Pro-inflammatory effector Th cells transmigrate through anti-inflammatory environments into the murine fetus.

The presence of maternal DNA or even maternal cells within the offspring (microchimerism) has been reported for many fetal tissues, including the liver, heart, and spleen. Microchimerism is believed to be involved in the pathogenesis of autoimmune diseases; however, the cellular origin of this phenomenon remains unknown. Here, we determined whether differentiated T lymphocytes could transmigrate through the immunosuppressive environment of the placenta to reach the fetus. In vitro-differentiated effector/memory Th1 and Th17 cells from OVA323₋339-specific TCR(tg) T cells of OT-II mice were adoptively transferred (i.v.) into the tail veins of pregnant Ly5.1 mice at d15 and d19 of gestation. Mice were then sacrificed 40 h after adoptive cell transfer. Using radioactive labeling of T cells with sodium chromate [Cr5¹] prior to adoptive transfer, we observed that homing of pro-inflammatory Th cells was equally efficient in both pregnant and non-pregnant mice. Transmigration of Th1- and Th17-like cells through the highly immunosuppressive environment of the placenta into the fetus was significantly enhanced in experimental mice compared to control mice (P < 0.0001). In addition, a substantial amount of effector Th cells accumulated in the placenta. Finally, we found that treatment with Pertussis Toxin resulted in a 3-fold increase in the transmigration of effector Th17 cells into the fetus (P < 0.0001). When pro-inflammatory Th1-or Th17-like cells were injected into syngeneic mothers, almost all of the fetuses analyzed exhibited radioactivity, suggesting that transmigration of effector T cells occurs frequently. Our results suggest the possibility of novel roles for these maternal effector cells in the pathogenesis or reduction of disease.

Value of cine phase contrast magnetic resonance imaging to predict obstructive hydrocephalus.

BACKGROUND: This is a prospective study to evaluate the role of CINE MRI to predict obstructive hydrocephalus in the preoperative work-up. PATIENTS/MATERIAL AND METHODS: A total of 16 patients with aqueductal obstruction demonstrated by CINE MRI who were undergoing ETV were included. MRI was performed preoperatively, at 3 months, at 12 months and at 24 months after surgery. Prior to the fenestration of the third ventricular floor aqueductal patency was evaluated using intraoperative ventriculography. A successful outcome was defined by using radiological and clinical criteria. RESULTS: In 8 patients with aqueductal obstruction on preoperative CINE MRI aqueductal patency was proven intraoperatively. ETV failed in all patients with intraoperatively proven aqueductal patency. Out of these 8 patients, 1 patient had no risk factors for ETV failure, 3 had 1 risk factor, 3 had 2 risk factors, and 1 had 3 risk factors. Most of the failure (6 out of 8 patients) occurred within 8 weeks of the initial procedure. A lumbar puncture was performed in these patients to avoid misinterpretation of the clinical course. CONCLUSION: The present study demonstrates that cine phase constrast MR may be a poorer choice to determine aqueductal patency compared to high resolution structural imaging. Interestingly, intraoperative ventriculography was an adjunct to better predict outcome after ETV in patients with obstructive hydrocephalus. In cases with non-conclusive preoperative imaging, postoperative decision making may be supported by the use of intraoperative ventriculography with the goal of reducing unnecessary tests and procedures. However, the analysis of the study data has to be considered as explorative. Therefore, findings should be validated with a larger patient population.

Stress alters rates and types of loss of heterozygosity in Candida albicans.

UNLABELLED: Genetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis. Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination in C. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated during in vitro exposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus, C. albicans generates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term "stress-induced LOH" that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation. IMPORTANCE: Stress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms. Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this "stress-induced LOH" facilitates the rapid adaptation of C. albicans, which does not undergo meiosis, to changing environments within the host.

CTLA-4 (CD152) blockade does not cause a pro-inflammatory cytokine profile in regulatory T cells.

