RESUMO
BACKGROUND: Physicians' recognition of end of life (EOL) has key influences on patients' 'good death'. AIM: We aimed to study physicians' attitude toward EOL, and to analyze the relationship between physicians' assessment and patients' actual survival and the trigger effect on patient's access to palliative consultation and palliative care. DESIGN: This is a multi-center retrospective cohort study in seven community hospitals in Taiwan. METHODS: Inpatients admitted between 1 March 2016 and 31 December 2020, scored ≥4 points using Taiwan version-Palliative Care Screening Tool (TW-PCST), and expired before 31 December 2020 were enrolled. Physicians answered three questions regarding these inpatients: 'surprised of mortality within 6-12 months', 'EOL' and 'in need of palliative care'. We followed up patients' actual survival and access to palliative consultation and services. RESULTS: We enrolled 10 304 cases. There was high correlation among the three questions. The median survival of patients with 'not surprised of death within 6-12 months', 'EOL', and 'needing palliative care' were 68, 60 and 58 days, respectively. Those with opposite responses were 206, 166 and 186 days, respectively. Patients' main diagnosis, TW-PCST score, physicians' palliative care qualifications and reward measures were all associated with physicians' recognition of EOL. Physicians' assessment, physicians' training, disease characteristics and TW-PSCT scores were all associated with palliative consultation and palliative care. CONCLUSIONS: Physicians are still over optimistic in recognizing inpatients' survival and palliative care needs. EOL talks can be initiated when the TW-PCST score is high. Universal palliative care training can be integrated into medical education.
Assuntos
Médicos , Assistência Terminal , Humanos , Cuidados Paliativos , Pacientes Internados , Estudos Retrospectivos , Taiwan/epidemiologiaAssuntos
Betacoronavirus , Temperatura Corporal , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Monitorização Fisiológica/métodos , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , COVID-19 , Humanos , SARS-CoV-2 , TaiwanRESUMO
WHAT IS KNOWN AND OBJECTIVE: Rhabdomyolysis is a severe potential adverse drug reaction of statin therapy. We report a case of rhabdomyolysis due to drug-drug interaction (DDI) between atorvastatin and fluconazole and review the literature. CASE SUMMARY: A 70-year-old woman received atorvastatin for hyperlipidaemia without any problem for 4 years. When intravenous fluconazole was added for treating a fungal infection, rhabdomyolysis developed 2 weeks later. Removal of atorvastatin led to the resolution of her rhabdomyolysis. WHAT IS NEW AND CONCLUSION: Our case demonstrates that in some subjects even a moderate CYP3A4 inhibitor such as fluconazole may lead to rhabdomyolysis in subjects receiving a statin.
Assuntos
Atorvastatina/efeitos adversos , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Fluconazol/efeitos adversos , Rabdomiólise/induzido quimicamente , Idoso , Interações Medicamentosas , Feminino , HumanosRESUMO
AIMS: Soluble guanylyl cyclase (sGC) is a key modulator in the regulation of vascular tone. However, its role and involving mechanism in cholesterol metabolism of macrophages and atherosclerosis remain unclear. METHODS: Oil red O staining, Dil-oxidized low-density lipoprotein (oxLDL)-binding assay and cholesterol efflux assay were performed in biology of foam cells. Levels of cytokines or intracellular lipid were evaluated by ELISA or colorimetric kits. Expression of gene or protein was determined by quantitative real-time PCR or Western blotting. Histopathology was examined by haematoxylin and eosin staining. RESULTS: Soluble guanylyl cyclase was expressed in macrophages of mouse atherosclerotic lesions. Treatment with 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, sGC inhibitor) exacerbated oxLDL-induced cholesterol accumulation in macrophages. In contrast, 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1, sGC activator) attenuated the oxLDL-induced cholesterol accumulation because of increased cholesterol efflux. Additionally, YC-1 dose dependently increased the protein expression of ATP-binding cassette transporter A1 (ABCA1) but did not alter that of scavenger receptor class A (SR-A), CD36, SR-BI or ABCG1. Moreover, YC-1-upregulated ABCA1 level depended on liver X receptor α (LXRα). Inhibition of the LXRα-ABCA1 pathway by LXRα small interfering RNA (siRNA), ABCA1 neutralizing antibody or ABCA1 siRNA abolished the effect of YC-1 on cholesterol accumulation and cholesterol efflux. In vivo, YC-1 retarded the development of atherosclerosis, accompanied by reduced serum levels of cholesterol and pro-inflammatory cytokines, in apolipoprotein E-deficient mice. CONCLUSION: Activation of sGC by YC-1 leads to LXRα-dependent upregulation of ABCA1 in macrophages and may confer protection against atherosclerosis.
