Search

When Dr. Fields called some weeks ago to ask me to come to this conference and speak on the classification of gliomas, I did not have time to ponder on the request. However, during the ensuing days, as I thought about my presentation, I began to grasp the difficult task I had accepted. To talk on such a subject to this audience, most of whom have spent a large part of their professional lives grappling with brain tumors, is no mean undertaking.

The guided wave acousto-optic Bragg interaction has been investigated in proton exchanged waveguides on X and Y-cut lithium niobate. 220 MHz Z-propagating surface acoustic waves were used to probe the piezoelectric, electro-optic, and acousto-optic properties of the proton exchanged waveguides. We have found that the electromechanical coupling coefficient is reduced significantly in these structures, as is the overall acousto-optic interaction efficiency. The reduced interaction efficiency is attributed to the lack of an electro-optic contribution resulting primarily from a reduced magnitude of the r33 electro-optic constant. We have also seen a very marked increase and strong temperature dependence in the surface acoustic wave attenuation.

An experimental and clinical study was undertaken to determine whether Zenker's solution without glacial acetic acid (modified Zenker's solution) applied to the external surface of the dura mater can penetrate to injure the underlying cortex. Adult cats and dogs, the dura of which had an average thickness of 0.2 and 0.25 mm, respectively, were given intravenous Evans blue dye as an indicator of blood-brain barrier breakdown. This was followed by the application of modified Zenker's solution to the dura in a manner identical to the clinical practice. When the animals were killed 1 or 2 hours later, the cortex beneath the dura painted with modified Zenker's solution was stained massively. The thickness of human dura was measured; it varied from 0.22 to 0.28 mm in infants of 3 months or less, 0.27 to 0.42mm in infants 4 months to 12 months of age, and 0.32 to 0.45 mm in children to 1 to 18 years of age. Modified Zenker's solution applied to fresh dura for 3 minutes at autopsy gave visual evidence 1 hour later of penetration to the cortex beneath. In operative procedures for craniosynostosis, 69 patients were treated with modified Zenker's solution; of these, 7 developed seizures in the immediate postoperative period. No seizures occurred among the 39 patients on whom modified Zenker's solution was not used. It is concluded that modified Zenker's solution applied to the dura can damage the cortex beneath.

Progressive ascending myelitis was the presenting feature of the acquired immune deficiency syndrome (AIDS) in a homosexual man who also had Kaposi's sarcoma, Pneumocystis pneumonia, and disseminated cytomegalovirus (CMV) infection. Neuropathological studies showed profuse cytomegalic cells throughout the brain and spinal cord, but no inflammatory response. At postmortem examination, CMV and herpes simplex virus, type 2 (HSV-2), were recovered from multiple sites throughout the central nervous system (CNS). HSV-2 was isolated from the anus, but from no other extraneural site; in contrast, pathology typical of CMV was also seen in the liver, gastrointestinal tract, adrenals, and lungs. Although histopathological evidence suggesting prior CMV infection has been seen in the brains of AIDS patients, the virus has never been cultured from the CNS in these immunosuppressed hosts, nor has it been known to infect the spinal cord. The absence of an inflammatory response suggests that the pathogenesis of CNS viral infections is altered in AIDS patients. Evidence for CMV infection of the CNS in AIDS patients is no longer circumstantial.

A 46-year-old man with a known metastatic tumor developed the sudden onset of upgaze paralysis, impaired convergence, eyelid retraction, pupillary light-near dissociation, convergence-retraction nystagmus, and ocular skew deviation in association with subarachnoid hemorrhage. Selective interruption of the posterior commissure by metastatic melanoma provided a precise anatomic correlation of the pretectal syndrome in man.

