Estimation of photon dose generated by a short pulse high power laser.

The authors obtain a new equation to estimate the forward component of a photon dose generated through the interaction between a target and a short pulse high power laser. As the equation is quite simple, it is useful for calculating the photon dose. The equation shows that the photon dose is proportional to the electron temperature in the range>3 MeV and proportional to the square of the electron temperature in the range<3 MeV. The dose estimated with this method is roughly consistent with the result of Monte Carlo simulation. With some assumptions and corrections, it can reproduce experimental results obtained and the dose result calculated at other laboratories.

Increased brain tumor microvessel permeability after intracarotid bradykinin infusion is mediated by nitric oxide.

Nitric oxide (NO), a free radical gas implicated in a wide variety of biological reactions, is a novel signaling molecule that may regulate vasodilation, cerebral blood flow, and vascular permeability. This study was performed to determine whether NO mediates the selective increase in brain tumor microvessel permeability after intracarotid infusion of bradykinin in the RG2 rat glioma model. Intracarotid infusion of bradykinin selectively increased the transport of radiolabeled alpha-aminoisobutyric acid and dextran into brain tumors. Transport into normal brain was not increased. The administration of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester, significantly inhibited the increased transport into tumors for both tracers. The inhibitory effect of NG-nitro-L-arginine methyl ester on the response to bradykinin was reversed by L-arginine. The expression of two NO synthase (NOS) isoforms in cultured RG2 glioma cell lines and intracerebral RG2 glioma was examined by immunohistochemistry and Western blot analysis. High levels of expression of neuronal NOS were detected in cultured and intracerebral RG2 cells but not in normal brain tissue, except in rare neuronal cells. The endothelial form of NOS was also expressed in cultured RG2 cells, but not as strongly as neuronal NOS expression. In intracerebral RG2 gliomas, expression of endothelial NOS in the tumor was detected at higher levels than in normal brain. These findings indicate that RG2 rat gliomas express high levels of NOS, which regulate the production of NO, compared with normal brain. We suggest that the selective permeability increase in brain tumor microvessels after bradykinin infusion is mediated by NO. Furthermore, the absence of high levels of NOS in normal brain may account for the attenuated permeability response to bradykinin in normal brain microvessels.

Intracarotid low dose bradykinin infusion selectively increases tumor permeability through activation of bradykinin B2 receptors in malignant gliomas.

Intracarotid low dose bradykinin infusion can selectively increase permeability in brain tumor capillaries. However, the mechanism by which bradykinin selectively increases transport into brain tumors and not normal brain has not been clearly defined. This study therefore sought to determine whether the mechanism by which bradykinin increases tumor permeability specifically involves the bradykinin B2 receptor in brain tumor tissue. In permeability studies, 27 Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [14C] sucrose was determined using quantitative autoradiography. Bradykinin (10 microg kg-1 min-1) increased the transport of sucrose to tumors 2.1-fold compared to saline infusion alone (p<0.001). The uptake of sucrose in tumors was significantly inhibited by the bradykinin B2 receptor antagonist, d-Arg, [Hyp3, Thi5,8, d-Phe7]-bradykinin (p<0.01), but not by the B1 receptor antagonist, des-Arg9, [Leu8]-bradykinin. The distribution of B2 receptors in normal brain and tumor tissue was examined by immunohistochemistry using the B2 receptor antiserum, AS 424. High levels of B2 receptors were detected in intracerebral RG2 glioma and brain surrounding tumor (BST), but not in normal brain tissue. These results indicate that the permeabilizing effects of bradykinin are mediated through bradykinin B2 receptors, and that differences in distribution of B2 receptors between tumor tissue and normal brain may be responsible for the selective effects on tumor tissue.

Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7.

OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas. METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation. RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%). CONCLUSION: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Surgery on a saccular vertebral artery-posterior inferior cerebellar artery aneurysm via the transcondylar fossa (supracondylar transjugular tubercle) approach or the transcondylar approach: surgical results and indications for using two different lateral skull base approaches.

