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Biomedical subjects

M R Gilbert

Publications and source records attributed to M R Gilbert.

At least 19 recordsLinked to original sources
PubMed2006

Validation of the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT).

BACKGROUND: Symptom occurrence has been shown to predict treatment course and survival in patients with solid tumors. Primary brain tumor (PBT) patients are unique in the occurrence of neurologic symptoms. Currently, no instrument exists that measures both neurologic and cancer-related symptoms. METHODS: Patients diagnosed with PBT participated in this study. Data was collected at one point in time and included demographic and clinical factors, and the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). The study evaluated the reliability and validity of the MDASI-BT in primary brain tumor patients. RESULTS: Two hundred and one patients participated in this study. Mean symptom severity of items as well as cluster analysis was used to reduce the number of total items to 22 (13 core, 9 brain tumor items). Regression analysis showed more than half (56%) of the variability in symptom severity was explained by brain module items. The MDASI-BT measures six underlying constructs including affective, cognitive, focal neurologic deficit, constitutional, generalized symptom, and a gastrointestinal related factor. The internal consistency (reliability) of the instrument was 0.91. The MDASI-BT was sensitive to disease severity based on performance status (P<0.001), tumor recurrence (P<0.01), and mean symptom interference (P<0.001). CONCLUSIONS: The 22 item MDASI-BT demonstrated validity and reliability in patients with PBT. This instrument can be used to identify symptom occurrence throughout the disease trajectory and to evaluate interventions designed for symptom management.

Adolescent↗
PubMed2001

Brain metastases: still an 'orphan' disease?

The diagnosis of brain metastases from systemic cancer has been associated with a poor prognosis. In fact, most chemotherapy clinical trials exclude patients with metastatic disease. In the past, clinical and basic research activity in this area has been only moderate. Recent developments in clinical trial design, as evidenced by recursive partitioning analysis and complemented by new treatment strategies in neurosurgery and radiotherapy, suggest a change in attitude and approach to the management of brain metastases. The role of chemotherapy will require more focused investigation, but recent advances in our understanding of the biology of brain metastases suggest that the next generation of chemotherapy treatments will involve targeting specific pathways of metastatic disease.

Age Factors↗
PubMed2000

Application of advances in molecular biology to the treatment of brain tumors.

Recent advances in molecular biology have substantially improved our understanding of the molecular genetics of primary brain neoplasms. Soon each histopathologic category of glioma will be further divided into subgroups according to similar genetic background, gene expression profile, and similarity of biologic responses to radiotherapy or chemotherapy. Identification of key molecules that are specifically altered in neoplastic cells will provide candidate molecular targets for tumor treatment. Novel therapeutic tools for targeting tumor cells, such as viral vectors for gene therapy, have been created. In the near future, the accumulation of new knowledge in brain tumor biology and genetics, combined with rational drug design, will revolutionize the treatment of malignant gliomas, which are among the most lethal human cancers.

Apoptosis↗
PubMed1998

Chemotherapy of astrocytomas: an overview.

OBJECTIVES: To provide an overview of the use of chemotherapy in the treatment of malignant brain tumors, with an emphasis on malignant gliomas. DATA SOURCES: Published articles, research studies, and reference books. CONCLUSIONS: Chemotherapy has primarily been used in a adjuvant setting after radiation therapy for primary brain tumors. This focus has not had a significant effect on survival. In an effort to more effectively treat the tumor, innovative chemotherapy treatments have been developed. These include the use of neoadjuvant chemotherapy, changes in timing of administration, new classes of chemotherapeutic agents, new routes of delivery, and augmentation of the body's own immune system to treat the tumor. IMPLICATIONS FOR NURSING PRACTICE: It is the challenge of the oncology nurse caring for the patient with a malignant brain tumor to gain knowledge of the disease process, side effect management, and the most up-to-date treatment regimens.

Antineoplastic Agents↗
PubMed1996

Phase II study of paclitaxel in patients with recurrent malignant glioma.

