RESUMO
Current trends in undergraduate medical education are moving away from traditional ward based learning to ambulatory care teaching. We wanted to know whether students gain more learning outcomes from a dedicated ambulatory teaching environment than a conventional outpatient clinic. A comparative evaluation study using a semi-structured student questionnaire and a structured patient questionnaire was performed. Results indicated the learning environment and organization of the teaching in the Ambulatory Care Teaching Centre (ACTC) rated higher. Surprisingly, however, more learning outcomes were achieved in the conventional outpatient clinic setting, but each venue demonstrated particular strengths with regard to individual outcomes. The level of patient satisfaction in the ACTC was high implying patient care was not adversely affected utilizing this setting. This information will inform practice for the content of future teaching sessions in the outpatient setting.
Assuntos
Assistência Ambulatorial , Educação de Graduação em Medicina/métodos , Aprendizagem , Humanos , Escócia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Breast pain is a common symptom in patients attending breast clinics. The purpose of this study was to evaluate the efficacy of goserelin (Zoladex) as compared with sham injection in patients with mastalgia. STUDY DESIGN: One hundred forty-seven premenopausal women were randomized to treatment with either goserelin injection (3.6 mg/month) or sham injection for a total of 6 injections. Patients' daily self-assessment of breast pain using Cardiff breast pain chart was recorded during the 6-month treatment period and for 6 months in the posttreatment period. RESULTS: A significant treatment difference between the 2 groups in favor of goserelin was noted during the treatment period. Mean breast pain score improved by 67% in the goserelin group and 35% in the sham group during the treatment period. The mean pain scores increased in both groups in the posttreatment period. No significant posttreatment difference was found between the two groups. Side effects were more common with goserelin than sham injection. Patients receiving goserelin experienced vaginal dryness, hot flushes, decreased libido, oily skin or hair, and a decrease in breast size more frequently than sham patients. CONCLUSION: Goserelin is an effective short-term treatment for mastalgia. However, side effects are common, and thus, goserelin should be kept in reserve for patients who are refractory to other forms of treatment. Potentially, goserelin could be used to induce a rapid relief of symptoms that could be maintained with alternative therapies.
Assuntos
Doenças Mamárias/tratamento farmacológico , Gosserrelina/uso terapêutico , Dor/tratamento farmacológico , Adulto , Análise de Variância , Doenças Mamárias/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Dor/diagnóstico , Medição da Dor , Satisfação do Paciente , Probabilidade , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Insoluble beta-amyloid deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls (p=0.002). There was no change in the mRNA levels of KPI-(APP 695) (p=0.898). Therefore, whilst KPI-mRNA levels remained stable the KPI(+) species increased specifically in the AD brains.
Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Córtex Cerebral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Precursor de Proteína beta-Amiloide/classificação , Precursor de Proteína beta-Amiloide/genética , Análise de Variância , Estudos de Casos e Controles , Feminino , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/genética , Humanos , Modelos Lineares , Masculino , Proteínas Associadas aos Microtúbulos/análise , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Isoformas de Proteínas/análise , Isoformas de Proteínas/classificação , Isoformas de Proteínas/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores SexuaisRESUMO
The quantification of mRNA in postmortem human brain is often made complicated by confounding factors. To assess the importance of potential confounders TaqMan real-time RT-PCR was used to measure seven mRNAs (beta-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin, microtubule-associated protein (MAP) 2, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), amyloid precursor protein (APP) isoform 770) in cortical samples taken from 90 Alzheimer's disease (AD) and 81 control brains. Demographic data for the brain samples were assessed for interaction between factors and amounts of mRNA. Gender was found to play a role in that females had lower levels of mRNA relative to males; this was consistent in both the AD and control brains. Age at death had inconsistent but significant correlations to amounts of mRNA; male and female controls both had negative correlations, female AD a positive correlation and male AD no correlation. Positive correlations were found between brain pH and amount of mRNA in all genes except glial fibrillary acidic protein (GFAP); correlations were consistent across all groupings of pathology and gender. Mean brain pH was significantly lower in AD (6.4) than in control subjects (6.5, ANOVA, p<0.01), though there was no difference between male and females of either group. No correlation was found between brain pH and age at death. Postmortem interval was correlated with brain pH in Alzheimer's disease brains but not controls. Agonal state was generally a poor predictor of mRNA levels whilst inter-lobe variance of mRNA was found to be non-significant in control brains. Given that gender, age at death and brain pH all have significant effects upon mRNA levels it is recommended that these factors be taken into account when quantifying gene expression in postmortem human brain.
