A cannula for use in ultrasonically guided biopsies of the brain

1983 ◽  
Vol 59 (5) ◽  
pp. 905-907 ◽  
Author(s):  
Jonathan M. Rubin ◽  
George J. Dohrmann
Keyword(s):  
Precise Location ◽  
Content Type ◽  
Biopsy Procedure ◽  
The Brain ◽  
Fine Print ◽  
Guidance Device

✓ The authors describe a cannula that has been modified to improve its visibility during ultrasonically guided biopsies of the brain. To enhance the echogenicity of the tip of the cannula, six parallel rings, 0.25 to 0.30 mm deep and 0.40 to 0.50 mm apart, were etched into the tip of the cannula. The cannula was also lengthened to approximately 19 cm to permit its unencumbered passage through any biopsy guidance device that may be employed. Detailing the precise location of the tip of the biopsy cannula is most important. The tip of this modified probe is much more echogenic and hence more easily seen ultrasonically than it would be otherwise, both in vivo and in vitro. This modified cannula is useful in any ultrasonically guided intracranial biopsy procedure.

A realistic brain tissue phantom for intraparenchymal infusion studies

2004 ◽  
Vol 101 (2) ◽  
pp. 314-322 ◽  
Author(s):  
Zhi-Jian Chen ◽  
George T. Gillies ◽  
William C. Broaddus ◽  
Sujit S. Prabhu ◽  
Helen Fillmore ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Bromophenol Blue ◽  
Agarose Gel ◽  
Convection Enhanced Delivery ◽  
Content Type ◽  
Force Profile ◽  
The Brain ◽  
Fine Print

Object. The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery. Methods. Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 µl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] ∼690) and gadodiamide (MW ∼573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured. Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10–20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution. Conclusions. Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors

1994 ◽  
Vol 80 (3) ◽  
pp. 535-540 ◽  
Author(s):  
Zvi Ram ◽  
Stuart Walbridge ◽  
John D. Heiss ◽  
Kenneth W. Culver ◽  
R. Michael Blaese ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Interleukin 2 ◽  
Lymphocytic Infiltration ◽  
Content Type ◽  
The Brain ◽  
Tumor Eradication ◽  
Fine Print

✓ The authors have recently shown the feasibility of eradicating brain tumors using in vivo retroviral-mediated transduction of tumors with the herpes simplex thymidine kinase (HStk) gene and ganciclovir therapy. However, thymidine kinase-transduced subcutaneous tumors in immunocompromised (athymic) mice were less responsive to this therapy than in immunocompetent animals, suggesting a role of the immune system in the process of tumor eradication. Broad suppression of humoral and cell-mediated immunity is found in patients with malignant gliomas. Interleukin-2 (IL-2) production and IL-2 receptor expression are decreased in glioma patients. These findings and the proposed association between lymphocytic infiltration of brain tumors and survival suggest that immune response modifiers may be useful in treating glioma patients. To evaluate the role of local cytokine expression by tumor cells, alone or combined with HStk gene transfer and ganciclovir therapy, the authors investigated the efficacy of tumor (9L gliosarcoma) eradication in Fischer rats by in vitro and in vivo tumor transduction with the IL-2 gene alone or with a combined vector carrying both the HStk and IL-2 genes. Tumors injected with HStk vector-producer cells alone, with or without ganciclovir, and rats inoculated in the brain and subcutaneously with 9L cells that had previously been transduced in vitro served as controls. Murine vector-producer cells (3 × 106/50 µl) were injected into the brain tumors 7 days after tumor inoculation. Ganciclovir (15 mg/kg) was administered intraperitoneally twice daily for 10 days to animals that received HStk with or without IL-2 vector-producer cells, starting 5 days after producer-cell injection. The experiment was repeated with continuous daily treatment of all rats with oral dexamethasone (0.5 mg/kg). Rats were sacrificed 21 days after tumor inoculation, and the brains were removed for histological and immunohistochemical analysis for IL-2. Within each experimental group, tumors were found in a similar proportion in the dexamethasone-treated and untreated rats. Large brain tumors developed in all 10 rats that had been inoculated with 9L cells which had been pretransduced in vitro with the IL-2 gene, whereas only three of eight rats receiving subcutaneous inoculation of similar cells developed palpable tumors. No enhancement of tumor eradication was observed by adding the IL-2 gene in the HStk vector construct compared to the use of the vector with HStk alone. Lymphocytic infiltration was absent in all dexamethasone-treated rats but was observed in all treatment groups not receiving steroids. The degree of lymphocytic infiltration was not enhanced by intratumoral injection of IL-2 or IL-2/HStk vector-producer cells. The findings suggest a limited role, if any, for immune enhancement by transduction with IL-2 to eradicate brain tumors, either used alone or in combination with HStk.

