Showing papers by "Dennis E. Bullard published in 1987"

Clinicopathologic correlations in the oligodendroglioma

Abstract: To determine the prognostic significance of histologic variables in oligodendroglial neoplasms, the presence and degree of 15 such variables were correlated with postoperative survival rates in 71 patients. By univariate analysis, prognostically significant factors, in order of decreasing importance, were mitoses (log), necrosis, nuclear cytologic atypia, vascular hypertrophy, and vascular proliferation. When studied by stepwise regression, necrosis and the number of mitoses contained all of the prognostically useful information. When each of the five variables significant by univariate analysis was tested in the Cox model by adding a variable to the model containing the other four, necrosis was found to be the only independently significant variable. There were significant positive pairwise correlations between each of the five significant histologic variables except for cytologic atypia with necrosis. The only histologic variable with a significant association with older age was the number of mitoses. These results suggest that necrosis and, to a lesser extent, the mitotic count are features that, in the appropriate setting, can be used to identify the "anaplastic" oligodendroglioma.

Diencephalic seizures: responsiveness to bromocriptine and morphine.

Abstract: Two patients with posttraumatic diencephalic seizures, characterized by autonomic dysfunction and extensor posturing, had partial responses to bromocriptine and complete responses to morphine. Probable synergism between the two agents was noted. These 2 cases suggest the potential effectiveness of this regimen for the treatment of diencephalic seizures, raise questions regarding the role of the dopaminergic and opioid systems in this disease entity, and support the hypothesis that diencephalic seizures represent a release phenomenon in the brain.

Oligodendroglioma: An analysis of the value of radiation therapy

Abstract: The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

Delayed foreign-body reaction to silk sutures in pediatric neurosurgical patients.

Abstract: Nonabsorbable silk sutures have been a frequently used foreign material in neurosurgery. In general, they are reliable and safe with minimal bio-incompatibility. Three pediatric neurosurgical patients came to clinical attention, however, because of delayed foreign-body reactions to silk sutures. The delayed atypical presentation of these patients delayed appropriate diagnosis and therapy. In two patients, the reaction presented as a delayed inflammation 7 years following surgical suture placement. In the other patient, the reaction caused delayed recurrent shunt failures and surgical wound breakdown. These three cases are used to introduce a discussion of the delayed response of the host to foreign material and its pertinence to neurosurgery.

The development of Lhermitte's sign during cisplatin chemotherapy. Possible drug-induced toxicity causing spinal cord demyelination.

Abstract: Cisplatin is a recognized neurotoxic agent that commonly causes ototoxicity and peripheral neuropathy. In conjunction with characteristic peripheral neuropathy, two patients treated with high-dose cisplatin developed Lhermitte's sign, a manifestation of posterior column spinal cord pathology. After cisplatin therapy was stopped, this symptom gradually resolved. This suggests that at high doses cisplatin may also cause demyelinating central nervous system lesions involving the spinal cord.

Comparison of monoclonal antibody delivery to intracranial glioma xenografts by intravenous and intracarotid administration

Abstract: Monoclonal antibody 81C6, which is directed against a human gliomamesenchymal extracellular matrix antigen, was used to evaluate the potential advantage of intracarotid (i.c.) administration versus i.v. delivery to D-54 MG human glioma intracranial xenografts in immunosuppressed rats. Two approaches were taken. In paired-label analysis, 125I-labeled 81C6 and 131I-labeled isotype control antibody were given to separate groups of animals by either the i.v. or i.c. route. Biodistribution measurements as a function of time were analyzed in terms of the percentage of injected dose/g of tissue and localization indices. No significant difference ( P > 0.19 to P > 0.56) was demonstrated between the i.v. and i.c. routes. To control for the large localization variation inherent in the animal model used, an alternative experimental design, paired-injection analysis, was performed in which 125I-and 131I-labeled 81C6 were simultaneously administered by the i.c. and i.v. routes to the same animal. Significantly higher levels of percentage of dose/g of tissue and localization ratios ( P < 0.05 to P < 0.005) were shown from Day 1 to Day 3 for 81C6 given i.c. Approximately 20% more antibody was delivered to the D-54 MG intracranial tumor by the i.c. route during the experimental period of 5 days. No difference in the levels of normal tissue exposure between the two routes of administration was seen. These data suggest an advantage exists for whole monoclonal antibody given i.c. and that, theoretically, a greater advantage may be present for smaller molecules such as Fab and F(ab′)2 fragments.