One hundred forty-three patients with gliomas of astrocytic origin (61 with glioblastomas multiforme (GM) and 82 with astrocytomas) received an intravenous infusion of bromodeoxyuridine (BUdR), 150–200 mg/m2 at the time of surgery, to label tumor cells undergoing DNA synthesis. BUdR-labeled cells were identified by the indirect immunoperoxidase method using anti-BUdR monoclonal antibodies. The percentage of BUdR-labeled cells, or BUdR labeling index (LI), was calculated by microscopic examination of selected viable areas of the tissue sections. The GMs had a median LI of 7.5%, and three quarters of these tumors had LIs greater than 5%. Highly anaplastic astrocytomas (HAAs) and moderately anaplastic astrocytomas (MoAAs) had median Lls of 2.3% and less than 1%, respectively. Among the HAAs, the Ll was 1% to 5% in 56% of tumors, greater than 5% in 26%, and less than 1% in 18%. More than 60% of MoAAs had LIs less than 1%, which agrees with the slow clinical progression of this type of tumor, and the remainder had LIs of 1.4% to 9.3%. These results show that histopathologically similar tumors may have different proliferative potentials. Measuring the proliferative potential of individual gliomas is therefore crucial for predicting the prognosis more accurately and for devising more tumor-specific treatment regimens for individual patients.

Twenty cases of primary lymphoma of the central nervous system associated with acquired immune deficiency syndrome were seen over a period of four years and were studied clinically and pathologically. Biopsy established the diagnosis in 11 cases, and autopsy confirmed it in 9. Multicentricity was demonstrated in all cases for which there was adequate autopsy material. Both large-cell immunoblastic and small noncleaved lymphomas were seen, and marker studies in 5 patients established that the lymphomas were of B-cell origin. Neurological symptoms and signs, cerebrospinal fluid characteristics, and radiographic appearance were reviewed. The clinical and radiographic picture is nonspecific and histological confirmation is essential for diagnosis. Although the tumor appears to be radiosensitive, prognosis is extremely poor, with an average survival of less than two months.

Thin films of V2O5, Nb2O5, and Ta2O5 have been grown under a variety of conditions including reactive rf sputtering, reactive bias sputtering, and post deposition oxidation. The refractive index and guided-wave attenuation have been measured for both as-grown and annealed films. Except for V205, where low losses were not achieved, general guidelines were established for optimal growth conditions resulting in high refractive index low loss films. Films of Nb2O5 and Ta2O5 have been used in the fabrication of guided wave Bragg cells and waveauidp Lunphura lenses.© (1983) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Meningiomas are common neoplasms in the central nervous system. Although most of these tumors are encapsulated and grow very slowly, some meningiomas invade into adjacent brain tissue and skull, grow faster, and recur more frequently than classic meningiomas. These malignant meningiomas, however, are not well defined histopathologically, and their biological characteristics have never been well documented. We studied the cell kinetics of human meningiomas immunohistochemically using a monoclonal antibody against bromodeoxyuridine (BUdR) (2), a thymidine analogue that is incorporated into nuclear DNA during the synthesis phase of the cell cycle. BUdR-labeled S-phase cells can be identified by anti-BUdR monoclonal antibodies, which can then be detected by indirect immunoperoxiase methods (3, 6).

The diagnosis of malignant glioma of the optic nerves and chiasm may be difficult because these rare lesions may mimic other suprasellar lesions. We report a case of glioblastoma multiforme of the optic chiasm in which the appearance of the lesion on computed tomographic (CT) scan was consistent with that of craniopharyngioma or cystic pituitary adenoma. We suggest that malignant optic glioma should be considered in the differential diagnosis of an adult with progressive visual loss of rapid onset, even when ophthalmological examination strongly suggests extrinsic compression of the anterior optic pathways and when the CT scan apparently indicates a cystic mass lesion.

The intracerebral 9L rat brain tumor was resected from 38 rats with the use of standard microsurgical techniques, the carbon dioxide laser, or the argon laser. The extent of resection was evaluated by histological examination, and the effect on survival of the three methods was compared. All three methods achieved histologically verifiable gross total resection, and tumor recurrence after resection by all three methods occurred at the same rate.