PURPOSE: To assess the efficacy and toxicity of paclitaxel administered as a 3-hour infusion to patients with recurrent malignant glioma. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma following radiation therapy, who had received no more than one prior chemotherapy regimen and who had a Karnofsky performance status (KPS) > or = 60, were treated with a 3-hour infusion of paclitaxel every 3 weeks. The initial dose was 210 mg/m2; dose escalation to 240 mg/m2 was allowed. Tumor response was assessed at 6-week intervals using radiographic and clinical criteria. Treatment was continued until documented tumor progression or a total of 12 paclitaxel infusions. RESULTS: Of 41 eligible patients, all were assessable for treatment toxicity and 40 (98%) were assessable for response. The response rate (disease stabilization or better) was 35%. Twenty-nine patients (71%) underwent dose escalation to 240 mg/m2 without the use of growth factors. Toxicities included alopecia (98%), nausea (22%), arthralgias (32%), CNS toxicity (24%), peripheral neuropathy (15%), cardiac toxicity (7%), and myelosuppression (10% grade 3 or 4 hematologic toxicity). No patient developed febrile neutropenia. There was one allergic reaction (2%). CONCLUSION: Paclitaxel is well tolerated at this dose schedule in patients with recurrent malignant glioma, and affords a modest response rate. Because minimal myelotoxicity was encountered in our patients, a dose-escalating phase I/II study of paclitaxel is planned to determine the maximal-tolerated dose (MTD).

Adult↗
PubMed1996

Glial neoplasms: classification, treatment, and pathways for the future.

PURPOSE/OBJECTIVES: To provide a review of glial neoplasms including histologic classification, signs and symptoms, diagnostic evaluation, treatment options, and nursing care. DATA SOURCES: Articles, books, proceedings of national meetings. DATA SYNTHESIS: Glial neoplasms vary according to prognosis and treatment options based on histologic classifications. Prediction of deficits and potential complications of disease and treatment can prepare the patient and healthcare provider in management. Treatment options include surgery, radiation therapy, and chemotherapy or combinations of these options. New treatment regimes currently are being investigated. CONCLUSIONS: Despite advances in the diagnosis and treatment of malignant gliomas, the outlook remains poor. As new combination treatment regimens become available, nursing care will significantly affect outcome and quality of life. IMPLICATIONS FOR NURSING PRACTICE: Goals of nursing care include prevention and education related to tumor- and treatment-related side effects, providing support and coordinating referrals to appropriate services during the disease process, and helping the patient and family cope with this devastating disease.

Brain Neoplasms↗
PubMed1995

Glial differentiation: a review with implications for new directions in neuro-oncology.

Major advances in cell culture techniques, immunology, and molecular biology during the last 10 years have led to significant progress in understanding the process of normal glial differentiation. This article summarizes our current understanding of the cellular and molecular basis of glial differentiation based on data obtained in cell culture and reviews current hypotheses regarding the transcriptional control of the gene switching that controls differentiation. Understanding normal glial differentiation has potentially far-reaching implications for developing new forms of treatment for patients with glial neoplasms. If oncogenesis truly involves a blockage or a short circuiting of the differentiation process in adult glial progenitor cells, or if it results from dedifferentiation of previously mature cells, then a clear understanding of differentiation may provide a key to understanding and potentially curtailing malignancy. Differentiation agents represent a relatively new class of drugs that effect cellular gene transcription at the nuclear level, probably through alterations in chromatin configuration and/or differential gene induction. These exciting new agents may provide a means of preventing the dedifferentiation of low-grade gliomas or inducing malignant glioma cells to differentiate with minimal toxicity. In the future, genetic therapy has the potential of more specifically rectifying the defect in genetic control that led to oncogenesis in any given tumor.

Adult↗
PubMed1995

Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier.

