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Biomedical subjects

E Alexander

Publications and source records attributed to E Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1994

Long term results of stereotactic brachytherapy used in the initial treatment of patients with glioblastomas.

BACKGROUND: Despite optimal therapy with surgery and radiotherapy, the prognosis of patients with glioblastomas remains poor. Stereotactic brachytherapy involves the accurate placement of radioactive isotopes within brain tumors, significantly increasing the dose of radiation that can be delivered to the tumor bed without substantial risk to surrounding normal tissue, potentially improving local tumor control and patient survival. METHODS: Between February 1987 and July 1993, the authors treated 56 patients with glioblastomas with stereotactic brachytherapy as part of their initial therapy. Patients underwent surgery, limited field external beam radiotherapy, and brachytherapy with temporary high-activity iodine 125 sources, giving an additional 50 Gy to the tumor bed. RESULTS: Median survival for patients undergoing brachytherapy was 18 months compared with 11 months for a matched brachytherapy control group with similar clinical and radiologic features (P < 0.0007). Survival rates at 1, 2, and 3 years after diagnosis of 83%, 34%, and 27%, respectively, for patients receiving brachytherapy were significantly increased compared with survival rates of 40%, 12.5%, and 9%, respectively, for control subjects. Thirty-six patients (64%) underwent reoperation for symptomatic radiation necrosis from 3 to 42 months (median, 11 months) after brachytherapy. The median survival of patients undergoing reoperation was 22 months compared with 13 months for those who did not have further surgery (P < 0.02). Thirty-five percent of patients relapsed locally within the brachytherapy target volume, whereas 65% had marginal or distant relapses. CONCLUSIONS: Brachytherapy may improve local tumor control and prolong survival when used in the initial treatment of selected patients with glioblastomas.

Adolescent↗
PubMed1994

A phase I study of etanidazole and radiotherapy in malignant glioma.

PURPOSE: To determine the maximum tolerable total dose (MTD) of etanidazole (ETA) when administered with external beam radiotherapy (XRT) and as a continuous infusion during stereotactic brachytherapy for patients with malignant glioma (anaplastic astrocytoma or glioblastoma multiforme or mixed cell tumors). METHODS AND MATERIALS: Seventy previously untreated patients were entered in a Phase I study. Prior to initiation of treatment, patients were stratified according to whether or not they were candidates for interstitial implantation. The implant patients (IMP, n = 17 pt) received accelerated fractionation XRT 20 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break and then interstitial implant to 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 h. The two sequentially conducted nonimplant arms started with accelerated fractionation XRT 2 Gy BID (6 h apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. NonIMP 1 arm (n = 38) received a 2-week break before standard fractionated boost XRT of 20 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. NonIMP 2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA. RESULTS: The dose-limiting toxicity (DLT) in the IMP group was the cramping/arthralgia syndrome (4) and the cumulative MTD was 26 gm/m2. For both nonIMP 1 and 2 the DLTs were peripheral neuropathy and the cramping-arthralgia syndrome. The MTD for nonIMP 1 was 34 gm/m2 and nonIMP 2, 30 gm/m2. CONCLUSION: The clinical efficacy and radiation-related toxicity of these regimens are being evaluated. The doses of ETA that can be used with accelerated fractionation and with external beam irradiation plus brachytherapy have been established.

Adult↗
PubMed1994

Image fusion for stereotactic radiotherapy and radiosurgery treatment planning.

PURPOSE: We describe an image fusion application that addresses two basic problems that previously limited the use of magnetic resonance imaging (MRI) for geometric localization in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). The first limitation is imposed by the use of a relocatable, MRI-incompatible, stereotactic frame for stereotactic radiotherapy. The second limitation is an inherent lack of geometric fidelity in current MRI scanners that invalidates the use of MRI for stereotactic localization. METHODS AND MATERIALS: We recently developed and implemented a novel automated method for fusing computerized tomography (CT) and MRI volumetric image studies. The method is based on a chamfer matching algorithm, and provides a quality assurance procedure to verify the accuracy of the fused image set. The image fusion protocol removes the need for stereotactic fixation of the patient for the MRI study. RESULTS: The image fusion protocol significantly improves on the spatial accuracy of the MRI study. We demonstrate the effect of distortion and the effectiveness of the fusion with a phantom study. We present two case studies, an acoustic neurinoma treated with SRS, and a pilocytic astrocytoma treated with SRT. CONCLUSION: The image fusion protocol significantly improves our logistical management of treating patients with radiosurgery and makes conformal therapy practical for treating patients with SRT. The image fusion protocol demonstrates both the superior diagnostic quality and the poor geometric fidelity of MRI. MRI is a required imaging modality in stereotactic therapy. Image fusion combines the superior MRI diagnostic quality with the superior CT geometric definition, and makes the use of MRI in stereotactic therapy possible and practical.