Assuntos
Aterosclerose/metabolismo , Ativação Enzimática/fisiologia , Células Espumosas/fisiologia , Guanilato Ciclase/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Linhagem Celular , Células Espumosas/citologia , Guanilato Ciclase/genética , Indazóis/farmacologia , Metabolismo dos Lipídeos , Lipoproteínas LDL/metabolismo , Fígado/enzimologia , Receptores X do Fígado , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Miocárdio/enzimologia , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismoRESUMO
WHAT IS KNOWN AND OBJECTIVE: Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross-reactivity between these two glycopeptides is controversial. Our aim was to study the cross-reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. METHODS: Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. RESULTS AND DISCUSSION: Thirty-eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty-four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1-46 days). The time of onset of sequential teicoplanin-induced ADRs was 11·7 ± 4·7 days (range, 2-20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross-reactivity between vancomycin and teicoplanin. The incidence of vancomycin-induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin-induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin-induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. WHAT IS NEW AND CONCLUSION: Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross-reactivity between the two glycopeptides.
Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Teicoplanina/efeitos adversos , Vancomicina/efeitos adversos , Adulto , Idoso , Antibacterianos/administração & dosagem , Reações Cruzadas , Toxidermias/epidemiologia , Toxidermias/etiologia , Toxidermias/imunologia , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/fisiopatologia , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Febre/epidemiologia , Febre/etiologia , Febre/imunologia , Hospitais Universitários , Humanos , Incidência , Infusões Intravenosas , Leucopenia/epidemiologia , Leucopenia/etiologia , Leucopenia/imunologia , Masculino , Pessoa de Meia-Idade , Risco , Centro Cirúrgico Hospitalar , Taiwan/epidemiologia , Teicoplanina/administração & dosagem , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombocitopenia/imunologia , Vancomicina/administração & dosagemRESUMO
Hypersensitivity syndrome associated with teicoplanin has rarely been reported. We report a case with a preceding episode of vancomyin-related neutropenia. A 47-year-old female with cervical spine infection was treated with vancomycin. Neutropenia occurred after 17 days of vancomycin therapy. Vancomycin was changed to teicoplanin, and the neutropenia resolved 4 days later. After 11 days of teicoplanin therapy, a new episode of hypersensitivity syndrome manifested as fever, bilateral neck lymphadenopathy, mild wheezing, hepatitis and increased CRP occurred. Neutropenia and thrombocytopenia developed 3 days later. The patient's symptoms settled over 1 week following withdrawal of teicoplanin. Naranjo's ADR algorithm categorized the neutropenia associated with vancomycin and the hypersensitivity syndrome associated with teicoplanin as 'probable'.