OBJECTIVES: The activation of T cells is closely regulated. One cell intrinsic mechanism is based on the expression of inhibitory molecules; another is mediated by regulatory T (Treg) cells. The co-regulatory molecule CTLA-4 is constitutively expressed by Treg cells and up-regulated in effector-T-cells after activation. Recently, it was described that Treg cells can display an unstable phenotype and convert into pathogenic pro-inflammatory cytokine secreting cells. Here we have analysed the role of CTLA-4 in the regulation of cytokine production by T-helper (Th) cells with a special focus on Treg cells. METHODS: Proliferation of unstimulated CTLA-4 knock-out and wild-type cells as well as their activation status and the impact of CTLA-4 blockade on proliferation of Treg and effector T cells under stimulation were analysed by flow cytometry. Furthermore, the cytokine concentrations were analysed by a multiplex suspension assay. RESULTS: CTLA-4 knock-out T cells proliferated without stimulation and displayed an activated phenotype ex vivo. Proliferation of effector but also that of Treg cells was controlled by CTLA-4. The blockade of CTLA-4 led to an increased secretion of GM-CSF, IL-1ß, IL-2, and IFN-γ by Th cells. However, the blockade of CTLA-4 in Treg cells did not cause any conversion into pathogenic pro-inflammatory T cells, since the non-cytokine secreting phenotype remained unchanged. CONCLUSIONS: These results have major implications on therapies targeting the CTLA-4-system, e.g. by CTLA4-Ig or anti-CTLA-4-antibodies, as the blockade of CTLA-4 did not unlock the stability of Treg cells.

Glycogen synthase kinase-3ß is a crucial mediator of signal-induced RelB degradation.

The immediate early transcription factor nuclear factor (IκBs) kappa B (NF-κB) is crucially involved in the regulation of numerous physiological or pathophysiological processes such as inflammation and tumourigenesis. Therefore, the control of NF-κB activity, which is mainly regulated by signal-induced degradation of cytoplasmic inhibitors of NF-κB (IκBs), is of high relevance. One known alternative pathway of NF-κB regulation is the stimulus-induced proteasomal degradation of RelB, a component of the NF-κB dimer. Here, we identified the serine/threonine protein kinase glycogen synthase kinase-3ß (GSK-3ß) as a critical signalling component leading to RelB degradation. In Jurkat leukaemic T cells as well as in primary human T cells, tetradecanoylphorbolacetate/ionomycin- and CD3/CD28-induced RelB degradation were impaired by a GSK-3ß-specific pharmacological inhibitor, an ectopically expressed dominant-negative GSK-3ß mutant and by small-interfering RNA-mediated silencing of GSK-3ß expression. Furthermore, a physical interaction between RelB and GSK-3ß was shown by co-immunoprecipitation, which was already notable in unstimulated cells. Most importantly, as demonstrated by in vitro kinase assays, human RelB is inducibly phosphorylated by GSK-3ß, indicating a direct substrate-enzyme relationship. The serine residue 552 is a target of GSK-3ß-mediated phosphorylation in vitro and in vivo. We conclude that GSK-3ß is a crucial regulator of RelB degradation, stressing the relevant linkage between the NF-κB system and GSK-3ß.

Obstruction of cerebral venous sinus secondary to idiopathic intracranial hypertension.

BACKGROUND: Whether cerebral venous sinus obstruction is a cause or consequence of idiopathic intracranial hypertension (IIH) is uncertain. METHODS AND RESULTS: Among the nine children with IIH, five showed stenosis (n = 5) and occlusion (n = 1) of cerebral venous sinus on cranial magnetic resonance imaging (n = 4) or conventional angiography (n = 1), respectively. Follow-up magnetic resonance imaging performed in four children showed complete regression of the venous pathology in one and partial regression in two of them. CONCLUSIONS: Our data demonstrate that cerebral venous sinus obstruction is frequent and frequently transient in pediatric IIH and suggest that stenoses may result from elevated intracranial pressure.

Off-midline Sinus Pericranii Associated with Ipsilateral Venous Anomaly: Case Report and Therapeutic Considerations.

A case of lateral sinus pericranii associated with ipsilateral venous anomaly is reported. No treatment was instituted in accordance with the parents' wishes. The role of MRI and cerebral angiography in the diagnostic workup is discussed.

Management of hydrocephalus in children with plasminogen deficiency.

