RESUMO
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Transtornos Relacionados ao Uso de Álcool/genética , Metilação de DNA/efeitos dos fármacos , Adulto , Idoso , Consumo de Bebidas Alcoólicas/metabolismo , Transtornos Relacionados ao Uso de Álcool/metabolismo , Biomarcadores/sangue , População Negra/genética , Ilhas de CpG/genética , Epigênese Genética , Etanol/sangue , Etanol/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , População Branca/genéticaRESUMO
AIM: Quality of life varies in patients with anal incontinence. The severity of symptoms is a surprisingly modest predictor, but they reliably elicit disgust. The current work assessed prospectively whether dispositional sensitivity to disgust predicted the quality of life in patients with anal incontinence. METHOD: Seventy-five patients with anal incontinence identified from the waiting list for the pelvic floor clinic at the Greenlane Clinical Centre, Auckland, New Zealand, completed questionnaires assessing symptom severity (Fecal Incontinence Severity Index) and disgust sensitivity (Disgust Sensitivity-Revised scale) prior to a first appointment. Three months later incontinence-specific (Fecal Incontinence Quality of Life Scale, FI QLS) and general quality of life (World Health Organization Quality of Life-BREF, WHOQOL-BREF) were assessed. RESULTS: Greater severity of symptoms prospectively predicted lower incontinence-specific quality of life (FI QLS lifestyle domain) and lower general quality of life (WHOQOL-BREF environmental domain). Greater disgust sensitivity predicted poorer psychological and environmental well-being, and moderated the link between symptom severity and outcome. Persons low in disgust sensitivity reported a higher quality of life when symptom severity was low, but those with a high disgust sensitivity had a low quality of life regardless of symptom severity. CONCLUSION: The functional status of patients with anal incontinence explains some but not all of the variation in quality of life. Emotional factors such as disgust appear to have a role. Disgust sensitivity warrants further attention.
Assuntos
Incontinência Fecal/psicologia , Qualidade de Vida/psicologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Saúde , Estudos Transversais , Emoções , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Individuals reporting greater insecure attachment are more likely to report maladaptive sexual motivations, such as sex to avoid negative relational and personal outcomes (e.g., conflict). Despite the costs of such sexual motivations, research is less clear regarding what might buffer the extent to which attachment insecurities manifest in such motives. The current study examined whether trait mindfulness moderates the links between attachment insecurity and maladaptive sexual motives. Participants (N = 194) completed measures of trait mindfulness, general sexual motivations, and attachment. As predicted, the links between attachment anxiety and having sex to cope and affirm the self were eliminated among individuals reporting higher levels of the acting with awareness facet of trait mindfulness. No such buffering effects were seen for attachment avoidance. Instead, acting with awareness mindfulness appeared to increase the extent to which more avoidantly attached individuals reported coping and self-affirmation-based sexual motives. These findings contribute to knowledge regarding the potential utility and limits of mindfulness in relational and sexual contexts, perhaps suggesting that mindfulness may help anxiously attached individuals manage the extent to which attachment concerns manifest in maladaptive sexual motivations. Findings of the study may inform both theory regarding mindfulness in interpersonal functioning and how mindfulness interventions might be deployed in sex therapy contexts.
Assuntos
Atenção Plena , Motivação , Humanos , Comportamento Sexual , Ansiedade , Transtornos de AnsiedadeRESUMO
Research is increasingly linking mindfulness with better relationship outcomes. Less clear is whether these benefits extend to the sexual domain or whether the benefits of mindfulness are moderated by individual characteristics. Accordingly, the current report tested whether a brief online mindfulness intervention improved the cognitive, affective, and behavioral aspects of sexual experiences and whether effects varied by attachment anxiety and avoidance. Participants (N = 90) first completed a measure of attachment before reporting their sexual experiences each day for 7-days. Participants then listened to a mindfulness recording every day for 4 weeks. Finally, sexual experiences were reported on every day for 7 days again. Consistent with previous studies, no benefits of the mindfulness intervention were detected for more avoidant persons. Less consistent with expectation, however, the mindfulness intervention did not improve sexual outcomes in general, nor did it buffer other-focused avoidance-based sexual motivations or bolster sexual communal strength among more anxiously attached persons. However, the intervention did increase reports of positive sexuality among more anxious persons. Results are discussed in terms of the differential utility and limits of short mindfulness interventions looking to enhance sexual functioning in different populations and the potential mechanisms behind the presence and absence of effects.
