1,721,023 research outputs found
On the use of flexible endoscopes to aspirate intraventricular hemorrhage, off-label innovations, and regulations
No full text[no abstract available
The role of mitotic slippage, USP1-regulated apoptosis, and multiple treatments in the action of temozolomide in glioblastoma multiforme
Full text linkBackground. Temozolomide (TMZ) is a methylating drug that is commonly used in the treatment of glioma. Although many features are still unclear, its general mechanism of action is well described. TMZ induces O6-methylguanine (O6MeG) lesions in DNA, which, in the absence of repair by O6-methylguanine methyltransferase (MGMT), mispair with thymine and start a futile cycle of repair-resynthesis events. The resultant DNA double-strand breaks (DSBs) activate the components of G2 checkpoint, and cells with a 4N DNA content accumulate and remain arrested at the G2/M boundary for several days. Cell death subsequently occurs by senescence, necrosis, or mitotic catastrophe, while apoptosis has been ruled out in many studies. Moreover, the effect of multiple TMZ treatments on G2 arrest and apoptosis induction is not clear. Repair of methylating drug-induced DNA lesions requires monoubiquitination of PCNA and FANCD2. Loss of either protein or inhibition of their monoubiquitination increases drug toxicity. USP1 is a hydrolase that removes monoubiquitin from PCNA and FANCD2, and can potentially play a role in TMZ mechanism of action.
Materials and methods. U87, U251 (TMZ-sensitive, low MGMT), and GBM8 (TMZ-resistant, high MGMT) cell lines were used for experiments. The treatment was scheduled with 100μM TMZ for 3 hours for 1, 2, or 3 consecutive days. Cell cycle progression was studied with both FACS-based analysis and a novel time-lapse microscopic real-time analysis using FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator), and apoptosis was measured with FACS-based Annexin V-PI analysis. To address the possible role of USP1 in TMZ action, we examined expression of USP1 at the mRNA levels in expression microarray databases derived from primary GBM. We also used siRNA targeting USP1 to modulate USP1 expression, and studied the effect of USP1 downregulation on TMZ-induced G2 arrest, cell death, and clonogenicity.
Results. Compared to single treatment, multiple TMZ treatments cause a significant reduction of clonogenicity in TMZ-sensitive cells and induce a significant increase of apoptosis, particularly in a late stage. However, multiple treatments don’t have any major effect on cell cycle profile. Time-lapse microscopic analysis with FUCCI system showed that TMZ-sensitive glioma cells arrest at the G2 checkpoint for less than 48 hours and, in the presence of an activated G2 checkpoint, they replicate their DNA without cellular division, re-enter the cell cycle at the next G1 phase, and repeat the cycle, ultimately giving rise to polyploid cells. siRNA-mediated suppression of USP1 had no effect on cell cycle progression or the extent of temozolomide-induced G2 arrest. However, while USP1 knockdown alone had minimal effect on cell death, it increased temozolomide-induced loss of clonagenicity both in TMZ-sensitive and TMZ-resistant cells. Further examination of the mechanism of cell death suggested that while control cells, control cells exposed to TMZ, or USP1-suppressed cells rarely underwent apoptotic cell death, temozolomide-treated cells in which USP1 levels were suppressed underwent high rates of apoptosis.
Conclusions. The present studies show that TMZ can induce apoptosis in TMZ-sensitive glioma cells, which is visible after 3 days but significant after 7 days. Multiple TMZ treatments don’t affect cell cycle profile, but significantly increase apoptosis. Moreover, time-lapse studies suggest a novel mechanism of action for TMZ, alternative to the one commonly accepted. These results have significant implications for the development of TMZ resistance. Furthermore, rather than sensitizing cells to DNA damaging agents, USP1 appears to suppress latent apoptotic pathways and to protect cells from temozolomide-induced apoptosis. These results identify a new function for USP1 and suggest that suppression of USP1 and/or USP1 controlled pathway may be a means to enhance the cytotoxic potential of temozolomide and to sensitize TMZ-resistant GBM cell
Wound complication associated with bovine serum albumin-glutaraldehyde (BioGlue®) in ventricular neuroendoscopic surgery
No full text[no abstract available
Split cerebral aqueduct: a neuroendoscopic illustration
No full textPURPOSE:
Forking of the cerebral aqueduct is a developmental malformation that is infrequently encountered by neurosurgeons as a rare cause of hydrocephalus, sometimes with a delayed onset. The etiology of an apparently forked aqueduct might be different. However, neuroendoscopy can often be the optimal treatment. The purpose of this study was to review the literature by analyzing the anatomical, functional, diagnostic, and therapeutic features of this unusual condition and adding our personal cases.