Congenital plasminogen deficiency is an infrequent disorder, which usually becomes symptomatic as ligneous conjunctivitis. However, pseudomembranous lesions in the mucosa of the pharynx, tracheobronchial tree, and the peritoneum may likewise occur. An accompanying hydrocephalus is extremely rare; only 16 cases have been reported to date. The reports indicate that hydrocephalus, even if treated by ventriculoperitoneal (VP) cerebrospinal fluid (CSF) shunting, worsens the prognosis substantially. Thus, VP CSF shunting does not seem to be the optimal therapy for hydrocephalic children with plasminogen deficiency. We add two cases to the literature, and, on the base of our experience, we propose a management strategy for the hydrocephalus. We report the case history of two children with plasminogen deficiency and associated hydrocephalus. Both children initially were treated with VP shunts and had a very similar clinical course with multiple shunt malfunctions due to nonabsorption by the peritoneum. In the first child, the attempt to treat the hydrocephalus with a ventriculoatrial (VA) shunt failed due to catheter thrombosis. Finally, a ventriculocholecystic shunt was placed in both children, which worked well. In patients with plasminogem deficiency and associated hydrocephalus, special care must be taken in the management of hydrocephalus. The absorptive capacity of the peritoneum is reduced by pseudomembrane formation, which results in VP shunt malfunction. The plasminogen deficiency results in early thrombus formation if atrial catheters are used. Therefore, the authors believe that ventriculocholecystic shunting should be considered early on in the course of the disease.

Combined motor and somatosensory evoked potentials for intraoperative monitoring: intra- and postoperative data in a series of 69 operations.

The primary objective of neurophysiologic monitoring during surgery is to avoid permanent neurological injury resulting from surgical manipulation. To prevent motor deficits, either somatosensory (SSEP) or transcranial motor evoked potentials (MEP) are applied. This prospective study was conducted to evaluate if the combined use of SSEP and MEP might be beneficial. Combined SSEP/MEP monitoring was attempted in 100 consecutive procedures, including intracranial and spinal operations. Repetitive transcranial electric motor cortex stimulation was used to elicit MEP from muscles of the upper and lower limb. Stimulation of the tibial and median nerves was performed to record SSEP. Critical SSEP/MEP changes were defined as decreases in amplitude of more than 50% or increases in latency of more than 10% of baseline values. The operation was paused or the surgical strategy was modified in every case of SSEP/MEP changes. Combined SSEP/MEP monitoring was possible in 69 out of 100 operations. In 49 of the 69 operations (71%), SSEP/ MEP were stable, and the patients remained neurologically intact. Critical SSEP/ MEP changes were seen in six operations. Critical MEP changes with stable SSEP occurred in 12 operations. Overall, critical MEP changes were recorded in 18 operations (26%). In 12 of the 18 operations, MEP recovered to some extent after modification of the surgical strategy, and the patients either showed no (n = 10) or only a transient motor deficit (n = 2). In the remaining six operations, MEP did not recover and the patients either had a transient (n = 3) or a permanent (n = 3) motor deficit. Critical SSEP changes with stable MEP were observed in two operations; both patients did not show a new motor deficit. Our data again confirm that MEP monitoring is superior to SSEP monitoring in detecting impending impairment of the functional integrity of cerebral and spinal cord motor pathways during surgery. Detection of MEP changes and adjustment of the surgical strategy might allow to prevent irreversible pyramidal tract damage. Stable SSEP/MEP recordings reassure the surgeon that motor function is still intact and surgery can be continued safely. The combined SSEP/ MEP monitoring becomes advantageous, if one modality is not recordable.

Motor evoked potentials following highly frequent transcranial magnetoelectrical motor cortex stimulation: normal data and potential modulation by stimulation-dependent inhibitory and activating mechanisms.

OBJECTIVE: To determine the normal values (latency, amplitude) of motor evoked potentials (MEP) of the abductor pollicis brevis (APB) and tibialis anterior (TA) muscle after high-frequency repetitive transcranial magnetic stimulation of the motor cortex (rTCMS), and to evaluate stimulation-dependent MEP modulations. PATIENTS AND METHODS: 29 healthy volunteers underwent rTCMS with 2 and 4 stimuli. The interstimulus interval (ISI) was 2, 3, and 4 ms respectively, which corresponded to frequencies between 250 and 500 stimuli/s. The evoked potentials of the relaxed and voluntarily contracted APB and TA were registered. RESULTS: Depending on the frequency and number of stimuli, the mean corticomuscular latency to the relaxed APB varied between 22.2 and 22.9 ms, and to the relaxed TA between 30.4 and 32.0 ms. The intra- and interindividual variability of the amplitudes was substantial. Voluntary contraction of the target muscle always led to a decrease in latency and increase in amplitude (p < 0.05). CONCLUSION: The high variability of the amplitudes does not allow the computation of meaningful normal values. The latencies after rTCMS are close to those of normal data after single TCMS, which indicates that in awake humans identical cortical and spinal structures are similarly activated. The discrete variations of latency and amplitude after changing the frequency and stimulus number suggest that inhibitory and excitatory mechanisms on the cortical and/or spinal level modulate the muscle response.