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Tumor Volume ◽  
Collagen Gel ◽  
Antitumor Effects ◽  
Histological Changes ◽  
Content Type ◽  
The Relationship ◽  
Fine Print

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

scholarly journals Efficacy of Guanabenz Combination Therapy against Chronic Toxoplasmosis across Multiple Mouse Strains

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Jennifer Martynowicz ◽  
J. Stone Doggett ◽  
William J. Sullivan
Keyword(s):  
Limit Of Detection ◽  
Acute Infection ◽  
Antagonistic Effect ◽  
Mouse Strains ◽  
Chronic Infections ◽  
Content Type ◽  
Brain Cyst ◽  
The Brain

ABSTRACT Toxoplasma gondii, an obligate intracellular parasite that can cause life-threatening acute disease, differentiates into a quiescent cyst stage to establish lifelong chronic infections in animal hosts, including humans. This tissue cyst reservoir, which can reactivate into an acute infection, is currently refractory to clinically available therapeutics. Recently, we and others have discovered drugs capable of significantly reducing the brain cyst burden in latently infected mice, but not to undetectable levels. In this study, we examined the use of novel combination therapies possessing multiple mechanisms of action in mouse models of latent toxoplasmosis. Our drug regimens included combinations of pyrimethamine, clindamycin, guanabenz, and endochin-like quinolones (ELQs) and were administered to two different mouse strains in an attempt to eradicate brain tissue cysts. We observed mouse strain-dependent effects with these drug treatments: pyrimethamine-guanabenz showed synergistic efficacy in C57BL/6 mice yet did not improve upon guanabenz monotherapy in BALB/c mice. Contrary to promising in vitro results demonstrating toxicity to bradyzoites, we observed an antagonistic effect between guanabenz and ELQ-334 in vivo. While we were unable to completely eliminate the brain cyst burden, we found that a combination treatment with ELQ-334 and pyrimethamine impressively reduced the brain cyst burden by 95% in C57BL/6 mice, which approached the limit of detection. These analyses highlight the importance of evaluating anti-infective drugs in multiple mouse strains and will help inform further preclinical studies of cocktail therapies designed to treat chronic toxoplasmosis.

Efficacy of LY233053, a competitive glutamate antagonist, in experimental central nervous system ischemia

1992 ◽  
Vol 76 (1) ◽  
pp. 106-110 ◽  
Author(s):  
Kenneth P. Madden ◽  
Wayne M. Clark ◽  
Abha Kochhar ◽  
Justin A. Zivin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Excitatory Amino Acids ◽  
Neurological Damage ◽  
Content Type ◽  
Glutamate Antagonist ◽  
Fine Print

✓ Antagonists of excitatory amino acids appear to serve a neuroprotective role during ischemic conditions in a variety of in vivo and in vitro models. The usefulness of such agents in the clinical setting, however, may be limited by poor central nervous system (CNS) entry and intolerable side effects. The authors report high efficacy in reducing neurological damage and relatively limited side effects of LY233053, a novel competitive glutamate antagonist, in two models of experimental CNS ischemia in the rabbit.

Treatment of murine primary brain tumors with systemic interleukin-2 and tumor-infiltrating lymphocytes

1992 ◽  
Vol 76 (3) ◽  
pp. 513-519 ◽  
Author(s):  
Stephen C. Saris ◽  
Paul Spiess ◽  
Daniel M. Lieberman ◽  
Shan Lin ◽  
Stuart Walbridge ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Similar Response ◽  
Content Type ◽  
Primary Brain Tumors ◽  
Infiltrating Lymphocytes ◽  
The Brain ◽  
Fine Print

