RESUMO
Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002-2004 to 13% in 2008-2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.
Assuntos
Antibacterianos/administração & dosagem , Cefazolina/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Febre de Causa Desconhecida/tratamento farmacológico , Neutropenia/diagnóstico , Tobramicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecções Comunitárias Adquiridas/mortalidade , Infecção Hospitalar/mortalidade , Feminino , Febre de Causa Desconhecida/complicações , Febre de Causa Desconhecida/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Animals receiving low-intensity electrical stimulation of the basolateral nucleus of the amygdala while drinking plain tap water were injected with toxic doses of lithium chloride to examine whether brain stimulation can serve as a conditioned stimulus in a bait-shyness paradigm. Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning. Pairing lithium chloride with stimulation of the amygdala had no effect on subsequent water intake in the absence of brain stimulation. This effect appears to be locus specific, as caudate stimulation could not serve as a conditioned stimulus.
Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Paladar/fisiologia , Animais , Mapeamento Encefálico , Núcleo Caudado/fisiologia , Estimulação Elétrica , Masculino , Ratos , Retenção Psicológica/fisiologiaRESUMO
We have produced yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD). YAC46 and YAC72 mice show early electrophysiological abnormalities, indicating cytoplasmic dysfunction prior to observed nuclear inclusions or neurodegeneration. By 12 months of age, YAC72 mice have a selective degeneration of medium spiny neurons in the lateral striatum associated with the translocation of N-terminal htt fragments to the nucleus. Neurodegeneration can be present in the absence of macro- or microaggregates, clearly showing that aggregates are not essential to initiation of neuronal death. These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration.
Assuntos
Cromossomos Artificiais de Levedura/genética , Corpo Estriado/patologia , Doença de Huntington/genética , Mutação/fisiologia , Degeneração Neural/patologia , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Adaptação Fisiológica/fisiologia , Animais , Comportamento Animal/fisiologia , Encéfalo/patologia , Citoplasma/patologia , Modelos Animais de Doenças , Eletrofisiologia , Embrião de Mamíferos/fisiologia , Proteína Huntingtina , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos/genética , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismoRESUMO
The present study examined the disruptive effects of low-intensity electrical stimulation in the caudate or amygdala on retention of inhibitory shock avoidance. Caudate stimulation administered during a training trial disrupted inhibitory avoidance on a retest trial. However, animals receiving caudate stimulation during both training and retention trials displayed good retention of this behavior and did not differ significantly from implanted controls. These data suggest a role for state-dependent learning in mediating the disruptive effects of caudate stimulation on inhibitory shock avoidance. No evidence was found for state-dependent effects with amygdaloid stimulation. Animals receiving stimulation only during training or during both training and retest trials showed comparable disruption of inhibitory shock avoidance. These data provide evidence for locus-specific state-dependent effects of electrical brain-stimulation. The implications of these state-dependent effects are discussed with respect to the use of electrical brain-stimulation to study the neural substrates of memory.
Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Núcleo Caudado/fisiologia , Inibição Psicológica , Animais , Estimulação Elétrica , Masculino , Ratos , Retenção Psicológica/fisiologiaRESUMO
Unilateral kainic acid lesions of the dorsal striatum provided evidence for a dissociation of neural substrates of brain-stimulation reward at sites in the ventral tegmental area and substantia nigra. The lesions caused a significant increase in current intensity thresholds at substantia nigra placements, whereas similar lesions had no effect on self-stimulation thresholds at sites in the ventral tegmentum. In addition, the rate-increasing effects of D-amphetamine (0.1-1.0 mg/kg) on self-stimulation were determined before and after lesions to the dorsal striatum. No significant changes in dose-response curves were observed at either loci. Amphetamine-induced rotation was used to confirm damage to the dorsal striatum and lesioned animals were observed to rotate towards the side of the lesion. In contrast, sham-lesioned animals showed turning away from the side stimulated electrically in previous tests. The results of the self-stimulation and rotation experiments are discussed in the context of neural substrates of reward and motor activity.
