Diederik bulters – academia.edu severe anoxic brain injury

Although many disease models exist for neurodegenerative disease, the translation of basic resear… More although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the likelihood of success in clinical trials. Herein, the authors discuss key issues in the lack of translation from basic research to clinic. They also review the evidence that human neurons, both freshly resected brain tissue and stem cell-derived neurons, such as induced pluripotent stem cells (ipscs), can be used for analysis of physiological and molecular mechanisms in health and disease.Severe anoxic brain injury furthermore, the authors compare and contrast studies using live human brain tissue and studies using induced human stem cell-derived neuron models. Using an example from the area of neurodegeneration, the authors suggest that replicating elements of research findings from animals and stem cell models in resected human brain tissue would strengthen our understanding of disease mechanisms and the therapeutic strategies and aid translation. The use of human brain tissue alongside ipsc-derived neural models can validate molecular mechanisms identified in rodent disease models and strengthen their relevance to humans. If drug target engagement and mechanism of cellular action can be validated in human brain tissue, this will increase the success rate in clinical research.Severe anoxic brain injury the combined use of resected human brain tissue, alongside ipsc-derived neural models, could be considered a standard step in pre-clinical research and help to bridge the gap to clinical trials.

Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Fr… More long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after hemorrhage. Using cerebrospinal fluid and tissue from patients with SAH and control individuals, the activity of the intracranial CD91-hemopexin system was examined using ELISA, ultrahigh performance liquid chromatography, and immunohistochemistry.Severe anoxic brain injury in control individuals, cerebrospinal fluid hemopexin was mainly synthesized intrathecally. After SAH, cerebrospinal fluid hemopexin was high in one third of cases, and these patients had a higher probability of delayed cerebral ischemia and poorer neurological outcome. The intracranial CD91-hemopexin system was active after SAH because CD91 positively correlated with iron deposition in brain tissue. Heme-hemopexin uptake saturated rapidly after SAH because bound heme accumulated early in the cer…

To assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces … More to assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces the risk of poor outcome because of vasospasm following aneurysmal subarachnoid haemorrhage relative to conventional hypervolemic therapy (HT).Severe anoxic brain injury this was a single-center, parallel group randomized controlled trial. Patients suffering a subarachnoid hemorrhage at high risk of vasospasm were eligible. Patients were randomly allocated to receive prophylactic IABC (n=35) or HT (n=36). The primary end point was glasgow outcome and SF-36 scores assessed at 6 months by a blinded and independent observer and analyzed by intention to treat. Secondary analysis of physiological parameters was by treatment performed. Twenty-seven patients in each arm had a good outcome (P=0.55). There was no statistical difference in mean SF-36 score (t=0.39, P=0.70). There were no long-term complications secondary to IABC. There were no differences in preload (pulmonary artery wedge pressure, P=0.97) or afterload (mean arterial pressure, P=0.97).Severe anoxic brain injury IABC was associated with a lower cardiac output (P=0.002) and higher systemic vascular resistance (P=0.005), although for both groups mean cardiac output was amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 L/min. Cerebral blood flow was not different between groups: HT=41.5 (SD 7.2), IABP=44.9 (SD 8.6) ml/100 g/min (P=0.14). In this study, prophylactic IABC did not improve perfusion indices or confer any clinical benefit following subarachnoid haemorrhage in patients with normal cardiac function. The study was small, however, and cannot be extrapolated to patients with cardiac failure and medically refractory symptomatic cerebral vasospasm.Severe anoxic brain injury clinical trial registration- this trial was not registered because enrolment began prior to july 1, 2005.

Epidural analgesia is considered one of the optimal methods for provision of postoperative pain r… More epidural analgesia is considered one of the optimal methods for provision of postoperative pain relief in patients recovering from major upper abdominal operations. Concerns regarding the potential risk of neurological complications prompted an evaluation of an alternative strategy using a continuous intermuscular bupivacaine (CIB) infusion combined with patient-controlled analgesia (PCA). Two fine-bore catheters are inserted in the deep intermuscular intercostal neuronal plane during abdominal wound closure, and a continuous infusion of bupivacaine 0.25% is commenced for 72 h postoperatively.Severe anoxic brain injury simultaneously, patient-controlled analgesia provided intravenous morphine on demand. The study comprised 10 consecutive patients undergoing liver resection in whom CIB infusion and PCA were employed. The feasibility, safety and efficacy of the technique were investigated, analysing postoperative pain scores, morphine requirements, spirometry and oxygen saturation. There were no postoperative deaths. Postoperative morbidity included one urinary tract infection, one minor chest infection and acute confusional episodes in two patients. Median pain scores and morphine requirements at 12, 24, 48 and 72 h postoperatively were satisfactory. Spirometry and oxygen saturation values also remained within the normal range.Severe anoxic brain injury preliminary experience with CIB infusion/PCA in the aftermath of major liver resection has demonstrated its simplicity and safety as an alternative method of postoperative pain control. Further study is required to investigate the role of CIB infusion/PCA as a practical alternative to epidural analgesia or PCA alone.