OBJECT: The authors report on the surgical results they achieved in caring for patients with vertebral artery-posterior inferior cerebellar artery (VA-PICA) saccular aneurysms that were treated via either the transcondylar fossa (supracondylar transjugular tubercle) approach or the transcondylar approach. In this report they clarify the characteristics of and differences between these two lateral skull base approaches. They also present the techniques they used in performing the transcondylar fossa approach, especially the maneuver used to remove the jugular tubercle extradurally without injuring the atlantooccipital joint. METHODS: Eight patients underwent surgery for VA-PICA saccular aneurysms (six ruptured and two unruptured ones) during which one of the two approaches was performed. Clinical data including neurological and radiological findings and reports of the operative procedures were analyzed. The Glasgow Outcome Scale was used to estimate the activities of daily living experienced by the patients. In all cases the aneurysm was successfully clipped and no permanent neurological deficits remained, except for one case of severe vasospasm. In seven of the eight patients, the transcondylar fossa approach provided a sufficient operative field for clipping the aneurysm without difficulty. In the remaining patient, in whom the aneurysm was located at the midline on the clivus at the level of the hypoglossal canal, the aneurysm could not be found by using the transcondylar fossa approach; thus, the route was changed to the transcondylar approach, and clipping was performed below the hypoglossal nerve rootlets. CONCLUSIONS: Both approaches offer excellent visualization and a wide working field, with ready access to the lesion. This remarkably reduces the risk of development of postoperative deficits. These approaches should be used properly; the transcondylar fossa approach is indicated for aneurysms located above the hypoglossal canal and the transcondylar approach is indicated for those located below it.

Enhanced cytokines delivery and intercellular adhesion molecule 1 (ICAM-1) expression in glioma by intracarotid infusion of bradykinin analog, RMP-7.

The effect of intracarotid infusion of the bradykinin analog, RMP-7, on blood-to-tumor and blood-to-brain transport of three cytokines were investigated. Wistar rats with RG2 gliomas were utilized and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) were labeled with 125Iodine for quantitative transport studies using autoradiography. Radiolabeled cytokines were injected as an intravenous bolus. Intracarotid infusion of RMP-7 (0.1 microgram kg-1 min-1) increased the selective transport to tumors of IFN-gamma by 3.97-fold (p < 0.005), of TNF-alpha by 5.30-fold (p < 0.005), and of IL-2 by 4.34-fold (p < 0.005), compared to intracarotid saline infusion. To determine whether the increased IFN-gamma or TNF-alpha transport to tumors with RMP-7 could enhance expression of intercellular adhesion molecule 1 (ICAM-1) in tumors, ICAM-1 expression in RG2 glioma was evaluated by immunohistochemistry. Both IFN-gamma and TNF-alpha increased ICAM-1 expression of RG2 cells in vitro. In vivo, intracarotid infusion of IFN-gamma combined with RMP-7 significantly enhanced ICAM-1 expression in intracerebral RG2 gliomas compared to infusion of IFN-gamma without RMP-7. Expression of ICAM-1 was not enhanced by TNF-alpha combined with RMP-7. Intracarotid infusion of RMP-7 is a novel method of cytokines delivery to brain tumors.

Effects of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat brain tumour.

We studied the effect of intracarotid administration of prostacyclin analogue iloprost on the regional cerebral blood flow in transplanted rat C6 glioma by the hydrogen clearance method. Iloprost at doses of 0.1 and 0.5 micrograms/kg/min produced a selective increase of the regional cerebral blood flow in the tumour (17.8 +/- 5.6%, p < 0.05 and 27.3 +/- 10.3%, p < 0.05, respectively) without significant change of the regional cerebral blood flow in the ipsilateral hemisphere and the systemic arterial pressure. At a dose of 1 microgram/kg/min, iloprost produced a significant reduction of a systemic blood pressure, but did not change the regional cerebral blood flow significantly both in the tumour and the ipsilateral hemisphere. These results indicated that brain tumour vessels could respond to iloprost in a different fashion from the normal brain capillaries. The selective action of iloprost to the tumour vessels might contribute to the drug-delivery in malignant brain tumour.