RESUMO
WHAT IS KNOWN ON THE SUBJECT?: Serious gaming can support learning and development. The use of serious games for skills development and the rehearsal of the management of events that cannot be replicated in real life is well established. Few serious games have been used in mental health services, and none in forensic mental health care. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: How a serious game may be coproduced by forensic mental health service users and game developers The acceptability of the therapeutic use of serious gaming by forensic mental health service users and providers. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Computer games may be used by practitioners in their therapeutic work with forensic mental health service users. Mental health nurses to use serious games to creatively and safely bridge the gap for service users between receiving care in controlled environments and living more independent in the community. ABSTRACT: Introduction Assessment of users' skills and confidence to safely respond to risky community-based situations underpins discharge planning. Serious games have been used for skills development, and this study trialled their use in forensic mental health services. Aim The aim was to develop and test the acceptability and usability of an innovative serious game to support forensic mental health service users' preparation for discharge. Method A prototype serious game was developed by service users and researchers. Acceptability and usability testing was undertaken and service providers interviewed about the acceptability of serious gaming for forensic mental health services. Result A prototype game was produced and successfully trialled by service users. However, both service users and providers identified that work needed to be done to develop and test a game with greater complexity. Discussion The acceptability and usability of using serious games to support service users to develop skills needed for successful discharge was demonstrated. Implications for practice Mental health practitioners may use gaming to support their practice and work innovatively with other professions such as game developers to create new ways of working in forensic mental health services.
Assuntos
Adaptação Psicológica , Psiquiatria Legal/métodos , Alta do Paciente/normas , Satisfação do Paciente , Enfermagem Psiquiátrica/métodos , Reabilitação Psiquiátrica/métodos , Jogos de Vídeo/normas , Adulto , Estudos de Viabilidade , Jogos Experimentais , Hospitais Psiquiátricos , Humanos , Masculino , População UrbanaRESUMO
Young children undergoing complex cardiac operation lose more blood after cardiopulmonary bypass than do older patients. This study was designed to investigate the effect of desmopressin on blood loss during the first 24 hours after cardiac operation in children undergoing principally complex surgical procedures. The study consisted of a randomized, blinded comparison of 112 pediatric patients who received either desmopressin 0.3 microgram/kg or saline solution placebo after cardiopulmonary bypass. A coagulation profile including bleeding time, quantitation of von Willebrand factor, and qualitative analysis of the factor VII:von Willebrand factor complex was performed before, 30 minutes after, and 3 hours after the operation. Blood loss and blood replacement were recorded for the first 24 hours after the operation. The surgeon classified the technical difficulty of each procedure as simple or complex. Statistical analysis was performed with Student's unpaired t test and chi 2 analysis. Significance was defined as p < 0.05. Results are listed as mean +/- standard deviation. Data collection was completed for 95 patients. The mean age of all patients was 26 +/- 40 months, and the mean weight was 10 +/- 11 kg, with 84% undergoing complex procedures. There were no differences between the desmopressin and placebo groups with respect to age, weight, or surgical complexity. Twenty-four-hour blood loss and replacement between the desmopressin and placebo groups were not different (blood loss: desmopressin 30 +/- 33 ml/kg, placebo 35 +/- 36; blood replacement: desmopressin 65 +/- 43 ml/kg, placebo 64 +/- 46 ml/kg). Coagulation profiles between the desmopressin and placebo groups were not different at any time. We conclude that desmopressin does not reduce blood loss or blood replacement in young children after cardiopulmonary bypass for either simple or complex cardiac surgical procedures.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Desamino Arginina Vasopressina/uso terapêutico , Adolescente , Volume Sanguíneo , Ponte Cardiopulmonar/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Método Simples-CegoRESUMO
The fatty acid composition of phospholipids from differentiated human neuroblastoma SH-SY5Y cells, human and rat brain tissue and rat brain synaptosomes was determined using high pressure liquid chromatography. Comparison of the fatty acid composition of the cells with that derived from brain tissue identified differences in the cells including a profound deficit of docosahexaenoic acid and an elevation of arachidonic acid. The phospholipid fatty acid content could be modified by addition of free fatty acids to the growth medium, and this was shown to influence the susceptibility of the SH-SY5Y cells to the cell death induced by a mitochondrial toxin, 3-nitropropionic acid.
