| 1. |
- Hostmann, Arwed, et al.
(författare)
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Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins.
- 2008
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Ingår i: Critical care (London, England). - : Springer Science and Business Media LLC. - 1466-609X .- 1364-8535. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions.Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples.HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were inversely expressed within the 72-hour observation period, thereby supporting significant pro-apoptotic changes. Solely at t = 24 hours, expression of the anti-apoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased.Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro- and anti-apoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.
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| 2. |
- Przkora, René, et al.
(författare)
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Operative treatment of unstable odontoid fractures in the geriatric population
- 2006
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Ingår i: Topics in Spinal Cord Injury Rehabilitation. - 1082-0744 .- 1945-5763. ; 12:2, s. 12-19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Odontoid fractures, often in combination with C1 fractures, are a common fracture of the cervical spine in geriatric patients. The optimal treatment of this fracture in this patient population is often controversial. We report the surgical outcome of unstable type II odontoid fractures in the elderly. Method: 8 patients (median age, 80.5 years; range, 72-93) with unstable type II odontoid fractures according to the Anderson and d'Alonzo classification were included in this prospective study. 2 patients sustained a C1 fracture (1 had an unstable type III fracture according to the Gehweiler classification, and 1 had a stable type III fracture). There were no neurological complications. All patients were classified as ASA class III. 7 patients were treated with anterior odontoid double-screw compression osteosynthesis followed by a firm neck support for 6 weeks. 1 patient with an unstable C1 and C2 fracture was treated with an occipital cervical (C2) fusion in combination with a C1-C2 fusion according to Magerl technique. Follow-up was 18 months. Results: No deaths occurred during the study period. All patients demonstrated fracture healing at followup. Median length of hospital stay was 31.4 days (range, 16-64). Preexisting comorbidities complicated final outcome in 2 patients, both of whom received a temporary tracheostomy for respiratory failure. Conclusion: Type II odontoid fracture healing can occur predictably with anterior double-screw compression osteosynthesis. The outcome in this patient population may be complicated by preexisting medical comorbidities.
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| 3. |
- Robinson, Yohan, 1977, et al.
(författare)
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Erythropoiesis in multiply injured patients.
- 2006
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Ingår i: The Journal of trauma. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5282 .- 1529-8809. ; 61:5, s. 1285-91
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Forskningsöversikt (refereegranskat)abstract
- Posttraumatic anemia in multiply injured patients is caused by hemorrhage, reduced red blood cell survival, and impaired erythropoiesis. Trauma-induced hyperinflammation causes impaired bone-marrow function by means of blunted erythropoietin (EPO) response, reduced iron availability, suppression and egress of erythroid progenitor cells. To treat posttraumatic anemia in severely injured patients, symptomatic therapy by blood transfusion is not sufficient. Furthermore, EPO, iron, and the use of red cell substitutes should be considered. The posttraumatic systemic inflammatory response syndrome (SIRS) induces posttraumatic anemia. Thus, a worsening of SIRS by a "second-hit" through blood transfusion ought to be avoided.
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| 4. |
- Robinson, Yohan, et al.
(författare)
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Impaired erythropoiesis after haemorrhagic shock in mice is associated with erythroid progenitor apoptosis in vivo
- 2008
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 52:5, s. 605-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Multiply traumatised patients often suffer from blood loss and from subsequent therapy-resistant anaemia, possibly mediated by apoptosis, necrosis, or humoral factors. Therefore, the underlying mechanisms were investigated in bone marrow (BM) and peripheral blood in a murine resuscitated haemorrhagic shock (HS) model. METHODS: In healthy male mice, pressure-controlled HS was induced for 60 min. The BM was analysed for Annexin-V, 7-amino-actinomycin D, apoptotic enzymes (caspases-3/7, -8, and -9), expression of death receptors (CD120a, CD95), mitochondrial proteins (Bax, Bcl-2, Bcl-x), as well as erythropoietin (EPO) receptor (EPO-R). Blood cell count, peripheral EPO, and tumour necrosis factor-alpha response were additionally monitored. RESULTS: Twenty-four and 72 h after HS, EPO and EPO-R were strongly up-regulated in peripheral blood and BM, respectively. Decreasing numbers of erythroid progenitors in BM after HS correlated with significant apoptotic changes confirmed by increased caspases-3/7, -8, -9 activity in total BM, death receptor CD95 and CD120a expression on erythroid progenitors, and down-regulated mitochondrial Bcl-2 expression in total BM. Erythroid progenitors in peripheral blood were found to be increased after 72 h. CONCLUSION: Despite the massive EPO response and up-regulation of EPO-R, BM erythroblasts (EBs) decreased. This could be due to deficient maturation of erythroid progenitors. Furthermore, the increased intrinsic and extrinsic apoptosis activation suggests programmed death of erythroid progenitors. We propose that both apoptosis and negatively regulated erythropoiesis contribute to BM dysfunction, while erythroid progenitor egress plays an additional role.
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| 5. |
- Robinson, Yohan, 1977, et al.
(författare)
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Postoperative multisegmental lumbar discitis treated by staged ventrodorsoventral intervention.