Assuntos
Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Neutropenia/induzido quimicamente , Teicoplanina/efeitos adversos , Vancomicina/efeitos adversos , Antibacterianos/uso terapêutico , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Infecções/tratamento farmacológico , Pessoa de Meia-Idade , Doenças da Coluna Vertebral/tratamento farmacológico , Teicoplanina/uso terapêutico , Vancomicina/uso terapêuticoRESUMO
OBJECTIVES: To investigate dual-phase multi-detector computed tomography (MDCT) for assessing extent and severity of jeopardised and infarcted myocardium subtended by infarct-related artery (IRA), and its indication for revascularisation after acute myocardial infarction (AMI). Designs, setting and PATIENTS: Prospective, single-centre study included 107 patients with uncomplicated post-AMI 3-7 days, who met criteria and underwent dual-phase 64-slice MDCT. IRA, culprit lesion and extent of jeopardised/infarcted myocardium were assessed by three-dimensional (3D) volume-rendered images with myocardium maps and computed tomography angiography (CTA), compared with stress-redistribution thallium-201 single-photon emission computed tomography (SPECT) plus conventional coronary angiography (CCA). MDCT-jeopardised score (severity of jeopardised myocardium) was defined as extent of jeopardised myocardium multiplied by the weighted factor dependent on culprit lesion severity compared with SPECT-SRS (summation of segmental reversible score). The IRA indication for revascularisation was evaluated by MDCT-jeopardised score plus CTA. SPECT-SRS > or =2 plus CCA-culprit lesion > or =50% was the standard reference. RESULTS: The presence of MDCT-delayed enhancement was found in 101 (94.4%) patients. The IRA and culprit lesion were identified in 99 (92.5%) patients by MDCT-myocardium maps plus CTA. The concordance between MDCT and SPECT for detecting infarcted myocardium was good (kappa = 0.702). The correlation between MDCT-jeopardised score and SPECT-SRS was 0.741. The correlation between CTA and CCA for culprit lesion severity was 0.85. The sensitivity, specificity, negative and positive predictive values of MDCT-jeopardised score > or =2.5 plus CTA for indicating revascularisation were 90.2%, 80.4%, 86.0% and 85.9%, respectively. CONCLUSIONS: Dual-phase MDCT has good accuracy for identifying IRA, and assessing infarcted and jeopardised myocardium for clinical relevance. It provides an alternative for triage and therapeutic planning in post-AMI.
Assuntos
Infarto do Miocárdio/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Estenose Coronária/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Amoebiasis is one of the most common protozoal diseases of reptiles, but amoebic myositis has not been reported in any animal species. An 11-year-old, male common water monitor lizard (Varanus salvator) was found dead with several subacute ulcerated skin wounds. Gross examination revealed multiple discrete to coalescing, white-yellow to gray, caseous foci scattered in the skeletal muscles and liver. The mucosa of small intestine was thickened, red, and contained many variably sized, dark red ulcers, with depressed and hemorrhagic centers. Histopathologic examination revealed severe necrotizing and granulomatous myositis, hepatitis, and enteritis accompanied by large numbers of intralesional, 10-20-microm diameter, periodic acid-Schiff-positive, amoeboid protozoa. Gene sequence analysis of a 136-bp region of the 18S ribosomal RNA amplified by polymerase chain reaction revealed 98-100% similarity with Entamoeba invadens. Aside from intestinal and hepatic involvement, no other internal organs were affected. The muscular infection by E. invadens likely resulted from a combination of direct invasion of trophozoites via skin wounds and hematogenous spread.