Assuntos
Corpo Estriado/fisiologia , Autoestimulação/fisiologia , Substância Negra/fisiologia , Tegmento Mesencefálico/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Dextroanfetamina/farmacologia , Dopamina/fisiologia , Humanos , Ácido Caínico/toxicidade , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Ratos , Ratos Endogâmicos , Autoestimulação/efeitos dos fármacos , Comportamento Estereotipado/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Tegmento Mesencefálico/efeitos dos fármacosRESUMO
Changes in extracellular concentrations of dopamine (DA) were measured in vivo in the nucleus accumbens of the rat during intravenous self-administration of either cocaine (0.25, 0.5, 1.0mg/infusion) or d-amphetamine (0.05, 0.1, 0.2mg/infusion). Drug intake was limited to 12 self-administered infusions per session for each drug/dose combination. Changes in extra-cellular DA concentrations were measured by two different techniques: chronoamperometry in conjunction with chronically-implanted stearate-modified carbon paste electrodes, or intracerebral microdialysis with off-line analyses using high performance liquid chromatography with electrochemical detection (HPLC-ED). Significant increases in extracellular DA concentrations were observed with both in vivo techniques during self-administration of each dose of cocaine or d-amphetamine. For each drug, the magnitude of change during the first hour of the test session was comparable across doses. However, the change observed over the first 2h period, as measured by microdialysis and HPLC-ED, revealed a dose effect for cocaine, but no dose-response effect for d-amphetamine. The duration of the drug-induced elevation was increased significantly as a function of dose with both cocaine and d-amphetamine. Data from the microdialysis experiments indicated that the high dose of d-amphetamine (0.2mg/infusion) produced a significantly greater increase in extracellular DA concentrations in the nucleus accumbens than did the high dose of cocaine (1.0mg/infusion), but that comparable changes were induced by doses of 0.1mg/infusion of d-amphetamine and 1.0mg/infusion of cocaine, respectively. Each dose of both psychostimulant drugs also produced a significant decrease in dihydroxyphenylacetic acid (DOPAC) levels. The latter finding indicated that the electrochemical signal measured in these studies was not due to the oxidation of DOPAC. These results confirm that self-administration of cocaine or d-amphetamine by the rat is accompanied by a significant increase in extracellular DA concentrations in the nucleus accumbens. The fact that two different psychomotor stimulant drugs of abuse have qualitatively similar neurochemical correlates when self-administered, adds credence to the hypothesis that their reinforcing properties are related to dynamic changes in DA concentrations in the ventral striatal region of the brain.
RESUMO
A conditioned place preference paradigm was employed to demonstrate the rewarding property of unilateral injections of 200 ng (D-ala2)-met5-enkephalinamide into the ventral tegmental area of the rat brain. This effect was attenuated in a dose-related manner by systemic injections of the dopamine receptor blocker haloperidol. In addition, selective lesions of the ascending dopamine (DA) pathways ipsilateral to the injection site blocked the rewarding effect when DA levels were reduced by more than 90%. Similar lesions in the contralateral hemisphere had no influence on this behavior. These data suggest that forebrain DA pathways can mediate some of the rewarding properties of opioid drugs.
Assuntos
Dopamina/fisiologia , Encefalina Metionina/análogos & derivados , Recompensa , Animais , Relação Dose-Resposta a Droga , Encefalina Metionina/farmacologia , Haloperidol/farmacologia , Hidroxidopaminas/farmacologia , Injeções Intraventriculares , Masculino , Oxidopamina , Ratos , Ratos EndogâmicosRESUMO
Positive and negative contrast effects with brain-stimulation reward were inferred from significant differences in rate/intensity curves obtained by ascending, random and descending orders of current presentation. The neuroleptic drug pimozide caused a dose-related attenuation of both positive and negative contrast. A dose of 0.1 mg/kg blocked positive contrast obtained by comparing ascending and random rate/intensity curves. Negative contrast and threshold current intensities for brain-stimulation reward at sites in the ventral tegmental area were unaffected by the low dose (0.1 mg/kg) of pimozide. Higher doses of pimozide (0.25, 0.4 mg/kg) blocked both positive and negative contrast effects, and caused a significant elevation in threshold current intensities under the random order condition. Two doses (0.25, 0.4 mg/kg) of pimozide were associated with performance deficits as the response rates at the maximum current intensities were attenuated significantly with each order of current presentation. These demonstrations of both positive and negative contrast are consistent with the theoretical position linking brain-stimulation reward to incentive motivation. Furthermore the effects of the dopamine receptor antagonist pimozide are consistent with a role for dopamine in brain-stimulation reward and also raise the possibility of dopaminergic involvement in incentive contrast phenomena.