Assuntos
Ácidos Graxos/toxicidade , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fosfolipídeos/toxicidade , Sinaptossomos/efeitos dos fármacos , Animais , Ácido Araquidônico/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Convulsivantes/toxicidade , Ácidos Docosa-Hexaenoicos/farmacologia , Relação Dose-Resposta a Droga , Humanos , Nitrocompostos , Propionatos/toxicidade , Ratos , Sinaptossomos/fisiologia , Células Tumorais CultivadasRESUMO
Magnetic resonance imaging was used to assess prefrontal brain structure in 17 schizophrenic, 18 psychiatric control, and 19 normal control subjects of comparable age, social background, and educational status, while three neuropsychological measures were used to assess prefrontal functioning. Schizophrenic patients had significantly smaller prefrontal areas than both psychiatric control and normal control subjects in all three planes. When posterior brain area and temporal lobe were entered into statistical analysis as covariates, they did not explain the prefrontal deficits. Schizophrenic patients made more perseveration errors on the Wisconsin Card Sorting Task and had fewer correct responses on the Spatial Delayed Response Task than normal control subjects. Schizophrenic patients performed more poorly than psychiatric control subjects on the Block Design Test. No group differences were found on three other nonfrontal tasks. These data lend some support to the role of prefrontal deficits in the development of schizophrenia.
Assuntos
Lobo Frontal/patologia , Esquizofrenia/diagnóstico , Adulto , Antipsicóticos/uso terapêutico , Encefalopatias/tratamento farmacológico , Testes com Listas de Dissílabos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Escalas de Graduação Psiquiátrica , Esquizofrenia/classificação , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Fatores SexuaisRESUMO
Hypophysectomy is claimed to prevent increased forebrain dopamine turnover produced by administration of sulpiride. We have measured the increase in dopamine metabolite concentrations caused by sulpiride following surgical removal of the pituitary. In saline-treated control animals and in hypophysectomized rats 1 week or 1 month following surgery, administration of sulpiride caused marked elevations of striatal, nucleus accumbens and tuberculum olfactorium, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations which were maximal 4-8 h following drug administration. The maximal increases in nucleus accumbens and tuberculum olfactorium were generally comparable in control and hypophysectomized animals, except for a greater increase in HVA levels in the nucleus accumbens 1 month following hypophysectomy. However, maximal increases in HVA and DOPAC in striatum were more pronounced in hypophysectomized rats 1 week or 1 month following surgery compared with control animals. At 30 min following sulpiride administration only inconsistent changes in dopamine turnover were observed in both control and hypophysectomized rats. Hypophysectomy does not prevent sulpiride from increasing forebrain dopamine turnover suggesting this is due to a direct interaction with cerebral dopamine receptors.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Hipofisectomia , Sulpirida/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Biotransformação , Ácido Homovanílico/metabolismo , Masculino , Prolactina/sangue , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/efeitos dos fármacosRESUMO
Residues of DDT were detected in 76 of 101 samples of rainwater collected during spring and summer at several sites in the Province of New Brunswick in 1967 and 1968, and at one site in the Magdalen Islands, Quebec, in 1968. The dominant residue was p,p'-DDT. Levels of DDT and metabolites combined ranged from less than 0.01 to 1.33 microgram/kg. Levels of DDT and metabolites in the pollen of four species of forest trees in New Brunswick ranged from 0.544 to 1.01 mg/kg; such contaminated pollen possibly contributed to residues in rainwater. Residue data for rainwater from two sites were used to estimate the amount of DDT aerially transported into the Gulf of St. Lawrence during July to October 1968.