Assuntos
Entamoeba/genética , Entamebíase/patologia , Entamebíase/veterinária , Lagartos/parasitologia , Miosite/patologia , Miosite/veterinária , Animais , Sequência de Bases , Evolução Fatal , Masculino , Dados de Sequência Molecular , Músculo Esquelético/parasitologia , RNA Ribossômico 18S/genética , Análise de Sequência de DNA , Homologia de Sequência , TaiwanRESUMO
OBJECTIVES: To determine whether the standard techniques of measuring tumour size could be applied to the measurement of nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of case notes from the Buddhist Tzu Chi Dalin General Hospital archives was performed. SETTINGS: The Buddhist Tzu Chi Dalin General Hospital is a teaching hospital in Taiwan. PARTICIPANTS: All patients with nasopharyngeal carcinoma were included. MAIN OUTCOME MEASURES: Ninety-eight patients with newly diagnosed nasopharyngeal carcinoma were treated with high-dose radiotherapy and chemotherapy were enrolled in this study. Computed tomography-derived primary tumour volume, bidimensional measurement and unidimensional measurement were recorded. Intrarater reliability was measured. To examine the validity of various measurements, we estimated the Spearman's correlation co-efficients between those measurements and the gold standard value (primary tumour volume measurement with summation of area techniques). Univariate and multivariate analyses were performed and Kaplan-Meier survival curves constructed. RESULTS: There was a significant association between primary tumour volume and bidimensional measurement with respect to tumour size at diagnosis (Spearman's correlation co-efficient = 0.845, P < 0.001). Using age, gender, chemotherapy status and T-stage as covariate, bidimensional measurement remained an independent prognostic factor for any relapse [Hazard ratio = (HR) 1.066; P = 0.029], and overall survival (HR = 1.097; P = 0.007). Patients with small bidimensional measurement (<10 cm(2)) had better prognosis and fewer recurrences. CONCLUSIONS: When using simple measurement to evaluate nasopharyngeal carcinoma, the bidimensional measurement may be used to measure size at diagnosis. Patients with small bidimensional measurement had better prognosis and fewer recurrences. Bidimensional measurement may be further considered to improve the current staging system.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Radioterapia de Alta Energia , Estudos RetrospectivosRESUMO
Traumatic brain injury (TBI) is a major cause of death and disability. In the 2000 guidelines, one of the suggestions for TBI treatment was to maintain cerebral perfusion pressure (CPP) < or = 70 mmHg. But in the 2003 guidelines, the suggestion was changed to < or = 60 mmHg. There have been some discrepancies of opinions about this recommendation in recent publications. In this study, we retrospectively reviewed 305 severe TBI (STBI) patients with Glasgow Coma Scales (GCS) < or = 8 between January 1, 2002 and March 31, 2003. The study group was stratified according to use or nonuse of intracranial pressure (ICP) monitoring, ICP levels, ages, and GCS levels in order to test the correlation between CCP and the prognosis. The patients < 50-year-old, with higher GCS level, with ICP monitoring, and with ICP levels < 20 mmHg had lower mortality rates and better prognosis (GOS) (p < 0.05 or 0.001). The patients in the GCS 3-5 subgroup had a significantly lower mortality and better prognosis if the CPP value was maintained higher than 70 mmHg (p < 0.05) The optimal CPP maintained < or = 60 mmHg did not fit in all STBI patients. Our study concludes that it is critical to maintain CPP substantially higher in lower GCS level patients.
Assuntos
Lesões Encefálicas/fisiopatologia , Circulação Cerebrovascular/fisiologia , Pressão Intracraniana/fisiologia , Feminino , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Masculino , Estudos RetrospectivosRESUMO
Genetic studies in several human autoimmune diseases suggest that the pericentromeric region of chromosome 16 might harbor an autoimmune modifier gene. We hypothesized that the sodium-dependent glucose cotransporter gene SLC5A11 is such a gene, and so might interact with immune-related genes. Herein, this hypothesis was tested in a genetic evaluation of the multiple gene effect in systemic lupus erythematosus (SLE). We used the case-control candidate gene association approach. Eight immune-related genes involved in inflammation and autoantibody generation and clear-up [interleukin 1 receptor antagonist (IL1RN), interleukin 1-beta (IL1-beta), tumor necrosis factor-alpha (TNF-alpha), lymphotoxin-alpha (LTA), tumor necrosis factor ligand superfamily, member 6 (TNFSF6), programmed cell death 1 (PDCD1), C2, and complement component 4 (C4)] were selected for study. Frequency of each candidate's genotype and allele between case and control were compared. Results were stratified by reanalyzing genotype data with relevant symptoms. Finally, improved computational data mining was used to analyze the phenotypes in a large data set. In the frequency analysis, only IL1-beta was significantly associated with SLE. Stratification analysis showed a significant association with SLE symptoms between SLC5A11 and the other immune-related genes, with the exceptions of TNFSF6 and C4. SLC5A11 was significantly associated with low C4 (as was TNF-alpha), anti-Smith antibody (anti-Sm) (as was C2), serositis, and alopecia. Finally, SLC5A11 interacted with PDCD1, TNF-alpha, LTA, and C4. After our study, we concluded that SLC5A11 is involved with some immune effects and interacts with immune-related gene(s), consistent with its function as an autoimmune modifier gene. Furthermore, SLC5A11 might induce apoptosis through the TNF-alpha, PDCD1 pathway. The present genotype-phenotype mapping approach should be applicable to genetic study of other complex diseases.