Twenty patients with intracranial ependymoma (16) or anaplastic ependymoma (4) received post-operative radiation therapy at the University of California, San Francisco from 1959 through 1981. No patient received prophylactic spinal irradiation. The actuarial survival at 5, 10, and 15 years for 15 patients with ependymoma who received greater than 45 Gy was 67, 57, and 46%, respectively. Only one patient (7%) developed clinically recognized spinal metastases; this patient was eventually shown to have tumor at the primary site, within the irradiated volume. Six of 11 patients treated with partial brain irradiation had an intracranial recurrence, versus 1 of 4 patients treated with whole brain irradiation. Three patients were autopsied after failing partial brain irradiation for an ependymoma and the site of failure was within the irradiated volume of each patient. Partial brain irradiation was used to treat 4 patients with anaplastic ependymoma. One developed a local recurrence within the irradiated volume. The other three survived longer than 10 years. At UCSF, most patients with low grade epeadymmmms are presently treated with partial brain irradiation, but whole brain plus spinal irradiation is used for anaplastic tumors.

✓ One hundred fifty-two intracranial gliomas of various types were reviewed in order to correlate the histopathological features with the proliferative potential of each tumor as reflected by the bromodeoxyuridine (BUdR) labeling index (LI). Patients undergoing surgical removal of gliomas were given a 30-minute intravenous infusion of BUdR (150 to 200 mg/sq m) to label S-phase tumor cells. The tumor specimens were stained immunohistochemically for BUdR and processed for routine histopathological diagnosis. The BUdR LI was calculated as the percentage of labeled cells among cells analyzed. Twenty-seven histological features in three categories (degenerative, vascular, and cellular changes) were considered. A significantly higher BUdR LI (p < 0.05) was found in tumors with necrosis than in those without this feature; tumors with both coagulative and liquefactive necrosis had the highest BUdR LI (p < 0.05). Increased vascularity was also associated with a higher BUdR LI (p < 0.05). Although tumors with abnormal mitotic figures had a significantly higher BUdR LI than those without, the number of mitoses did not correlate with a higher BUdR LI. These results suggest that the number of mitoses is not a good indicator of tumor growth rate. Necrosis and increased vascularity should be heavily weighted in predicting the proliferative potential of individual gliomas.

Pituitary adenomas from 15 patients with Cushing's disease were studied histopathologically. The tumors were examined for the presence of neural axons by the Bodian silver impregnation technique and a specific immunohistologic technique based on a monoclonal antibody to axonal neurofilaments. Axons were not seen in any of the surgical specimens. This finding suggests that most, if not all, adrenocorticotropin-secreting pituitary adenomas are of anterior lobe origin.

Giant axonal neuropathy (GAN) is a disease characterized by a slowly progressive neuropathy and signs of central involvement, manifested by visual impairment, corticospinal tract dysfunction, ataxia, and dementia. Pathological hallmarks of the disease include axonal swellings packed with neurofilaments in both peripheral and central nervous systems, and accumulations of intermediate filaments in Schwann cells, fibroblasts, melanocytes, endothelial, and Langerhans cells. Rosenthal fibers, sometimes appearing in masses and mimicking Alexander's disease, emerge as a conspicuous characteristic in longstanding GAN.

The goal of the neuropathological examination of a cerebral neoplasm is to obtain an accurate measure of its proliferative potential. The underlying assumption made by those who must treat patients is that there is a direct correlation between the histological characteristics of a brain tumor and its prognosis and its response to treatment. However, experience has shown that there is often a considerable variation in the clinical behavior and rate of proliferation of neoplasms with the same histological characteristics.

The final report contains no magic or proprietary secrets. It is simply a logical review of what exists with an orderly recommendation of what should be done. To repeat -- many times the hardest part of any job is getting started. The purpose of this exercise is to provide a plan and a way to get started. This may seem like something so obvious that it is not needed. But a review of existing occupational health programs dispels that view. Five years after the enactment of the Occupational Safety and Health Act of 1970, hundreds of thousands of physical examinations are still being performed in a total vacuum; examinations whose contents bear little relationship to the hazards encountered. Countless laboratory determinations are being provided to personnel officers and plant managers who have absolutely no background in interpreting the meaning of those results. Millions of records are being meticulously kept with no goal in mind as to what purpose they should serve nor consideration for the privacy of individuals. In short, untold millions of dollars are being wasted while the things that should be done are left undone because, to quote, "the cost is too high." Often health professionals are employed by an organization because health crises have developed which force expert handling. The health professional enters chaos and is kept so busy answering fire-calls that there is no time for the orderly evaluation of needs and the development of operating routines required to prevent new crises from developing. Today's crises are being addressed while tomorrow's crises are developing out of routine situations. The health professional is not at fault; rather, executive management has failed to provide the necessary systems to meet its responsibilities. So long as this situation prevails, there is a need for someone to take the time to develop an orderly approach to occupational health surveillance. When such a condition exists, it is time to call in an independent auditor to provide an objective evaluation of what needs to be done. It is to provide a "handle" for getting hold of such situations that we developed our Occupational health Audit. It offers one way to get the job started.