Assuntos
DDT/análise , Água Doce/análise , Resíduos de Praguicidas/análise , Chuva , Água/análise , Tempo (Meteorologia) , Cromatografia Gasosa , DDT/análogos & derivados , Novo BrunswickRESUMO
Organochlorine and mercury concentrations are reported for 252 eggs of Leach's storm-petrel (Oceanodroma leucorhoa), double-crested cormorant (Phalarocorax auritus), common eider (Somateria mollissima), common tern (Sterna hirundo), razorbill (Alca torda), common murre (Uria aalge) black guillemot (Cepphus grylle), and Atlantic puffin (Fratercula arctica) from the Bay of Fundy, the Gulf of St. Lawrence, and the open Atlantic shore of Canada during 1970-76. Concentrations of all organochlorines except DDE and polychlorinated biphenyls (PCBs) were low. DDE, PCBs, and mercury residues were highest in cormorant and petrel, intermediated in alcids, and lowest in eider and tern. Temporal and spatial aspects of contamination patterns are discussed. Authors conclude that only in cormorants were DDE residues high enough to cause, through eggshell thinning, local population declines.
Assuntos
Casca de Ovo , Ovos/análise , Inseticidas/análise , Mercúrio/análise , Resíduos de Praguicidas/análise , Animais , Canadá , Bifenilos Policlorados/análiseRESUMO
BACKGROUND: Rocuronium's rapid onset and intermediate duration of action with intravenous administration suggests that intramuscular administration might facilitate tracheal intubation without producing prolonged paralysis. Accordingly, in infants and children, the authors measured onset at the adductor pollicis and respiratory muscles to determine the optimal dose (phase I), then gave this optimal dose to determine the optimal time for tracheal intubation (phase II). METHODS: The authors studied 45 unpremedicated patients aged 3 months to 5 yr. In phase I, 25 patients were anesthetized with nitrous oxide and halothane and breathed spontaneously; twitch tension and minute ventilation were measured. Rocuronium (800-2,400 micrograms/kg) was injected into the quadriceps or deltoid muscle; doses varied, using an "up-down" technique, the goal being to bracket the dose depressing twitch 75-90% within 5 min. In phase II, deltoid injections of the optimal dose from phase I (infants: 1,000 micrograms/kg; children: 1,800 micrograms/kg) were given to 20 patients anesthetized with 0.82-1.0% halothane. Tracheal intubation was attempted 1.5-3.0 min later; time to tracheal intubation was varied, using an "up-down" technique. RESULTS: In phase I, 5 of 7 patients given quadriceps injections (1,200-2,200 micrograms/kg) had slow onset of twitch and ventilatory depression. With deltoid injections (800-2,400 micrograms/kg), all patients developed complete twitch depression; median time to 50% depression of minute ventilation was 3.2 min in infants and 2.8 min in children. In phase II, intubating conditions were consistently adequate or good-excellent at 2.5 min in infants and 3.0 min in children. Initial twitch recovery was at 57 +/- 13 min (mean +/- SD) in infants and 70 +/- 23 min in children. CONCLUSIONS: Deltoid injections of rocuronium, 1,000 micrograms/kg in infants and 1,800 micrograms/kg in children, rapidly permit tracheal intubation in infants and children, despite a light plane of anesthesia. Duration of action of these large doses might limit clinical utility.
