Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen patients with intracranial lesions were submitted to a twist drill needle biopsy under computerized tomographic (CT) control, with sedation and local anesthesia. (The patients' ages ranged from 12 to 81 years.) The final diagnoses were glioblastoma in 7 patients and 1 case each of anaplastic astrocytoma, low grade astrocytoma, thrombosed arteriovenous malformation, cerebral infarct, 3rd ventricular epidermoid, and degenerative disease of the brain. Definitive diagnosis was obtained in all but 2 patients with this technique. Appropriate therapy was subsequently instituted in 11 patients without further operation. Transiently increased weakness of the previously affected limbs was the only untoward effect (4 patients). Intracranial hematoma after this procedure was seen in 1 patient in this series, as detected by the postprocedure CT scan, but there was no change in the clinical course. All patients were treated with dexamethasone for 24 to 48 hours before and for several days after the procedure to avoid decompensation of intracranial dynamics because of edema. The procedure, including appropriate level CT scans of the lesion area, was performed in approximately 1 hour in all patients. (Neurosurgery, 5: 671--674, 1979).
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PMID:Needle biopsy under computerized tomographic control: a method for tissue diagnosis in intracranial lesions. 53 75

Postoperative neurological deficit may result from ischaemic or hypoxic hypoxaemia. Postural cerebral hypoperfusion may ensue when a pre-existing asymptomatic vascular anomaly in combination with rotation of the head for surgical positioning compromises cerebral blood flow. CASE REPORT. A 30-year-old man was referred for recraniotomy for glioblastoma. Following uneventful induction of anaesthesia, increased diuresis and progressive hypothermia were observed. The postoperative period was complicated by a seizure, followed by apnoea requiring reintubation of the trachea. A CAT scan revealed global cerebral oedema with subtotal compression of the third ventricle. Intracranial pressure was 60 mm Hg as measured by an epidural probe. On the 1st postoperative day clinical and electroneurophysical signs of brain death were observed; the patient underwent organ explantation the next day. PATHOLOGY. Pathological examination revealed pronounced global hypoxaemic lesions and an S-shaped internal carotid artery with intimal proliferation (Fig. 1). The diagnostic conclusion was cerebral ischaemia following carotid occlusion caused by carotid kinking and completed by surgical positioning (rotation of the head). CONCLUSION. Carotid kinking is a rare abnormality, and patients at risk may not be identified preoperatively. Though it is questionable whether this disaster could have been prevented at all, electroneurophysiological monitoring would have been the only early monitoring system capable of detecting diminishing cerebral blood flow. Although a request for routine intraoperative neurophysiological monitoring seems unrealistic at present, it has to be acknowledged that only such monitoring could have provided the information needed to save this patient.
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PMID:[A fatal intraoperative cerebral ischemia following kinking of the internal carotid artery?]. 163 22

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary's criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month follow-up examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disabled. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.
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PMID:Direct surgery for brainstem tumours. 180 73

The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 micrograms/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p less than 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.
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PMID:Intra-arterial ACNU therapy for malignant brain tumors. Experimental studies and preliminary clinical results. 657 43

Surgical procedures near to language related brain regions may cause severe morbidity in relation to speech. Operations performed under local anesthesia and intraoperative cortical mapping may minimize these risks. Six patients with tumors near the Wernicke's area were treated (2 low-grade astrocytomas, 1 ganglioglioma, 1 xanthoastrocytoma, 1 metastasis, 1 glioblastoma). Their clinical presentation consisted of epilepsy (n = 4) and dysphasia (n = 2). The skin and periosteum were infiltrated with local anesthetic and an ample craniotomy was performed. Cortical stimulation with an unipolar electrode was then carried out with concomitant speech testing (mainly comprehension and sequential speech). After mapping, the best surgical approach aiming to avoid the mapped area was elected. In 5 cases the resection was total and in 1, partial (glioblastoma). There was a transitory (10 days) worsening of the pre-operative deficit in 1 case (glioblastoma). In 3 patients, the speech areas were displaced: posteriorly (n = 2) or anteriorly (n = 1). Surgical procedures under local anesthesia are safe and may avoid post-operative language disturbances in patients with tumors near to Wernicke's area.
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PMID:Surgical approaches to tumors and epileptogenic zones close to Wernicke's area. 858 14

Twenty-seven patients received boron neutron capture therapy during craniotomy at our research reactor from 1991 to 1999. This is a form of intra-operative radiation therapy, which uses neutrons from a nuclear reactor. There are three additional major problems to anaesthetists: boron neutron capture therapy must be given beside the nuclear reactor, with no hospital facilities; neutrons cannot be shielded effectively by ordinary protectors; and neutrons are detrimental to metal devices and especially to electrical appliances. Boron neutron capture therapy has been adopted as an effective therapy for glioblastoma/astrocytoma, but special considerations are required for anaesthesia.
Anaesthesia 2001 Jul
PMID:Anaesthetic management of 27 cases of boron neutron capture therapy for glioblastoma. 1143 67