A Case of Ollier's Disease Associated with Two Intracranial Gliomas

Abstract: Ollier's disease or multiple enchondromatosis is a deforming dysplastic disease of cartilage involving primarily the metaphyses and diaphyses of long bones It is only rarely associated with sarcomatous degeneration of the enchondromas or other generalized neoplasms A related disease, Maffucci's syndrome, is, however, associated with generalized tumors We present the case of a 29-year-old, albino, black man with Ollier's disease who, as a child, underwent a number of orthopedic procedures for multiple limb deformities and fractures At age 25, he developed hydrocephalus, progressive cranial nerve palsies, and a large enchondroma of the skull base He subsequently underwent multiple shunt procedures and two suboccipital craniectomies Eighteen months later, a brain computed tomographic (CT) scan revealed an intracerebellar mass, which was found to be an anaplastic astrocytoma Two years later, he developed a right hemiparesis and sensory dysfunction with a diffuse supratentorial mass on CT scan A stereotactic biopsy showed this to be a similar anaplastic astrocytoma The literature concerning Ollier's disease is reviewed, and the intracerebral lesions associated with both Ollier's disease and Maffucci's syndrome are examined

The use of a panel of monoclonal antibodies in the evaluation of cytologic specimens from the central nervous system.

Abstract: A panel of monoclonal antibodies was tested immunohistochemically to determine the utility of such reagents in distinguishing among metastatic carcinoma, lymphoma, leukemia and primary brain tumors. The monoclonal antibodies used were: (1) a cocktail comprised of three anti-glial fibrillary acidic protein antibodies (alpha-GFAP); (2) UJ13A, a panneuroectodermal antibody; (3) B72.3, which recognizes a carcinoma-distinctive tumor-associated glycoprotein complex; and (4) 2D1, a pan-leukocyte antibody. Fifty-three specimens (21 cerebrospinal fluids, 1 ventricular fluid, 2 brain cyst fluids, 12 needle washings, 15 imprints, 1 subdural fluid and 1 post-shunt fluid) were obtained from 21 gliomas, 2 meningiomas, 1 pineoblastoma, 11 metastatic tumors, 3 lymphomas, 1 leukemia and 14 cases without tumor. alpha-GFAP stained all 21 gliomas and 5 of 5 cases containing reactive brain fragments. UJ13A had a reactivity pattern similar to that of alpha-GFAP, but also stained the meningiomas, pineoblastoma, oat-cell carcinoma and embryonal rhabdomyosarcoma. B72.3 stained all adenocarcinomas and the large-cell carcinoma. 2D1 stained lymphoma and leukemia, all inflammatory cells and 4 of 12 glioblastomas. Although no single antibody was diagnostic of a specific tumor type, this panel accurately differentiated among most primary brain tumors, metastases, leukemias and lymphomas.

Phase II diaziquone-based chemotherapy trials in patients with anaplastic supratentorial astrocytic neoplasms.

Abstract: We treated 103 patients with histologically confirmed anaplastic supratentorial astrocytic neoplasms with either diaziquone (AZQ) and carmustine (BCNU) or AZQ and procarbazine. There were 74 patients with glioblastoma multiforme (GBM) and 29 patients with anaplastic astrocytoma (AA). AZQ plus BCNU produced partial (PR) or unequivocal responses in seven of 32 (21.9%) patients with GBMs and three of ten (30%) patients with AAs. Two patients with GBMs (6.3%) and five patients with AAs (50%) showed stable disease (SD). AZQ plus procarbazine produced PRs or unequivocal responses in five of 42 (11.9%) patients with GBMs and nine of 19 (47.4%) patients with AAs. Eight patients with GBMs (19%) and one patient with an AA (5.2%) showed SD. In addition to histologic diagnosis, only the Karnofsky performance-status (KPS) rating independently influenced response and survival. Differences in response rates between the two regimens were not significant, although estimated median survival after adjusting for performance status was slightly better with AZQ plus BCNU than with AZQ plus procarbazine (P = .031). Neither age nor prior chemotherapy were significant independent risk factors. Toxicity was mild and primarily hematologic. We conclude that these AZQ-based regimens have activity in patients with recurrent anaplastic gliomas, but that they are not clearly superior to other agents in current use. The histologic diagnosis of GBM is associated with a significantly worse prognosis than AA, and we believe that this important distinction must be recognized in phase II as well as phase III trials.

The Applications of Monoclonal Antibodies in Neuro-Oncology

Abstract: Central nervous system (CNS) malignancies represent one ofthe most devastating forms of cancer. Malignant gliomas, the most commonly occurring primary tumor of the CNS, have a particularly bleak prognosis despite surgery and combined radiation and chemotherapy (1, 2). Immunological approaches to diagnosis and treatment have seemed attractive, but in the past have been frustrated by technological limitations (3, 4). Monoclonal antibody methodology offers major advantages over conventional methods of antiserum production: a practically unlimited source of homogeneous, highly specific reagent which may be prepared using impure or complex antigens. This has led to a new age in neuroimmunology and neuro-oncology, with the potential for better understanding of the basic cell biology of CNS neoplasia, and for improvement in diagnosis, imaging, and therapy.