RESUMO
OBJECTIVES: To examine the association of maternal pregravid body mass index (BMI) and child offspring, all-cause hospitalisations in the first 5 years of life. METHODS: Prospective birth cohort study. From 2006 to 2011, 2779 pregnant women (2807 children) were enrolled in the Environments for Healthy Living: Griffith birth cohort study in South-East Queensland, Australia. Hospital delivery record and self-report baseline survey of maternal, household and demographic factors during pregnancy were linked to the Queensland Hospital Admitted Patients Data Collection from 1 November 2006 to 30 June 2012, for child admissions. Maternal pregravid BMI was classified as underweight (<18.5 kg m(-)(2)), normal weight (18.5-24.9 kg m(-)(2)), overweight (25.0-29.9 kg m(-)(2)) or obese (⩾30 kg m(-)(2)). Main outcomes were the total number of child hospital admissions and ICD-10-AM diagnostic groupings in the first 5 years of life. Negative binomial regression models were calculated, adjusting for follow-up duration, demographic and health factors. The cohort comprised 8397.9 person years (PYs) follow-up. RESULTS: Children of mothers who were classified as obese had an increased risk of all-cause hospital admissions in the first 5 years of life than the children of mothers with a normal BMI (adjusted rate ratio (RR) =1.48, 95% confidence interval 1.10-1.98). Conditions of the nervous system, infections, metabolic conditions, perinatal conditions, injuries and respiratory conditions were excessive, in both absolute and relative terms, for children of obese mothers, with RRs ranging from 1.3-4.0 (PYs adjusted). Children of mothers who were underweight were 1.8 times more likely to sustain an injury or poisoning than children of normal-weight mothers (PYs adjusted). CONCLUSION: RESULTS suggest that if the intergenerational impact of maternal obesity (and similarly issues related to underweight) could be addressed, a significant reduction in child health care use, costs and public health burden would be likely.
Assuntos
Macrossomia Fetal/epidemiologia , Hospitalização/estatística & dados numéricos , Hipoglicemia/epidemiologia , Mães , Defeitos do Tubo Neural/epidemiologia , Obesidade/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Adulto , Índice de Apgar , Austrália/epidemiologia , Índice de Massa Corporal , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Obesidade/complicações , Gravidez , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: Nursing and midwifery are demanding professions. Efforts to understand the health consequences and workforce needs of these professions are urgently needed. Using a novel electronic approach, the Nurses and Midwives e-cohort Study (NMeS) aims to investigate longitudinally Australian and New Zealand nurses' and midwives' work/life balance and health. This paper describes NMeS participation; provides key baseline demographic, workforce and health indicators; compares these baseline descriptions with external norms; and assesses the feasibility of the electronic approach. METHODS: From 1 April 2006 to 31 March 2008, nurses in Australia and New Zealand, and midwives in Australia were invited to participate. Potential participants were directed to a purpose-built NMeS Internet site, where study information was provided and consent sought. Once obtained, a range of standardized tools combined into one comprehensive electronic questionnaire was elicited. RESULTS: Overall, 7633 (2.3%) eligible nurses and midwives participated (6308 from Australia and 1325 from New Zealand) from a total pool of 334,400. Age, gender, occupational and health profiles were similar between countries and to national figures. However, some differences were noted; for instance, Queensland participants were over-represented, while Victorian and South Australian participants were under-represented, and 28.2% of Australians were in high strain positions compared with 18.8% of New Zealanders. CONCLUSIONS: Using an internationally novel web-based approach, a large cohort, which appears generally similar to population norms, has been established. Provided participant retention is adequate, the NMeS will provide insight into understanding the drivers of nurses' and midwives' workforce retention and work-related factors associated with their health.
