RESUMO
BACKGROUND: Intensive home treatment (IHT) is an intervention that provides intensive psychiatric (crisis) care in the home environment. AIM: To formulate indication criteria for IHT in children and adolescents, to improve assessment and to reduce the time needed for triage. METHOD: The Delphi method was used to assess the opinion of experts on the indication for IHT in children and adolescents. In round 1, 18 employees of the IHT team of Levvel (Academic Centre for Child and Adolescent Psychiatry) list the indication criteria that they thought should be used to determine whether a patient belonged to the IHT target group. Open coding was used to analyze the responses and to derive statements that, in the following three rounds, were rated by the participants on their importance. RESULTS: 33 statements were deemed important enough (> 80% consensus) to include in the final list. These statements concerned the aim, target group, treatment services, the role and responsibilities of the referrer and logistical issues. CONCLUSION: The list with assessment indicators is a promising tool to help IHT teams working with children and adolescents improve and standardize their triage.
Assuntos
Terapia Familiar/métodos , Visita Domiciliar , Transtornos Mentais/terapia , Adolescente , Criança , Consenso , Técnica Delphi , Serviços de Assistência Domiciliar , Humanos , Fatores de Tempo , Resultado do TratamentoRESUMO
Venous air embolism activates platelets in vitro and can evoke platelet dysfunction in swine. We tested the hypothesis that venous air embolism during semi-sitting craniotomy induces thrombocytopenia in humans. We analysed the charts of 799 patients who had an elective craniotomy in the semi-sitting position between 1990 and June 2009. Venous air embolism occurred in 52 patients (6.5%) and was associated with a decrease in mean (SD) in platelet count from 270 (75) × 109 l⻹ to 194 (62) × 109 l⻹ (p < 0.001). In age-matched controls without venous air embolism mean (SD) platelet count did not change (254 (82) × 109 l⻹ vs. 250 (97) × 109 l⻹ (NS). While mean (SD) haematocrit fell slightly in both groups (venous air embolism: 0.40 (0.05) to 0.32 (0.04), p <0.001; no venous air embolism: 0.41 (0.04) to 0.35 (0.05), p < 0.001), normalising platelet count to haematocrit did not alter the results.
Assuntos
Craniotomia/efeitos adversos , Embolia Aérea/complicações , Trombocitopenia/etiologia , Adulto , Idoso , Testes de Coagulação Sanguínea , Transfusão de Eritrócitos , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Postura , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/terapiaRESUMO
BACKGROUND: Cyclooxygenase inhibitor treatment is viewed increasingly critical because of safety considerations, and there are several open questions on their optimal use. METHODS: In a randomized placebo-controlled study in 320 patients undergoing discectomy, we administered parecoxib 40 mg either perioperatively (before operation and after operation), after operation (first dose given in the evening after surgery), or before operation (single parecoxib dose given 45 min before surgery). We measured the main outcome variables: average pain score, morphine consumption, and opioid-related symptom distress at 25, 49, and 73 h after surgery. RESULTS: Perioperative parecoxib significantly (i) improved the pain score compared with both placebo and postoperative parecoxib, (ii) decreased morphine consumption, and (iii) reduced the opioid-related symptom distress score. Neither a single preoperative dose nor postoperative parecoxib (first dose given in the evening after surgery) significantly improved morphine's analgesic effectiveness. CONCLUSIONS: Perioperative parecoxib compared with postoperative parecoxib improves post-discectomy pain and results in a reduction in adverse effects associated with opioid therapy. Postoperative parecoxib, or a single pre-incisional parecoxib dose, does not significantly improve post-discectomy pain or opioid side-effects up to 3 days after surgery.
Assuntos
Analgésicos não Narcóticos/administração & dosagem , Inibidores de Ciclo-Oxigenase/administração & dosagem , Discotomia , Isoxazóis/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Humanos , Pessoa de Meia-Idade , Morfina/administração & dosagem , Medição da Dor/métodos , Assistência Perioperatória/métodos , Cuidados Pós-Operatórios/métodos , Medicação Pré-Anestésica , Estudos ProspectivosRESUMO
Human induced pluripotent stem cell (iPSC)-derived neurons have been proposed to be a highly valuable cellular model for studying the pathomechanisms of Alzheimer's disease (AD). Studies employing patient-specific human iPSCs as models of familial and sporadic forms of AD described elevated levels of AD-related amyloid-ß (Aß). However, none of the present AD iPSC studies could recapitulate the synaptotoxic actions of Aß, which are crucial early events in a cascade that eventually leads to vast brain degeneration. Here we established highly reproducible, human iPSC-derived cortical cultures as a cellular model to study the synaptotoxic effects of Aß. We developed a highly efficient immunopurification procedure yielding immature neurons that express markers of deep layer cortical pyramidal neurons and GABAergic interneurons. Upon long-term cultivation, purified cells differentiated into mature neurons exhibiting the generation of action potentials and excitatory glutamatergic and inhibitory GABAergic synapses. Most interestingly, these iPSC-derived human neurons were strongly susceptible to the synaptotoxic actions of Aß. Application of Aß for 8 days led to a reduction in the overall FM4-64 and vGlut1 staining of vesicles in neurites, indicating a loss of vesicle clusters. A selective analysis of presynaptic vesicle clusters on dendrites did not reveal a significant change, thus suggesting that Aß impaired axonal vesicle clusters. In addition, electrophysiological patch-clamp recordings of AMPA receptor-mediated miniature EPSCs revealed an Aß-induced reduction in amplitudes, indicating an impairment of postsynaptic AMPA receptors. A loss of postsynaptic AMPA receptor clusters was confirmed by immunocytochemical stainings for GluA1. Incubation with Aß for 8 days did not result in a significant loss of neurites or cell death. In summary, we describe a highly reproducible cellular AD model based on human iPSC-derived cortical neurons that enables the mechanistic analysis of Aß-induced synaptic pathomechanisms and the development of novel therapeutic approaches.
Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Neurônios/metabolismo , Neurônios/patologia , Sinapses/metabolismo , Sinapses/patologia , Proteínas tau/metabolismoRESUMO
BACKGROUND: We studied 120 children aged 2-7 yr in a prospective, randomized, assessor-blinded fashion to define the optimal rocuronium dose which provides a 95% probability of acceptable intubation conditions (ED95TI) during inhalation induction with sevoflurane. METHODS: After inhalation induction with 8% sevoflurane in 60% nitrous oxide and 40% oxygen, and loss of the eyelash reflex, we administered rocuronium (0.1, 0.15, 0.22, 0.3, or 0.6 mg kg-1) or placebo. We quantified neuromuscular function by stimulation of the ulnar nerve at 0.1 Hz to produce contraction of the adductor pollicis muscle using accelerometry. Intubation conditions were assessed 2 min after test drug injection. The optimal rocuronium dose was defined as the lowest dose, which allowed acceptable intubation conditions in 95% of children (ED95TI). RESULTS: Two minutes after injection of placebo or rocuronium, intubation conditions were acceptable in 35, 45, 80, 90, 95, and 100% of children, respectively. Rocuronium 0.07 [CI 0.02-0.11], 0.24 [0.19-0.31], and 0.29 [0.23-0.38] mg kg-1 provided 50, 90, and 95% probability of acceptable intubating conditions. When thumb acceleration was depressed by 50% or more, intubating conditions were considered acceptable in 97% of children. Recovery of the train-of-four ratio to 0.8 averaged 12 (7), 16 (7), 24 (7), 24 (8), and 50 (22) min after the respective dose of rocuronium. CONCLUSIONS: During inhalation induction with 8% sevoflurane in 60% nitrous oxide, rocuronium 0.29 mg kg-1 (ED95) optimizes intubation conditions for surgery of short duration.
Assuntos
Androstanóis/administração & dosagem , Anestésicos Inalatórios , Intubação Intratraqueal/métodos , Éteres Metílicos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Pressão Sanguínea , Criança , Pré-Escolar , Esquema de Medicação , Frequência Cardíaca , Humanos , Bloqueio Neuromuscular , Medicação Pré-Anestésica , Estudos Prospectivos , Rocurônio , Sevoflurano , Método Simples-CegoRESUMO
Both retroperitoneoscopic and laparoscopic surgical approaches to kidney and adrenal gland have been reported but their cardiopulmonary pathophysiology has been incompletely characterized. To test the hypothesis that these approaches have markedly different impact on the circulatory and respiratory systems, we assessed at similar insufflation pressures alterations in cardiovascular and respiratory variables during retroperitoneal and intraperitoneal CO2 insufflation. Eighteen healthy, anesthetized (propofol, alfentanil, vecuronium), mechanically ventilated pigs were randomly instrumented for either retroperitoneoscopic (n = 9) or laparoscopic (n = 9) surgery. After CO2 insufflation cardiovascular and respiratory variables were measured at four cavity pressures (baseline, 10, 15, and 20 mmHg), while end-expiratory CO2 tension was maintained by adjusting tidal volume. Data were analyzed for both insufflation-pressure-dependent and group effects by one-way and two-way ANOVA for repeated measurements, respectively, followed by Newman-Keuls post hoc test (P < 0.05). Cardiac output, mean arterial, pulmonary artery, central venous, and femoral venous pressures increased significantly in both groups in an insufflation-pressure-dependent fashion. However, changes in cardiac output (P < 0.001), pulmonary artery (P < 0.007), central venous (P < 0.001), and iliac venous pressures (P < 0.001) for the same insufflation pressure were markedly and significantly greater with intraperitoneal than retroperitoneal CO2 insufflation. Most important, intraperitoneal unlike retroperitoneal insufflation induced a marked inferior vena caval pressure gradient (8.9 +/- 1.1 mmHg vs 1.0 +/- 0.5 mmHg, P < 0.00001). While both retroperitoneal and intraperitoneal CO2 insufflation required increased tidal volumes to adjust endtidal CO2 tension to baseline, intraperitoneal CO2 insufflation resulted in a significantly greater increase of mixed venous and arterial carbon dioxide tensions (P < 0.007) even at similar insufflation pressures. Furthermore, significantly greater peak airway pressures (P = 0.018) were required with intraperitoneal than with retroperitoneal insufflation to administer the same tidal volume, indicating a greater decrease in quasi-static compliance with intraperitoneal insufflation (P = 0.0436). Thus, (i) cardiovascular and respiratory changes are much less during retroperitoneal than intraperitoneal CO2 insufflation, even at the same insufflation pressures, and (ii) retroperitoneal CO2 insufflation unlike intraabdominal CO2 insufflation does not induce an inferior vena caval pressure gradient and hence does not appear to impair systemic lower body venous return up to insufflation pressures of 20 mmHg.