Astrocytoma↗
PubMed1994

Autocrine regulation of the production of the gaseous messenger nitric oxide in a glioblastoma cell line.

We used a glioblastoma multiform (GBM) cell line to study the mechanism of cellular regulation of nitric oxide (NO) production. Our experiments indicate a confluent monolayer of GBM cells to release NO as measured through its oxidized NO2 form which gradually accumulates and reaches a peak by 7 to 10 days of culture. the addition of the L-arginine analogs L-NG-monomethyl-L-arginine and L-N omega-nitro-L-arginine and dexamethasone to the GBM cultures caused a substantial inhibition of NO production. The addition of monoclonal antibodies against IL-1 and TNF alpha to the cultures resulted in an inhibition of NO production, whereas the addition of anti-TGF beta monoclonal antibodies resulted in an increase in NO production. These findings suggest the presence of an autocrine regulatory mechanism for NO production in some tumor cell lines.

Arginine↗
PubMed1994

Stereotactic radiotherapy: a technique for dose optimization and escalation for intracranial tumors.

Stereotactic radiosurgery offers the ability to treat relatively small volume intracranial lesions with single fraction, high dose radiotherapy while sparing surrounding tissue due to rapid fall off of dose outside of the treatment volume. Conventional radiotherapy takes advantage of the sparing effects of dose fractionation, but includes relatively large amounts of normal brain in the treatment volume the tolerance of which is dose-limiting. For some intracranial lesions it may not be optimal to treat with large single fractions due to tumor location or size. Conventional fractionated radiotherapy may not be optimum in all cases due to the necessary inclusion of normal structures. Through the development of relocatable head frames, the precision of stereotactic techniques and the biologic advantages of fractionation may be combined in stereotactic radiotherapy (SRT). We report on the treatment of 68 patients with intracranial lesions using a dedicated stereotactic linear accelerator to deliver SRT between June 1992 and June 1993. SRT was used either in order to optimize dose distribution and spare normal tissues in patients with excellent prognosis or in order to increase the dose to tumor while keeping doses to normal tissues below tolerance levels in patients with poorer prognosis (dose escalation). Histologies treated included meningioma, low grade astrocytoma, pituitary adenoma and acoustic neuroma. The most common treatment sites were the parasellar region and cavernous sinuses. Most patients (79%) had surgical debulking prior to SRT. 10-12 patients were treated daily. Patient positioning using relocatable stereotactic frames was highly precise. Acute and subacute side effects were minimal and radiographic responses have been similar to those expected with conventional radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The prevention of radiosurgery-induced nausea and vomiting by ondansetron: evidence of a direct effect on the central nervous system chemoreceptor trigger zone.

Nausea and emesis are significant side effects in patients undergoing stereotactic radiosurgery for brain lesions in the region of the chemoreceptor trigger zone (area postrema of the brain). Even with the current antiemetic treatment (prochlorperazine +/- corticosteroids), those side effects remain significant. The purpose of this study is twofold: [1] to evaluate the efficacy of ondansetron in inhibiting nausea and emesis in stereotactic radiosurgery patients and [2] to demonstrate that ondansetron's locus of action is the central nervous system (CNS) chemoreceptor trigger zone in the area postrema. In a pilot study, 10 patients receiving > or = 350 cGy in a single fraction of radiosurgery to the region of the area postrema received 32 mg ondansetron iv 1 hour prior to treatment +/- corticosteroids. In a retrospective analysis these results were compared to those of patients with similar features (and matched for radiation dose to the area postrema and the dose of corticosteroids) who received prochlorperazine +/- corticosteroids. Nine of 10 patients in the ondansetron group had no nausea or emesis within 48 hours after treatment; one patient experienced one episode of emesis. In the prochloreperazine group, eight patients had symptoms, three patients needed hospitalization or a physician's care for emesis within 24 hours, and five had nausea with no specific treatment. These preliminary results suggest that ondansetron is a safe and efficient drug to prevent nausea and emesis in this patient group. The precise mechanism of action of ondansetron in these patients is unknown, but is likely due to the drug's serotonin-blocking effect within the CNS. A randomized, prospective study has been started at our institution to confirm these preliminary results.

