RESUMO
The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.
Assuntos
Circulação Cerebrovascular , Força da Mão , Insuficiência Cardíaca/fisiopatologia , Idoso , Feminino , Hemodinâmica , Homeostase , Humanos , Contração Isométrica , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.
Assuntos
Neoplasias Abdominais/reabilitação , Neoplasias Abdominais/cirurgia , Terapia por Exercício/métodos , Tolerância ao Exercício , Avaliação de Programas e Projetos de Saúde/métodos , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: Intra-aortic balloon pump (IABP) is commonly used as mechanical support after cardiac surgery or cardiac shock. Although its benefits for cardiac function have been well documented, its effects on cerebral circulation are still controversial. We hypothesized that transfer function analysis (TFA) and continuous estimates of dynamic cerebral autoregulation (CA) provide consistent results in the assessment of cerebral autoregulation in patients with IABP. APPROACH: Continuous recordings of blood pressure (BP, intra-arterial line), end-tidal CO2, heart rate and cerebral blood flow velocity (CBFV, transcranial Doppler) were obtained (i) 5 min with IABP ratio 1:3, (ii) 5 min, starting 1 min with the IABP-ON, and continuing for another 4 min without pump assistance (IABP-OFF). Autoregulation index (ARI) was estimated from the CBFV response to a step change in BP derived by TFA and as a function of time using an autoregressive moving-average model during removal of the device (ARI t ). Critical closing pressure and resistance area-product were also obtained. MAIN RESULTS: ARI with IABP-ON (4.3 ± 1.2) were not different from corresponding values at IABP-OFF (4.7 ± 1.4, p = 0.42). Removal of the balloon had no effect on ARI t , CBFV, BP, cerebral critical closing pressure or resistance area-product. SIGNIFICANCE: IABP does not disturb cerebral hemodynamics. TFA and continuous estimates of dynamic CA can be used to assess cerebral hemodynamics in patients with IABP. These findings have important implications for the design of studies of critically ill patients requiring the use of different invasive support devices.
Assuntos
Circulação Cerebrovascular , Hemodinâmica , Balão Intra-Aórtico/efeitos adversos , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.
Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Velocidade do Fluxo Sanguíneo , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicaçõesRESUMO
There is great controversy about which surgical approach is the most selective and efficient for resection of mesial structures of the temporal lobe for treatment of mesial temporal lobe epilepsy. Selective approaches have been described in an attempt to preserve the neocortex and the temporal stem. Nonselective approaches, such as anterior temporal lobectomy (ATL), result in injuries in these structures. We describe a modified selective technique for resection of the amygdala and hippocampus with resection of the temporal pole performed through the Sylvian fissure based on anatomical landmarks and diligent microsurgical techniques. Briefly, after opening the Sylvian fissure, the temporal pole is resected and the temporal horn is directly accessed through the uncus, in an anteroposterior direction, preserving the temporal stem and the neocortex of the temporal lobe. The surgical technique used by our group is described in detail with illustrations. Precise microsurgical techniques associated with knowledge of microsurgical anatomy are of paramount importance for temporal lobe epilepsy surgery. According to our analysis, the modified ATL approach to the temporal mesial structures is a feasible selective technique that can be used as an alternative to traditional surgical procedures.
Assuntos
Tonsila do Cerebelo/cirurgia , Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Microcirurgia/métodos , Lobo Temporal/cirurgia , Lobectomia Temporal Anterior/normas , Humanos , Microcirurgia/normasRESUMO
BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.
Assuntos
Estado Terminal/mortalidade , Neoplasias/mortalidade , Neoplasias/fisiopatologia , Equilíbrio Hidroeletrolítico/fisiologia , APACHE , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Idoso , Área Sob a Curva , Feminino , Humanos , Intubação Intratraqueal , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Valor Preditivo dos Testes , Respiração Artificial , Choque Séptico/etiologia , Choque Séptico/fisiopatologia , Sobrevida , Resultado do Tratamento , Vasoconstritores/uso terapêuticoRESUMO
: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.