- 2007
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Ingår i: Surgical infections. - : Mary Ann Liebert Inc. - 1096-2964 .- 1557-8674. ; 8:5, s. 529-34
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Forskningsöversikt (refereegranskat)abstract
- Postoperative spinal infections are relatively rare. They can become life-threatening.A 56-year-old man developed multisegmental spinal infection with methicillin-resistant Staphylococcus aureus after discectomy at L3/4. A staged ventrodorsoventral intervention was needed for radical debridement and stabilization. After femoral head necrosis developed as a result of the infection, a Girdlestone hip was maintained until the joint was aseptic and a hip prosthesis could be implanted. Two years postoperatively, the patient remained free of infection recurrence.Radical debridement and a tightly controlled antibiotic regimen are necessary for the management of postoperative spinal infections. This should include staged interventions until recovery from infection is possible. Early intervention can prevent systemic sepsis caused by widespread bacterial dissemination.
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| 6. |
- Robinson, Yohan, 1977, et al.
(författare)
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Successful treatment of spondylodiscitis using titanium cages: a 3-year follow-up of 22 consecutive patients.
- 2008
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 79:5, s. 660-4
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Tidskriftsartikel (refereegranskat)abstract
- The use of metal implants in large defects caused by spinal infection to support the anterior column is controversial, and relatively few results have been published to date. Despite the fact that there is bacterial adhesion to metal implants, the strong immunity of the highly vascularized spine because of rich muscle covering is unique. This possibly allows the use of metal implants, which have the advantage of high stability and reduced loss of correction. This is a retrospective study of patients with spondylodiscitis treated with metal implants.We retrospectively analyzed the outcome in 22 consecutive patients (mean age 69 (43-82) years, 15 men) with spondylodiscitis (20 lumbar and 12 thoracic discs) who had received an anterior titanium cage implantation. In 13 cases, the pathogen could be identified. Antibiotic treatment was continued for at least 12 weeks postoperatively.The mean follow-up was 36 (32-47) months. Healing of inflammation was confirmed by clinical, radiographic, and laboratory parameters. The mean VAS improved from 9.1 (6-10) preoperatively to 2.6 (0-6) at the final follow-up, and the mean Oswestry disability index was 17 (0-76) at the final follow-up.Our findings highlight the high healing rate and stability when titanium implants are used. Prerequisites are a radical debridement, correction of deformity, and additional bony fusion by bone grafting. The increased stability, with facilitated patient mobilization, and the relatively little loss of correction using anterior and posterior implants are of considerable advantage in the treatment of the patients with multiple co-morbidities.
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| 7. |
- Robinson, Yohan, 1977, et al.
(författare)
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Traumatic proximal tibiofibular joint dislocation treated by open reduction and temporary fixation: a case report.
- 2007
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 15:2, s. 199-201
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Forskningsöversikt (refereegranskat)abstract
- Isolated dislocations of the proximal tibiofibular joint are a rare condition. Missed diagnosis can lead to chronic knee pain and disability. Early recognition should be followed by immediate closed reduction or open reduction and joint transfixation. We present a young athlete with this injury which was treated successfully by open reduction.
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| 8. |
- Tschoeke, Sven K, et al.
(författare)
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Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways.
- 2008
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Ingår i: Journal of orthopaedic research : official publication of the Orthopaedic Research Society. - : Wiley. - 1554-527X .- 0736-0266. ; 26:7, s. 999-1006
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Tidskriftsartikel (refereegranskat)abstract
- Post-traumatic disc degeneration with consecutive loss of reduction and kyphosis remains a debatable issue within both the operative and nonoperative treatment regimen of thoracolumbar spine fractures. Intervertebral disc (IVD) cell apoptosis has been suggested to play a vital role in promoting the degeneration process. To evaluate and compare apoptosis-regulating signaling mechanisms, IVDs were obtained from patients with thoracolumbar spine fractures (n = 21), patients suffering from symptomatic IVD degeneration (n = 6), and from patients undergoing surgical resection of a primary vertebral tumor (n = 3 used as control samples). All tissues were prospectively analyzed in regards to caspase-3/7, -8, and -9 activity, apoptosis-receptor expression levels, and gene expression of the mitochondria-bound apoptosis-regulating proteins Bax and Bcl-2. Morphologic changes characteristic for apoptotic cell death were confirmed by H&E staining. Statistical significance was designated at p < 0.05 using the Student's t-test. Both traumatic and degenerative IVD demonstrated a significant increase of caspase-3/7 activity with evident apoptosis. Although caspase-3/7 activation was significantly greater in degenerated discs, both showed equally significant activation of the initiator caspases 8 and 9. Traumatic IVD alone demonstrated a significant increase of the Fas receptor (FasR), whereas the TNF receptor I (TNFR I) was equally up-regulated in both morbid IVD groups. Only traumatic IVD showed distinct changes in up-regulated TNF expression, in addition to significantly down-regulated antiapoptotic Bcl-2 protein. Our results suggest that post-traumatic disc changes may be promoted and amplified by both the intrinsic mitochondria-mediated and extrinsic receptor-mediated apoptosis signaling pathways, which could be, in part, one possible explanation for developing subsequent disc degeneration.
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