✓ Methods have recently been described for the isolation and expansion of lymphocytes that have trafficked into animal and human tumors. These CD8-positive tumor-infiltrating lymphocytes (TIL's) have exceptional trafficking ability to, and efficacy against, tumor targets in extracranial sites. Prior to Phase I clinical trials for patients with gliomas, adoptive immunotherapy with TIL's was studied in a mouse model of primary brain tumors to determine if intracerebral tumors have a similar response. Glioma 261 (GL261) tumors were grown in the subcutaneous space of C57BL/6 mice. After enzymatic digestion, the cells were incubated in vitro with interleukin-2 (IL-2) until a confluent population of T lymphocytes was present. The in vitro efficacy of these TIL's was tested against fresh GL261 targets with a chromium release assay; the in vivo efficacy was tested against GL261 tumors in the liver and against irradiated and nonirradiated GL261 tumors in the brain. Mice received one of the following: intraperitoneal saline; intraperitoneal IL-2 (7500 to 50,000 U three times daily for 5 days); IL-2 plus intravenous TIL's (1 to 3 × 107 cells); 10 Gy cranial irradiation; irradiation plus IL-2; or irradiation plus IL-2 plus TIL's. The TIL preparation killed 77% of tumor targets in 4 hours at an effector:target ratio of 100:1. In animals with GL261 tumors in the liver, at 2 weeks there were 93 ± 37, 128 ± 45, and 21 ± 14 liver metastases in the control, IL-2, and IL-2 plus TIL groups, respectively. However, in animals with GL261 tumors in the brain, no treatment group had an increased survival rate compared to the control group. It is concluded that, although TIL and IL-2 immunotherapy can be used effectively to treat brain tumors in vitro and at sites outside the central nervous system, it is ineffective against the same type of tumor in the brain. Different methods of delivery or different combinations of these immunomodulators may be more effective; however, based on these findings, treatment of patients with IL-2 and TIL cannot be recommended until efficacy has been demonstrated in an animal model.

Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema

1991 ◽  
Vol 74 (6) ◽  
pp. 956-961 ◽  
Author(s):  
Rafael J. Tamargo ◽  
Allen K. Sills ◽  
Carla S. Reinhard ◽  
Michael L. Pinn ◽  
Donlin M. Long ◽  
...  
Keyword(s):  
Controlled Release ◽  
Plasma Concentrations ◽  
Ethylene Vinyl Acetate ◽  
Peritumoral Edema ◽  
Content Type ◽  
9L Gliosarcoma ◽  
Dexamethasone Group ◽  
The Brain ◽  
Fine Print

✓ Controlled-release polymers have facilitated the interstitial delivery of drugs within the central nervous system. In the present study, dexamethasone was incorporated into ethylene-vinyl acetate polymers, which were then implanted adjacent to a 9L gliosarcoma in the brain of Fischer 344 rats. The effect of interstitial delivery of dexamethasone on peritumoral edema was assessed and compared to the effect of dexamethasone delivered systemically. Eighty-five rats underwent intracranial implantation of the 9L gliosarcoma. Five days later, the animals were randomly assigned to one of four treatment groups: Group 1 received intracranial implantation of controlled-release polymers containing dexamethasone; Group 2 received intraperitoneal implantation of controlled-release polymers containing dexamethasone; Group 3 received serial intraperitoneal injections of dexamethasone; and Group 4 received sham treatment. The animals were sacrificed 3 days after initiation of therapy and their brains were removed for measurement of the water content (edema) in the tumor-bearing and contralateral hemispheres. Brain and plasma samples were analyzed by reverse-phase high-performance liquid chromatography to determine the tissue and plasma concentrations of dexamethasone. Measurement of the release kinetics of dexamethasone from the ethylene-vinyl acetate polymers in an in vitro system showed that the drug was released in a controlled, tapering fashion. During the first 3 days of controlled release in vitro, 330 µg of a total content of 7.5 mg of dexamethasone was released into the medium. Analysis of tissue for drug levels demonstrated, however, that the interstitial delivery of this fractional amount of dexamethasone within the brain resulted in levels 19 times higher than those achieved by administering the full dose of 7.5 mg systemically over a 3-day period. Conversely, the systemic administration of dexamethasone resulted in plasma levels 16 times higher than those measured in the interstitial delivery of dexamethasone in the brain. Brain-water content determinations showed that the interstitial controlled release of the fractional amount of dexamethasone within the brain was as effective in controlling peritumoral edema as systemic administration of the full dose by serial intraperitoneal injections. The study demonstrates the following: 1) controlled-release polymeric carriers deliver biologically active dexamethasone in a sustained fashion; 2) very high concentrations of dexamethasone in brain tissue can be achieved using interstitial polymer-mediated drug delivery while minimizing plasma concentrations of this drug which are sometimes associated with serious systemic side effects; and 3) peritumoral brain edema can be effectively treated by the interstitial delivery of dexamethasone directly within the tumor bed.