The authors investigated the effects of glioma cells and pharmacological agents on the permeability of an in vitro blood-brain barrier (BBB) to determine the following: 1) whether malignant glia increase endothelial cell permeability; 2) how glucocorticoids affect endothelial cell permeability in the presence and absence of malignant glia; and 3) whether inhibiting phospholipase A2, the enzyme that releases arachidonic acid from membrane phospholipids, would reduce any malignant glioma-induced increase in endothelial cell permeability. Primary cultures of rat brain capillary endothelium were grown on porous membranes; below the membrane, C6, 9L rat glioma. T98G human glioblastoma, or no cells (control) were cocultured. Dexamethasone (0.1 microM), bromophenacyl bromide (1.0 microM), a phospholipase A2 inhibitor, or nothing was added to culture media 72 hours prior to assaying the rat brain capillary endothelium permeability. Permeability was measured as the flux of radiolabeled sucrose across the rat brain capillary endothelium monolayer and then calculated as an effective permeability coefficient (Pe). When neither dexamethasone nor bromophenacyl bromide was present, C6 cells reduced the Pe significantly (p < 0.05), whereas 9L and T98G cells increased Pe significantly (p < 0.05) relative to rat brain capillary endothelium only (control). Dexamethasone reduced Pe significantly for all cell preparations (p < 0.05). The 9L and T98G cell preparations coincubated with dexamethasone had the lowest Pe of all cell preparations. The Pe was not affected in any cell preparation by coincubation with bromophenacyl bromide (p > 0.45). These in vitro BBB experiments showed that: 1) malignant glia, such as 9L and T98G cells, increase Pe whereas C6 cells probably provide an astrocytic influence by reducing Pe; 2) dexamethasone provided significant BBB "tightening" effects both in the presence and absence of glioma cells; 3) the in vivo BBB is actively made more permeable by malignant glia and not simply because of a lack of astrocytic induction; 4) tumor or endothelial phospholipase A2 activity is probably not responsible for glioma-induced increased in BBB permeability; and 5) this model is useful for testing potential agents for BBB protection and for studying the pathophysiology of tumor-induced BBB disruption.

Acetophenones↗
PubMed1992

Aluminum-induced neurofilamentous changes in cultured rat dorsal root ganglia explants.

Intrathecal administration of aluminum (AI) salts to susceptible species causes prominent accumulations of neurofilaments (NFs) in neurons of the CNS. Involved nerve cells display abnormal phosphorylation of perikaryal NFs, impaired axonal transport of NFs, and reduced levels of mRNA for NF proteins. Further understanding of the pathogenesis of AI toxicity has been limited by difficulties inherent in the available in vivo systems. For this reason, we have developed a model to study the effects of AI on cultured sensory neurons. Explant cultures of rat dorsal root ganglia (DRG) were exposed to 1 mM aluminum lactate for 1 d, 3 d, or 7 d and then examined morphologically. Accumulations of NFs were noted as early as 1 d after exposure, and prominent masses of NFs were seen at 3 and 7 d. Northern analysis of mRNA extracted from the cultured ganglia showed that high, medium, and low molecular weight NF protein mRNA levels were markedly reduced compared to control values by 1 d of exposure. Class II beta-tubulin mRNA was also moderately decreased. Reversibility of toxicity was assessed by removing the aluminum lactate from the medium after a 3 d exposure and examining the cultures 1 week later. The perikaryal masses of NFs dispersed and the levels of mRNA coding for the NF proteins and class II beta-tubulin increased. The neurotoxic effects of AI on cultured DRG recapitulates the effects of intrathecal administration of AI on animals; this model produces similar changes in neuronal morphology with neurofilamentous masses and similar modifications of NF gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

Sequences of taxol and cisplatin: a phase I and pharmacologic study.

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.

Adult↗
PubMed1990

Early diagnosis of spinal epidural metastases using out-patient computed tomographic myelography.

Twenty patients with known malignancies, back pain, abnormal roentgenograms of the spine, and normal neurological examinations were evaluated by outpatient computed tomographic (CT) myelography to determine the presence and extent of epidural tumor. Spinal CT following the intrathecal administration of low doses of water soluble contrast agents provided high quality diagnostic information. Three patients experienced adverse effects from this procedure which were mild and easily managed in the outpatient setting. Epidural tumor was identified in 15 of 20 (75%) patients. Patients were followed for 9-27 months following myelography. The 14 patients with epidural tumor treated with local radiation experienced pain relief and only one of these patients developed signs or symptoms of recurrent epidural tumor in the treated site. This study documents the high incidence of epidural tumor in selected patients without neurological deficits and the excellent palliative results of non-emergent, carefully planned radiation therapy. It also demonstrates that high resolution CT myelography can be performed safely in an outpatient setting in patients at high risk for epidural tumor. Outpatient myelography facilitates the early diagnosis of epidural tumor and provides needed information on the extent of the tumor for radiation treatment planning while conserving health care resources. For these reasons, outpatient CT myelography should be considered in selected patients with cancer who are at high risk for epidural metastases.