Effect of intracarotid bradykinin infusion on cerebral blood flow in dogs.

We examined whether intracarotid infusion of bradykinin altered circulation in the normal canine brain. Twenty-four anesthetized dogs were divided into four groups receiving different doses of bradykinin (1, 2.5, 5, and 10 micrograms kg-1 min-1). Regional cerebral blood flow (rCBF) was measured continuously using laser Doppler flowmetry through a burr hole in the frontal bone. Systemic blood pressure (SBP) and heart rate (HR) were monitored simultaneously. Higher doses of bradykinin significantly but temporarily decreased rCBF and SBP immediately after the start of infusion; these parameters rapidly recovered and then were stable through the rest of the infusion. During this period, percent change in rCBF and SBP was small, and differences between groups were not significant. On the other hand, HR increased during infusion and remained high. SBP, rCBF, and HR returned to pre-infusion levels after bradykinin was stopped. The results suggest that intracarotid infusion of bradykinin for treatment of brain tumors would be safe in terms of circulation to the uninvolved brain.

Steroids decrease uptake of carboplatin in rat gliomas--uptake improved by intracarotid infusion of bradykinin analog, RMP-7.

This study sought to determine whether dexamethasone (DXN) treatment of rats with intracranial gliomas would 1) further impair delivery of carboplatin to brain tumors, and 2) whether intracarotid infusion of the bradykinin analog, RMP-7, would improve delivery during concurrent DXN treatment. In DXN pretreated animals, 3 mg/kg/day of DXN was administered intraperitoneally for 3 days prior to Ki determinations. Ki of [14C] carboplatin into DXN-treated tumors and brain surrounding tumor (BST) was significantly lower compared to non-DXN treated tumors and BST (3.30 +/- 0.91 vs. 4.47 +/- 1.80, p < 0.05, and 0.94 +/- 0.84 vs. 2.18 +/- 0.79, p < 0.05, respectively). Intracarotid infusion of RMP-7 significantly increased the Ki for carboplatin in DXN-treated tumors (6.35 +/- 3.10 vs. 3.30 +/- 0.91, p < 0.01), however, RMP-7 increased Ki to a greater extent in tumors not pretreated with DXN (12.07 +/- 3.60 vs. 4.47 +/- 1.80, p < 0.0001). Dexamethasone decreases transport of carboplatin into brain tumors. Intracarotid infusion of RMP-7 selectively increases carboplatin transport to tumors.

Multiple combined indirect procedure for the surgical treatment of children with moyamoya disease. A comparison with single indirect anastomosis and direct anastomosis.

Considering three different bypass procedures now in use, (single indirect nonanastomotic bypass procedure, multiple combined indirect (MCI) nonanastomotic procedure and direct anastomosis), the authors attempted to identify the most appropriate bypass procedure for treating ischemic-type moyamoya disease in children. The authors performed three procedures (the original encephaloduroarteriosynangiosis [EDAS] alone, the frontotemporoparietal combined indirect bypass procedure, and the superficial temporal artery--middle cerebral artery [STA-MCA] anastomosis with encephalomyosynangiosis [EMS]) on 72 hemispheres in 50 patients with pediatric moyamoya disease. Analyses were then performed to compare postoperative collateral vessel formation found on angiograms, complications, and clinical improvements. Postoperative collateral formations were observed in more than two-thirds of the MCA distribution after the EDAS alone, the MCI procedure, and the direct anastomosis in 44%, 52%, and 74% of the surgically treated hemispheres, respectively. In addition, frontal encephalomyoarteriosynangiosis of the MCI bypass procedure formed collateral vessels of the anterior cerebral artery distribution in 94% of the treated hemispheres. Postoperatively, clinical symptoms resolved in 56%, 63%, and 74% of the treated sides 1 year after EDAS alone, MCI procedure, and the direct anastomosis, respectively. One patient suffered a minor stroke after EDAS alone, two patients developed epidural hematomas after the MCI procedure, and one patient suffered a major stroke and one patient a minor stroke after undergoing direct anastomosis. The direct anastomosis procedure was found to result in the best postoperative collateral vessel formation and clinical improvement. However, the single and multiple combined indirect nonanastomotic bypass procedures were found to be safer than direct anastomosis. Furthermore, the frontotemporoparietal combined indirect bypass procedure caused the formation of collateral circulation not only in the MCA but also in the ACA distribution. Based on analysis of these findings, the authors recommend the MCI procedure as the appropriate surgical procedure in the treatment of children with moyamoya disease, although the best treatment is the STA-MCA anastomosis with EMS when feasible.

