Biomedical subjects

Christian Woiciechowsky

Publications and source records attributed to Christian Woiciechowsky.

15 recordsLinked to original sources

PubMed2007

A new qualitative interleukin-6 bedside test can predict pneumonia in patients with severe head injury--comparison to the standard Immulite test and a semiquantitative bedside test.

Severe head injury (SHI) leads to systemic immunosuppression, which is processed by central mechanisms and is associated with a high risk of pneumonia. The timely identification of an immunodepressed condition in SHI patients might help prevent infections by changing the intensive care strategy. The aim of this prospective study is to evaluate a new method for identifying immunodepression and predicting pneumonia. We correlated interleukin (IL)-6 levels determined by the standard test (Immulite) and performed by specialized laboratories with those obtained using the new bedside test (PicoScan) with the occurrence of pneumonia in patients with SHI. Thirty-two patients with isolated SHI were investigated. Analyses were performed on serum samples taken 2 to 24 hours after trauma. Pearson correlation coefficient was 0.924 (P<0.001) for IL-6 values determined by PicoScan versus Immulite and Spearman rho was 0.572 for visual interpretation versus Immulite (P=0.01). Immulite and PicoScan have a positive predictive value of 91% and 100%, respectively, and a negative predictive value of 76% and 86%. The present study investigated for the first time the determination of IL-6 concentrations by PicoScan in patients. Our findings show a good correlation with the results of the standard Immulite test and suggest that the PicoScan may be used as a handy tool to predict pneumonia in SHI patients.

Adolescent↗

PubMed2006

Anti-P- and E-selectin therapy prevents abortion in the CBA/J x DBA/2J combination by blocking the migration of Th1 lymphocytes into the foetal-maternal interface.

Leukocyte migration into inflamed tissues comprises dynamic interactions between immune and endothelial cells through events controlled by adhesion molecules, e.g., P- and E-selectins, which mediate Th1 cells recruitment after injury. Since miscarriage is known to be a Th1 event and selectins are expressed at the murine foetal-maternal interface, the purpose of our study was to investigate whether blocking P- and E-selectins before implantation could inhibit Th1 migration into the foetal-maternal interface and thus prevent foetal rejection. DBA/2J-mated CBA/J females were treated with monoclonal antibodies (mAbs) against P-selectin or with both, anti-P- and anti-E-selectins combined on days 2 and 4 of pregnancy. PBS-treated females served as controls. Our data revealed a significant improvement in pregnancy outcome in both treated groups compared to the control, which is due to the effectiveness of the mAb against P-selectin, since the treatment with anti-E-selectin alone could not prevent abortion. We further observed that there was diminished Th1 cytokine production by decidual immune cells in all treated groups in comparison to the controls. Our data first confirm the important role of P-selectin in mediating the extravasation of abortive cells, while opening new therapeutic opportunities.

Abortion, Spontaneous↗

PubMed2005

Protection from abortion by heme oxygenase-1 up-regulation is associated with increased levels of Bag-1 and neuropilin-1 at the fetal-maternal interface.

Tolerance mechanisms allowing pregnancy success resemble those involved in allograft acceptance. Heme oxygenase (HO) is a tissue-protective molecule, which allows graft acceptance and is known to have antiapoptotic effects on several cell types. We previously reported down-regulated levels of HO-1 and HO-2 in placenta from allopregnant mice undergoing abortion. In this study, we analyzed whether the up-regulation of HO-1 by cobalt-protoporphyrin (Co-PP) during implantation window can rescue mice from abortion. Induction of HO-1 by Co-PP treatment prevented fetal rejection, whereas the down-regulation of HOs by zinc-protoporphyrin application boosted abortion. The beneficial effect of HO-1 induction was not related to a local shift to Th2-profile or to a change in the NO system. Interestingly, the expression of the antiapoptotic/cytoprotective molecule Bag-1 as well as the levels of neuropilin-1, a novel marker for T regulatory cells, were up-regulated after Co-PP treatment. Our data strongly support a very important role for HO-1 in fetal allotolerance and suggest that HO-1 might be protective by up-regulating tissue protective molecules, i.e., Bag-1, and by activating T regulatory cells rather than by changing the local cytokine profile.

Abortion, Spontaneous↗

PubMed2005

Distractable vertebral cages for reconstruction after cervical corpectomy.