Gangliosides: the relevance of current research to neurosurgery

1991 ◽  
Vol 74 (4) ◽  
pp. 606-619 ◽  
Author(s):  
Frank A. Rodden ◽  
Herbert Wiegandt ◽  
Bernard L. Bauer
Keyword(s):  
Nervous System ◽  
Mammalian Cells ◽  
Human Subjects ◽  
Laboratory Animals ◽  
Trophic Effect ◽  
Content Type ◽  
Degree Of Malignancy ◽  
Fine Print

✓ Gangliosides are complex glycolipids found on the outer surface of most cell membranes: they are particularly concentrated in tissues of the nervous system. Gangliosides form part of the immunological identity of mammalian cells and are involved in a variety of cell-surface phenomena such as cell-substrate binding and receptor functions. In tumorous tissue, the ganglioside composition is altered, sometimes in direct proportion to the degree of malignancy. The literature on the glycosphingolipid composition and immunology of intracranial tumors is reviewed. Some gangliosides induce neuritogenesis and exhibit a trophic effect on nerve cells grown in vitro. In vivo, a particular ganglioside, GM1, reduces cerebral edema and accelerates recovery from injury (traumatic and ischemic) to the peripheral and central nervous systems of laboratory animals. Preliminary clinical studies have shown that treatment with gangliosides may have corresponding effects on lesions of the human peripheral nervous system. Gangliosides have not been tested in human subjects with brain injury.

Assessment of brain tumor cell motility in vivo and in vitro

1995 ◽  
Vol 82 (4) ◽  
pp. 615-622 ◽  
Author(s):  
Michael R. Chicoine ◽  
Daniel L. Silbergeld
Keyword(s):  
Brain Tumor ◽  
Cell Motility ◽  
Human Brain Tumor ◽  
Content Type ◽  
Brain Tumor Cells ◽  
Tumor Cell Motility ◽  
Brain Tumor Cell ◽  
Fine Print

✓ Brain tumor dispersal far from bulk tumor contributes to and, in some instances, dominates disease progression. Three methods were used to characterize brain tumor cell motility in vivo and in vitro: 1) 2 weeks after implantation in rat cerebral cortex, single C6 cells labeled with a fluorescent tag had migrated to brain sites greater than 16 mm distant from bulk tumor; 2) time-lapse videomicroscopy of human brain tumor cells revealed motility of 12.5 µm/hr. Ruffling leading edges and pseudopod formation were most elaborate in more malignant cells; 3) an in vitro assay was devised to quantitatively evaluate motility from a region of high cell density to one of lower cell density. Human brain tumor cells were plated in the center of a petri dish, washed, and refed, establishing a 2-cm circular zone of cells in the dish center. Motility was determined by counting cells daily at predetermined distances from the central zone perimeter. Cells were found 1 cm from the perimeter by 24 hours and 3 cm from the perimeter by 4 days. Increasing serum concentration increased motility; however, neither fibronectin nor arrest of cells in the G0 phase by hydroxyurea altered motility. The addition of cytochalasin B to block cytoskeletal assembly prevented cell motility. Motility increased with increased malignancy. Subpopulations of cells were created by clonal amplification of cells that had migrated most rapidly to the dish periphery. Although morphologically indistinguishable when compared to the original cell line from which they were derived, these subpopulations demonstrated significantly increased motility.

CSF leukotriene C4 following subarachnoid hemorrhage

1988 ◽  
Vol 69 (4) ◽  
pp. 488-493 ◽  
Author(s):  
Pietro Paoletti ◽  
Paolo Gaetani ◽  
Guido Grignani ◽  
Lucia Pacchiarini ◽  
Vittorio Silvani ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Subarachnoid Hemorrhage ◽  
Arterial Spasm ◽  
Lipoxygenase Pathway ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Csf Levels ◽  
Fine Print

✓ Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p < 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p < 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.

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