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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 613 records · Page 34Linked to original sources

Microsurgical treatment of hermifacial spasm.

Five cases of idiopathic hemifacial spasm have been successfully treated by operative manipulation of arterial branches compressing the VIIth nerve in the posterior fossa. Terminology, clinical presentation, pathology and therapeutic approaches to hemifacial spasm are discussed. Hearing loss due to operatively induced vascular impairment of the inner ear, a complication in our first case, should be avoidable. Our experience indicates that hemifacial spasm reflects mild chronic compression of the facial nerve. The proposed mechanism is transaxonal excitation between afferent and efferent fibers.

Adult↗

Experimental cervical myelopathy: autoradiographic studies of spinal cord blood flow patterns.

The cervical spinal cord was compressed at one (C5) or two (C4,C5) levels in eight awake dogs by advancing screws through the vertebral bodies into the spinal canal until minimal limb weakness occurred. Ischemia of the cervical cord was produced by ligation of vertebral and spinal arteries in four anesthetized dogs, of which two had previously undergone cord compression at two levels. The neurological and histological findings were studied. By means of antipyrine [14C]autoradiography, qualitative changes of blood flow in dogs with compression and/or ischemia of the cervical spinal cord were compared to flow patterns in normal dogs. The authors conclude that the neurological and histological changes produced by spinal cord compression, ischemia and their combination correlate with altered patterns of blood flow within the cervical spinal cord.

Animals↗

BCNU (NSC-409962) and procarbazine (NSC-77213) treatment for malignant brain tumors.

Sixty-five patients with malignant brain tumors were treated with a combination of BCNU (100 mg/m2 qd X 1) and procarbazine (100 mg/m2 qd X 14); the cycle was repeated in 1 month and then on a 6-week schedule with procarbazine being given for 21 days. Forty-five patients had malignant gliomas (glioblastoma multiforme, anaplastic astrocytoma, malignant glioma, or gemistocytic astrocytoma) and were evaluated as a group. All patients had either shown evidence of tumor regrowth after previous surgery and/or radiotherapy, or had deep unbiopsied tumors presumed to be malignant gliomas. Of these 45 patients, 13 of 45 (30%) were judged to be unequivocal responders and an additional eight of 45 (17%) were designated as probable responders. The median duration of clinical response was 34 weeks for responders and 20 weeks for probable responders. The combination of BCNU and procarbazine, therefore, was somewhat inferior to a previous combination of procarbazine, CCNU, and vincristine.

Astrocytoma↗

Increased survival times of New Zealand hybrid mice immunosuppressed by graft-versus-host reactions.

New Zealand mice develop autoimmune disease usually accompanied by glomerulonephritis. A graft-versus-host reaction was induced in New Zealand Black X New Zealand White F1 hybrid mice by administration of New Zealand White spleen cells. The mice so treated had diminished antibody responses to both an exogenous antigen (sheep red blood cells) and an endogenous antigen (native DNA). They had much less glomerulonephritis and increased survival times compared to unmanipulated controls, apparently due to immunosuppression. Similar hybrid mice treated with high doses of cyclophosphamide (70mg/kg/week) were more immunosuppressed than mice with graft-versus-host reactions and had even greater survival times.

Animals↗

Chemotherapy of brain tumors.

Viewed in the light of recent advances and contemporary research, further refinements of surgery and radiotherapy hold little promise for the cure of glioblastomas, although both will continue to have important roles. Immunotherapy has quantitative limitations rendering it ineffective against tumors weighing much more than 1 mg (10(6) cells). Chemotherapy has neither anatomic nor quantitative restrictions, and in theory it has the potential for cure. Laboratory and clinical research have established the activity of several drugs whose important characteristics include penetration of the normal brain and activity against nonproliferating cells. Immediate objectives of current chemotherapeutic research are the identification of newer single agents, the formulation of more effective multiple drug protocols, and ultimately the application of chemotherapy in a multimodality approach to the cure of glioblastomas.

Brain Neoplasms↗

In vivo clonogenic tumor cell kinetics following 1,3-bis(2-chloroethyl)-1-nitrosourea brain tumor therapy.

An in vitro colony formation assay was modified to determine the effects of in vivo 1,3-bis(2-chloroethyl)-1-nitrosourea therapy on tumor cell kill and subsequent clonogenic cell kinetics. The measured surviving fraction must be multiplied by the relative total number of tumor cells for each posttreatment interval in order to eliminate inaccuracies caused by dead cell removal in vivo and the lysis of damaged cells by the disaggregation procedure. The assumptions, limitations, and applications of the technique are discussed. 1,3-Bis(2-chloroethyl)-1-nitrosourea doses of 0.25, 0.50, and 1.00 X dose lethal to 10% of animals resulted in approximately at 1-, 2-, and 3-log cell kill, respectively. Significant proliferation of surviving clonogenic cells was observed after a latency period of approximately 2 days, and the rate of tumor regrowth was dose dependent. The cell-doubling times following treatment with 0.25, 0.50, and 1.00 X doses lethal to 10% of animals were 15, 21, and 38 hr, respectively. The interval to complete repopulation of the clonogenic pool corresponds to the observed increase in animal life-span for the 2 larger doses and further validates the assay as a true measure of in vivo chemotherapeutic efficacy.