STUDY DESIGN: Retrospective study of 20 patients with degenerative cervical spinal canal stenosis who were treated with corpectomy followed by the placement of a distractable titanium cage (anterior distraction device [ADD]) (Ulrich GmbH & Co. KG, Ulm, Germany). OBJECTIVE: To investigate the efficacy of distractable titanium cages for reconstruction following decompressive cervical corpectomy. SUMMARY OF BACKGROUND DATA: Anterior corpectomy and reconstruction for extensive spinal canal stenosis are standard techniques. The reconstruction is commonly performed with bone graft and anterior plating. Alternatively, different fusion cages have gained acceptance in spine surgery. However, in traditionally designed cages, an over-distraction of the involved segment is necessary to place the cage into the defect, and to achieve tight contact between cage and endplates. The new designed cage (ADD) can be distracted in situ. Therefore, the height of the cage can be adjusted precisely to the size of the corpectomy. METHODS: All patients were treated with corpectomy followed by the placement of an ADD. A cervical plate was added in 13 cases, and an "All-in-one-system" (i.e., a cage with an attached plate with 2 holes for screw fixation on both sides, ADD) was used in 7. Follow-up was 18-60 months. Clinical evaluation and radiographs were performed after 3, 6, and 12 months, and then once a year. RESULTS: In all cases, a stable reconstruction of the anterior column was achieved, with no signs of instability on flexion/extension radiographs. However, there was one incidence of cage subsidence. According to Odom criteria, 11 patients (55%) had excellent outcome, 4 (20%) good, 3 (15%) satisfactory, and 2 (10%) poor. CONCLUSIONS: The results of the study show that distractable cages are useful vertebral body replacements because they can be adjust to the size of the corpectomy in situ and provide immediate strong anterior column support, avoiding bone graft site morbidity. The possibility of direct cage fixation without an additional plate simplifies the procedure.

Aged↗

PubMed2005

Heme oxygenase as a therapeutic target in immunological pregnancy complications.

The allogeneic fetus has been considered to be an allograft and the tolerance mechanisms involved in pregnancy maintenance resemble those leading to graft acceptance. Up-regulation of Heme Oxygenase-1 (HO-1) promotes graft acceptance. Additionally, HO-1 has been proposed to have tissue-protective properties. Previous studies reported the presence of HO-1 and HO-2 in mammalian placenta and postulated a protective role for HO during pregnancy. Here, we analyze HO-1 and HO-2 expression at the feto-maternal interface from normal pregnant and abortion mice and correlate these findings with inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression as well as with Th1/Th2 cytokine production by immune cells. DBA/2-mated CBA/J females undergoing abortion and BALB/c-mated CBA/J females having normal pregnancies were included in our study. The mice received no treatment. On day 14 of pregnancy, the mice were sacrificed, the abortion rate was calculated and the ex vivo Th1/Th2 production by decidual immune cells was analyzed by flow cytometry. The expression of HO-1 and HO-2, iNOS and eNOS was analyzed by immunohistochemistry (IHC) and Western blot in placenta samples. The Th1/Th2 cytokines ratio was augmented in decidua from abortion mice. We further observed a significant down-regulation of HO-1, HO-2, iNOS and eNOS molecules in placental tissue from mice undergoing abortion when compared to normal pregnant mice. Since we found diminished HOs and nitric oxide synthase (NOS) levels at the feto-maternal interface from abortion mice when compared to normal pregnant mice, which were further associated with increased Th1/Th2 cytokine production, we propose HO as a putative therapeutic target in immunological abortions. Up-regulation of HO-1 or HO-2 would favour the Th2-cytokine production, which could avoid abortion onset.

Abortion, Spontaneous↗

PubMed2005

A spine frame for intra-operative fixation to increase accuracy in spinal navigation and robotics.

OBJECTIVE: Intra-operative movements due to mechanical ventilation or manipulations are a limiting factor for accurate spinal navigation or robotic-assisted spinal surgery. The purpose of this study was to assess the accuracy of an intra-operative spinal fixation device in an experimental setup. MATERIALS AND METHODS: We developed a fixation device, attached to the operating table, that combines soft tissue retraction with spinal process fixation. Using a lumbar spine cadaver, tightness of fixation was evaluated using two measurement systems. Accuracy measurements using changes in spatial co-ordinates of implanted reference markers were performed in three segments, following different manipulations of the spine. In addition, for intra-operative movements of the spine during mechanical ventilation, the range of motion was determined in 10 patients during lumbar interbody fusion. RESULTS: The spine frame was easy to use and did not restrict screw insertion. Mean deviations of the markers' in all segments were measured at between 0.35 and 0.8 mm, following pedicle screw insertion and lateral traction. Intra-operative range of motion of the spine was measured with a mean value of 8.7 +/- 3.3 mm. CONCLUSION: Using our spine frame, a rigid fixation following manipulation of the spine was demonstrated. By overcoming the intra-operative movement-dependent inaccuracy, safety in navigated spine surgery and robotic-assisted procedures might be improved.