Tumoral calcinosis in the upper cervical spine causing progressive radiculomyelopathy--case report.

A 54-year-old woman with chronic renal failure presented with tumoral calcinosis manifesting as progressive radiculomyelopathy. Magnetic resonance imaging revealed a spinal epidural mass in the C-2 to C-4 levels. The clinical and radiological findings suggested malignant tumor. Resection of the lesion was performed with total C-2 laminectomy and C-3 and C-4 laminoplasty. The symptoms totally disappeared after surgery. The histological diagnosis was tumoral calcinosis. Tumoral calcinosis is a rare tumoral calcium pyrophosphate dihydrate crystal deposition disease which presents as periarticular soft tissue calcification. Tumoral calcinosis should be considered in patients with a mass lesion involving the upper cervical spine and associated with metabolic abnormalities. Surgical excision is the treatment of choice, because this is completely curative without known recurrence.

[Radiation-induced leiomyosarcoma of the dura mater: a case report].

A 31-year-old man underwent total resection for a fibrillary astrocytoma in the right frontal lobe followed by 6MV x-ray radiotherapy. The portal field size was a square of 8 cm x 7 cm, and the total dose of irradiation was 50Gy, with single fractions of 2Gy. For the next 6.5 years there was no recurrence of the astrocytoma. At 38 years of age, the patient noticed a subcutaneous mass in the scar of the previous operation and developed generalized convulsive seizures. MRI revealed a dural tumor within the previous radiation field, and the tumor was partially removed. Histologically, it was diagnosed as a leiomyosarcoma. This dural sarcoma satisfies the widely used criteria for definition of radiation-induced malignancies first described by Cahan et al. Both the clinical features and the possible histogenesis of this secondary tumor are briefly discussed.

[Epstein-Barr virus-associated malignant lymphoma in an immuno-deficiency patient: a case report].

Human infection with Epstein-Barr (EB) virus occurs commonly, and EB virus exists in the B cell as a cryptic infection. Infected B cells become immortal by expressing both the EBNA2 and the LMP1 genes derived from the EB virus. Under normal condition of cellular immunity, the T cells recognize the EBNA2 and LMP1 as foreign proteins and attack the immortal B cells. However, under the condition of immunodeficiency, the immortal B cells can proliferate and form a tumor. We report a case of malignant lymphoma associated with immuno-deficiency which may correspond to this mechanism. A 33-year-old woman, who had an immuno-deficiency due to treatment for leukemia, had a progressing hemiparesis on her left extremities. Magnetic resonance imagings revealed a ring enhanced tumor with massive brain edema in the right fronto-parietal lobe. Stereotactic biopsy was performed and histological examination showed it to be a malignant lymphoma. The tumor cells were positive for L26 (B cell marker), CD79a LMP1, and EBNA2. They were negative for UCHL-1 and CD3 (T cell marker). According to these results, this lymphoma was caused by EB virus infection under the condition of immuno-deficiency.

A multichannel time-of-flight system for observation of energetic ions of multispecies generated from relativistic laser plasma.

