Biomedical subjects
T N Byrne
Publications and source records attributed to T N Byrne.
Disorders of the spinal cord and cauda equina.
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Spinal cord compression from epidural metastases.
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Syphilitic meningitis causing paraparesis in an HIV-negative woman.
Syphilitic meningitis, which can occur near the time of secondary syphilis, is frequently asymptomatic. There has been one recent report of an HIV-positive patient who developed syphilitic polyradiculopathy following a recent history of secondary syphilis. We describe an HIV-negative woman in whom paraparesis occurred secondary to syphilitic meningitis. Complete recovery followed a course of high-dose intravenous penicillin therapy, emphasizing the treatable nature of this cause of paraparesis.
The effect of calmodulin inhibitors with bleomycin on the treatment of patients with high grade gliomas.
Glioblastoma multiforme is a fatal malignancy of the central nervous system, demanding new methods of treatment. The combination of a calmodulin antagonist with bleomycin has shown synergistic activity in several preclinical models and has been evaluated in a Phase I clinical trial. Since phenothiazines reach high concentrations in the central nervous system, and bleomycin has been reported to have antitumoral activity as well, we studied this combination in a Phase II clinical trial. In addition, we purified calmodulin from normal brain and malignant gliomas to determine its biochemical and pharmacological characteristics. Seventeen patients were entered onto this study and all were evaluable. There were no partial or complete responses. There was one case of fatal pulmonary toxicity in a patient showing an objective tumor response. Otherwise, the treatment was well tolerated. Calmodulin purified from the normal brain and gliomas of patients undergoing resection was identical to each other and to calmodulin prepared from rat cerebrum and glioma. These characteristics included elution from a TSK phenyl high pressure liquid chromatography column, migration on 16% sodium dodecyl sulfate gels, amino acid composition, and inhibition by drugs. Therefore, the failure of this combination therapy was not due to a difference in human glioma calmodulin as compared to previously reported studies with calmodulin from murine sources.
Meningioma associated with aneurysm and subarachnoid hemorrhage: case report and review of the literature.
A patient presented with spontaneous subarachnoid hemorrhage after a prolonged episode of coughing. A preoperative computed tomographic (CT) scan confirmed subarachnoid hemorrhage, but demonstrated no other lesion. Arteriography revealed an ophthalmic artery aneurysm. Operation revealed the aneurysm to be intracavernous without sign of prior rupture; however, a small hemorrhagic meningioma was removed from the ipsilateral anterior clinoid process. In this case, coincidental meningioma and aneurysm presented as a subarachnoid hemorrhage secondary to tumor hemorrhage. The follow-up of cases of subarachnoid hemorrhage with negative arteriography with sequential CT scans is discussed.
Intra-arterial BCNU in the treatment of metastatic brain tumors.
Thirty-one patients with metastatic brain tumors that either failed to respond or recurred after conventional therapy were treated by intra-arterial infusion of 100 mg/m2 of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into either a carotid or vertebral artery. Five patients (three with lung cancer, one with breast cancer and one with melanoma) had a partial response of the tumor(s) in the distribution of the injected artery. In two patients, brain metastases not in the distribution of the injected artery enlarged, while the tumors perfused by the injected artery responded. In one of these patients, subsequent infusion of BCNU to the enlarging tumor resulted in a partial response. Among responders, the median survival following onset of BCNU was 17 weeks. One patient remains alive and well at 30 weeks. No permanent neurological, retinal or systemic toxicity was observed.
Brain metastasis from melanoma.
Eighty-one patients with brain metastasis from melanoma were identified at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1980. Of 78 evaluable patients, 51 (65%) had multiple brain metastases. Of 64 patients with non-contrast CT scans, 29% had hemorrhagic metastases. Leptomeningeal metastases were found in 15 patients. Patients were grouped into three categories: Group 1, multiple brain metastases treated with radiation therapy (RT) (n = 49); Group 2, single brain metastasis treated with RT (n = 17); Group 3, single brain metastasis treated with surgery with or without RT (n = 9). Median survivals for Groups 1, 2 and 3 were 11, 9 and 41 weeks, respectively. Eighty-six percent, 65% and 33% of patients in Groups 1, 2 and 3, respectively, were steroid-dependent until death. Seizures occurred in 38 patients (48%). In 17 (21%), seizures were the first manifestation of metastasis. Of 51 patients not receiving prophylactic anticonvulsants, 37% had seizures. Of 12 patients treated prophylactically, 17% developed seizures. Surgical extirpation should be considered in highly selected patients with brain metastasis from melanoma. Prophylactic anticonvulsants are recommended if there is no contraindication.
Myoclonic seizures following chlorambucil overdose.
A 3 1/2-year-old child developed myoclonic seizures following a chlorambucil overdose. Serial electroencephalograms showed paroxysmal discharges that continued several days beyond clinical seizure activity. The use of the electroencephalogram when chlorambucil toxicity is suspected is discussed.
Leptomeningeal cancer in leukemia and solid tumors.
Although some patients with overt leptomeningeal cancer can now be cured, the proportion of patients who survive is very small, and the cost of cure, in terms of neuropsychological and educational morbidity, is substantial. Yet the incidence of central nervous system infiltration of systemic cancer is generally increasing, in most instances because control of systemic cancer has sufficiently prolonged survival to permit leptomeningeal metastases to develop and become symptomatic or detectable. The best chance for prolongation of life and possible cure is early detection and aggressive therapy in those forms of cancer that are amenable to therapy. We review the incidence of the various forms of leptomeningeal metastases, current concepts of pathogenesis and pathophysiology, clinical and laboratory features of leptomeningeal cancer, the available therapies, and the associated toxicities. The various methods that have been used to prevent and treat leptomeningeal cancer are described with an emphasis on childhood acute lymphoblastic leukemia (ALL) because it plays a predominant role in our understanding of meningeal neoplasms in general.