Assuntos
Córtex Cerebral/química , Córtex Cerebral/metabolismo , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Causas de Morte , Córtex Cerebral/patologia , Feminino , Variação Genética/genética , Humanos , Concentração de Íons de Hidrogênio , Hipóxia Encefálica/genética , Hipóxia Encefálica/metabolismo , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Insuficiência Respiratória/genética , Insuficiência Respiratória/metabolismo , Fatores SexuaisRESUMO
Quantitative human mRNA data are derived from post-mortem or biopsied tissue. RNA degradation, poor replication, a large mRNA variance and confounding factors such as brain pH and age of death are often cited, however, as objections to the data's reliability. A central question is whether post-mortem human mRNA can be treated as a statistically ordered system. TaqMan real-time RT-PCR was used to measure seven mRNAs in 513 cortical samples taken from 90 Alzheimer's disease and 81 control brains. Despite a high mRNA variance strong correlations were found between the mRNA transcripts in a single brain. Where a brain has a high/low level of one mRNA, the same brain invariably has a high/low level of other mRNAs; correlated order is present and allows removal of that source of variation common to all genes. Although levels of mRNA are highly variable between subjects (>1000-fold), quantitative order is present in post-mortem human mRNA, allowing effects due to pathology or gender to be isolated and tested for significance.
Assuntos
Química Encefálica , RNA Mensageiro/análise , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Cadáver , Estudos de Casos e Controles , Feminino , Proteína Glial Fibrilar Ácida/genética , Gliceraldeído-3-Fosfato Desidrogenases/genética , Humanos , Modelos Lineares , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Fragmentos de Peptídeos/genética , Mudanças Depois da Morte , Estabilidade de RNA , RNA Mensageiro/química , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores Sexuais , Taq PolimeraseRESUMO
Beta-secretase (BACE) and glycogen synthase kinase (GSK 3) are two enzymes thought to play a role in Alzheimer's disease. We extracted mRNA from 90 Alzheimer and 81 control brains. Levels of mRNA were quantified for BACE and GSK 3 with TaqMan real-time RT-PCR. We found no change in the Alzheimer's disease brains relative to controls for either the BACE or the GSK 3alpha mRNA levels.
Assuntos
Doença de Alzheimer/enzimologia , Endopeptidases/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/análise , Precursor de Proteína beta-Amiloide/genética , Ácido Aspártico Endopeptidases , Endopeptidases/genética , Feminino , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/genética , Quinase 3 da Glicogênio Sintase/genética , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/análise , Proteínas Associadas aos Microtúbulos/genética , Fosfopiruvato Hidratase/análise , Fosfopiruvato Hidratase/genética , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Caracteres SexuaisRESUMO
Expression levels of mRNA are commonly measured as a ratio of test to reference gene. The assumption is that reference genes such as beta-actin or cyclophilin are unaffected by treatment and act as steady-state controls. TaqMan real-time RT-PCR was used to test these assumptions in a rat model of cerebral ischaemia (tMCAO). Following measurement of 24 genes, we show that reference genes in this animal model fail the criteria for steady-state controls. Neuronal loss, glial proliferation and an influx of leukocytes into the lesioned brain result in major disturbance to cell populations. The mRNA for reference genes, as for test genes, reflects these changes. Specific mRNA levels vary according to the choice of reference gene to which they are normalised. In the process of resolving reference gene issues, mRNA increases were discovered for leukaemia inhibitory factor, nestin and galanin in rat brain hemispheres affected by ischaemia. Results are reported for a further 21 genes and mathematical and statistical methods are described that allow in this study fraction-fold changes in mRNA to be detected.