A multichannel time-of-flight (TOF) system was constructed to observe the ions generated from relativistic laser plasma, where the ions have polychromatic energies and multiple species. The TOF system is composed of a ten-channel scintillation detector array and an electromagnet that generates a magnetic field of 0-1.24 T. The magnet field enables us to analyze protons, deuterons, and full-stripped carbon ions to 50, 25, and 150 MeV, respectively. The system experimentally identified protons of 0.27-1.6 MeV energy and ions of a half specific charge (deuterons of 0.3-0.8 MeV and full-stripped carbons of 1.8-4.8 MeV). The measured TOF values agree well with the calculated values within the designed accuracy; +/-2.5 ns for protons and +/-5 ns for the others (d or C(6+)) on each detector channel. Comparison of ion numbers detected by a track detector (CR-39) and the TOF system enabled us to obtain the number of ions detected on each scintillation counter with less than 16% error.

Surgical indications for arteriovenous malformations in patients over the age of 60 years: retrospective analysis of 33 patients.

This retrospective study investigated the surgical indications in 33 patients aged > 60 years with brain arteriovenous malformation (AVM) taken from a group of 294 cases between 1981 and 2004. These 33 patients were further classified to two age groups: 60 - 64 years (A group) and > or = 65 years (B group). The overall haemorrhagic rate at initial presentation was 46.6% in the 294 patients. The rate was 48.5% in patients aged > 60 years, and 72.2 and 20% in the A and B groups, respectively. In three of four cases with extremely poor outcome with modified Rankin Scale 5 and 6, the cause of poor outcome was haemorrhage in those aged > 65 years. Because of the high haemorrhagic rate and poor outcome after haemorrhage, surgical treatment is indicated for patients aged > 60 years.

Effect of histamine on the blood-tumor barrier in transplanted rat brain tumors.

We studied the effect of intracarotid administration of histamine on the blood-tumor barrier permeability and also on the blood-brain barrier permeability in transplanted rat C6 glioma. There was no definite Evans blue (EB) extravasation either in normal or tumor tissue after intracarotid saline infusion. In contrast, histamine at doses of 1 and 10 micrograms/kg/min produced slight to moderate EB extravasation in the tumor without any significant extravasation in the normal brain tissue. Intravenously administered H1 and H2 receptor antagonists (5 mg/kg each) reduced the histamine (10 micrograms/kg/min) induced extravasation of EB in the tumor tissue. These results indicated that brain tumor vessels responded to histamine in a different fashion from normal brain capillaries. Histamine could thus be utilized for selective drug delivery to brain tumors without affecting normal brain tissue.

Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors.

We studied the effect of intracarotid infusion of various calcium antagonists on regional CBF (rCBF) in the C6 rat glioma by a hydrogen clearance method. Nimodipine at doses of 0.1, 0.5 and 1 microgram/kg/min was found to produce tumor-specific increases in the rCBF (40.2 +/- 18.4%, p < 0.01, 67.8 +/- 32.6%, p < 0.001 and 37.3 +/- 37.2%, p < 0.05, respectively) without affecting systemic blood pressure. Regarding the time course of the nimodipine effects, at a dose of 0.5 micrograms/kg/min, rCBF in the tumor showed maximum value at fifteen minutes after the start of the intracarotid infusion. Diltiazem at doses of 5, 20, and 40 micrograms/kg/min also increased tumor rCBF in a dose-dependent manner (27.9 +/- 12.5%, p < 0.001, 52.0 +/- 21.8%, p-AN 0.001 and 54.5 +/- 18.4%, p < 0.001, respectively). Both nifedipine and flunarizine significantly increased the rCBF in the tumor, while they did not cause a higher percent increase of the rCBF when compared with those of nimodipine and diltiazem. No significant percent increase of the rCBF in the tumor was observed in verapamil treated rats. These results indicate that tumor vessels may have an altered response to calcium antagonists, especially to nimodipine and diltiazem, when compared to normal brain capillaries. The varied responses to calcium antagonists could be explained by their differences in tissue selectivity and affinity to calcium channels.

