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OBJECTIVE: To determine the optimal total serum bile acid (TSBA) threshold and sampling time for accurate intrahepatic cholestasis of pregnancy (ICP) diagnosis. DESIGN: Case-control, retrospective cohort studies. SETTING: Antenatal clinics, clinical research facilities. POPULATION: Women with ICP or uncomplicated pregnancies. METHODS: Serial TSBA measurements were performed pre-/postprandially in 42 women with ICP or uncomplicated pregnancy. Third-trimester non-fasting TSBA reference ranges were calculated from 561 women of black, south Asian and white ethnicity. Rates of adverse perinatal outcomes for women with ICP but peak non-fasting TSBA below the upper reference range limit were compared with those in healthy populations. MAIN OUTCOME MEASURES: Sensitivity and specificity of common TSBA thresholds for ICP diagnosis, using fasting and postprandial TSBA. Calculation of normal reference ranges of non-fasting TSBA. RESULTS: Concentrations of TSBA increased markedly postprandially in all groups, with overlap between healthy pregnancy and mild ICP (TSBA <40 µmol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA ≥40 µmol/l to define severe ICP, fasting measurements identified 9% (1/11), whereas non-fasting measurements detected over 91% with severe ICP. The highest upper limit of the non-fasting TSBA reference range was 18.3 µmol/l (95% confidence interval: 15.0-35.6 µmol/l). A re-evaluation of published ICP meta-analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA <19 µmol/l. CONCLUSIONS: Postprandial TSBA levels are required to identify high-risk ICP pregnancies (TSBA ≥40 µmol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non-fasting threshold of ≥19 µmol/l would improve diagnostic accuracy. TWEETABLE ABSTRACT: Non-fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.
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Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática/diagnóstico , Complicações na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Colestase Intra-Hepática/sangue , Estudos de Coortes , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Marfan syndrome (MFS) due to mutations in FBN1 is a known cause of thoracic aortic aneurysms and acute aortic dissections (TAAD) associated with pleiotropic manifestations. Genetic predisposition to TAAD can also be inherited in families in the absence of syndromic features, termed familial TAAD (FTAAD), and several causative genes have been identified to date. FBN1 mutations can also be identified in FTAAD families, but the frequency of these mutations has not been established. We performed exome sequencing of 183 FTAAD families and identified pathogenic FBN1 variants in five (2.7%) of these families. We also identified eight additional FBN1 rare variants that could not be unequivocally classified as disease-causing in six families. FBN1 sequencing should be considered in individuals with FTAAD even without significant systemic features of MFS.
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Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Fibrilina-1/genética , Predisposição Genética para Doença/genética , Mutação , Adulto , Idoso , Dissecção Aórtica/patologia , Aneurisma da Aorta Torácica/patologia , Exoma/genética , Saúde da Família , Feminino , Humanos , Masculino , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Pessoa de Meia-Idade , Linhagem , Análise de Sequência de DNA/métodosRESUMO
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
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Doença de Addison/genética , Antígeno CTLA-4/genética , Adulto , Feminino , Estudos de Associação Genética , Determinismo Genético , Predisposição Genética para Doença , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We describe an inertial rotation sensor with a 30-cm cylindrical proof-mass suspended from a pair of 14 µm thick BeCu flexures. The angle between the proof-mass and support structure is measured with a pair of homodyne interferometers, which achieve a noise level of â¼5prad/Hz. The sensor is entirely made of vacuum compatible materials, and the center of mass can be adjusted remotely.
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Control noise is a limiting factor in the low-frequency performance of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we model the effects of using new sensors called Homodyne Quadrature Interferometers (HoQIs) to control the suspension resonances. We show that if we were to use HoQIs, instead of the standard shadow sensors, we could suppress resonance peaks up to tenfold more while simultaneously reducing the noise injected by the damping system. Through a cascade of effects, this will reduce the resonant cross-coupling of the suspensions, allow for improved stability for feed-forward control, and result in improved sensitivity of the detectors in the 10-20 Hz band. This analysis shows that improved local sensors, such as HoQIs, should be used in current and future detectors to improve low-frequency performance.