MRI and intraoperative findings in cavernous haemangiomas of the spinal cord.

More sensitive imaging techniques, such as MRI, have led to an increase in the number of reported cases of spinal cord cavernous haemangioma (SCCH). Complete surgical resection has been performed with good outcomes. However, operative findings do not always confirm preoperative MRI as to the size and site (superficial or deep) of the lesion. We evaluated whether MRI can be used to predict whether or not SCCH reach the surface of the spinal cord, since this has an impact on surgical strategy. We reviewed the preoperative MRI, case-notes and video recordings of 12 patients who underwent surgery, at which five superficial and seven deep-seated lesions were identified. T1-weighted images correctly indicated the site of the lesion in ten, T2-weighted images in only eight. One deep lesion was thought to be superficial on both T1- and T2-weighted images. Intravenous contrast medium was not helpful in diagnosis or localisation. In no case was a surgically proven superficial lesion interpreted as deep in the spinal cord.

Measurement of motor evoked potentials following repetitive magnetic motor cortex stimulation during isoflurane or propofol anaesthesia.

BACKGROUND: Isoflurane and propofol reduce the recordability of compound muscle action potentials (CMAP) following single transcranial magnetic stimulation of the motor cortex (sTCMS). Repetition of the magnetic stimulus (repetitive transcranial magnetic stimulation, rTCMS) might allow the inhibition caused by anaesthesia with isoflurane or propofol to be overcome. METHODS: We applied rTCMS (four stimuli; inter-stimulus intervals of 3, 4, 5 ms (333, 250, 200 Hz), output 2.5 Tesla) in 27 patients and recorded CMAP from the hypothenar and anterior tibial muscle. Anaesthesia was maintained with fentanyl 0.5-1 microg kg(-1) x h(-1) and either isoflurane 1.2% (10 patients) or propofol 5 mg kg(-1) x h(-1) with nitrous oxide 60% in oxygen (17 patients). RESULTS: No CMAP were detected during isoflurane anaesthesia. During propofol anaesthesia 333 Hz, four-pulse magnetic stimulation evoked CMAP in the hypothenar muscle in 75%, and in the anterior tibial muscle in 65% of the patients. Less response was obtained with 250 and 200 Hz stimulation. CONCLUSIONS: In most patients, rTCMS can overcome suppression of CMAP during propofol/nitrous oxide anaesthesia, but not during isoflurane anaesthesia. A train of four magnetic stimuli at a frequency of 333 Hz is most effective in evoking potentials from the upper and lower limb muscles. The authors conclude that rTCMS can be used for evaluation of the descending motor pathways during anaesthesia.

Focused high frequency repetitive transcranial magnetic stimulation for localisation of the unexposed primary motor cortex during brain tumour surgery.

OBJECTIVES: To investigate if intraoperative focused high frequency repetitive transcranial magnetic stimulation (rTMS) can localise the primary motor cortex without exposure of the cortical surface. METHODS: A high frequency train (357 Hz) of four suprathreshold magnetic stimuli was delivered transcranially to the region of the rolandic area during brain tumour operations in 12 patients. To induce a focal magnetoelectric field, the flat figure of eight coil (outer diameter of each loop 7 cm) was used. Motor evoked potentials (MEP) were recorded in eight muscles of the upper and lower contralateral extremities. The first stimulation site was 2.5 cm behind the bregma, the second site 2 cm, and the third site 4 cm dorsal to the first stimulation site. If no MEP were obtainable, stimulation was repeated in anteroposterior direction at more laterally located sites. Using neuronavigation, each positive stimulation site was correlated with the underlying cortical anatomy. RESULTS: Stimulation was performed at a total of 42 sites (in two patients, maximum stimulation at the three initial sites failed to evoke a motor response). In four patients, MEP were obtained only from one stimulation site. This site exactly overlayed the primary motor cortex. In eight patients, MEP could be elicited from more than one stimulation site. In seven of the eight patients, the site from which MEP with peak amplitudes were elicited, corresponded to the primary motor cortex. In total, the primary motor cortex was correctly identified on the basis of electrophysiological findings in 11 of 12 patients (92 %). In two patients, only the more lateral stimulation sites permitted MEP recording. CONCLUSION: Intraoperative focused rTMS is highly sensitive for localisation of the primary motor cortex. Focused rTMS as a localising instrument alleviates the need of motor cortex exposure and, thereby, can contribute to minimise the surgical approach to brain tumours in the rolandic area.