Assuntos
Atitude do Pessoal de Saúde , Nível de Saúde , Internet , Enfermeiros Obstétricos , Enfermeiras e Enfermeiros , Local de Trabalho , Austrália , Distribuição de Qui-Quadrado , Estudos de Coortes , Humanos , Nova Zelândia , Enfermeiros Obstétricos/provisão & distribuição , Enfermeiras e Enfermeiros/provisão & distribuição , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To appraise the published evidence regarding the accuracy of external cause-of-injury codes in hospital records. DESIGN: Systematic review. DATA SOURCES: Electronic databases searched included PubMed, PubMed Central, Medline, CINAHL, Academic Search Elite, Proquest Health and Medical Complete, and Google Scholar. Snowballing strategies were used by searching the bibliographies of retrieved references to identify relevant associated articles. SELECTION CRITERIA: Studies were included in the review if they assessed the accuracy of external cause-of-injury coding in hospital records via a recoding methodology. METHODS: The papers identified through the search were independently screened by two authors for inclusion. Because of heterogeneity between studies, meta-analysis was not performed. RESULTS: Very limited research on the accuracy of external cause coding for injury-related hospitalisation using medical record review and recoding methodologies has been conducted, with only five studies matching the selection criteria. The accuracy of external cause coding using ICD-9-CM ranged from approximately 64% when exact code agreement was examined to approximately 85% when agreement for broader groups of codes was examined. CONCLUSIONS: Although broad external cause groupings coded in ICD-9-CM can be used with some confidence, researchers should exercise caution for very specific codes until further research is conducted to validate these data. As all previous studies have been conducted using ICD-9-CM, research is needed to quantify the accuracy of coding using ICD-10-AM, and validate the use of these data for injury surveillance purposes.
Assuntos
Controle de Formulários e Registros/normas , Registros Hospitalares/normas , Prontuários Médicos/normas , Ferimentos e Lesões/etiologia , Humanos , Escala de Gravidade do Ferimento , Ferimentos e Lesões/classificaçãoRESUMO
OBJECTIVE: To assess extent of coder agreement for external causes of injury using ICD-10-AM for injury-related hospitalisations in Australian public hospitals. METHODS: A random sample of 4850 discharges from 2002 to 2004 was obtained from a stratified random sample of 50 hospitals across four states in Australia. On-site medical record reviews were conducted and external cause codes were assigned blinded to the original coded data. Code agreement levels were grouped into the following agreement categories: block level, 3-character level, 4-character level, 5th-character level, and complete code level. RESULTS: At a broad block level, code agreement was found in over 90% of cases for most mechanisms (eg, transport, fall). Percentage disagreement was 26.0% at the 3-character level; agreement for the complete external cause code was 67.6%. For activity codes, the percentage of disagreement at the 3-character level was 7.3% and agreement for the complete activity code was 68.0%. For place of occurrence codes, the percentage of disagreement at the 4-character level was 22.0%; agreement for the complete place code was 75.4%. CONCLUSIONS: With 68% agreement for complete codes and 74% agreement for 3-character codes, as well as variability in agreement levels across different code blocks, place and activity codes, researchers need to be aware of the reliability of their specific data of interest when they wish to undertake trend analyses or case selection for specific causes of interest.
Assuntos
Classificação Internacional de Doenças , Ferimentos e Lesões/classificação , Adulto , Austrália/epidemiologia , Criança , Controle de Formulários e Registros/normas , Registros Hospitalares/normas , Hospitalização/estatística & dados numéricos , Hospitais Públicos , Humanos , Pessoa de Meia-Idade , Controle de Qualidade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Adulto JovemRESUMO
PRIMARY OBJECTIVE: To quantify the 10 year health service use (HSU) and mortality outcomes for people with a traumatic brain injury (TBI). RESEARCH DESIGN: A population-based matched cohort study using linked administrative data from Manitoba, Canada (Manitoba Injury Outcome Study). METHODS AND PROCEDURES: An inception cohort (1988-1991) of hospitalized cases with TBI aged 18-64 years (n = 1290) was identified and matched to a non-injured comparison group (n = 1290). Survival analysis, Negative binomial and Poisson regression were used to quantify associations between injury and HSU/mortality outcomes for 10 years following the TBI event. MAIN OUTCOME AND RESULTS: The majority of deaths (47.2%) occurred in the first 60 days following injury. Excluding the first 60 days, the adjusted 10 year mortality remained elevated (mortality rate ratio = 1.48, 95% CI = 1.02-2.15). After adjusting for demographic characteristics and pre-existing health status, the TBI cohort had more post-injury hospitalizations (rate ratio (RR) = 1.54, 95% CI = 1.39-1.71), greater cumulative lengths of stay (RR = 5.14, 95% CI = 3.29-8.02) and a greater post-injury physician claims rate (RR = 1.44, 95% CI = 1.35-1.53) than the non-injured cohort. CONCLUSIONS: People who sustain a TBI and survive the initial acute phase of care experience substantially increased long-term morbidity compared to the general population, regardless of the level of injury severity.
