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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 397 records · Page 22Linked to original sources
PubMed1983

Pediatric brain stem tumors: radiographic, pathological, and clinical correlations.

A retrospective analysis of the case histories of 21 pediatric patients (ages, 2.5 to 18 years) with a histologically proven diagnosis of brain stem glioma was performed to determine whether patterns of radiographic appearance could be correlated with pathology. Based on the computed tomographic or pneumoencephalographic appearance of the tumor at the time of clinical diagnosis, tumors were divided into four types: central intrinsic (Type I), central exophytic expansion into the 4th ventricle (Type II), eccentric exophytic expansion not involving the 4th ventricle (Type III), and both eccentric and central exophytic expansion (Type IV). Regardless of the radiographic classification, all patients except one, who harbored a well-differentiated astrocytoma in the area of the pons, had an anaplastic astrocytoma (n = 14) or a glioblastoma multiforme (n = 6). There was no appreciable difference in survival between patients with either tumor histology. The presence of a cystic component did not affect survival. High resolution computed tomographic scans, with reconstructed images of the posterior fossa, can predict the presence and location of brain stem tumors and associated cysts and probably the histological nature of the tumor.

Adolescent↗
PubMed1983

Stem cell studies of human malignant brain tumors. Part 1: Development of the stem cell assay and its potential.

A stem cell assay for human malignant gliomas has been developed. Cells obtained from tumor biopsies grew into colonies composed of malignant glial cells, as documented by histochemical, immunohistochemical, and immunobiological techniques. Studies suggest that the disaggregated cells are representative of the cells within the solid tumor. Clonogenic cells were obtained from 48 tumors and analyzed for their in vitro sensitivity to graded doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The in vitro anti-tumor activity of BCNU at clinically achievable doses was compared to clinical response to the agent based on changes in computerized tomographic scan, radionuclide brain scan, and neurological examinations. Twenty-two patients received nitrosoureas before or after tumor specimen analysis, and were eligible for in vitro-in situ correlations. Clinical tumor sensitivity to nitrosoureas was predicted by culture results in 42% of all evaluable patients, and clinical resistance was predicted in 100%. The capability of the assay can be appreciated best for the 13 patients not treated with BCNU prior to culture; the in vitro prediction of clinical sensitivity and resistance was 71% and 100%, respectively. Preliminary findings show that clinical tumor resistance to BCNU may result from "intrinsic" cell resistance in some patients and from inadequate delivery of drug to tumor cells in other cases. The potential utility of this method to study the reason(s) for tumor cell resistance to drugs, to screen new chemotherapeutic agents, to individualize patient treatment, and to investigate tumor biology is discussed.

Biological Assay↗
PubMed1983

Improved treatment of a brain-tumor model. Part 1: Advantages of single- over multiple-dose BCNU schedules.

Clonogenic cell and animal survival studies were used to determine the most effective BCNU therapy schedule in the 9L rat brain-tumor model. Survival of tumor cells following a single LD10 dose of BCNU (13.3 mg/kg intraperitoneally) was compared to cell survival after one to four daily 0.5 X LD10 doses. The posttreatment kinetics of surviving clonogenic cells were investigated at various times after BCNU was given in single doses of 0.25 to 1 X LD10 and in two daily doses of 0.5 X LD10. The cell kill was greater, time to reinitiation of cell growth was later, posttreatment rate of clonogenic cell proliferation was slower, and the interval to total repopulation of the clonogenic cell pool was longer with a single LD10 dose as compared to the multiple-dose schedules. Animal survival studies confirmed that a single LD10 dose of BCNU was at least as effective as a cumulative level of up to 1 1/2 times that amount when treatment was administered in smaller doses, regardless of the fractionation schedule. Clinical experience with patients harboring malignant brain tumors has shown that a single BCNU dose of 185 to 200 mg/sq m is tolerated well. Results of these animal experiments suggest that this therapy should have anti-tumor activity at least equivalent to the more commonly employed schedule of 80 mg/sq m/day given for 3 days. Although direct comparison of treatment efficacy using the two schedules is not possible, no adverse clinical effects have been observed with the recently adopted single-dose schedule. Furthermore, the duration of patient hospitalization for chemotherapy has decreased.