Experience with a new concept to lower non-infectious complications in infants with programmable shunts.

In neonates and infants less than 1 year of age who are treated with a ventriculo-peritoneal shunt, non-infectious complications are almost as frequent and dangerous as infectious complications. While the incidence of infections can be reduced, using perioperative antibiotics, special surgical techniques and postoperative care non-infectious complications such as wound break-down, cerebrospinal fluid (CSF) fistula and subcutaneous CSF collection are preventable, but seem difficult to manage, especially in the group of patients at a susceptible age. The authors present their experience with the programmable Hakim valve in 40 neonates and infants less than 1 year of age, who were treated with de novo implantation of a ventriculo-peritoneal shunt due to various pathologies. The uneventful wound healing during the first weeks after shunt implantation, avoiding the above mentioned non-infectious complications, was supported by initial, temporary overdrainage and readjustment of the programmable valve after completed wound healing. All patients tolerated this procedure well and showed no pathological signs or symptoms of overdrainage like premature closure of cranial sutures, clinical low-pressure syndrome, slit ventricle syndrome (SVS), subdural fluid collection or brain collapse during an average follow-up period of 2.6 years (2 - 65 months). Infectious and other mechanical, non-infectious complications were analysed as well during the follow-up period. These results suggest that an initial, temporary overdrainage in infants and neonates with shunted hydrocephalus may contribute to further lower the incidence of non-infectious complications like wound break-down, CSF-fistula or subcutaneous CSF accumulation, without negative side effects. This technique could be a valuable option in the regimen of shunt-treatment of this age group in order to optimise the overall success rate and lower the general complication rate.

Extended pterional orbital decompression in severe orbital cellulitis.

BACKGROUND: Bacterial orbital cellulitis is a relatively uncommon infective process, which can threaten the function of orbital structures. Apart from antibiotic therapy, sinus surgery with or without abscess drainage via an orbito-otorhinolaryngological approach might be necessary. CASE DESCRIPTION: We present three cases of severe orbital cellulitis, leading to increasing loss of vision, proptosis, afferent pupillary disturbances and restriction of extra-ocular movements, despite antibiotic therapy. After extended pterional orbital decompression and reducing the orbital pressure by removal of the lateral and superolateral orbital walls, all patients showed distinct improvement of initial symptoms, without any complications related to the operation. INTERPRETATION: Extended pterional orbital decompression represents an effective treatment alternative and supplement in cases of a severe, threat to ocular function due to orbital cellulitis, where acute reduction of pressure on orbital, neural and vascular structures is intended.

Acute psychological stress simultaneously alters hormone levels, recruitment of lymphocyte subsets, and production of reactive oxygen species.

Very little is known about the effects of acute psychological stress on the production of reactive oxygen species (ROS) by human phagocytic cells and the interplay between subjectively perceived stress, mediating hormones, variations in the number of peripheral leukocytes and ROS production. We measured psychological reactions, cardiovascular parameters, plasma catecholamines, plasma prolactin and cortisol as well as peripheral lymphocyte subsets in 13 experimental subjects undergoing a brief psychological stressor, and production of ROS, as indicated by chemiluminescence (CL), in stressed subjects and in healthy controls. The stressor elevated anger (p<0.01) and cardiovascular activation (p<0.01). There were significant changes in plasma levels of cortisol (p<0.01) and prolactin (p<0.001). During psychological stress natural killer (NK) cells (p<0.01) and CD8/CD38 cells (p<0.05) increased and returned to baseline only 25 minutes later. Significant changes in the number of naive CD4+/CD45RA+ (p<0.01) and antigen-experienced CD8+/CD45RO+ T cells (p<0.05) occurred. Subjects with stronger cardiovascular reaction showed higher stress-related plasma levels of norepinephrine (p<0.05) and were mainly responsible for the increase in NK cells. We observed a significantly reduced production of ROS following the stress test (p<0.05). Our results show that psychological stress is expressed simultaneously on psychological, hormonal and immunological levels of the organism. We show the existence of a circadian rhythm leading to a pronounced increase in CL during the morning hours. This first study taking this circadian rhythm in account revealed a significant suppressive effect of stress on ROS production.

[Treatment options in traumatic epidural hematomas]. / Behandlungsmöglichkeiten bei traumatischen Epiduralhämatomen.