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.
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PMID:Change of oxygen pressure in glioblastoma tissue under various conditions. 1216 Jan 40

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) is a minimal invasive method to produce thermonecrosis in cerebral tumour tissue. Clinical data are sparse due to its limited application until now and the value of this approach for tumour control and survival time remain to be defined. Twenty-four patients (7 low-grade gliomas, 11 anaplastic gliomas, 6 glioblastomas) with brain tumours, most recurrences, were treated with SLITT, in total 30 laser procedures were performed. Under local anaesthesia a 600 micro m laser-fiber was inserted by the stereotactic-guided technique. In open low-field MR the denaturation of the tumour by a Nd-YAG-laser (1064 nm) was monitored using T 1 -weighted 3-D turbo FLASH sequences. The ablation procedure had to be stopped twice because of neurological deficit, one major infection occurred. In two cases neurological improvement was observed. Mean survival times for low grade astrocytomas, anaplastic gliomas and glioblastomas were 144 months, 39 months, 17 months, respectively. Mean survival times after SLITT were 34 months, 30 months and 9 months, respectively. Mean times to progression after SLITT for the 3 histological subgroups were 16 months, 10 months and 4 months, respectively. Five patients with low grade astrocytoma and a KI greater or equal 70 maintained a high quality functional status for 11, 20, 21, 33 and 43 months. In anaplastic tumours patients maintained a KI of 70 for a median time of 15 months and for those with glioblastoma the respective high quality duration was 7.5 months after SLITT. SLITT for selected patients with glioma could have a clinical value in a multimodality treatment schedule maintaining quality of live. Due to the minimal invasive technique, the method is a therapy of choice and may be favoured to reoperation. Major indications of this treatment are small tumours, in eloquent regions and deep seated, as well as in older patients or patients in poor functional status.
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PMID:Stereotactic guided laser-induced interstitial thermotherapy (SLITT) in gliomas with intraoperative morphologic monitoring in an open MR: clinical expierence. 1249 54

Efaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. This first-of-its-class compound is particularly applicable for the treatment of certain tumour types that lack oxygen, such as brain metastases. In contrast to conventional chemotherapeutic agents or radiation sensitisers, there is no requirement for efaproxiral to be administered directly into tumours or to cross the blood-brain barrier for it to display efficacy. Efaproxiral is under review for approval in the US and EU as an adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain metastases originating from breast cancer. It is also under clinical evaluation for a variety of other cancers, including glioblastoma, non-small cell lung cancer (NSCLC) and cervical cancer. Allos is seeking partnership opportunities for efaproxiral's development and marketing. The company has indicated that the development of efaproxiral would be in cooperation with a corporate partner, according to its 2003 Annual Report. In 1994, Allos Therapeutics acquired exclusive worldwide rights to intellectual property relating to efaproxiral from the Center for Innovative Technology (CIT). Allos has entered into arrangements with two contract manufacturers for the supply of efaproxiral, and a third manufacturer for the supply of the formulated drug product. Hovione FarmaCiencia is the primary supplier of efaproxiral, and is contracted to manufacture sufficient quantities on a commercial scale. In addition, a second manufacturer, Raylo Chemicals, is also producing quantities of efaproxiral. In December 2003, Allos entered into a long-term development and supply agreement with Baxter Healthcare who will formulate the efaproxiral into an injection. Allos is also seeking to establish an alternate supplier of efaproxiral injection. Allos submitted a rolling NDA to the US FDA consisting of three data components. Submission began in the third quarter of 2003 and was completed by the fourth quarter of 2003. The first part of the application containing non-clinical information was submitted on 5 August 2003. The second part of the NDA containing information about efaproxiral's chemistry, manufacture and controls (CMC) was submitted in October 2003. Allos submitted its final component of the rolling NDA in December 2003. In February 2004, Allos announced that the FDA had accepted the company's NDA under priority review status. The FDA granted efaproxiral orphan drug status in August 2004 as an adjunct to WBRT for the treatment of brain metastases among breast cancer patients. Efaproxiral also received fast-track status in November 2000 for the same indication in the US. In February 2004, Allos initiated a phase III trial, called ENRICH (Enhancing Whole Brain Radiation Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases) to investigate efaproxiral as an adjunct to WBRT for the treatment of brain metastases. Median survival time is the primary endpoint of the study. The National Breast Cancer Coalition (NBCC) is collaborating with the company to support trial enrolment and to gain additional insight about ways to improve radiation treatment in this patient population. The ENRICH trial protocol was approved by the FDA under a Special Protocol Assessment process; as part of the protocol, two interim analyses for safety and efficacy will be performed.This multicentre, randomised, open-label study has a target enrolment of approximately 360 patients at >100 medical centres across the US, Canada, Europe and South America. Allos announced in September 2004 that recruitment of clinical sites for the trial is ongoing across the US and Canada. Completion of trial enrolment in North America is anticipated in December 2005. Subsequently, Allos announced in January 2005 that recruitment into the ENRICH trial has commenced and is ongoing in Europe; enrolment at European sites is expected to conclude by the third quarter of 2006. Allos Therapeutics announced in June 2004 that it had filed an MAA with the EMEA for marketing of exaproxiral as an adjunct to WBRT for treatment of patients with brain metastases originating from breast cancer. The application is based on positive data from a pivotal phase III (REACH, RT-009) trial in this indication. The completed REACH trial investigated efaproxiral among patients with brain metastases undergoing WBRT. The trial was conducted at multiple sites in 11 countries, including the US, Canada, Europe and Australia. In August 2002 Allos completed the enrolment of 538 patients in the study. Initially only 408 patients were to be enrolled, but the company increased the size of the trial to conduct an appropriately powered subgroup analysis in patients with brain metastases from breast and NSCLC. The study was designed to demonstrate a 35% increase in median survival in the subgroup of patients compared with standard WBRT alone. The primary endpoint was survival. Allos began screening US patients for a phase III trial in NSCLC in early 2003. However, in May 2003, the company announced that as part of its revised operating plan it had suspended the screening of patients for this trial. The trial, which was known as ELITE (Enhanced Lung cancer treatment with Induction chemotherapy and Thoracic radiation and Efaproxiral), was comparing induction chemotherapy followed by thoracic radiation therapy with supplemental oxygen, with or without efaproxiral. The trial was enrolling patients with locally advanced, unresectable NSCLC. ELITE was planned to enrol up to 600 patients across North America and Western and Eastern Europe. Phase II trials in patients with inoperable NSCLC have been conducted in the US and Canada. Patient enrolment in one of these studies was completed in August 2000, with a total of 52 patients enrolled. This was an open-label, multicentre study of induction therapy with paclitaxel plus carboplatin followed by chest irradiation and efaproxiral in patients with locally advanced NSCLC. Positive results from this study were reported at the annual meeting of the European Society for Therapeutics Radiology and Oncology in September 2002. Efaproxiral has completed phase I trials as a treatment of surgical hypoxia in elective surgery patients receiving general anaesthesia. However, no recent development has been reported for these indications. In 1994, Allos signed an agreement with CIT for the exclusive worldwide rights to 17 US patents, a European patent covering the UK, France, Italy and Germany plus two pending patents in these territories, two issued patents in Japan, and a pending patent in Canada. These patents cover methods of allosterically modifying haemoglobin with efaproxiral and other compounds, the binding site of efaproxiral and therapy in certain indications including cancer, ischaemia and hypoxia. In addition to the licensed patents from CIT, Allos exclusively owns two patent families with pending applications directed to a formulation of efaproxiral and to methods of its use in BLOD MRI (blood oxygenation level-dependent magnetic resonance imaging) applications. These patents are pending in the US, Canada and Europe, and include an international patent application. In a May 2002 interview with the Wall Street Transcript, the CEO of Allos estimated the overall market for radiation therapy to be approximately 750 000 patients/year. Of this, brain metastases, NSCLC and glioblastoma therapy accounts for about 170 000, 140 000 and 6000 patients, respectively. Allos intend to use a speciality sales force to market efaproxiral directly to radiation therapists in North America. To penetrate the non-oncology market in the US, the company will seek partnership with one or more pharmaceutical companies with direct sales forces and with established distribution systems. Allos is also hoping to secure an oncology marketing partner for non-North American territories. At the time, the company had been issued 21 patents in the US, Canada, Europe and Japan.
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PMID:Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13. 1586 22

A 67-year-old man with glioblastoma was scheduled for craniotomy. Before anesthesia induction, asymptomatic bradycardia (40 beats x min(-1)) occurred, and was resistant to atropine 0.4 mg. The surgery was postponed. He was diagnosed as sick sinus syndrome (sinus arrest). He received implantation of a temporary cardiac pacemaker on the day before the rescheduled surgery. Anesthesia was induced with thiopental 400 mg, fentanyl 200 microg, vecuronium 10 mg and isoflurane 5%, and maintained with isoflurane 1-2% in oxygen 3 l x min(-1) and air 3 l x min(-1). Pacing mode was set to fixed rate asynchronous pacing in the ventricle with a rate of 50 beats x min(-1) after anesthesia induction. Surgery was completed in 8 hours and 45 minutes without any complications. The pacing wire was removed the next day. For patients with sick sinus syndrome, implantation of the pacemaker is indicated in case of bradycardia-tachycardia syndrome or with any clinical symptoms. However, a pacemaker should be implanted before general anesthesia even in a patient with no clinical symptoms because of cardiovascular instability induced by anesthesia.
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PMID:[General anesthesia for a patient with asymptomatic sick sinus syndrome]. 1610 50


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