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BACKGROUND: Skin disorders are common in children in Ethiopia, and it is estimated that 92,000 Ethiopian children are infected with human immunodeficiency virus (HIV). HIV infection increases the prevalence of cutaneous disease, but the effect of antiretroviral therapy (ART) on the pattern of skin disease affecting children in sub-Saharan Africa (SSA) is unclear. AIM: To assess the prevalence and nature of skin disorders in HIV-infected children living in a dedicated orphanage in Addis Ababa, Ethiopia. METHODS: Two dermatologists performed a clinical examination, including the skin, hair, nails and oral cavity of all the residents of an orphanage in Addis Ababa. The examiners knew that all the children were infected with HIV, but did not know their treatment or immune status. Diagnoses were made clinically and recorded anonymously, and treatment recommendations were made. Details of the children's treatment and CD4 lymphocyte counts were obtained after the examination had been completed. RESULTS: In total, 84 children [53 male (63%); 31 female (37%); median age 10 years] were examined. Of the 84 children, 57 (68%) were on ART, with 51 (61%) of these on cotrimoxazole prophylaxis. The median CD4 percentage was 27.1%. There were 66 children (79%) with at least one skin disorder; 21 of these had two disorders and 6 had three disorders. The commonest diagnosis was tinea capitis, affecting 39% of children. The other common diagnoses were: molluscum contagiosum (MC) (21%), verruca vulgaris (13%), plane warts (8%) and seborrhoeic dermatitis (7%). There was no significant difference in the prevalence of skin disease between children receiving ART and those who were not. Children with MC had significantly lower recent CD4 counts than children who did not have skin disease. CONCLUSIONS: Skin disorders in this population were very common, and the disorders identified were those that commonly affect children without HIV in Ethiopia. However, MC and plane warts appeared to have a higher frequency than would be expected in uninfected children.
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Crianças Órfãs , Infecções por HIV/complicações , Dermatopatias/epidemiologia , Adolescente , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos de Coortes , Etiópia/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Lactente , Masculino , Prevalência , Dermatopatias/imunologiaRESUMO
Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct efforts to identify the gene. The chromosome location of the NF1 gene has been previously mapped genetically to 17q11.2, and data from two NF1 patients with balanced translocations in this region have further narrowed the candidate interval. The use of chromosome jumping and yeast artificial chromosome technology has now led to the identification of a large (approximately 13 kilobases) ubiquitously expressed transcript (denoted NF1LT) from this region that is definitely interrupted by one and most likely by both translocations. Previously identified candidate genes, which failed to show abnormalities in NF1 patients, are apparently located within introns of NF1LT, on the antisense strand. A new mutation patient with NF1 has been identified with a de novo 0.5-kilobase insertion in the NF1LT gene. These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.
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Neurofibromatose 1/genética , RNA Neoplásico/genética , Translocação Genética , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , Linhagem Celular , Clonagem Molecular , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Células Híbridas , Masculino , Camundongos , Dados de Sequência Molecular , Mutação , Biossíntese de Proteínas , Transcrição Gênica , Células Tumorais CultivadasRESUMO
BACKGROUND: Defects of the mitochondrial genome are recognised as common causes of genetic disease. Sequencing of large portions or even the entire mitochondrial genome is routine in many laboratories for the investigation of mitochondrial disease. However, establishing whether a detected sequence change is polymorphic or pathogenic is still a major difficulty because of its highly polymorphic nature. This has major implications for the patient and the family. OBJECTIVE: To describe a scoring system for determining the likelihood that a given sequence variant in one of the seven mitochondrially encoded complex I (MTND) genes is truly pathogenic. RESULTS: The scoring system was applied to 50 reported MTND mutations. Using this system, 21 of the mutations analysed fell into the group of neutral sequence variants, 10 were classified as possibly pathogenic, three as probably pathogenic, and 16 as almost certainly pathogenic. CONCLUSIONS: The proposed scoring system should advance the interpretation of sequence variants and ensure that candidate pathogenic mutations are rigorously investigated.