The authors report 118 consecutive cases of patients with traumatic extradural hematoma (EDH) which were analyzed according to different clinical parameters and treatment modalities. Patients, treated for EDH between 1992 and 1998 in our department were distributed into 5 treatment groups depending on their clinical and neuroradiological findings on admission and during the hospitalization. Group I consisted of 75 patients (64%) who required immediate surgical evacuation of the hematoma after admission. Group II included 12 patients (10%) with initially conservative treatment despite visible EDH on the first CT-scan, which had to be operated on in the course because of neurological deterioration or increase of hematoma size. The 14 patients (12%) forming group III developed an acute EDH after the initial CT-scan revealed no extradural blood; 7 patients (6%) out of group IV showed a chronic EDH (delay trauma/diagnosis > 72 h), which required operative evacuation. All 10 patients (8%) comprising group V were treated conservatively. In each group the following parameters were analyzed: patient age, size and location of hematoma, trauma mechanism, additional intracranial lesions or skull fractures, intraoperative findings and neurostatus on admittance and during the hospitalization. The decision for non-operative treatment of EDH and the timing of a delayed intervention has to be made individually in each case in dependence of parameters like patient age, hematoma-size and -location and neurological status and course. Chronic EDH should be operated immediately, as well as hematomas presenting with an increase in size. Delayed developing EDH imply worse outcome and make adequate surveillance of high-risk patients mandatory.

Occurrence and therapy of space-occupying cystic lesions after brain tumor surgery.

OBJECTIVES: Space-occupying cystic lesions may develop in a variable time after resection of particular intracranial tumors, representing a small amount of complications of these procedures. We present our experience with the development and operative treatment of such postoperative cystic lesions in order to identify possible risk factors and to optimize the treatment. METHODS: The records and neuroradiological findings of patients, operated on either gliomas and meningeomas or craniopharyngeomas, who developed symptomatic cystic lesions in the former tumor resection area during the last ten years, were analyzed. RESULTS: 31 patients (2.5%) out of a total of 1240 corresponding tumor operations were identified. The mean age among the 20 female and 11 male patients was 47 years (12-74 years). In 17 patients (55%) the cystic lesion occured within 6 months after tumor resection (mean 5.6 weeks) and in 14 patients (45%) later than 6 months postoperatively (mean 3.6 years). 22 patients (71%) had malignant tumors and 16 patients (52%) had previous radiation therapy. 14 patients (45%) had more than one tumor resection at the same location and one patient had a postoperative meningitis as predisposing factor for the cyst-formation. All patients profited of the various definitive treatment modalities: repetitive percutaneous puncture/external drainage (5 patients), craniotomy for cyst-resection/-fenestration without (5 patients) and with Rickham-catheter implantation (10 patients), endoscopic cyst-fenestration with Rickham-catheter implantation (3 patients) and implantation of cysto-atrial or cysto-peritoneal shunts (8 patients). CONCLUSIONS: Symptomatic cystic lesions developing after brain tumor resection may occur as early - (5.6 weeks) or as late - (3.6 years) complications and though predisposing factors, like malignant primary tumor, preceding radiation therapy and multiple tumor resections can be identified, the reason for their occurrence remains unclear. A variety of effective therapy options is applicable but should consider the patients condition and prognosis.

Sustained induction of heme oxygenase-1 in the traumatized spinal cord.

Oxidative stress contributes to secondary injury after spinal cord trauma. Among the consequences of oxidative stress is the induction of heme oxygenase-1 (HO-1), an inducible isozyme that metabolizes heme to iron, biliverdin, and carbon monoxide. Here we examine the induction of HO-1 in the hemisected spinal cord, a model that results in reproducible degeneration in the ipsilateral white matter. HO-1 was induced in microglia and macrophages from 24 h to at least 42 days after injury. Within the first week after injury, HO-1 was induced in both the gray and the white matter. Thereafter, HO-1 expression was limited to degenerating fiber tracts. HSP70, a heat shock protein induced mainly by the presence of denatured proteins, was consistently colocalized with HO-1 in the microglia and macrophages. This study to demonstrates long-term induction of HO-1 and HSP70 in microglia and macrophages after traumatic injury and an association between induction of HO-1 and Wallerian degeneration. White matter degeneration is characterized by phagocytosis of cellular debris and remodeling of surviving tissue. This results in the metabolism, synthesis, and turnover of heme and heme proteins. Thus, sustained induction of HO-1 and HSP70 in microglia and macrophages suggests that tissue degeneration is an ongoing process, lasting 6 weeks and perhaps even longer.