Assuntos
Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Nitratos/metabolismo , Nitritos/metabolismo , Pilocarpina , Piracetam/análogos & derivados , Convulsões/induzido quimicamente , Animais , Anticonvulsivantes/farmacologia , Encéfalo/enzimologia , Encéfalo/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Levetiracetam , Masculino , Malondialdeído/metabolismo , Camundongos , Piracetam/farmacologia , Convulsões/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
BACKGROUND: Oral avascular bone necrosis is an important adverse effect of chemotherapy and biphosphate therapy. OBJECTIVE: To report our experience in oral avascular bone necrosis in cancer patients assigned to undergo chemotherapy. PATIENTS AND METHODS: Fourteen patients presenting oral avascular bone necrosis were selected from the clinical files of five Stomatological Clinics in Brazil. Clinical data as well as treatment and prognosis information were obtained from all 14 patients. RESULTS: Twelve patients (86%) were submitted to biphosphonate therapy. The most important symptom was pain, present in all cases, and the mandible was the most common involved site. Most patients (79%) had their conditions managed by antibiotic therapy and surgical debridation; however complete response was achieved in only three cases (21%). CONCLUSION: Avascular bone necrosis is a serious oral side-effect of cancer chemotherapy, particularly in patients using biphosphonates, and antibiotic therapy and surgical debridation were not able to promote complete response in most cases.
Assuntos
Antineoplásicos/efeitos adversos , Difosfonatos/efeitos adversos , Doenças da Boca/induzido quimicamente , Osteonecrose/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Fatty acid synthase (FAS) is the enzyme that synthesizes palmitate from malonyl-CoA and acetyl-CoA. Recent studies have shown that FAS is overexpressed in human cancers and that its activity is necessary for cell proliferation. Hereditary gingival fibromatosis (HGF) is a genetic disease manifested as a progressive enlargement of the gingiva. The pathogenesis of this condition is not understood; however, a proliferative advantage of HGF fibroblasts in comparison with cells from normal gingiva (NG) has been described. The aim of this study was to investigate the role of FAS in NG and HGF fibroblast proliferation. METHODS: NG and HGF fibroblasts had their proliferative potential assessed by automated cell counting and immunocytochemistry against Ki-67 or proliferating cell nuclear antigen (PCNA). The production of FAS, androgen receptor (AR), and ErbB2 was analyzed by Western blot and the pattern of FAS expression studied by immunocytochemistry. FAS activity was blocked by the specific inhibitor cerulenin. RESULTS: Higher proliferation rates were found in fibroblasts isolated from HGF than from NG. HGF fibroblasts with greater proliferative potential produced more FAS and AR than the cell lines with lower growth rates, and all studied cell lines produced similar amounts of the ErbB2 protein. In addition, the FAS inhibitor cerulenin was able to significantly reduce the proliferation of both NG and HGF cells. CONCLUSIONS: These results show that FAS is expressed by gingival fibroblasts and that highly proliferative HGF cells produced more FAS and AR than the other fibroblast cell lines. Moreover, FAS inhibition significantly reduced both NG and HGF fibroblast growth, suggesting a role for the androgen-driven fatty acid biosynthesis in their proliferation.
Assuntos
Ácido Graxo Sintases/metabolismo , Fibromatose Gengival/enzimologia , Gengiva/enzimologia , Adulto , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cerulenina/metabolismo , Inibidores Enzimáticos/metabolismo , Ácido Graxo Sintases/antagonistas & inibidores , Feminino , Fibroblastos/enzimologia , Gengiva/citologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Receptor ErbB-2/biossíntese , Receptores Androgênicos/biossíntese , Testosterona/metabolismoRESUMO
For this study, we investigated the changes in the electrophysiological parameters of Sertoli cells in seminiferous tubules from 17 - 19 day-old rats induced by testosterone. Using conventional intracellular microelectrode techniques, we analysed the membrane potential and its input resistance. The entire tubules were fixed in a superfusion chamber continuously perfused with Krebs-Ringer bicarbonate buffer (pH 7.4, 32 degrees C). Visual control of cell impalement was achieved using an inverted microscope. The parameters analysed were passed through an amplifier and recorded using a proprietary software system. The topical application of testosterone (0.1 to 10 microM) led to an immediate (within 30 seconds) and significant dose-dependent depolarization of the membrane potential of the cell at all concentrations used. Concomitantly, the input resistance of the cell membrane underwent a significant increment at 30 seconds. These changes returned to resting values after washout. Topical administration of 17beta-estradiol or progesterone (10 microM) did not change the membrane potential. The addition of the K +ATP channel agonist diazoxide to the perfusion buffer nullified the depolarization effect of testosterone at 30 seconds. This result suggests that the immediate action of testosterone is associated with the closing of K +ATP channels, thereby depolarizing the membrane.