in 5 California counties and 111 licensed child care centers (73 intervention, 38 comparison) participated at the baseline and postintervention times. Trained research assistants conducted objective observations with a Policies Checklist and Health and Safety Checklist, which were composed of key national health and safety standards. RESULTS: At baseline, both groups were not significantly different on the Policies Checklist and the Health and Safety Checklist. At the post-intervention time, intervention centers had significantly more and higher-quality written health and safety policies on 9 of the 10 policies rated (medication administration, care of mildly ill children, exclusion of ill children, cleaning and sanitizing, handwashing, daily health checks, inclusion of children with special needs, emergency preparedness, staff health) than comparison centers. At the postintervention time, intervention centers improved their health and safety practices in the areas of emergency preparedness and handwashing, controlling for consultation model, time in study, and director turnover. Both groups improved their indoor and outdoor facilities and overall Health and Safety Checklist means. CONCLUSIONS: Child care health consultation programs can improve the written health and safety policies and may improve practices in child care centers.


Assuntos
Creches/organização & administração , Serviços de Saúde da Criança , Educação em Saúde , Política Organizacional , Encaminhamento e Consulta , Segurança , Adulto , Criança , Pré-Escolar , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Avaliação de Programas e Projetos de Saúde
14.
J Pediatr Health Care ; 22(6): 368-77, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18971083

RESUMO

INTRODUCTION: To assess health and safety in early care and education (ECE) programs, an objective, standardized instrument was developed based on the recommended national health and safety standards. METHOD: The California Childcare Health Program Health and Safety Checklist was developed by conducting a literature review, identifying a gold standard, revising and updating the original Checklist, consulting with an advisory group, and pilot testing the Checklist. The Checklist included 66 items grouped into 10 subscales, and each item was rated on a three-point scale: meeting, partially meeting, or not meeting national standards. Face, content, and construct validity along with measures of reliability, inter-rater reliability, and internal consistency were established. RESULTS: The Checklist was completed in 127 ECE centers. The highest subscale score was for emergency preparedness and the lowest was for handwashing routines and equipment maintenance. Cronbach's alpha subscale scores ranged from moderate to strong (0.27 to 0.70). DISCUSSION: The Checklist provides valid and reliable information to assess adherence to key national health and safety standards and objective data to develop intervention programs to improve health and safety in ECE programs.


Assuntos
Cuidado da Criança , Educação , Segurança , Criança , Pré-Escolar , Humanos
15.
Public Health Nurs ; 25(2): 126-39, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18294181

RESUMO

OBJECTIVE: To summarize findings from a descriptive evaluation study of 20 county-level child care health consultation programs, services provided, and factors that facilitated the development of the programs. DESIGN: A 3-year intervention study of 20 county-level child care health consultation programs, selected through a competitive review process, was conducted in California. SAMPLE: Study participants were the child care health consultation program staff, lead agency administrators and health consultants, and early care and education (ECE) staff, including health advocates and directors. MEASUREMENT AND INTERVENTION: Data collection included focus groups, interviews, consultant activity logs, and surveys. Health consultation intervention services included health and safety assessments, on-site consultation, and workshops for ECE providers and parents. RESULTS: 4 child care health consultation models were established based on the type of administrative agency. Health consultants and advocates primarily provided on-site consultation and education and training on child health promotion issues. Consultation programs were facilitated by the linkages formed among agencies, community characteristics, personal relationships, lead agency support, and consultant training and knowledge. CONCLUSIONS: Child care health consultation programs can address the health and safety needs for ECE programs, but they need administrative support, trained staff, and sustainable relationships with local ECE programs.


Assuntos
Atitude do Pessoal de Saúde , Cuidado da Criança , Serviços de Saúde da Criança/organização & administração , Educação em Saúde/organização & administração , Encaminhamento e Consulta/organização & administração , California , Criança , Feminino , Grupos Focais , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Modelos Organizacionais , Pesquisa em Avaliação de Enfermagem , Pesquisa Metodológica em Enfermagem , Enfermagem Pediátrica/educação , Enfermagem Pediátrica/organização & administração , Avaliação de Programas e Projetos de Saúde , Enfermagem em Saúde Pública/educação , Enfermagem em Saúde Pública/organização & administração , Pesquisa Qualitativa , Inquéritos e Questionários
16.
J Clin Endocrinol Metab ; 87(1): 57-62, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11788623

RESUMO

Cushing's syndrome invariably presents with a classical phenotype comprising central adiposity, prominence of dorsal, supraclavicular and temporal fat pads, bruising, abdominal striae, proximal myopathy, and hypertension. We report the case of a 20-yr-old student with pituitary-dependent Cushing's syndrome who was spared this classical phenotype because of a defect in the peripheral conversion of cortisone to cortisol. She presented to her general practitioner with secondary amenorrhea. Clinical examination revealed normal fat distribution (body mass index, 20.9 kg/m(2)), absence of hirsutism, myopathy, or bruising; her blood pressure ranged from 115/70 to 122/82 mm Hg. She was investigated for biochemical hypercortisolemia because of a mildly elevated random circulating cortisol (serum cortisol, 661 nmol/liter). Cushing's syndrome was confirmed on the basis of repeatedly elevated urinary free cortisols (831-1049; reference range, <350 nmol/24 h), failure of low-dose dexamethasone suppression (611 nmol/liter) and loss of circadian cortisol secretion. Investigations suggested Cushing's disease; there was suppression after high-dose dexamethasone (<20 nmol/liter) and a 950% increase in ACTH after stimulation with CRH. Pituitary magnetic resonance imaging revealed a 3-mm adenoma within the pituitary gland. Urinary corticosteroid metabolites were analyzed by gas chromatography-mass spectrometry and demonstrated a decreased THF+allo-THF/THE ratio of 0.66 (mean +/- SE in Cushing's disease, 1.74 +/- 0.24) suggesting a defect in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), an enzyme that converts the inactive glucocorticoid cortisone to active cortisol. Transphenoidal microadenomectomy was performed, and histology confirmed the diagnosis of a corticotroph adenoma. Postoperatively, serum cortisol was undetectable and replacement therapy was commenced. Subsequent investigations revealed a significantly impaired ability to convert an oral dose of cortisone acetate (25 mg) to cortisol, reduced serum cortisol to cortisone ratios, and a reduced serum half-life for cortisol (57.3 min). These results provide strong evidence for a partial defect in 11beta-HSD1 activity and concomitant increase in cortisol clearance rate. We have described a case of Cushing's disease that failed to present with a classical phenotype, and we postulate that this is due to a partial defect of 11beta-HSD1 activity, the defect in cortisone to cortisol conversion increasing cortisol clearance and thus protecting the patient from the effects of cortisol excess. This observation may help to explain individual susceptibility to the adverse effects of glucocorticoids.


Assuntos
Síndrome de Cushing/genética , Hidroxiesteroide Desidrogenases/deficiência , 11-beta-Hidroxiesteroide Desidrogenases , Adulto , Cortisona/sangue , Cortisona/metabolismo , Síndrome de Cushing/metabolismo , Síndrome de Cushing/patologia , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Fenótipo
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