Adult↗
PubMed1994

Compensation equity between men and women in academic medicine: methods and implications.

BACKGROUND: Compensation inequity by gender is a problem across occupations in the United States. Most compensation-monitoring efforts in academic medicine have been informal. The authors developed an analytic method for formal, ongoing evaluation of compensation equity in academic medicine. METHOD: A historical cohort study was conducted at Michigan State University College of Medicine using data from 1990, 1991, and 1992 to (1) evaluate methods for monitoring compensation equity, (2) test the feasibility of compensation-equity monitoring as part of administrative information systems, and (3) determine whether compensation inequity existed in a case study of faculty salaries. Internal market adjustments for specialty, clinical or basic science "type," and calendar- or academic-year appointments were made before establishing a male cohort for each female faculty member. RESULTS: The method developed appears feasible for routine administrative monitoring of compensation equity. When the compensations of women of each type and rank were compared with the compensations of their male cohorts, inequities appeared to exist for basic scientists, but not clinicians, based on a criterion of the groups' compensations being 4% or more below those of their cohorts for two successive years. CONCLUSION: The authors suggest that formal monitoring of compensation equity is an important and feasible administrative undertaking to correct historical inequities. This is an area in which leadership by U.S. medical colleges is needed.

Cohort Studies↗
PubMed1994

Video registration virtual reality for nonlinkage stereotactic surgery.

We have combined three-dimensional (3D) computer-reconstructed neuroimages with a novel video registration technique for virtual reality-based, image-guided surgery of the brain and spine. This technique allows the surgeon to localize cerebral and spinal lesions by superimposing a 3D-reconstructed MR or CT scan on a live video image of the patient. Once the patient's scan has been segmented into the relevant components (e.g., tumor, edema, ventricles, arteries, brain and skin), the surgeon studies the 3D anatomy to determine the optimal surgical approach. The proposed intraoperative surgeon's perspective is displayed in the operating room at the time of surgery using a portable workstation. The patient is then brought to the operating room and positioned according to the planned approach. A video camera is trained on the patient from the proposed intraoperative surgeon's perspective. A video mixer merges the images from the video camera and the 3D computer reconstruction. This video mixer can vary the output intensity of the two input images between 100% of either and 50% of both. This visually superimposes the two images, not unlike a photographic double exposure. The patient's position and the 3D reconstruction are then adjusted until the images on the video mixer's output monitor are identical in terms of scale, position and rotation. This superimposition is facilitated by aligning various surface landmarks such as the external auditory canal, lateral canthus, and nasion. In some cases, such as with spinal tumors, capsules placed on the skin prior to scanning serve as fiducials.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Ethics, so far.

Explore the source record for details and available documents.

Attitude to Death↗
PubMed1994

Evolution of the Journal of Neurosurgery.

The Journal of Neurosurgery, begun in 1944, has successfully fulfilled the purposes of its founders. During the 50 years of its existence it has remained pre-eminent in its field, while evolving in presentation, size, and content in response to the needs of succeeding generations of neurosurgeons and allied specialists. This article draws from the memories of many people, from the minutes of meetings of the Editorial Board, and from reports of successive editors, and touches on some of the knotty problems faced by those dedicated individuals.

History, 20th Century↗
PubMed1994

Preventive health care for adolescents.

Physicians, parents or guardians, and the community all have an important role in preventive care for adolescents. Adolescents desire more interaction with their primary care providers. Physicians can influence the health care of adolescents by developing a collaboration with them that augments protective factors and allows a reduction in risk behaviors.

Adolescent↗