Animals↗

The kinetics of cultured human glioma cells: autoradiographic studies.

The kinetics of monolayer cell cultures, derived from brain tumors which had been labeled with 3H-thymidine just prior to surgical removal, have been investigated. Analysis of autoradiographs indicates that: 1. the distribution of cell types in primary cultures is similar to that of the viable areas of the parent tumor in vivo; 2. the first week of culture constitutes a lag phase; and 3. vigorous proliferation commences during the second week of culture. Double labeling of the tritiated cultures with 14C-thymidine indicates that the pulse labeling index (PLI) of primary cultures during the second week is lower than that of the parent tumor and that the PLI of the culture increases during the second week. In contrast, we found that long-term established cultures in our laboratory have a high PLI during the first few days after passage, quickly reach a maximum, and then drop precipitously 1 week after passage. These latter variations in PLI correspond to the following growth pattern: 1. exponential growth; 2. a stationary phase due to medium exhaustion; or 3. a a plateau due to overcrowding. There are indications that some cell types, which have the capacity to divide in the parent tumor, lose this ability after transfer to tissue culture.

Autoradiography↗

Diagnosis and surgical treatment of childhood brain tumors.

As the most frequent solid tumor occurring in childhood, brain tumors constitute an important segment of pediatric oncology. Neurologic manifestations may be deceptively mild and easily overlooked or misinterpreted, particularly in the very young, because of the remarkable resiliency of the immature central nervous system and the skull's ability to expand throughout the pre-adolescent years. The majority of childhood tumors produce increased intracranial pressure, usually the consequence of obstructive hydrocephalus. Specific neurologic deficits correspond to the tumor's location. The posterior fossa harbors two-thirds of childhood tumors, and each of the four common tumors in this location produces a characteristic syndrome. Supratentorial tumors occupy the cerebral hemisphere, the suprasellar area, and the pineal gland. Diagnostic studies have reached a state of great sophistication and precise anatomical localization. Surgery, either alone or with adjuvant radiotherapy, cures no more than one-third of all tumors; for the remainder, it has a diagnostic and palliative role. The introduction of operative microsurgery has advanced the art, particularly in the surgical treatment of craniopharyngiomas and pinealomas, but any significant improvement in the treatment of brain tumors as a group seems unlikely to be achieved by surgery alone.

Animals↗

Phase II study of procarbazine, CCNU, and vincristine combination chemotherapy in the treatment of malignant brain tumors.

Forty-eight patients with primary or metastatic malignant tumors of the central nervous system (CNS) were treated with combination chemotherapy, consisting or procarbazine (100 mg/m2 X 14 days), CCNU (75 mg/m2), and vincristine (1.4 mg/m2 X 2, 1 week apart) (PCV) every 4 weeks. Most patients had undergone initial resection of primary tumors, postoperative radiotherapy, and a post irradiation interval of 3 months or more. Other patients harbored unbiopsied, newly-discovered primary or metastatic tumors. All patients were deteriorating neurologically when treatment began. Overall response rate for PCV combination therapy was 44%, no better than results obtained with single agent procarbazine or BCNU, the most effective drugs used alone in previous brain tumor chemotherapy studies.

Brain Neoplasms↗

Polyamine metabolism in a rat brain tumor cell line: its relationship to the growth rate.

To investigate whether the metabolism of the polyamines putrescine, spermidine and spermine is related to cellular growth rate, we have measured the activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase as well as the levels of the polyamines in rat brain tumor cells at various stages of a 7-day in vitro growth period and correlated them with the continuous changes in specific growth rate ([dN[t]/dt]/N[t]). L-Ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase both exhibited their maximal activities at the time of most rapid growth. A high positive correlation between the activities of these enzymes and the specific growth rate of the tumor cells during the entire growth period was demonstrated statistically. The pattern of fluctuation of the spermidine content during the culture cycle was similar to those of the enzyme activities and likewise showed a high positive correlation with the specific growth rate of the tumor cells during the entire growth period. The putrescine content exhibited a low positive correlation, whereas the spermine content exhibited a somewhat higher, but negative correlation with the specific growth rate. The high correlation between the specific growth rate of the tumor cells and the synthesis of the polyamines indicates that these events are primarily associated with processes involved in cell replication. Putrescine and spermidine are thought to participate in the regulation of cellular growth rate; a high content may augment, and a low content may restrain, cellular growth rate.

Adenosylmethionine Decarboxylase↗

Extraglomerular immunoglobulin deposits in human nephritis.