Assuntos
Androstanóis/administração & dosagem , Intubação Intratraqueal/métodos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Androstanóis/efeitos adversos , Anestesia por Inalação/métodos , Pressão Sanguínea/efeitos dos fármacos , Pré-Escolar , Depressão Química , Diafragma/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Injeções Intramusculares , Contração Muscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Respiração/efeitos dos fármacos , RocurônioRESUMO
BACKGROUND: Intramuscular rocuronium, in doses of 1,000 microg/kg in infants and 1,800 microg/kg in children, produces complete twitch depression in 5-6 min. To determine the rate and extent of absorption of rocuronium after intramuscular administration, blood was sampled at various intervals after rocuronium administration by both intramuscular and intravenous routes to determine plasma concentrations (Cp) of rocuronium. METHODS: Twenty-nine pediatric patients ages 3 months to 5 yr were anesthetized with N2O and halothane. The trachea was intubated, ventilation was controlled, and adductor pollicis twitch tension was measured. When anesthetic conditions were stable, rocuronium (1,000 microg/kg for infants and 1,800 microg/kg for children) was injected either intramuscularly (in the deltoid muscle) or intravenously. Four venous plasma samples were obtained from each child 2-240 min after rocuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak Cp with intramuscular administration. RESULTS: With intramuscular administration, rocuronium's bioavailability averaged 82.6% and its absorption rate constant was 0.105 min(-1). Simulation indicated that Cp peaked 13 min after rocuronium was given intramuscularly, and that 30 min after intramuscular administration, less than 4% of the administered dose remained to be absorbed from the intramuscular depot. CONCLUSIONS: After rocuronium is administered into the deltoid muscle, plasma concentrations peak at 13 min, and approximately 80% of the administered drug is absorbed systemically.
Assuntos
Androstanóis/farmacocinética , Fármacos Neuromusculares não Despolarizantes/farmacocinética , Androstanóis/administração & dosagem , Androstanóis/efeitos adversos , Disponibilidade Biológica , Pré-Escolar , Humanos , Lactente , Injeções Intramusculares , Taxa de Depuração Metabólica , RocurônioRESUMO
BACKGROUND: A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. METHODS: Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. RESULTS: Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. CONCLUSIONS: In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.
Assuntos
Anestesia , Fármacos Neuromusculares não Despolarizantes/farmacocinética , Brometo de Vecurônio/análogos & derivados , Algoritmos , Disponibilidade Biológica , Pré-Escolar , Feminino , Meia-Vida , Humanos , Lactente , Injeções Intramusculares , Injeções Intravenosas , Masculino , Modelos Biológicos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Brometo de Vecurônio/administração & dosagem , Brometo de Vecurônio/farmacocinéticaRESUMO
BACKGROUND: Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. METHODS: Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. CONCLUSIONS: This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.
Assuntos
Intubação Intratraqueal , Fármacos Neuromusculares não Despolarizantes , Brometo de Vecurônio/análogos & derivados , Pré-Escolar , Feminino , Humanos , Lactente , Injeções Intramusculares , Injeções Intravenosas , Laringoscopia , Masculino , Contração Muscular/efeitos dos fármacos , Fármacos Neuromusculares Despolarizantes , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Projetos Piloto , Mecânica Respiratória/efeitos dos fármacos , Succinilcolina , Fatores de Tempo , Brometo de Vecurônio/administração & dosagem , Brometo de Vecurônio/efeitos adversosRESUMO
The combined effects of polychlorinated biphenyls (PCBs) or a polybrominated biphenyl (PBB) with mirex, kepone, or photomirex were investigated in rats. Groups of 10 animals were fed diets containing the organohalogens alone or in various combinations for 28 d. Body weight gain and food consumption were not affected by any treatment. Liver weight was increased in the group fed Aroclor 1260/photomirex and in all groups receiving PBB. Hepatic microsomal enzyme activities were elevated in the groups treated with halogenated biphenyls alone; this effect was not potentiated in the presence of mirex-related compounds. Serum biochemical parameters were, for the most part, normal. Hematology tests revealed no abnormalities. Histological changes occurred in the liver, thyroid, and kidney of rats treated with the organohalogens alone or in combination. Liver alterations consisted of central lobular cytoplasmic enlargement, exaggerated periportal perinuclear halos, and increased nuclear hyperchromicity and anisokaryosis. Fatty degeneration was observed in all treated groups. Thyroid changes were characterized by a generalized reduction in follicular size and colloid density with collapse of the follicles. Kidneys suffered mild eosinophilic cytoplasmic inclusions in the proximal convoluted tubule and focal lymphoid aggregates. Histological changes due to PCBs and PBB were aggravated by mirex and related compounds. The degree of damage appeared to be additive rather than potentiative. Mirex and photomirex levels in livers of rats concomitantly exposed to halogenated biphenyls were four to six times higher than those in rats fed mirex-related compounds alone. However, the toxic response in this organ was not potentiated as a result of the increased accumulation. It was concluded that mirex-related compounds at the dose levels studied did not potentiate the effects produced by halogenated biphenyls and vice versa.