Analysis of Variance↗

PubMed2005

An atypical spinal meningioma with CSF metastasis: fatal progression despite aggressive treatment. Case report.

The authors report the case of a 23-year-old man who presented with a C1-3 spinal mass. Following intraspinal decompression the tumor was histologically classified as an atypical meningioma (World Health Organization grade II). Two further surgical interventions resulted in almost total removal of the meningioma. In addition, radiotherapy was performed. During the 1.5-year follow-up period the diagnostic examinations identified a local tumor recurrence, an intraspinal C-6 metastasis, and a segmental instability with anterior C2-3 slippage and C3-4 kyphosis. The tumor was resected and occipitocervical stabilization was performed. Histological examination showed no change in malignancy. Despite additional hydroxyurea-based chemotherapy, the patient presented 4 months later with a hemiparesis and a massive recurrence of the tumor mass involving the posterior fossa and the upper thoracic spine. Because there were no further therapeutical options, the patient died. The authors discuss more aggressive therapeutic options in addition to surgery in patients with metastatic atypical meningiomas. The results in the reported case indicate that meningiomas associated with cerebrospinal fluid metastasis may represent a higher grade of malignancy.

Adult↗

PubMed2004

Brain-IL-1 beta triggers astrogliosis through induction of IL-6: inhibition by propranolol and IL-10.

BACKGROUND: Gliosis is a characteristic pathology in many central nervous system (CNS) diseases. Cytokines are considered to be effectors of gliosis. It has been shown that pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 boost glia scar formation. On the other hand, anti-inflammatory cytokines, such as IL-10 and IL-1 receptor antagonist (ra), can act neuroprotectively. Furthermore, various immune mediators and neurotransmitters can modulate the onset of gliosis. MATERIAL/METHODS: We used 100 male Sprague-Dawley rats to investigate the mechanisms of brain-cytokine-induced astrogliosis using an in vivo model of convection-enhanced delivery of cytokines (IL-beta, IL-6, tumor necrosis factor (TNF)-alpha) into the cerebro-ventricular system. The protective effects of the anti-inflammatory cytokine IL-10 and the neurotransmitter propranolol were also investigated. RESULTS: With this paradigm, we could clearly demonstrate that IL-6 is a key cytokine mediating astrogliosis, noticeable in the increased expression of glial fibrillary acidic protein (GFAP). Thus intra-cerebroventricular infusion of IL-6 increased GFAP expression in a dose-dependent manner. Furthermore, GFAP expression was also increased by IL-beta, which correspondingly triggered an IL-6 release into the CSF. Accordingly, TNF-alpha, which did not induce IL-6 release, also did not induce gliosis. On the other hand, substances which decrease IL-beta-induced IL-6 production, such as propranolol and IL-10, also dramatically decreased IL-beta triggered gliosis. CONCLUSIONS: IL-6 infusion, as well as IL-beta-induced IL-6 release into the CSF, increase GFAP expression in the cerebral cortex and hippocampus. Accordingly, blockade of the IL-beta-induced IL-6 release by IL-10 and propranolol decreases GFAP expression.

Animals↗

PubMed2004

Intratumoral infusion of interleukin-1beta and interferon-gamma induces tumor invasion with macrophages and lymphocytes in a rat glioma model.

Malignant gliomas are hard to treat successfully. Like other treatments immune therapy fails presumably due to low concentration of immune modifiers within the tumor. However, convection-enhanced delivery (CED) may overcome this problem. So, we analyzed the effect of intratumoral delivery of interleukin (IL)-1beta and interferon (IFN)-gamma by CED on tumor immune cell invasion in a rat glioma model. Tumors were implanted into the left caudate nucleus and tumor growth was demonstrated by MRI. Afterwards intratumoral infusion of IL-1beta or IFN-gamma was started for 48 h. Then animals were sacrificed and the number of tumor infiltrating CD4+ and CD8+ lymphocytes as well as macrophages was analyzed by immunohistochemistry. Our results demonstrate that intratumoral cytokine infusion using CED leads to a strong tumor invasion with macrophages and lymphocytes suggesting a tumor specific immune response.