Assuntos
Autoimunidade/genética , Lúpus Eritematoso Sistêmico/imunologia , Proteínas de Transporte de Sódio-Glucose/fisiologia , Adulto , Feminino , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas de Transporte de Sódio-Glucose/genéticaRESUMO
Healthy patients with asymmetric sensorineural hearing loss who had received examination of auditory brainstem responses (ABR) were gathered for retrospective analysis. The effects of sex, age and hearing asymmetry on the interaural differences of ipsilateral ABR were determined by multivariant linear regression. Our results showed that the interaural differences of ABR wave III and wave V latencies were significantly affected by hearing asymmetry but not by sex or age. However, in female subjects younger than 50 years, differences of III-V intervals could be negatively correlated with hearing asymmetry. We suggest that plasticity in the auditory brainstem in younger females might account for asymmetrical peripheral hearing in this group.
Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Lateralidade Funcional/fisiologia , Perda Auditiva Neurossensorial/fisiopatologia , Audição/fisiologia , Plasticidade Neuronal/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores SexuaisRESUMO
The interleukin-1 receptor antagonist (IL1RN or IL-1Ra) is a natural antagonist of IL-1-beta. Using IL1RN as a possible marker in patients with systemic lupus erythematosus (SLE), we evaluated whether uIL1RN single nucleotide polymorphisms (SNPs) were associated with the pathogenesis of SLE in Taiwanese, and specifically whether IL1RN (rs315952) was significantly associated with end-stage renal disease. We examined IL1RN isoform expression patterns in patients with SLE to determine whether the expressions play a role in the pathogenesis of SLE. Both case-control and family-based association studies were used. For the case-control study, 104 patients with SLE and 97 normal controls were recruited, and for the family-based study, 11 families with SLE without renal disorder were recruited from the 104 patients with SLE. Eight IL1RN SNPs (rs2234678, rs2234679, rs315951, rs315952, rs419598, rs432014, rs447713, and rs451578) were selected for the family-based study. Reverse-transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expression pattern of each isoform. Our results showed that IL1RN (rs315952) was significantly associated with SLE in patients without renal disorder in the family-based study, after disease stratification, but was not significantly associated with SLE in the case-control study. In the family-based study, the haplotype of IL1RN (AGCCTTAG) was significantly associated with SLE (chi2 = 11.714, P < 0.001). Using RT-PCR to determine the expression pattern of the IL1RN isoforms, we found different expression patterns between normal controls and patients with SLE, with an addition of IL1RN isoform4 or the low expression of IL1RN isoform1. We concluded that IL1RN and its isoforms were involved in the pathogenesis of SLE.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Alelos , Povo Asiático , Sequência de Bases , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Dados de Sequência Molecular , Linhagem , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Alinhamento de SequênciaRESUMO
Previously we found postnatal binge-like ethanol exposure using an artificial-rearing method in the rat delayed developmental up-regulation of GABA(A) receptors (GABA(A)Rs) in both medial septum/diagonal band (MS/DB) and cerebellar Purkinje neurons. In the present study, the impact of ethanol on developing GABA(A)Rs in MS/DB neurons was further tested under conditions not requiring anesthesia or maternal deprivation. Nursing rat pups received ethanol (4.5-5.25 g/kg/day) on postnatal days (PD) 4-9, which was administrated manually by oral intragastric intubation. This treatment caused dose-dependent blunting of peak GABA(A) receptor whole cell currents in acutely dissociated MS/DB cells on PD 12-15. The threshold with oral intubation was slightly higher than previously observed for artificial-rearing (4.9 vs. 4.5 g/kg/day). The previously observed reduced sensitivity of GABA(A)Rs to Zn(2+)-inhibition after ethanol was not found with the intubation model. In studies only carried out using the intubation method, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) caused an allosteric concentration-dependent potentiation of currents activated by non-saturated concentrations of GABA. A bicuculline sensitive direct activation of GABA(A)Rs also occurred with higher concentrations of 3alpha-OH-DHP alone. Ethanol intubation up-regulated allosteric neurosteroid potentiation with low concentrations of GABA, but did not change direct agonist actions of 3alpha-OH-DHP. Finally, 3alpha-OH-DHP did not prime ethanol insensitive GABA(A)Rs to become sensitivity to acute ethanol potentiation. These results indicate ethanol consistently blunts postnatal GABA(A) receptor up-regulation across early postnatal binge-type ethanol exposure models and may increase positive modulation of GABA(A) receptors by endogenous neurosteroids.