Assuntos
Compostos de Bifenilo/toxicidade , Clordecona/toxicidade , Inseticidas/toxicidade , Mirex/toxicidade , Bifenil Polibromatos/toxicidade , Bifenilos Policlorados/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dieta , Fígado Gorduroso/induzido quimicamente , Masculino , Mirex/análogos & derivados , RatosRESUMO
A pulse oximeter sensor is used to monitor changes in arterial hemoglobin oxygen saturation (SpO2) in anesthetized pediatric patients. The authors compared the kinetics of desaturation and resaturation measured by sensors placed over central (tongue, cheek) and peripheral (finger, toe) vascular beds in children with congenital heart disease. Desaturation time was defined as the time which elapsed between the onset of apnea and a 4% decrease in SpO2 from baseline. The desaturation times averaged 24 +/- 12 s, 56 +/- 34 s, and 58 +/- 28 s for the cheek, finger, and toe, respectively (n = 40; P < 0.0001 for cheek versus finger or toe). Resaturation time was defined as the interval between the resumption of ventilation and a 4% increase in SpO2 above the nadir. Resaturation times averaged 12 +/- 8 s for the cheek, 40 +/- 36 s for the finger, and 47 +/- 25 s for the toe (n = 40; P < 0.0001 for cheek versus finger or toe). A comparison of the kinetics at two central sensor sites, cheek and tongue, respectively, revealed no significant differences in desaturation times (20 +/- 10 s vs 21 +/- 9 s) or resaturation times (10 +/- 6 s vs 7 +/- 3 s) (n = 13). The authors conclude that both desaturation and resaturation are detected earlier by centrally placed sensors.
Assuntos
Hemoglobinas/metabolismo , Oximetria/métodos , Oxigênio/farmacocinética , Técnicas Biossensoriais , Procedimentos Cirúrgicos Cardíacos , Bochecha , Pré-Escolar , Dedos , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Oxigênio/sangue , Pressão Parcial , Dedos do Pé , LínguaRESUMO
Cytotoxic T cells are believed to be an important immune response in HIV infection, both in the initial response to viraemia, and in controlling HIV replication and maintaining clinical stability. We report here the detailed findings in two vertically infected children, from the Edinburgh perinatal cohort. Both were clinically stable for the first 7 years of life. One had vigorous HIV-specific cytotoxic T lymphocyte (CTL) responses, and non-lytic suppression, measured in vitro, while the second had no CTL activity against HIV. Despite her HIV-specific immunity, the first child had a declining CD4 count, and a high and fluctuating viral load, whereas the second child maintained a stable CD4 count, a low viral load and had a virus which could not be cultured in peripheral blood mononuclear cells (PBMC) in vitro. The first child subsequently progressed to AIDS and has now died, while the second remains clinically well. More detailed investigations showed the clinically stable child to be heterozygous for the CCR5 receptor, and to be HLA-B49--both of which markers have been associated with slow HIV disease progression. These findings question the role of CTL in maintaining stable HIV disease, and stress the need for immunological investigations to be considered in the light of the genetic make-up of the patient. They may also reflect a different immunopathogenesis of HIV disease in children compared with adults.