bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas
Authors: Brem Henry , Mahaley M. Stephen , Vick Nicholas A. , Black Keith L. , Schold S. Clifford , Burger Peter C. , Friedman Allan H. , Ciric Ivan S. , Eller Theodore W. , Cozzens Jeffrey W. , Kenealy James N. 
Published: May 2009

✓ Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I–II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks.
Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy.
Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.
Characterization of astrocytomas, meningiomas, and pituitary adenomas by phosphorus magnetic resonance spectroscopy
Authors: Arnold Douglas L. , Emrich Joseph F. , Shoubridge Eric A. , Villemure Jean-Guy , Feindel William 
Published: May 2009

✓ Phosphorus magnetic resonance (MR) spectroscopy allows noninvasive measurement of phosphate-containing compounds and pH within brain cells. The authors obtained localized phosphorus MR spectra from 10 normal brains, four low-grade astrocytomas, six glioblastomas, four meningiomas, and three pituitary adenomas and found differences in the spectra of each tumor type. Compared to normal brain, the spectra from low-grade astrocytomas showed a significant reduction of the phosphodiester (PDE) peak. Glioblastomas were characterized by a significant reduction of the PDE peak, elevation of the phosphomonoester (PME) peak, and a relatively alkaline intracellular pH. The spectra from meningiomas and pituitary adenomas were markedly different from the glial tumors. Meningiomas showed significant reductions in phosphocreatine, PDE, and inorganic phosphate, as well as a relatively alkaline pH. Pituitary adenomas resembled meningiomas, but had a much higher PME peak.
Although the number of tumors studied was small, there appears to be a characteristic spectrum associated with these different tumor types. The present findings can be useful in the preoperative identification of these tumors and in furthering understanding of their growth and metabolism in vivo.
Expression of P-glycoprotein in human glioma cell lines and surgical glioma specimens
Authors: Matsumoto Tsuyoshi , Tani Eiichi , Kaba Keizo , Shindo Hideki , Miyaji Katsuya 
Published: May 2009

✓ The expression of P-glycoprotein, a product of multidrug resistance gene 1, was studied by Western blotting and immunohistochemistry in five human glioma cell lines. One glioma cell line was resistant to vincristine, Adriamycin (doxorubicin), and etoposide, and the other four glioma cell lines were sensitive to each drug. The multidrug-resistant cell line showed a high expression of P-glycoprotein in Western blot analysis and a positive immunostaining for P-glycoprotein mainly along the cell membrane, whereas all multidrug-sensitive glioma cell lines demonstrated no expression of P-glycoprotein in Western blotting and no immunostaining for P-glycoprotein, thus showing a good correlation between the expression level of P-glycoprotein and the extent of multidrug resistance.
In 18 human surgical glioma specimens, there was no evidence of complete absence of immunostaining for P-glycoprotein. With a definition of more than 20% of P-glycoprotein-positive cells as positive, from 10% to 20% as intermediate, and less than 10% as negative, immunostaining for P-glycoprotein was positive in one specimen and intermediate in six of 15 specimens taken from virgin gliomas, and positive in two specimens and intermediate in one of three recurrent gliomas treated previously with irradiation, ACNU (1-(4-amino-2-methyl-pyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), cisplatin, vincristine, and/or procarbazine.
Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects
Authors: Albeck Michael J. , Børgesen Svend E. , Gjerris Flemming , Schmidt Jes F. , Sørensen Per Soelberg 
Published: May 2009

✓ Conductance of cerebrospinal fluid (CSF) outflow (Cout) is an important parameter to be considered in patients with CSF circulation abnormalities. In patients with normal-pressure hydrocephalus it is the single most important parameter in determining if the patient needs CSF shunting. The lower normal limit for Cout has been estimated from the effect of shunting in patients with normal-pressure hydrocephalus, from patients retrospectively reevaluated after recovering from illness, and from patients with known abnormalities in the brain or the CSF system. The true value of Cout in normal individuals, however, has hitherto not been reported.
In the present study, Cout has been measured by a lumbar infusion test in eight young volunteers with no suspicion of disease. The mean intracranial pressure (ICP) was 11 mm Hg and a linear relationship was found between CSF absorption and ICP. The mean Cout was 0.11 ml/min/mm Hg and the lower 95% confidence level was 0.10 ml/min/mm Hg. These values are in accordance with those obtained from previous studies.
Cytosolic calcium changes in cultured rat aortic smooth-muscle cells induced by oxyhemoglobin
Authors: Takenaka Katsunobu , Yamada Hiromu , Sakai Noboru , Ando Takashi , Nakashima Toshihiko , Nishimura Yasuaki , Okano Yukio , Nozawa Yoshinori 
Published: May 2009