In order to evaluate the incidence of extraglomerular immunoglobulin deposits and to correlate their presence with histopathologic abnormalities, we performed both prospective and retrospective immunofluorescence studies of renal biopsy specimens. Of 200 diagnostic biopsy specimens examined prospectively, 21 had extraglomerular deposits, 19 in association with presumed immunologically-mediated glomerulonephritis. Nine had linear immunoglobulin deposits on tubular basement membrane (antitubular basement membrane antibodies), in one case coexisting with granular deposits, and 13 had granular deposits on tubular basement membrane, in peritubular capillaries and/or arteries, or in tubular cytoplasm (probably immune complexes). Linear deposits on tubular basement membrane were usually associated with antiglomerular basement membrane nephritis or methicillin-associated interstitial nephritis; granular extraflomerular deposits were seen primarily in systemic lupus erythematosus, cryoglobulinemia or membranoproliferative glomerulonephritis.. The incidence of immunoglobulin deposits was high in the three groups of patients examined retrospectively being present in 37 or 47 patients with antiglomerular basement membrane mephritis, 22 or 32 patients with systemic lupus erythematosus of 24 of 130 renal allograft recipients. The contribution of antitubular basement membrane antibodies to renal damage was difficult to assess, although studies in experimental animals attest to their pathogenicity. The occurrence of granular extraglomerular deposits appeared to correlate roughly with the degree of tubulointerstitial injury in the patients with systemic lupus erythematosus.

Autoimmune Diseases↗

Failure of heparin to affect two types of experimental glomerulonephritis in rabbits.

Anticoagulation has been reported to ameliorate antiglomerular basement membrane glomerulonephritis (anti-GBM-GN) while its effect on chronic immune complex glomerulonephritis (IC-GN) as studied in the NZB mouse is unclear. Chronic serum sickness IC-GN was induced in rabbits by injecting bovine serum albumin (BSA) daily. Anti-GBM-GN was induced by i.v. injection of a known amount of heterologous anti-GBM antibody. Heparin was administered beginning at two to six weeks after the first BSA injections or before the administration of anti-GBM antibody, on various schedules from 5000 U every 12 hr to 8000 U every 8 hr. With this dosage the partial thromboplastin time remained greater than 1-1/2 to 2-1/2 times the control at the time of the subsequent heparin injection. Heparinized and nonheparinized groups were matched according to duration of disease, maximum anti-BSA concentrations or anti-GBM antibody dosage--and no significant differences were found in proteinuria; severity of the glomerular histologic lesions; or immunofluorescence patterns of immunoglobulin G (IgG), third component of complement (C3), BSA or fibrinogen-related antigen(s) (FRA). Crescent formation was not prevented. This study shows that heparin in the maximum permissible dosage is ineffective in preventing glomerular FRA deposition or altering the progression of experimental IC-GN or anti-GBM-GN in rabbits.

Animals↗

Ultrastructure of a "pineocytoma".

The commonest pineal gland tumor, the germinoma, is more apparently related to germ cells than to pineal cells. Although ultrastructural studies of this tumor have confirmed this similarity, comparable characterization of a pineocytoma has not been reported, due to its rarity. Here we define the electron microscopic features of a rapidly growing human pineocytoma and compare the tumor cells in the present study with normal mammalian pinealocytes, as well as with cells described in the literature of pineal body pathology. Two cell types populate the tumor: one resembles the neuron, while the second, less frequently encountered, is often indistinguishable from the fibrous astrocyte. Synaptic complexes and dense-cored vesicles were not conspicuous fine-structural elements. Whereas emphatic morphological differences exist between the germinoma and pineocytoma, the similarities in ultrastructure between the pineocytoma cells and adult mammalian pinealocytes are even more striking.

Adult↗

Review of basic concepts of cell kinetics as applied to brain tumors.

The authors review and discuss the basic concepts of cell kinetics as applied to brain tumors. Uncontrolled growth of a neoplasm represents an expanding tumor cell population. Four growth parameters characterize the behavior of a neoplastic population: cell cycle time, growth fraction, tumor doubling time, and cell loss. The concept of provisionally nondividing cells explains the disparity between cell cycle time and tumor doubling time. Human gliomas, like many non-neural solid tumors, contain variable proportions of actively proliferating and nonproliferating tumor cells; this ratio is expressed by the growth fraction. The major kinetic difference between glioblastomas and differentiated astrocytomas resides in their respective growth fractions, in all likelihood an inherent biological characteristic of each tumor. Glioblastoma proliferates at a rapid rate, and only a high rate of cell loss prevents this tumor from doubling its volume in less than 1 week. The selection of drugs and design of drug schedules for treatment of glioblastomas should be made with the knowledge that 60% to 70% of the cells in this tumor are resting (nonproliferating). If experience with other solid tumors is any guide, judicious selection and combined use of drugs according to kinetically sound schedules will produce more effective chemotherapy of brain tumors.

Alkylating Agents↗