A total of 38 reported cases of solitary abscess of the brainstem were studied. The route of infection may be direct extension usually from suppuration from the middle ear or hematogenous spread from a remote focus. In some instances, the route of infection is unknown. The clinical picture often is complicated by the prescence of basal meningitis or dural thrombophlebitis. The most frequent signs and symptoms described in all 38 patients were facial weakness, fever, headache, hemiparesis, dysphagia, and vomiting, but classical brainstem syndromes (that is, alternating cranial nerve and long tract signs) were present in only 11. (Author)

Two cases of delayed effects of radiation on the central nervous system of man are reported. One demonstrates the rare early delayed reaction which occurs approximately three months after radiation. The lesions resemble most closely the plaques of acute multiple sclerosis and are not associated with degenerative vascular changes. This patient probably represents an extreme of the early delayed reaction reported by Scholz in dogs. There is clinical evidence suggesting that some degree of damage of this type occurs more frequently than has been suspected. The other patient had the late delayed reaction in which there are marked degenerative vascular alternations and severe destruction of the white matter with little cortical involvement. This patient is an extreme example of the well-documented late delayed effects of radiation and is presented for contrast with the patient in case 1. The presence of hypertrophic neurons in the irradiated cortex is a new and unexplained finding. (Author)

Localized acute cardiac lesions containing fibrinoid were produced in rabbits by carotid-jugular cross circulation or temporary arteriovenous shunts, using small amounts of heparin as anticoagulant. Excessive amounts of heparin markedly reduced the incidence of fibrinoid in the lesions, which suggests that the formation of fibrinoid was inhibited or its deposition in the heart prevented. The results of the experiments suggest that the shunting procedures not only produce mechanical damage to the heart, but also participate in the production of fibrinoid or its precursors, which is deposited in localized sites of cardiac damage.

We have evaluated the use of 2,3,5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 +/- 2% of the coronal section for TTC, and 21 +/- 2% for H & E (mean +/- S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.

Neurons were isolated from the brain and spinal cord of five patients with clinical and pathologic evidence of amyotrophic lateral sclerosis (ALS). The following studies were carried out to detect the presence of infectious virus. Homogenates of isolated neurons were passaged in several cell lines at different temperatures; isolated neurons were cultured; and supernatant fluids were passaged on the cell lines. Neurons were also cocultivated and fused with continuous cell lines and subsequently passaged; isolated neurons were examined by electronmicroscopy and immunofluorescent techniques, using sera from ALS patients. No evidence of virus was found by these methods.

Delayed radiation damage of normal brain can be a devastating complication of radiation therapy and generally occurs months to years after the initiation of therapy. Primarily restricted to the white matter, radiation damage is characterized by a number of histopathologic changes including coagulation necrosis, vascular alterations with fibrinoid necrosis, edema, and demyelination. Normal dogs were exposed to either 10, 15, or 30 Gy of X rays to a single hemisphere and the gross and histopathologic changes were evaluated qualitatively. A spectrum of changes was observed ranging from white matter edema to extensive white matter necrosis, and the extent, location, and type of damage were dependent upon radiation dose. Histopathologic changes were separated into three major categories based on the character and size of the lesions, with the most severe changes being similar to the types of changes described in human patients who have developed delayed radiation necrosis. Less severe forms of damage such as multifocal, sometimes confluent areas of microscopic necrosis with spongiotic borders and edema with severe axonal swelling were also observed. These latter changes are not well recognized as being due to radiation. The findings of this study also indicate that many of the changes ascribed to combined treatment with methotrexate and radiation in humans are induced in the normal dog brain by radiation alone. The results of his study show that the dog is a suitable model of the human brain for studying radiation brain injury and may be useful for investigation of drug-radiation interactions.