Assuntos
Anticonvulsivantes/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Neurônios/efeitos dos fármacos , Pregnanolona/análogos & derivados , Pregnanolona/farmacologia , Receptores de GABA-A/metabolismo , Fatores Etários , Regulação Alostérica , Animais , Animais Lactentes , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Feminino , Intubação Gastrointestinal , Masculino , Neurônios/metabolismo , Técnicas de Patch-Clamp , Gravidez , Prosencéfalo/citologia , Ratos , Regulação para Cima/efeitos dos fármacos , Zinco/farmacologiaRESUMO
Recently, we found that early postnatal ethanol exposure inhibits the maturation of GABAA receptors (GABAARs) in developing medial septum/diagonal band (MS/DB) neurons, suggesting that these receptors may represent a target for ethanol related to fetal alcohol syndrome (FAS). To determine whether GABAARs on other neurons are also sensitive to a postnatal ethanol insult, postnatal day (PD) 4-9, rat pups were artificially reared and exposed to ethanol (4.5 g kg-1 day-1, 10.2% v/v). The pharmacological profile of acutely dissociated cerebellar Purkinje cell GABAARs from untreated, artificially reared controls and ethanol-treated animals was examined with conventional whole-cell patch clamp recordings during PD 12-16 (juveniles) and PD 25-35 (young adults). For untreated animals, GABA (0.3-100 microM) consistently induced inward Cl- currents in a concentration-dependent manner showing an age-related increase in maximum response without change in EC50 or slope value. Acute ethanol (100 mM) consistently inhibited 3 microM GABA currents (10-20%); positive modulators, pentobarbital (10 microM), midazolam (1 microM) and loreclezole (10 microM), consistently potentiated; the negative modulator, Zn2+ (30 microM), inhibited GABA currents across both juvenile and young adult groups. Loreclezole potentiation increased while Zn2+ inhibition decreased with age in untreated Purkinje neurons. Postnatal ethanol exposure (PD 4-9) decreased GABAAR maximum current density in young adult Purkinje cells but not in juvenile neurons. However, sensitivity to allosteric modulators did not change after ethanol. These data are consistent with the hypothesis that postnatal ethanol exposure during the brain growth spurt can disturb GABAAR development across the brain, although the mechanism(s) underlying this action remains to be determined.