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DNA Mitocondrial/genética , Complexo I de Transporte de Elétrons/genética , Mutação/genética , Polimorfismo Genético , Humanos , NADH Desidrogenase/genética , VirulênciaRESUMO
BACKGROUND: Cutis laxa is an acquired or inherited condition characterized by redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been described as a benign disease with minor systemic involvement. OBJECTIVE: To report a family with autosomal dominant cutis laxa and a young girl with sporadic cutis laxa, both with variable expression of an aortic aneurysmal phenotype ranging from mild dilatation to severe aneurysm or aortic rupture. METHODS AND RESULTS: Histological evaluation of aortic aneurysmal specimens indicated classical hallmarks of medial degeneration, paucity of elastic fibres, and an absence of inflammatory or atherosclerotic lesions. Electron microscopy showed extracellular elastin deposits lacking microfibrillar elements. Direct sequencing of genomic amplimers detected defects in exon 30 of the elastin gene in affected individuals, but did not in 121 normal controls. The expression of mutant elastin mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant tropoelastins, including C-terminally truncated and extended forms as well as for molecules lacking the constitutive exon 30. CONCLUSIONS: ELN mutations may cause severe aortic disease in patients with cutis laxa. Thus regular cardiac monitoring is necessary in this disease to avert fatal aortic rupture.
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Aneurisma Aórtico/genética , Cútis Laxa/genética , Elastina/genética , Mutação , Adulto , Aneurisma Aórtico/patologia , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.
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Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Europa (Continente) , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/epidemiologia , Oftalmopatia de Graves/metabolismo , Humanos , Guias de Prática Clínica como Assunto , Qualidade de Vida , Doenças Raras/metabolismoRESUMO
The PRINTS database houses a collection of protein fingerprints. These may be used to make family and tentative functional assignments for uncharacterised sequences. The September 2001 release (version 32.0) includes 1600 fingerprints, encoding approximately 10 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here its use as a source of annotation in the InterPro resource, and the use of its relational cousin, PRINTS-S, to model relationships between families, including those beyond the reach of conventional sequence analysis approaches. The database is accessible for BLAST, fingerprint and text searches at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.
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Bases de Dados de Proteínas , Evolução Molecular , Proteínas/genética , Motivos de Aminoácidos , Animais , Armazenamento e Recuperação da Informação , Internet , Proteínas/fisiologia , Alinhamento de SequênciaRESUMO
The PRINTS database houses a collection of protein fingerprints. These may be used to assign uncharacterised sequences to known families and hence to infer tentative functions. The September 2002 release (version 36.0) includes 1800 fingerprints, encoding approximately 11 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here the development of an automatic supplement, prePRINTS, designed to increase the coverage of the resource and reduce some of the manual burdens inherent in its maintenance. The databases are accessible for interrogation and searching at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.