Animals↗

PubMed2004

Degenerative spondylolisthesis of the cervical spine--symptoms and surgical strategies depending on disease progress.

BACKGROUND: Degenerative spondylolisthesis of the cervical spine is rare. Patients show signs of progredient myelopathy, radiculopathy and pain. Treatment strategies include ventral, dorsal and combined fusion techniques with or without repositioning and decompression. METHODS: In this study, we present 16 patients with degenerative cervical spondylolisthesis. The leading symptom was severe myelopathy in 8 patients, radiculomyelopathy in 5 patients and neck pain in 3 patients. However, neck pain was the initial symptom in all the patients and decreased when neurological symptoms became more evident. Radiographic examinations included plain radiography, MRI, CT, myelography and lateral tomography. RESULTS: Spondylolisthesis was located five times at level C3/4, C4/5 and C5/6. In three cases spondylolisthesis was located at level C7/T1. There were two patients with spondylolisthesis on two levels. Instability could be demonstrated by flexion/extension radiography in five cases. Patients were divided into three groups according to a newly introduced classification system. The surgical approach corresponded to this classification. In ten patients the spondylolisthesis could be corrected by extension and positioning, so discectomy and fusion on one or two levels with cage, plate and screws was sufficient. In five cases a corpectomy was necessary due to severe spondylosis. In one case a combined approach with dorsal decompression and release followed by ventral fusion was applied due to additional dorsal spinal cord compression. The follow-up period was 6-52 months. After surgery, none of the patients showed any signs of neurological deterioration. In all cases, a stable fusion was achieved with no signs of instability on flexion/extension radiographs. Neurological improvement was seen in 6 of 8 patients with myelopathy and 4 of 5 patients with radiculomyelopathy. The others showed stable disease. Pain relief was seen in all patients who complained of pain preoperatively. CONCLUSION: The aims of treatment for cervical spondylolisthesis are spinal cord decompression (ventral, dorsal or both), correction and fusion. The used procedure should depend on the severity of the cervical deformity, degree and side of the spinal cord compression, and the possibility of correction by extension and positioning.

Aged↗

PubMed2004

Inflammatory response after neurosurgery.

Investigation into the inflammatory response in the central nervous system (CNS) is a rapidly growing field, and a vast amount of information on this topic has accumulated over the past two decades. Inflammation is a particularly interesting issue in the (traditionally non-regenerating) CNS, owing to its dual role in worsening or improving regeneration and functional outcome in certain circumstances. This paper reviews the current literature on the interactions between the immune system and the CNS in physiological and pathological states. The first part will provide an overview of the cellular and molecular components of CNS inflammation, this being followed by a discussion of the concept of systemic immunodepression after neurotrauma and neurosurgery. Finally, the delicate balance of immune responses in the CNS, with an emphasis on the beneficial effects of inflammation and possible therapeutic options, will be discussed.

Animals↗

PubMed2004

Multiple cerebral aneurysms and subarachnoid hemorrhage in a patient with Alagille syndrome.

Although intracranial hemorrhage has frequently been found responsible for mortality in adult patients with Alagille syndrome (AGS), no specific underlying cause has been identified. We describe the case of severe subarachnoid hemorrhage in a 30-year-old woman harboring five intracranial aneurysms and multiple peripheral vascular anomalies. To evaluate a possible higher incidence of intracranial aneurysms, a study of the cerebral vasculature in all AGS patients by using noninvasive imaging techniques should be considered.

Adult↗

PubMed2003

Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats.

BACKGROUND: Significantly increased plasma and CSF IL-6 levels reflect underlying tissue damage following clinical and experimental traumatic brain injury (TBI). Catecholamines, used under clinical conditions to maintain adequate cerebral perfusion pressure, induce a sustained IL-6 release. Thus an additional elevation in IL-6 could aggravate brain edema in the acute posttraumatic phase. We studied the changes in plasma and cerebrospinal fluid (CSF) IL-6 levels 4 and 24 hours after experimental TBI and assessed possible time-dependent effects of norepinephrine infusion on IL-6 and brain edema. MATERIAL/METHODS: Paired plasma and CSF IL-6 measured at 4 and 24 hours following TBI (n=10) were compared to levels in non-traumatized rats (n=5). In a placebo-controlled trial, 20 brain-injured male Sprague-Dawley rats were randomized to receive norepinephrine or NaCl for 90 minutes at 4 or 24 hours after TBI. Plasma IL-6 was measured before, during, and after the infusion period. One hour after stopping the infusion, CSF IL-6 and hemispheric swelling were determined. RESULTS: During the first posttraumatic day, plasma and CSF IL-6 levels were significantly increased compared to non-traumatized rats, reaching the highest values at 24 hours (p<0.05). Norepinephrine infusion significantly increased plasma IL-6 at 7 and 27 hours after TBI; IL-6 was significantly elevated in CSF only at 7 hours (p<0.05). Brain edema was not aggravated. CONCLUSIONS: The norepinephrine-induced increase in plasma and CSF IL-6 suggests that concomitant norepinephrine administration needs to be considered when interpreting systemic and local changes in IL-6 levels in TBI patients.