✓ To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium ([Ca++]1) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM.
Oxyhemoglobin induced a significant elevation of [Ca++]1 in vascular smooth-muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (β-aminoethylether)-N,N′-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5)). The oxyhemoglobin-induced elevation of [Ca++]1 was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]1 followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]1 elevation, but the [Ca++]1 level declined more quickly to the basal level in treated compared with control cells.
These results indicate that oxyhemoglobin-induced [Ca++]1 elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long-lasting high elevation of [Ca++]1 caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells.
Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma
Authors: Grabel Jordan C. , Zappulla Rosario A. , Ryder John , Wang Weijia , Malis Leonard I. 
Published: May 2009

✓ The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors.
Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p < 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p < 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p < 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression.
Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve.
Immunocytochemical evidence of lymphocytic derivation of neoplastic cells in malignant angioendotheliomatosis
Authors: Clark W. Craig , Dohan F. Curtis , Moss Timothy , Schweitzer John B. 
Published: May 2009

✓ Neoplastic angioendotheliomatosis is a rare disorder usually characterized by primarily cutaneous or neurological symptoms. Approximately 40 cases of malignant angioendotheliomatosis with primary central nervous system (CNS) symptoms have been reported. Some investigators have postulated a hematopoietic origin for this neoplasm. Most of the literature, however, has perpetuated the idea that the often bizarre symptoms seen with this entity result from neoplastic endothelial cell proliferation within the small vessels of affected organs, including the brain and spinal cord. This report describes the immunohistochemical examination and confirmation of the cell of origin of this neoplasm based on five previously unpublished cases of malignant angioendotheliomatosis with primarily CNS symptoms. It includes the first documentation of a T-cell lymphoma presenting as malignant angioendotheliomatosis.
All cases include autopsy findings, and in four cases the diagnosis was made postmortem. One case was proven by stereotactic biopsy, but the patient succumbed as a result of severe intracranial bleeding that occurred at the time of biopsy. Tissues were studied with avidin-biotin peroxidase immunohistochemical techniques using a panel of monoclonal antibodies directed against the leukocyte common antigen, LN-1, LN-2, and anti-Factor VIII, and also using Ulex europaeus agglutinin 1.
Based on the results obtained, the authors conclude that the proliferative cells seen within the vessel lumina are of lymphocytic origin and agree that the condition should more properly be designated intravascular lymphomatosis. The therapeutic implications of this conclusion point to the possible administration of chemotherapy and radiotherapy in an effort to achieve remissions in an otherwise relentlessly progressive neurological disorder.
Tissue plasminogen activator thrombolysis of a middle cerebral artery embolus in a patient with an arteriovenous malformation
Authors: Jafar Jafar J. , Tan Walter S. , Crowell Robert M. 
Published: May 2009

✓ A patient harboring a cerebral arteriovenous malformation (AVM) underwent angiography in an attempt to embolize the AVM. During catheterization (and prior to embolization) he became hemiplegic and aphasia Angiography revealed a complete middle cerebral artery (MCA) occlusion by an embolus. The patient was treated with recombinant tissue plasminogen activator (t-PA), a thrombolytic agent. Restoration of MCA flow was achieved, and the patient recovered.
Immediately after MCA embolus, t-PA infusion may lead to thrombolysis and neurological recovery. The decision-making process as well as the risks associated with the use of t-PA are discussed.
The risks of metastases from shunting in children with primary central nervous system tumors
Authors: Berger Mitchel S. , Baumeister Brenda , Geyer J. Russell , Milstein Jerry , Kanev Paul M. , LeRoux Peter D. 
Published: May 2009

✓ The authors reviewed the hospital charts of 415 pediatric patients treated for benign or malignant primary brain tumors over the past 20 years at the Children's Hospital Medical Center, Seattle. Patients' ages ranged from the neonatal period to 18 years. A shunt was placed in 152 patients (37%), 45 before and 94 after surgery. Confirmation of extraneural metastases was based on clinical and diagnostic examination. Factors analyzed as possibly influencing the occurrence of extraneural metastases were: 1) the shunt: type, valve, location, filter, and revisions; 2) extent of resection; 3) pathology; and 4) treatment regimen.
Eight of the 415 patients developed extraneural metastases during life. All eight patients had a medulloblastoma (cerebellar primitive neuroectodermal tumor). These eight patients were separated into Group A (without a shunt) and Group B (with a shunt). In Group A (five patients), the mean interval from primary diagnosis to metastasis was 15 months. Two children had gross total resection of the tumor. The predominant location of metastases in Group A was: bone (two cases); cervical lymph nodes (one); lung/bone (one); and retroperitoneal pelvic mass (one). Three Group A patients had a simultaneous central nervous system (CNS) recurrence. Of the three Group B patients, two had a ventriculoperitoneal (VP) shunt and one a ventriculoatrial (VA) shunt; all were placed postoperatively. One Group B patient had a simultaneous CNS recurrence. No shunt revisions were performed in these three patients. The mean time from primary diagnosis to metastasis was 25 months. One patient had a total tumor resection. The predominant location of metastases was bone (one case), retroperitoneal pelvic mass (one), and abdominal cavity with ascites (one case). Only one patient in the entire series had a filter placed; this resulted in shunt obstruction and was removed 1 month following placement.
It is concluded that cerebrospinal fluid shunts, regardless of type, location, revision rate, or filter insertion, do not predispose pediatric patients with brain tumors to develop extraneural metastases. A diagnosis of shunt-related metastases should be based on the development of intra-abdominal (VP shunt) or pulmonary (VA shunt) dissemination primarily with or without additional sites. The diagnosis of medulloblastoma is an important factor related to metastasis occurrence while the extent of resection and postoperative therapy are not influential.
Pyogenic osteomyelitis of the spine in the elderly
Authors: Cahill David W. , Love Lucy C. , Rechtine Glenn R. 
Published: May 2009