Although many disease models exist for neurodegenerative disease, the translation of basic resear… More although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the likelihood of success in clinical trials.Severe anoxic brain injury herein, the authors discuss key issues in the lack of translation from basic research to clinic. They also review the evidence that human neurons, both freshly resected brain tissue and stem cell-derived neurons, such as induced pluripotent stem cells (ipscs), can be used for analysis of physiological and molecular mechanisms in health and disease. Furthermore, the authors compare and contrast studies using live human brain tissue and studies using induced human stem cell-derived neuron models. Using an example from the area of neurodegeneration, the authors suggest that replicating elements of research findings from animals and stem cell models in resected human brain tissue would strengthen our understanding of disease mechanisms and the therapeutic strategies and aid translation.Severe anoxic brain injury the use of human brain tissue alongside ipsc-derived neural models can validate molecular mechanisms identified in rodent disease models and strengthen their relevance to humans. If drug target engagement and mechanism of cellular action can be validated in human brain tissue, this will increase the success rate in clinical research. The combined use of resected human brain tissue, alongside ipsc-derived neural models, could be considered a standard step in pre-clinical research and help to bridge the gap to clinical trials.

Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Fr… More long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme.Severe anoxic brain injury free heme is bound by hemopexin and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after hemorrhage. Using cerebrospinal fluid and tissue from patients with SAH and control individuals, the activity of the intracranial CD91-hemopexin system was examined using ELISA, ultrahigh performance liquid chromatography, and immunohistochemistry. In control individuals, cerebrospinal fluid hemopexin was mainly synthesized intrathecally. After SAH, cerebrospinal fluid hemopexin was high in one third of cases, and these patients had a higher probability of delayed cerebral ischemia and poorer neurological outcome. The intracranial CD91-hemopexin system was active after SAH because CD91 positively correlated with iron deposition in brain tissue.Severe anoxic brain injury heme-hemopexin uptake saturated rapidly after SAH because bound heme accumulated early in the cer…

To assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces … More to assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces the risk of poor outcome because of vasospasm following aneurysmal subarachnoid haemorrhage relative to conventional hypervolemic therapy (HT). This was a single-center, parallel group randomized controlled trial. Patients suffering a subarachnoid hemorrhage at high risk of vasospasm were eligible. Patients were randomly allocated to receive prophylactic IABC (n=35) or HT (n=36). The primary end point was glasgow outcome and SF-36 scores assessed at 6 months by a blinded and independent observer and analyzed by intention to treat.Severe anoxic brain injury secondary analysis of physiological parameters was by treatment performed. Twenty-seven patients in each arm had a good outcome (P=0.55). There was no statistical difference in mean SF-36 score (t=0.39, P=0.70). There were no long-term complications secondary to IABC. There were no differences in preload (pulmonary artery wedge pressure, P=0.97) or afterload (mean arterial pressure, P=0.97). IABC was associated with a lower cardiac output (P=0.002) and higher systemic vascular resistance (P=0.005), although for both groups mean cardiac output was amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 L/min. Cerebral blood flow was not different between groups: HT=41.5 (SD 7.2), IABP=44.9 (SD 8.6) ml/100 g/min (P=0.14).Severe anoxic brain injury in this study, prophylactic IABC did not improve perfusion indices or confer any clinical benefit following subarachnoid haemorrhage in patients with normal cardiac function. The study was small, however, and cannot be extrapolated to patients with cardiac failure and medically refractory symptomatic cerebral vasospasm. Clinical trial registration- this trial was not registered because enrolment began prior to july 1, 2005.

Epidural analgesia is considered one of the optimal methods for provision of postoperative pain r… More epidural analgesia is considered one of the optimal methods for provision of postoperative pain relief in patients recovering from major upper abdominal operations. Concerns regarding the potential risk of neurological complications prompted an evaluation of an alternative strategy using a continuous intermuscular bupivacaine (CIB) infusion combined with patient-controlled analgesia (PCA).Severe anoxic brain injury two fine-bore catheters are inserted in the deep intermuscular intercostal neuronal plane during abdominal wound closure, and a continuous infusion of bupivacaine 0.25% is commenced for 72 h postoperatively. Simultaneously, patient-controlled analgesia provided intravenous morphine on demand. The study comprised 10 consecutive patients undergoing liver resection in whom CIB infusion and PCA were employed. The feasibility, safety and efficacy of the technique were investigated, analysing postoperative pain scores, morphine requirements, spirometry and oxygen saturation. There were no postoperative deaths. Postoperative morbidity included one urinary tract infection, one minor chest infection and acute confusional episodes in two patients.Severe anoxic brain injury median pain scores and morphine requirements at 12, 24, 48 and 72 h postoperatively were satisfactory. Spirometry and oxygen saturation values also remained within the normal range. Preliminary experience with CIB infusion/PCA in the aftermath of major liver resection has demonstrated its simplicity and safety as an alternative method of postoperative pain control. Further study is required to investigate the role of CIB infusion/PCA as a practical alternative to epidural analgesia or PCA alone.