Assuntos
Lesões Encefálicas/reabilitação , Adolescente , Adulto , Lesões Encefálicas/mortalidade , Lesões Encefálicas/psicologia , Estudos de Casos e Controles , Seguimentos , Escala de Resultado de Glasgow , Hospitalização , Humanos , Masculino , Manitoba , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Análise de Regressão , Análise de Sobrevida , Resultado do TratamentoRESUMO
Priorities for prevention activities and planning for services depend on comprehensive knowledge of the distribution of the injury-related burden in the community. The aim of this systematic review was to quantify the effect of being injured, compared with not being injured, on long-term mortality in working age adults. Cohort studies were selected that were population-based, measured mortality post-discharge from inpatient treatment, included a non-injured comparison group and related to working-age adults. Data synthesis was in tabular and text form with a meta-analysis not being possible because of the heterogeneity between studies. Eleven studies met the inclusion criteria. All studies found an overall positive association between injury and increased mortality. While the greatest excess mortality was evident during the initial period post-injury, increased mortality was shown in some studies to persist for up to 40 years after injury. Due to the limited number of injury types studied and heterogeneity between studies, there is insufficient published evidence on which to calculate population estimates of long-term mortality, where injury is a component cause. The review does suggest there is considerable excess mortality following injury that is not accounted for in current methods of quantifying injury burden, and is not used to assess quality and effectiveness of trauma care.
Assuntos
Ferimentos e Lesões/mortalidade , Adulto , Fatores Etários , Austrália/epidemiologia , Canadá/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Vigilância da População , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Ferimentos e Lesões/epidemiologiaRESUMO
BACKGROUND: Estimating the contribution of non-fatal injury outcomes remains a considerable challenge and is one of the most difficult components of burden of disease analysis. The aim of this systematic review was to quantify the effect of being injured compared with not being injured on morbidity and health service use (HSU) in working age adults. METHODS: Studies were selected that were population based, had long term health outcomes measured, included a non-injured comparison group, and related to working age adults. Meta-analysis was not attempted because of the heterogeneity between studies. RESULTS: Nine studies met the inclusion criteria. In general, studies found an overall positive association between injury and increased HSU, exceeding that of the general population, which in some studies persisted for up to 50 years after injury. Disease outcome studies after injury were less consistent, with null findings reported. CONCLUSION: Because of the limited injury types studied and heterogeneity between study outcome measures and follow up, there is insufficient published evidence on which to calculate population estimates of long term morbidity, where injury is a component cause. However, the review does suggest injured people have an increased risk of long term HSU that is not accounted for in current methods of quantifying injury burden.
Assuntos
Serviços de Saúde/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Perfil de Impacto da DoençaRESUMO
Injury indicators are used for monitoring the impact of injury prevention initiatives on the population burden of injury. The object of the present study was to identify the types of injury responsible for the major component of the population health burden of injury in a large cohort in Manitoba, Canada. Injury cases (ICD-9-CM 800-995) aged 18-64 years were identified from all Manitoba hospital data between 1988 and 1991. Morbidity data were obtained from hospital discharge abstracts 12 months prior to date of injury and for 12 months post-injury. Outcomes for individuals were calculated as the difference pre- and post-injury in hospital inpatient days. Death outcomes in the 12 months post-injury were obtained by linking the cohort with the population registry. Summed outcomes across the population were stratified into injury types based on the International Code of Diseases (ICD) code of the index injury. Outcomes were also stratified by injury severity score categories where the injury severity score was obtained using ICDMAP-90. When ranked by contribution to the cohort's cumulative hospital inpatient days in the 12 months post-injury, the six most common ICD subchapter groups accounted for 65% of the total inpatient days. These six injury types also accounted for 62% of the total number of deaths in this cohort in 12 months after injury. The suggested injury types to use as indicators of burden include fracture of the lower limb, fracture of the head and neck, poisonings, intracranial injury, fracture of the upper limb, and fracture of skull.