✓ The authors report 10 cases of spontaneous pyogenic spinal osteomyelitis encountered within a 3-year period. There were six women and four men, ranging in age from 60 to 84 years. Six cases occurred at the thoracic level, three at the lumbar level, and one in the cervical spine. No patient was diabetic, immunocompromised, or receiving steroid therapy, and none had a history of endocarditis or intravenous drug abuse. No patient had undergone previous spinal surgery. There were no instances of coexisting tuberculosis or malignancy. Contemporaneous cases with known predisposing factors have been excluded from this report; however, three patients did have a recent history of somatic infection, one with known sepsis. All 10 patients had been previously misdiagnosed, frequently by neurosurgeons and orthopedists as well as by internists and family practitioners. Three had undergone inappropriate or unnecessary surgical procedures, and two had received inappropriate radiation therapy. Seven cases were caused by Staphylococcus species, Gram-negative bacteria, or anaerobic infections. In the other three, no bacteriological diagnosis was made, secondary to prolonged antibiotic therapy before surgery. Each patient had developed symptomatic neural element compression, spinal instability, or both by the time of their referral.
The patients with subcervical pyogenic spinal osteomyelitis underwent transthoracic or retroperitoneal decompression and corpectomy with simultaneous autologous bone grafting, followed by 6 weeks of bed rest and 6 weeks of intravenous broad-spectrum or organism-specific antibiotic therapy. They were then mobilized in orthoses for an additional 6 weeks. In no case were foreign implants employed or further stabilization procedures necessitated. One patient required an additional 6 weeks of antibiotics for recalcitrant Pseudomonas colonization.
Despite the patients' advanced age and the extensive surgical procedures, there was no mortality and no neurological morbidity. All patients were asymptomatic or demonstrated objective improvement upon discharge from the hospital. In this subset of patients with spontaneous pyogenic vertebral osteomyelitis, the only predisposing factor was advanced age.
Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema
Authors: Tamargo Rafael J. , Sills Allen K. , Reinhard Carla S. , Pinn Michael L. , Long Donlin M. , Brem Henry 
Published: May 2009

✓ 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.
The use of visible light-curing resin for vertebral body replacement
Authors: Segal Ricardo , Alsawaf Moufid , Tabatabai Ali , Saito Reisuke , Segal Eduardo D. , McKinstry Robert 
Published: May 2009

✓ The technology of visible light-curing resin has recently been developed for use in removable prosthodontics. A quartz halogen lamp producing a 400- to 500-nanometer wave-length spectrum of visible light is used to polymerize high-molecular-weight acrylic resin monomers. While several in vitro and in vivo studies of visible light-curing resin are found in the dental literature, no studies have yet been performed to evaluate it as an intracorporeal implant in surgery.
The authors have designed a rat model of microcervical corpectomy to assess vertebral body replacement with visible light-curing resin in comparison to conventional autopolymerizing methyl methacrylate. Spinal cord function tests, spinal-implant stability assessments, and histological evaluations were made in a total of 41 rats at 2, 4, or 6 months postimplant. No animal developed a neurological deficit or radiographic instability, and at sacrifice there was no evidence of implant fracture-extrusion. In addition, there were no signs of adverse reaction in the surrounding tissues. Morphological investigation of the resin/bone interface at 6 months revealed very good implant anchorage.
Visible light-curing resin was found to be far superior to methyl methacrylate for construction of spinal implants. Its waxy consistency makes it easy to handle. It remains pliable until light is applied, allowing adjustments in shape for a well-fitted implant without time constraints. Applied in layers, adjustments can be made even after polymerization of a previous layer. This new implantable resin will allow safer, immediate stabilization in patients with neoplastic destruction of the spine, and may also be advantageous for other neurosurgical applications, such as cranioplasty.