Animals↗

PubMed2002

Oligodeoxynucleotides induce brain inflammation in rats when infused intracerebroventricularly.

Antisense oligodeoxynucleotides (ODNs) can inhibit gene expression in a specific manner. However, several studies described problems with cerebral ODN application. Here, we investigated the immune effects (interleukin-6 (IL-6) release, cell invasion into cerebrospinal fluid (CSF) and brain parenchyma) of 'non-sense' randomized ODNs with different counterions (NH(4)(+), Na(+)) and modifications (with or without thioat-backbone) which were administered intracerebroventricularly for 48 h using osmotic mini-pumps in a rat model. All animals receiving ODNs showed increased IL-6 levels in the CSF as well as cell invasion into the CSF and brain parenchyma (P<0.05). However, the use of thioat-backbone and ammonium as the counterion induced the highest IL-6 levels (7210+/-1696 pg/ml, P<0.05) and the highest cell numbers in the CSF (31.6+/-15.5x10(5)/ml, P<0.05) as well as brain parenchyma (268.1+/-143.2 HIS-48+ cells/mm(2), P<0.01; and 31.3+/-10.7 OX-6+cells/mm(2), P<0.05) compared with the other groups.

Animals↗

PubMed2002

Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients.

BACKGROUND: Brain injury as well as early inflammatory and endocrine responses were found to be indicators for infectious complications in patients with multiple injuries. In this context, brain-derived inflammatory response as well as centrally triggered neuroendocrine activation and systemic immunodepression seem to be of major importance. Therefore, we hypothesize that a circulating index of inflammatory or endocrine function measured soon after brain injury (in patients with admission Glasgow Coma Scale [GCS] score of 4-7) would discriminate severe from moderate injury as indexed by GCS status on postinjury day 7. METHODS: In a retrospective study, 25 patients with either acute traumatic brain injury or cerebral hemorrhage and an initial GCS score of 4 to 7 were examined. Blood samples were obtained at different time points, and different immune variables and neuroendocrine hormones were determined. According to the GCS score on day 7, patients were divided into two groups (GCS score > or = 8, moderate brain injury; and GCS score < 8, severe brain injury or patients who died within the first week) for comparison of variables. Concluding from the results of this retrospective analysis, in a prospective study patients (n = 26) were divided into two groups according to their interleukin (IL)-6 plasma concentrations on day 1 (IL-6 > or = 100 pg/mL and IL 6 < 100 pg/mL). After 7 days, the GCS score, the infection rate, and the mortality were compared between these two groups. RESULTS: In the retrospective study, we could show that severe brain injury (as assessed by GCS score and mortality on day 7) was associated with high plasma levels of pro- and anti-inflammatory cytokines, acute phase proteins, and neuroendocrine hormones within 2 to 6 hours after the acute event. Among the investigated variables, elevated IL-6 plasma concentrations were stable up to 1 day after the acute event with a high predictive value with regard to the short-term prognosis and incidence of infectious complications within the first week. Because of this stability during the first 24 hours, we selected IL-6 for further studies. In the prospective study with a calculated cut-off IL-6 plasma concentration of 100 pg/mL on day 1, the predictive value of this parameter regarding the severity of the brain injury was fully confirmed (positive predictive value, 0.94; this value represents the observed pretest probability of 0.62). All patients who died (n = 5) or developed infectious complications within the first week (n = 8) showed plasma IL-6 levels > or = 100 pg/mL on day 1. CONCLUSION: The IL-6 plasma level 1 day after the acute event with a cut-off of 100 pg/mL (Immulite) seems to be a predictor for short-term prognosis and infectious complications in brain-injured patients.

Adult↗