Assuntos
Efeitos Psicossociais da Doença , Índices de Gravidade do Trauma , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Manitoba/epidemiologia , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Sistema de Registros , Resultado do Tratamento , Ferimentos e Lesões/classificação , Ferimentos e Lesões/terapiaRESUMO
There is an acknowledged need for valid and reliable injury scores, suitable for use at the population level, which can accurately predict the long-term outcome of injury. The objective was to quantify the extent to which the abbreviated injury severity score (AIS) and the functional capacity index score (FCI) predict use of health services in the 12 months following an injury event. A cohort of injured people (ICD-9-CM 800-995) aged 18 - 64 years was identified from Manitoba hospital discharge abstracts from January 1988 to December 1991. For each member of the cohort whose injuries could be mapped to an abbreviated injury scale unique identifier, a maximum AIS (maxAIS) and a maximum FCI (maxFCI) were obtained. The cohort was linked with hospital discharge abstracts, physicians' claims and deaths from the population registry for the 12 months following injury. Negative binomial regression was used to model the relationships between the severity scores and the three outcome measures, while controlling for potential confounding variables. In total, 20 677 (97%) eligible cases were identified, of which 16 834 (81%) could be assigned a maxAIS and 15 823 (77%) a maxFCI. MaxAIS and maxFCI were significantly associated with total days in hospital following injury, but explained little of the variation in any of the health service use outcome variables (maxAIS, partial pseudo r2 ranging from < 0.001 to 0.041; and maxFCI, partial pseudo r2 ranging from < 0.001 to 0.018). It was concluded that anatomical damage is only partly responsible for long-term injury outcome. Additional variables would need to be included in predictive models of health outcomes of injury before these models could be reliable.
Assuntos
Serviços de Saúde/estatística & dados numéricos , Escala de Gravidade do Ferimento , Perfil de Impacto da Doença , Resultado do Tratamento , Ferimentos e Lesões/fisiopatologia , Atividades Cotidianas , Adolescente , Adulto , Avaliação da Deficiência , Feminino , Humanos , Tempo de Internação , Masculino , Manitoba , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo , Ferimentos e Lesões/classificação , Ferimentos e Lesões/reabilitaçãoRESUMO
BACKGROUND: Oral myo-inositol (12--18 g/day) has shown beneficial effect in placebo-controlled studies of major depression, panic disorder, and obsessive compulsive disorder, and preliminary data suggest it also may be effective in bipolar depression. Evidence linking antidepressant activity to membrane phospholipid alterations suggested the examination of acute and chronic myo-inositol effects on rat brain membrane phospholipid metabolism. METHODS: With both (31)P nuclear magnetic resonance (NMR) and quantitative high-performance thin-layer chromatography (HPTLC; hydrolysis) methods, rat brain phospholipid levels were measured after acute (n = 20, each group) and chronic myo-inositol administration (n = 10, each group). With (31)P NMR, we measured myo-inositol rat brain levels after acute and chronic myo-inositol administration. RESULTS: Brain myo-inositol increased by 17% after acute myo-inositol administration and by 5% after chronic administration, as compared with the control groups. Chronic myo-inositol administration increased brain phosphatidylethanolamine (PtdEtn) plasmalogen by 10% and decreased brain PtdEtn by 5%, thus increasing the ratio PtdEtn plasmalogen (PtdEtn-Plas)/PtdEtn by 15%. Phosphatidylethanolamine plasmalogen levels quantified by (31)P NMR and HPTLC were highly correlated. The validity and reliability of the (31)P NMR method for phospholipid analysis were demonstrated with phospholipid standards. CONCLUSIONS: The observed alteration in the PtdEtn-Plas/PtdEtn ratio could provide insights into the therapeutic effect of myo-inositol in affective disorders.
Assuntos
Encéfalo/metabolismo , Inositol/farmacocinética , Plasmalogênios/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Inositol/administração & dosagem , Espectroscopia de Ressonância Magnética , Masculino , Fosfolipídeos/sangue , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. METHODS: We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versus control subjects using a proton magnetic resonance spectroscopy technique. Cerebrospinal fluid samples were obtained from 18 hospitalized patients with acute unmedicated severe depression without medical problems and compared with those of 22 control subjects. RESULTS: Compared with the control group, the depressed patient group had significantly higher CSF glutamine concentrations, which correlated positively with CSF magnesium levels. CONCLUSIONS: These findings suggest an abnormality of the brain glial-neuronal glutamine/glutamate cycle associated with N-methyl-D-aspartate receptor systems in patients with depression.
