Inflammation and cell death are critical to pathogenesis of acute pancreatitis. Here we show that transcription factor nuclear factor-κB (NF-κB), which regulates these processes, is activated and plays a role in rat cerulein pancreatitis. NF-κB was strongly activated in the pancreas within 30 min of cerulein infusion; a second phase of NF-κB activation was prominent at 3–6 h. This biphasic kinetics could result from observed transient degradation of the inhibitory protein IκBα and slower but sustained degradation of IκBβ. The hormone also caused NF-κB translocation and IκB degradation in vitro in dispersed pancreatic acini. Both p65/p50 and p50/p50, but not c-Rel, NF-κB complexes were manifest in pancreatitis and in isolated acini. Coinfusion of CCK JMV-180, which abolishes pancreatitis, prevented cerulein-induced NF-κB activation. The second but not early phase of NF-κB activation was inhibited by a neutralizing tumor necrosis factor-α antibody. Antioxidant N-acetylcysteine (NAC) blocked NF-κB activation and significantly improved parameters of pancreatitis. In particular, NAC inhibited intrapancreatic trypsin activation and mRNA expression of cytokines interleukin-6 and KC, which were dramatically induced by cerulein. The results suggest that NF-κB activation is an important early event that may contribute to inflammatory and cell death responses in acute pancreatitis.
1. Reconstruction should occur after temperature, coagulopathy, and acidosis are corrected, usually within 36 hours after the damage control procedure. 2. Emergent reoperation should occur in any normothermic patient with unabated bleeding (greater than 2 U packed cells/hr). 3. ACS occurs in 15% of patients and is characterized by high peak inspiratory pressure, CO2 retention, and oliguria. Lethal reperfusion syndrome is common but preventable.
Object. Diagnosing and managing cervical spine trauma in head-injured patients is problematic due to an altered level of consciousness in such individuals. The reported incidence of cervical spine trauma in head-injured patients has generally ranged from 4 to 8%. In this retrospective study the authors sought to define the incidence of cervical injury in association with moderate or severe brain injury, emphasizing the identification of high-risk patients.
Methods. The study included 447 consecutive moderately (209 cases) or severely (238 cases) head injured patients who underwent evaluation at two Level 1 trauma centers over a 40-month period. Of the 447 patients, 24 (5.4%) suffered a cervical spine injury (17 men and seven women; mean age 39 years; median Glasgow Coma Scale [GCS] score of 6, range 3–14). Of these 24 patients, 14 (58.3%) sustained spinal cord injuries (SCIs), 14 sustained injuries in the occiput—C3 region, and 10 underwent a stabilization procedure. Of the 14 patients with SCIs, nine experienced an early hypotensive and/or hypoxic insult. Regarding the mechanism of injury, cervical injuries occurred in 21 (8.2%) of 256 patients involved in motor vehicle accidents (MVAs), either as passengers or pedestrians, compared with three (1.6%) of 191 patients with non-MVA-associated trauma (p < 0.01). In the subset of 131 MVA passengers, 13 (9.9%) sustained cervical injuries. Patients with an initial GCS score less than or equal to 8 were more likely to sustain a cervical injury than those with a score higher than 8 (odds ratio [OR] 2.77, 95% confidence interval [CI] = 1.11–7.73) and were more likely to sustain a cervical SCI (OR 5.5, 95% CI 1.22–24.85). At 6 months or more postinjury, functional neurological recovery had occurred in nine patients (37.5%) and eight (33.3%) had died.
Conclusions. Head-injured patients sustaining MVA-related trauma and those with an initial GCS score less than or equal to 8 are at highest risk for concomitant cervical spine injury. A disproportionate number of these patients sustain high cervical injuries, the majority of which are mechanically unstable and involve an SCI. The development of safer and more rapid means of determining cervical spine integrity should remain a high priority in the care of head-injured patients.
Cytokines produced by pancreatic acinar cells may mediate cell death and recruitment of inflammatory cells into pancreas in pancreatitis and other disorders. Here, we demonstrate mRNA expression for a number of cytokines in acini isolated from rat pancreas. Using RNA from microscopically selected individual cells, we confirmed the acinar cell as a source for cytokine expression. Competitive RT-PCR, Western blot analysis, and immunocytochemistry showed large amounts of monocyte chemotactic protein-1 and interleukin-6 compared with other cytokines. Cytokine expression was inhibited by either inhibitors of p38 mitogen-activated protein kinase (MAPK), SB-202190 and SB-203580, or (less strongly) by the transcription factor nuclear factor (NF)-kappaB inhibitor MG-132. A combination of SB-203580 and MG-132 inhibited mRNA expression of all cytokines by >90%. The results suggest a major role for p38 MAPK and involvement of NF-kappaB in cytokine expression in pancreatic acinar cells. In contrast to isolated acini, we detected no or very low cytokine expression in normal rat pancreas. Our results indicate that activation of p38 MAPK, transcription factors, and cytokines occurs during removal of the pancreas from the animal and isolation of acini.
This article discusses the potential benefits and challenges of minimally invasive surgery for infants and small children, and discusses why pediatric minimally invasive surgery is not yet the surgical default or standard of care. Minimally invasive methods offer advantages such as smaller incisions, decreased risk of infection, greater surgical precision, decreased cost of care, reduced length of stay, and better clinical information. But none of these benefits comes without cost, and these costs, both monetary and risk-based, rise disproportionately with the declining size of the patient. In this review, we describe recent progress in minimally invasive surgery for infants and children. The evidence for the large benefits to the patient will be presented, as well as the considerable, sometimes surprising, mechanical and physiological challenges surgeons must manage.
Conventional incisions are subject to more total tension than any combination of trocar incisions of equal total length. This inequality yields three clinically relevant corollaries. First, it supports the practice of using the smallest effective trocars (or even no-trocar methods) to minimize pain and scar. Second, addition of a trocar in difficult cases adds relatively little morbidity. Finally, using two small trocars is better than using a single larger trocar.
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