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Motivos de Aminoácidos , Bases de Dados de Proteínas , Proteínas/química , Animais , Automação , Sequência Conservada , SoftwareRESUMO
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines. Recommendations ⢠Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R) ⢠FNAC should be considered for all nodules with suspicious ultrasound features (U3-U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R) ⢠Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R) ⢠Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R) ⢠Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R) ⢠Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G) ⢠In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R) ⢠For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R) ⢠Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R) ⢠Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G) ⢠Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R) ⢠Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R) ⢠Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R) ⢠I131 ablation should be carried out only in centres with appropriate facilities. (R) ⢠Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R) ⢠Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R) ⢠The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R) ⢠A post-ablation scan should be performed 3-10 days after I131 ablation. (R) ⢠Post-therapy dynamic risk stratification at 9-12 months is used to guide further management. (G) ⢠Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R) ⢠Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R) ⢠Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G) ⢠Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone assessments. (R) ⢠Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma free nor metanephrine estimation), serum calcium and parathyroid hormone. (R) ⢠Relevant imaging studies are advisable to guide the extent of surgery. (R) ⢠RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after surgery. (R) ⢠All patients with known or suspected MTC should have serum calcitonin and biochemical screening for phaeochromocytoma pre-operatively. (R) ⢠All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment neck dissection. (R) ⢠Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa-Vb). (R) ⢠Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R) ⢠Prophylactic thyroidectomy should be offered to RET-positive family members. (R) ⢠All patients with proven MTC should have genetic screening. (R) ⢠Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R) ⢠Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R) ⢠For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small proportion of patients with localised disease and good performance status, which may benefit from surgical resection and other adjuvant therapies. (G) ⢠The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G).
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Neoplasias da Glândula Tireoide/diagnóstico , Biópsia por Agulha/normas , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Humanos , Comunicação Interdisciplinar , Metástase Linfática/diagnóstico , Imageamento por Ressonância Magnética/normas , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias/normas , Cuidados Pós-Operatórios/normas , Proto-Oncogene Mas , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia/normas , Tomografia Computadorizada por Raios X/normas , Reino UnidoRESUMO
CONTEXT: Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. OBJECTIVE: We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. DESIGN: Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. CONCLUSION: We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.
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Doença de Addison/genética , Genes Ligados ao Cromossomo X , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/genética , Doença de Addison/imunologia , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , MasculinoRESUMO
Although the expression of the normal prion protein in the host is critical to the development of transmissible spongiform encephalopathies, the physiological role of this protein and the processes regulating its expression remain obscure. We now report that the messenger RNA for the prion protein is regulated in the rat brain in a marked circadian manner not only in the suprachiasmatic nuclei, the principal site for the generation of mammalian circadian rhythms, but also in other forebrain regions. The data show a remarkable consistency in the concurrence of a single peak of prion protein messenger RNA at each of the sites early in the animal's phase of increased locomotor activity; behavioural arousal does not, however, appear to affect this expression. We believe this to be the first study demonstrating that the expression of prion protein messenger RNA can change over a relatively short period in vivo. The results are discussed with reference to the range of recently discovered "clock-related" transcripts which also have widespread tissue expression; these include the messenger RNAs for D-box binding protein and thyroid embryonic factor, transcription factors which bind to the prion protein promoter.
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Ritmo Circadiano/fisiologia , Proteínas PrPC/genética , Prosencéfalo/metabolismo , RNA Mensageiro/metabolismo , Animais , Atividade Motora/fisiologia , Ratos , Núcleo Supraquiasmático/metabolismoRESUMO
Patients with dementia often manifest troublesome and disruptive behaviors in addition to intellectual impairments. This study evaluated behavioral disturbances in 126 demented patients examined sequentially, using questionnaires administered to primary caregivers to quantify the types and severity of behavioral disturbances. Eighty-three percent of the patients exhibited one or more of the targeted behaviors. The most common troublesome and disruptive behaviors clustered into three categories: aggressive, ideational, and vegetative. The prevalence and severity of the behaviors increased with global severity of dementia, but did not differ in either frequency or type when patients with three diagnoses were compared: Alzheimer's disease (AD), multi-infarct dementia (MID), and mixed AD and MID (MIX). The occurrence and severity of the target behaviors correlated modestly with the severity of dementia. Impairments of mental status correlated weakly with only a single troublesome and disruptive behavior--assaultiveness. These results suggest that troublesome and disruptive behaviors are a very frequent component of dementing disorders, are related to disease severity, and parallel (but are probably not determined by) intellectual deficit.