METHODS:
We present a case of forking of the cerebral aqueduct that was detected in vivo and treated with a flexible scope. A thorough review of the pertinent literature is also discussed. In the past years, diagnosis of forked aqueduct was possible only postmortem.
RESULTS:
A forked aqueduct is occasionally encountered in patients when a delayed hydrocephalic decompensation occurs.
CONCLUSIONS:
Flexible neuroendoscopy enables for a direct, in vivo diagnosis and immediate treatment through a third ventriculostomy
How I do it: flexible endoscopic aspiration of intraventricular hemorrhage
Full text linkBackground: As intraventricular blood is a strong negative prognostic factor, intraventricular hemorrhage requires prompt and aggressive management to reduce intracranial hypertension. Method: A flexible scope can be used to navigate and to aspirate blood clots from all four ventricles. Complete restoration of CSF pathways from the lateral ventricle to the foramen of Magendie can be obtained. Conclusion: Flexible neuroendoscopic aspiration of IVH offers the opportunity to immediately reduce intracranial hypertension, reduce EVD obstruction and replacement rates, and decrease infections and shunt dependency
Hemorrhagic Stroke: Endoscopic Aspiration
No full textIntracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) carry a very dismal prognosis. Several medical and surgical attempts have been made to reduce mortality and to improve neurological outcomes in survivors. Aggressive surgical treatment of ICH through craniotomy and microsurgical evacuation did not prove to be beneficial to these patients, compared to the best medical treatment. Similarly, the conventional treatment of IVH using an EVD is often effective in controlling ICP only initially, as it is very likely for the EVD to become obstructed by blood clots, requiring frequent replacements with a consequent increase of infection rates.Minimally invasive techniques have been proposed to manage these cases. Some are based on fibrinolytic agents that are infused in the hemorrhagic site through catheters with a single burr hole. Others are possible thanks to the development of neuroendoscopy. Endoscopic removal of ICH through a mini-craniotomy or a single burr hole, and via a parafascicular white matter trajectory, proved to reduce mortality in this population, and further randomized trials are expected to show whether also a better neurological outcome can be obtained in survivors. Moreover, endoscopy offers the opportunity to access the ventricular system to aspirate blood clots in patients with IVH. In such cases, the restoration of patency of the entire CSF pathway has the potential to improve outcome and reduce complications and now it is believed to decrease shunt-dependency
Amaurosis in infancy due to craniopharyngioma: a not-exceptional but often misdiagnosed symptom
No full textSince children may not be able to complain of progressive reduction in optic acuity, visual assessment in infancy may present practical difficulties. The authors report a case of craniopharyngioma, which led a young child to early blindness before the correct diagnosis could be made. Similar to other reported cases, the authors found that surgery did not substantially modify the preoperative visual deficit. They conclude that minimal improvement in visual acuity can be expected despite successful microsurgical removal of the tumor
Endoscopic third ventriculostomy in previously shunted children: a retrospective study. Reply to Professor Viroj Wiwanitkit MD, Wiwanitkit House, Bangkhae, Bangkok, Thailand
No full textHemangioblastoma with contrast-enhanced cystic wall: when the surgical rule must not be respected
No full textObjective: Purpose of this paper is to describe the variation of surgical plan and technique required in a rare subset of hemangioblastomas compared to the accepted general strategy. The established rule in hemangioblastoma surgery is to avoid cyst wall removal, as it is not neoplastic, and it will not recur if mural nodule is completely removed. However, the wall of the associated cyst is occasionally enhanced by gadolinium on preoperative MRI. Methods: We present the case of a patient with a hemangioblastoma that was progressively compressed by a growing cyst, with the final appearance of a contrast-enhanced cyst wall. We collected similar cases reported in the literature. Results: Our study points out the need for a tailored pre-operative strategy, the usefulness of intraoperative fluorescent dyes, and the crucial role of frozen section histopathological analysis to confirm diagnosis and optimize treatment. Conclusions: When a hemangioblastoma is associated with a contrast-enhanced cyst, care must be taken to intraoperatively confirm the presence of neoplastic cells, and eventually remove the neoplastic cyst wall to reduce the risk of recurrence
- …