Assuntos
Etanol/farmacologia , Células de Purkinje/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Regulação Alostérica , Animais , Animais Recém-Nascidos , Transtornos do Espectro Alcoólico Fetal/etiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
The impact of 'binge-like' ethanol exposure on postnatal days (PD) 4-9 was examined on development of gamma-aminobutyric acid type A receptors (GABAAR) during the first month of life in the rat. Whole-cell patch-clamp recordings in acutely isolated medial septum/diagonal band (MS/DB) neurons were used to define effects of rapidly applied ethanol and other allosteric modulators on bicuculline-sensitive GABA currents. Three age groups were examined including 'pups' (PD 4-10), 'juveniles' (PD 11-16) and 'young adults' (PD 25-35). In untreated neurons, maximum responses to GABA and the apparent GABA EC50 increased approximately 2-fold during the first month of life. Potentiation of GABA responses by pentobarbital, midazolam, and loreclezole all increased with age, while Zn2+ inhibition declined. Initial inhibition by ethanol switched to potentiation of GABA responses during this time. In vivo, binge-like ethanol treatment (4.5 g kg-1 day-1 divided into two doses, 2 h apart on PD 4-9) reduced both the GABA maximal response and GABA EC50 measured on PD 11-16. These measures returned to control levels by PD 25-35. After binge-like postnatal ethanol exposure, age-dependent loss of Zn2+ inhibition of GABA responses was increased, while potentiating actions of in vitro ethanol were blocked. GABAAR modulation by other drugs was unaffected. These data suggest that early postnatal ethanol exposure disrupts the expected developmental pattern of GABAAR function in MS/DB neurons, an action that could contribute to neurobehavioral deficits associated with the fetal alcohol syndrome. Whether these changes are due to cellular damage, delayed gene expression or post-translational modification needs to be determined.
Assuntos
Química Encefálica/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Neurônios/metabolismo , Receptores de GABA-A/metabolismo , Algoritmos , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Etanol/sangue , Feminino , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-DawleyRESUMO
A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.
Assuntos
Concussão Encefálica/complicações , Concussão Encefálica/fisiopatologia , Tronco Encefálico/fisiopatologia , Surdez/etiologia , Potenciais Evocados Auditivos do Tronco Encefálico , Vias Auditivas/fisiopatologia , Feminino , Humanos , Colículos Inferiores/fisiopatologia , Pessoa de Meia-IdadeRESUMO
The purpose of the present study is to test whether Wolinsky and Johnson's declaration that activities of daily living (ADL) can be divided into three subdimension (basic, household, and advanced ADL), and whether these three dimensions could be replicated or not in Taiwan. Furthermore, to confirm the relationship of advanced ADL and cognitive function. The analyses were based on a sample of 790 respondents over 65 years of age who lived in the community of Southern Taiwan. Fourteen items were adopted from the ADL section of OARS Multidimensional Functional Assessment (OMFAQ, Chinese Version) for performing a confirmatory factor analysis. In addition, 10 items from the Short Portable Mental Status Questionnaire (SPMSQ) were selected for a zero-order correlation and regression analyses to examine the relationship between the advanced ADL and cognitive function. The results support Wolinsky & Johnson's assertion, but some items that are comprised in each factor structure, however, are not consistent with those in Wolinsky & Johnson's study, such as taking medicine, grooming, eating, shopping, and transporting. Significant correlation between advanced ADL and cognitive function was also confirmed in the study (r = 0.612, p < 0.05).
Assuntos
Atividades Cotidianas , Idoso , Povo Asiático , Cognição , Análise Fatorial , Feminino , Humanos , MasculinoRESUMO
The study investigated the Taiwanese elderly in two different ethnic groups (Paiwan and Min-Nan) regarding their multifunctional status. The purpose was to make known and compare the subjective and objective health status of these two groups. The results for the objective measurements indicated that an elderly Paiwanese had 2.74 kinds of diseases on average. The most prevalent diseases among the Paiwan elderly were arthritis (rheumatism), circulation troubles in arms or legs, high blood pressure, stomach or intestinal disorders or gall bladder problems, cataract, heart trouble, emphysema (chronic bronchitis), skin disorder (leg ulcers or severe burns), asthma, and digestive system ulcers. Of all disease, five (arthritis, circulation trouble, emphysema, skin disorder, and tuberculosis) were statistically more prevalent among the Paiwan elderly than among the Min-Nan elderly. In terms of health scoring, the two groups were comparable except in the following two aspects: (1) more Paiwan elderly were unable to take medicine by themselves, and (2) the Paiwan elderly had lower cognitive ability ratings. In the subjective arena, the Paiwan elderly had a lower score in self-rating health status. Condensed, the health status of the Paiwan was worse than that of the Min-Nan elderly both in objective and subjective measurements.
Assuntos
Etnicidade , Nível de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Grupos Raciais , TaiwanRESUMO
Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.