The medical records, premortem biopsy specimens, and autopsy materials from 36 patients with acquired immune deficiency syndrome (AIDS) were reviewed. The majority of the patients were homosexual men. Widely metastatic Kaposi's sarcoma was seen in eight patients, while tumor was confined to the skin in an additional ten. Four patients had high-grade lymphomas. Thirty-five of the 36 patients had at least one opportunistic infection at some point in the course of their illness. Many patients had multiple infectious agents. The most consistent and striking autopsy finding was a severe depletion of lymphoid tissues. Death in the majority (83%) of the patients was attributable to opportunistic infections affecting most commonly the respiratory tract (64%) and meninges (11%). Three patients (9%) died with widely metastatic Kaposi's sarcoma and secondary hemorrhage. ( JAMA 1984;252:1152-1159)

Radiation damage induced by megavoltage X irradiation in normal brain tissue can manifest as one of several pathologic processes depending upon the time of brain examination after irradiation. Serial quantitative computed tomography (QCT) analyses were used to study the development of radiation damage in the normal canine brain. Tissue density, volume of low density areas, magnitude and volume of contrast uptake, and ventricular volume were measured following hemibrain irradiation and were correlated with histopathology. Low density areas correlated with edema, demyelination, axonal swelling, and necrosis and appeared 3-4 months after irradiation. Large regions of contrast enhancement (coagulation necrosis and associated vascular changes) appeared 5-6 months after irradiation. Results from this study demonstrated that the pathologic changes induced in the dog brain after single doses of X rays were similar to the changes observed in nonhuman primates and man after exposure to radiation.

From 1960 to 1977, 59 patients with histologically confirmed medulloblastoma were initially treated at Childrens Hospital of Los Angeles. Of this group, 49 have died and, of these, 34 were autopsied. Among the autopsied cases, 2 infants had neck masses that proved to be medulloblastoma that had spread from the cerebellar vermis before any surgical intervention. Four additional patients who had undergone a posterior fossa craniectomy without either the pre- or postoperative placement of a cerebrospinal fluid-diverting shunt were found to have extraneural metastatic medulloblastoma at autopsy. The extraneural metastatic medulloblastoma rate in the autopsied cases was 17.6% (6 of 34). Our series shows that the incidence of the extraneural spread of medulloblastoma is associated with being young, being male, and having diffuse tumor involvement of the subarachnoid space.

Efficient tapered Nb2O5 transition waveguide obtained by reactive sputtering has been demonstrated experimentally. It provides effective interconnection between two sections of Ti-indiffused waveguide with 0.8-dB total insertion loss. Chirped grating lenses have also been fabricated on Nb2O5 waveguides that have yielded 85% throughput efficiency. For signal processing applications in Ti-indiffused waveguides, the combination of grating lenses and the Nb2O5 transition waveguide will allow us to obtain lens functions that have both high efficiency and large angular field of view (∼4°).

• A 60-year-old man fell; a subdural hematoma developed and he lost consciousness. Visual evoked potentials demonstrated a total conduction block in the left optic nerve and slowed conduction on stimulation of the right eye. He died four weeks later, and necropsy showed focal infarcts in the intracranial portion of both optic nerves.

Two patients had bilateral tegmental medullary infarcts with resultant acute failure of automatic respiratory function. Both patients were eventually able to maintain respiration unaided while awake, but remained apneic during sleep. This condition, referred to as Ondine's curse, has been described in association with bilateral high cervical cordotomy, bulbar poliomyelitis, and in single instances of brain stem tumor and infarction. Our cases add further support to the concept of two separate respiratory systems: a voluntary system, with cerebral centers and descending pathways associated with the pyramidal system; and an automatic system, with medullary tegmental centers and pathways in the anterolateral portions of the high cervical cord.