Adult↗
PubMed1989

Methotrexate neurotoxicity: in vitro studies using cerebellar explants from rats.

The mechanism of methotrexate (MTX)-induced neurotoxicity was investigated using cerebellar explant cultures from fetal rats. After 3 weeks of growth, myelinated cultures were treated with MTX at 1 microM, lysolecithin at 1 mg/dl, or unaltered nutrient medium. Myelin sheaths devoid of axons were observed by histological and electron microscopic preparations after 2 weeks of MTX exposure. After 5 weeks, cultures were almost entirely devoid of myelin sheaths. Myelin basic protein in the media removed from the cultures showed an increase in concentration after 3 weeks of MTX exposure and was significantly greater than control after 5 weeks of exposure. 2',3'-Cyclic nucleotide 3'-phosphohydrolase activity, a measure of oligodendroglial function, was not significantly different in the MTX group compared to controls. Lysolecithin-treated cultures showed widespread destruction and an early increase in myelin basic protein release into the medium. These data indicate that, in the cerebellar explant cultures, MTX is primarily a neuronal toxin, and the demyelination is a consequence of axonal loss and is not related to a change in oligodendroglial cell function. These findings provide new insight into the pathogenesis of MTX-induced neurotoxicity.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1989

Decreased phenytoin levels in patients receiving chemotherapy.

PURPOSE AND METHODS: Seizures and unexpectedly low phenytoin levels prompted a retrospective review of phenytoin doses and serum levels in patients with primary brain tumors following the administration of cisplatin and carmustine (BCNU) chemotherapy. RESULTS: All patients who received three or more cycles of this chemotherapeutic regimen required an increase in their maintenance phenytoin dose to maintain therapeutic phenytoin levels. The average increase in the daily phenytoin dose was 41% (range, 20% to 100%). In addition, 17 of 26 (65%) assessable chemotherapy cycles were accompanied by a greater than 20% decrease in phenytoin levels or an increase in phenytoin requirements. Significant changes in phenytoin levels occurred as early as two days after administration of chemotherapy and were seen exclusively in treatment cycles that contained cisplatin. Five additional cases were found in the literature in which serum phenytoin concentrations decreased after the administration of antineoplastic agents. CONCLUSIONS: These observations are important to physicians treating patients who are receiving phenytoin. Serious consequences can be avoided by expecting changes in phenytoin dosage requirements after the administration of chemotherapy, monitoring serum levels frequently, and making appropriate adjustments in phenytoin dosages. Prospective evaluations are needed to confirm these observations, to define the chemotherapeutic agents that predispose patients to these alterations in phenytoin's pharmacology, and to determine if drugs other than phenytoin are affected by the administration of chemotherapy.

Adult↗
PubMed1987

Cryosurgical versus catheter ablation of the atrioventricular junction.

Results of catheter ablation of the atrioventricular (AV) junction in 41 patients were compared with results of cryosurgical ablation in 42 patients. Mean follow-up was 29 months among patients who underwent catheter ablation and 53 months among those who underwent cryosurgical ablation. In both groups complete heart block was produced in most patients (88% in the catheter ablation group, 86% in the cryosurgery group), and similar proportions of patients continued to receive antiarrhythmic drugs (27% in the catheter ablation group, 36% in the cryosurgery group). However, the short-term morbidity rate was significantly lower among patients who underwent catheter ablation (12% vs 42%) (p = 0.004). Long-term mortality and morbidity rates were not significantly different; most deaths were related to underlying cardiopulmonary disease and morbidity to problems with permanent pacemakers. Both catheter ablation and cryosurgical ablation of the AV junction are effective in creating complete AV block and controlling supraventricular tachycardia in medically refractory patients. Because catheter ablation is associated with lower short-term morbidity and avoids the need for a major surgical procedure, it is preferable to cryosurgical ablation of the AV junction when permanent abolition of AV conduction is necessary.

Atrioventricular Node↗