Selective increase in blood-tumor barrier permeability by calcium antagonists in transplanted rat brain tumors.

To clarify the altered response of calcium antagonists on pathological vessels, we investigated the effect of intracarotid infusion of nifedipine on the blood-brain barrier (BBB) permeability using a rat glioma model. Animals were treated with 0, 0.1, 1, 5, and 10 micrograms/kg/min of intracarotid continuous infusion of nifedipine. 2% Evans blue (EB, 2 ml/kg) was injected intravenously immediately after nifedipine infusion. BBB and blood-tumor barrier (BTB) permeability were evaluated by direct visual and histological observation. During the entire experiment, systemic parameters such as arterial blood pressure and blood analysis were not changed significantly. There was a dose-dependent increase of EB permeability selectively in the tumor tissue without affecting the normal brain. These results indicate that tumor vessels may show an altered response to calcium antagonists. Intracarotid administration of calcium antagonists contribute to a selective enhancement of drug delivery to malignant brain tumors without affecting the normal brain.

Surgical treatment of glossopharyngeal neuralgia as vascular compression syndrome via transcondylar fossa (supracondylar transjugular tubercle) approach.

OBJECTIVE: These are the first reported cases in whom the transcondylar fossa approach was applied for the treatment of glossopharyngeal neuralgia (GPN) as a vascular compression syndrome. CASES PRESENTATION: All three cases presented with severe paroxysmal pharyngeal pain which could not be controlled by medical treatment. The patients all underwent microvascular decompression surgery (MVD) via transcondylar fossa approach. The posterior inferior cerebellar artery or the anterior inferior cerebellar artery was clearly verified to be compressing the glossopharyngeal nerve and then was safely and completely moved and fixed to the dura mater by the sling retraction technique to effect decompression. No patient has since experienced any further pain or permanent neurological deficit after surgery. TECHNICAL ADVANTAGE: The transcondylar fossa approach is one of the lateral approaches which is different from the transcondylar approach. In this approach, the posterior part of the jugular tubercle is extradurally removed without injuring the atlanto-occipital joint. The entire course of the cisternal portion of the glossopharyngeal nerve can be sufficiently seen with gentle retraction of the cerebellar hemisphere, when using this approach. CONCLUSION: This approach makes the MVD for GPN both effective and safe.

Steroids decrease uptake of carboplatin in rat gliomas--uptake improved by intracarotid infusion of bradykinin analog, RMP-7.

A blood-tumor barrier (BTB) limits delivery of antitumor agents to brain tumors. This study sought to determine whether dexamethasone (DXN) treatment of rats with intracranial gliomas would 1) further impair delivery of carboplatin to brain tumors, and 2) whether intracarotid infusion of the bradykinin analog, RMP-7, would improve delivery during concurrent DXN treatment. Wistar rats with RG2 gliomas were utilized and a unidirectional transport, Ki, of radiolabeled [14C] carboplatin was determined using quantitative autoradiography. In DXN pretreatment animals, 3 mg/kg/day of DXN was administered intraperitoneally for 3 days prior to Ki determinations. At 10 days after tumor implantation, Ki of [14C] carboplatin into DXN-treated tumors and brain surrounding tumor (BST) was significantly lower compared to non-DXN treated tumors and BST (3.30 +/- 0.91 vs. 4.47 +/- 1.80, p < 0.05, and 0.94 +/- 0.84 vs. 2.18 +/- 0.79, p < 0.05, respectively). Intracarotid infusion of RMP-7 (0.1 mg/kg/min) significantly increased the Ki for carboplatin in DXN-treated tumors (6.35 +/- 3.10 vs. 3.30 +/- 0.91, p < 0.01), however, RMP-7 increased Ki to a greater extent in tumors not pretreated with DXN (12.07 +/- 3.60 vs. 4.47 +/- 1.80, p < 0.0001). Our studies show that dexamethasone decreases transport of carboplatin into brain tumors. Intracarotid infusion of RMP-7 selectively increases carboplatin transport to tumors.