Assuntos
Transtorno Bipolar/líquido cefalorraquidiano , Transtorno Depressivo/líquido cefalorraquidiano , Glutamina/líquido cefalorraquidiano , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Creatina/líquido cefalorraquidiano , Transtorno Depressivo/metabolismo , Feminino , Glutamina/metabolismo , Humanos , Hidroxibutiratos/líquido cefalorraquidiano , Magnésio/líquido cefalorraquidiano , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
In a double-blind, placebo study, acetyl-L-carnitine was administered to 7 probable Alzheimer's disease patients who were then compared by clinical and 31P magnetic resonance spectroscopic measures to 5 placebo-treated probable AD patients and 21 age-matched healthy controls over the course of 1 year. Compared to AD patients on placebo, acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer's Disease Assessment Scale test scores. Furthermore, the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients. Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients. This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD.
Assuntos
Acetilcarnitina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Idoso , Doença de Alzheimer/psicologia , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosfatos/metabolismo , Fosfolipídeos/metabolismoRESUMO
A 52-year-old Caucasian male was followed with Mattis and 31P MRS examinations every 6 months for 33 months. At entry into the study, the subject had a normal clinical examination and normal Mattis scores but had alterations in MRS measures of membrane phospholipid and high-energy phosphate metabolism indistinguishable from those previously reported in mildly demented AD patients. After 33 months of follow-up, the subject had clinical and Mattis findings suggestive of possible incipient dementia and after 46 months of follow-up there was sufficient cognitive decline to make the diagnosis of dementia with a frontal lobe preponderance. The findings in this subject support the contention that alterations in brain membrane phospholipid and high-energy metabolism can be noninvasively detected by 31P MRS years before any clinical manifestations of the disease.
Assuntos
Encéfalo/metabolismo , Demência/metabolismo , Fosfatos/metabolismo , Fosfolipídeos/metabolismo , Demência/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Membranas/metabolismo , Pessoa de Meia-IdadeRESUMO
Previous in vitro and in vivo 31P MRS studies of Alzheimer's disease patients have revealed alterations in membrane phospholipid metabolism and PET studies have shown alterations in glucose and oxidative metabolism. This study of probable Alzheimer's disease patients demonstrates severity dependent alterations in measures of both high-energy phosphate and membrane phospholipid metabolism. Mildly demented Alzheimer's patients compared to the controls, have increases in the levels of phosphomonoesters, decreases in the levels of phosphocreatine and probably adenosine diphosphate, and an increased oxidative metabolic rate. As the dementia worsens, the levels of phosphocreatine and adenosine diphosphate increase, the levels of phosphomonoesters decrease, and the oxidative metabolic rate decreases. The phosphomonoester findings replicate previous findings and provide a new dimension to the molecular pathology of Alzheimer's disease, implicating basic defects in membrane metabolism. The changes in oxidative metabolic rate suggest the AD brain is under energetic stress. The changes in energy metabolites with increasing dementia could be a consequence of nerve terminal degeneration and are consistent with previous PET findings. 31P MRS provides new diagnostic and metabolic insights into this disease and would be a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.
Assuntos
Doença de Alzheimer/metabolismo , Química Encefálica/fisiologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Fatores Etários , Idoso , Doença de Alzheimer/epidemiologia , Transtornos Cognitivos/metabolismo , Educação , Feminino , Humanos , Cinética , Estudos Longitudinais , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxirredução , Fosfocreatina/metabolismo , Fosfolipídeos/metabolismoRESUMO
A variety of metabolites present in perchloric acid extracts of brain tissue were measured by 1H and 31P magnetic resonance spectroscopy (MRS) and HPLC in the same tissue sample and the MRS results were expressed both in terms of mole % and mumole/g based on an internal standard. The levels of 16 metabolites were compared by linear regression analysis and the mole % results were found to correlate very well with the results expressed as mumole/g. To compare the two units under typical experimental conditions, the percent change in metabolites in a group of Alzheimer's disease brains was compared to a control group using both units. The results were essentially identical for the mole % and mumole/g methods. We conclude that the use of the mole % method of expressing MRS data yields results which are equivalent to those expressed in absolute units and suggest that, for in vivo MRS studies, use of the mole % method is preferable because fewer artifacts, such as partial volume effects, are introduced.