Assuntos
Encéfalo/fisiologia , Motivação/efeitos dos fármacos , Pimozida/farmacologia , Recompensa , Autoestimulação/efeitos dos fármacos , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/fisiologiaRESUMO
A neural substrate for the reinforcing property of an opiate drug was identified in the ventral tegmental area (VTA) by establishing conditioned reinforcement to salient environmental stimuli paired with intracerebral microinjections of morphine. Bilateral microinjections of morphine into the VTA in doses of 0.2 microgram and 1.0 microgram produced a subsequent change in place preference to a distinctive compartment previously associated with the stimulant effects of morphine. Microinjection of 1.0 microgram morphine at sites 2.5 mm dorsal to the VTA had no effect. Pretreatment with naloxone (2 mg/kg) antagonized the reinforcing effects of 1.0 microgram morphine as this group showed no significant change in place preference. Nor did control groups receiving microinjections of sterile physiological saline. Taken together, these data suggest that opiate receptors, located in the ventral tegmental area, play an important role in mediating the reinforcing effects of morphine. The possible involvement of dopaminergic neurons in these effects is discussed.
Assuntos
Morfina/farmacologia , Reforço Psicológico , Animais , Condicionamento Operante/efeitos dos fármacos , Masculino , Mesencéfalo/anatomia & histologia , Microinjeções , Morfina/administração & dosagem , Naloxona/farmacologia , Ratos , Tegmento MesencefálicoAssuntos
Encéfalo/fisiologia , Dopamina/metabolismo , Núcleo Accumbens/fisiologia , Autoestimulação , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Diálise/métodos , Estimulação Elétrica , Ácido Homovanílico/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Ratos , Fatores de TempoAssuntos
Tronco Encefálico/fisiologia , Memória/fisiologia , Núcleos da Rafe/fisiologia , Retenção Psicológica/fisiologia , Serotonina/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Estimulação Elétrica , Fenclonina/farmacologia , Masculino , Pré-Medicação , Núcleos da Rafe/efeitos dos fármacos , Ratos , Retenção Psicológica/efeitos dos fármacosRESUMO
The role of dopaminergic (DA) neurons in brain stimulation reward produced by electrical stimulation of the ventral tegmental area (VTA) was investigated in the rat. In the first experiment, extensive 6-hydroxydopamine lesions of the ascending fibers of the mesotelencephalic DA projections resulted in significant changes in intracranial self-stimulation (ICS) rate-current intensity functions when the lesion was ipsilateral to the stimulating electrode. Similar contralateral lesions had no effect on these functions, thus ruling out lesion-induced performance deficits as being responsible for the decreases in ICS rates across the wide range of current intensities that occurred after the ipsilateral lesions. In the second experiment, ICS obtained from electrodes in the VTA resulted in significant increases in the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, nucleus accumbens, and olfactory tubercle ipsilateral to the stimulating electrode. The ratios of DOPAC and HVA to DA, considered to be indices of DA utilization, were also increased in these brain regions ipsilateral to the electrode. No changes were observed in the contralateral striatum, nucleus accumbens, and olfactory tubercle. Similar increases were observed in stimulated "yoked" animals that received brain stimulation at identical rates and currents but did not lever-press for this stimulation. The third experiment examined the effects of lever-pressing for food on an FR8 schedule of reinforcement on DA utilization in the striatum, nucleus accumbens, and olfactory tubercle. Despite high rates of responding, no effects were observed on DOPAC:DA or HVA:DA ratios in these brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)