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Doença de Alzheimer/psicologia , Demência/psicologia , Transtornos do Comportamento Social/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Agressão/psicologia , Doença de Alzheimer/classificação , Doença de Alzheimer/diagnóstico , Demência/classificação , Demência/diagnóstico , Feminino , Humanos , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Estudos Retrospectivos , Transtornos do Comportamento Social/psicologia , ViolênciaRESUMO
OBJECTIVE: To evaluate the usefulness and reliability of the Caretaker Obstreperous-Behavior Rating Assessment (COBRA), a new test instrument for caretaker assessment of types and severity of "obstreperous behaviors" (OBs) in demented patients. DESIGN: COBRA was completed by caretakers of 31 outpatients and 36 nursing home inpatients with dementia. Test-retest reliability was determined when 25 of the outpatient caretakers re-evaluated their demented relative 1 week later; inter-rater reliability was determined on nursing home inpatients by comparing the reports of two nurse's aids with equivalent knowledge of seven of the patients. SETTING: (1) University medical center Alzheimer's Disease and Related Disorders Clinic; (2) community nursing home. PATIENTS: Thirty-one sequentially-seen outpatients with dementia; 36 nursing home patients with dementia. INTERVENTION: Following instruction in the use of the COBRA Scale, caretakers provided scores for their demented patient. The instrument has three unique features: (1) it divides OBs into four categories for ease of comprehension: Aggressive/Assaultive; Mechanical/Motor; Ideational/Personality; and Vegetative; (2) a companion videotape shown to caretakers in advance illustrates each behavior to improve reliability of reporting; (3) the significance of each OB is estimated with severity and frequency measures. MAIN OUTCOME MEASUREMENTS: Frequency and severity of OBs are epitomized in 12 summary scores. Test-retest correlations (for outpatients) and inter-rater correlations (for inpatients) were analyzed with Pearson Product Moment and Spearman Rank Order correlations. RESULTS: Prevalence of OBs and severity was reported for the experimental groups. Summary scores revealed test-retest correlations of .95 to .73 for 11 of 12 scores (outpatients), and inter-rater correlations of .99 to .73 for 8 of 12 scores (inpatients). Age, gender, and disease etiology were not significantly related to OBs; clinical severity correlated with type and severity of OBs. CONCLUSIONS: The COBRA scale provides a convenient, comprehensive, and reliable means for caretakers to identify the types and measure the severity of OBs in demented outpatients and nursing home inpatients. If additional studies confirm these observations, COBRA will be a useful instrument for assessing the effects of interventions on OBs in patients with dementia.
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Comportamento , Demência/psicologia , Escalas de Graduação Psiquiátrica , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Feminino , Humanos , Masculino , Casas de Saúde , Pacientes Ambulatoriais , Reprodutibilidade dos TestesRESUMO
The present study examined possible estrogen and/or progesterone effects on the mesolimbic dopamine (DA) system using brain stimulation reward (BSR). It is well known that BSR with electrical stimulation of the medial forebrain bundle (MFB) depends on the functioning of the mesolimbic DA system. If estrogen affects this system in a manner similar to its effects on the nigrostriatal DA system, reward measures would be expected to vary across the estrous cycle. Cycling female rats were trained to bar press for electrical stimulation to the MFB. Animals were tested at each stage of the estrous cycle, after ovariectomy and 4, 24, 48, 72 and 96 h after hormone replacement with estradiol (10 micrograms, s.c.), estradiol and progesterone (0.5 mg, s.c.), or oil (s.c.). The rewarding value of the stimulation and the maximum rate of bar pressing increased during estrus, but not during proestrus or metestrus, as compared with diestrus. Hormone replacement had differing effects on reward and motor performance. Motor performance increased 4 and 24 h after estrogen alone and 24 h after estrogen with the addition of progesterone 4 h before testing. The rewarding value of the stimulation increased only 24 h after estrogen together with an injection of progesterone 4 h before testing. These results indicate that gonadal steroids affect the functioning of the mesolimbic DA system.