Assuntos
Química Encefálica , Espectroscopia de Ressonância Magnética , Doença de Alzheimer/metabolismo , Cromatografia Líquida de Alta Pressão , Humanos , Hidrogênio , Percloratos/química , Isótopos de Fósforo , Pesos e Medidas , Proteínas tau/químicaRESUMO
Several previous studies have shown metabolic abnormalities in perchloric acid extracts of postmortem Alzheimer's disease (AD) brain by both proton (1H) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). In all of these studies the results were expressed in relative terms, in units of mol percent. The results of this study, expressed in the absolute units of mumol/g wet weight, verify the previous 1H and 31P MRS studies. Absolute increases were found for myo-inositol, aspartate, L-glutamate, alanine, phosphocholine, and the phosphodiesters,. Absolute decreases were found for phosphoethanolamine and N-acetyl-l-aspartate. Many of these changes also were observed in non-AD dementia brain extracts, but changes in myo-inositol, inositol-l-phosphate, aspartate, and L-glutamate appeared to be more specific for AD in extracts of many brain areas. These results suggest that compounds related to membrane degradation and excitatory neuro-transmission increase in Alzheimer's disease while compounds related to neuronal integrity and inhibitory neurotransmission are decreased.
Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Percloratos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cerebelo/metabolismo , Feminino , Lobo Frontal/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , MasculinoRESUMO
Alterations in phospholipid metabolites are a characteristic abnormality of Alzheimer's disease (AD). Many of these alterations have been demonstrated by magnetic resonance spectroscopy (MRS) studies of postmortem tissue. Phosphodiesters appear to be elevated late in the disease and phosphomonoesters appear to be elevated early in the disease and then decrease. Second to aging, the most robust risk factor for AD identified to date is the presence of the E4 allele of apolipoprotein-E (Apo-E). Because apolipoproteins are intimately involved in lipid metabolism, this study was performed to determine if the presence of the Apo-E4 allele affects the abnormalities in phospholipid metabolites in AD brain. Perchloric acid extracts from 12 Apo-E 3/3, 31 3/4, 6 4/4 AD brains and 5 Apo-E 3/3 control brains were studied by both proton magnetic resonance spectroscopy and phosphorus-31 magnetic resonance spectroscopy. When the E4-positive AD samples were compared with the 3/3 AD samples, an exaggeration in both phosphomonoester and phosphodiester abnormalities was observed. The decrease in N-acetyl-L-aspartate (NAA) was also exaggerated. These results suggest membrane phospholipid metabolite alterations observed in AD are more severe in the presence of the Apo-E4 allele.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteínas E/genética , Fosfolipídeos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Apolipoproteína E4 , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
We used proton nuclear magnetic resonance spectroscopy in this preliminary study of perchloric acid extracts of 12 Alzheimer's disease (AD) and five control brain samples to measure the relative levels of taurine, aspartate, glutamine, glutamate, gamma-aminobutyric acid (GABA), and the putative neuronal marker, N-acetyl-L-aspartate (NAA). We found no significant changes in taurine, aspartate, or glutamine. NAA was lower in AD compared with control, and this decrease correlated with the number of senile plaques and neurofibrillary tangles in adjacent tissue sections. GABA levels also were lower in AD brain. Glutamate levels were greater in AD than control and showed a close, inverse correlation with NAA levels. These findings suggest that the decrease in NAA reflects neuronal loss and that remaining neurons could be exposed to a relative excess of glutamate and a relative lack of GABA. If present in the neurotransmitter pool, this imbalance could result in neurotoxic cell damage. This hypothesis is further supported by in vitro and in vivo phosphorus 31 nuclear magnetic resonance findings.
Assuntos
Doença de Alzheimer/metabolismo , Aminoácidos/metabolismo , Ácido Aspártico/análogos & derivados , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Ácido Aspártico/metabolismo , Encéfalo/patologia , Cadáver , Feminino , Glutamatos/metabolismo , Ácido Glutâmico , Glutamina/metabolismo , Humanos , MasculinoRESUMO
In vitro and in vivo 31P magnetic resonance (MR) spectroscopy studies of Alzheimer's disease (AD) brain have revealed alterations in membrane phospholipid metabolism and high-energy phosphate metabolism. Mildly demented AD patients compared with control subjects have increased levels of phosphomonoesters, decreased levels of phosphocreatine and probably adenosine diphosphate and an increased oxidative metabolic rate. As the dementia worsens, levels of phosphomonoesters decrease and levels of phosphocreatine and adenosine di-phosphate increase. The changes in oxidative metabolic rate suggest that the AD brain is under energetic stress. The phosphomonoester findings support our in vitro findings and implicate basic defects in membrane metabolism in AD brain. MR spectroscopy provides new diagnostic insights and a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.