Animals↗
PubMed1983

Improved treatment of a brain-tumor model. Part 2: Sequential therapy with BCNU and 5-fluorouracil.

A combination chemotherapy regimen for brain tumors was developed, based on investigations of the survival of animals harboring the intracerebral 9L rat brain-tumor model and on analyses of their clonogenic tumor cells. Fischer 344 rats harboring 9L brain tumors were treated with 2-day courses of 5-fluorouracil (5-FU), in order to expose all cycling tumor cells to the drug during DNA synthesis and achieve maximum anti-tumor activity for this cell-cycle-specific anti-metabolite. Although a 74% cell kill was obtained for a total dose of 45 mg/kg or greater, animal life span was not increased over that of untreated tumor-bearing controls. However, when 5-FU (48 to 96 mg/kg total dose over 2 days) was administered after a single LD10 dose of BCNU (13.3 mg/kg), additive cell kill was suggested. In three large series, long-term animal survivors and occasional tumor cures were observed with this drug combination, a result never observed following BCNU alone. Schedule dependency was not apparent. A previously published protocol for treating recurrent malignant gliomas with sequential courses of BCNU and 5-FU was partially planned based upon these initial observations. Anti-tumor activity with the combination of drugs was superior to therapy with BCNU alone. Both animal and human studies confirm that, contrary to presently accepted oncological tenets, a chemotherapeutic agent that kills significant numbers of tumor cells but is clinically ineffective when given alone might, nevertheless, be useful in combination therapy regimens.

Animals↗
PubMed1983

Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases.

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate to the individual case in patients with hypercortisolism. The present series of 100 cases is derived from 104 patients with the diagnosis of Cushing's disease who underwent transsphenoidal pituitary exploration between 1974 and 1981. Excluding four patients in whom the pituitary gland was not exposed because of intraoperative technical difficulties, an overall cure rate of 78% was achieved. Among 71 patients with tumors confined to the sella turcica, 87% had correction of their hypercortisolism, 11% represented therapeutic failures, and one patient had tumor recurrence. In contrast, among 25 patients with extrasellar extension, correction of hypercortisolism was achieved in only 48%, 40% failed to respond, and 12% of the patients had recurrence. Four patients who failed to respond to total hypophysectomy have ectopic sources of adenocorticotropic hormone. The results indicate that transsphenoidal microsurgical exploration for a basophilic adenoma is the procedure of choice in adults and children with Cushing's disease. The diagnostic and surgical approach to these tumors, as well as pitfalls in the transsphenoidal treatment of Cushing's disease, are discussed.

Adenoma↗
PubMed1983

Primary cerebral neuroblastoma. Long-term follow-up review and therapeutic guidelines.

Primary cerebral neuroblastoma is a distinct pathological and clinical entity that differs from other primitive neuroectodermal tumors. To characterize the clinical course of this lesion, the authors performed a retrospective analysis in 11 patients who ranged in age from 17 months to 26 years. The tumor had no predilection for either sex. Signs and symptoms were mostly those associated with increased intracranial pressure. The lesions commonly involved the parietal and occipital lobes. Computerized tomography scans of nine patients showed five solid and four cystic lesions; calcifications were found more commonly in the solid lesions. Contrast enhancement was seen in all tumors, yet angiograms typically showed an avascular mass. Total removal of tumor was possible in only two patients, both with cystic tumors. The remaining nine underwent subtotal resection of a solid lesion (in five) or a cystic lesion (in four). All 11 patients underwent postoperative irradiation that included the spinal axis in two cases; only one received adjuvant chemotherapy (solid tumor). Four patients, all with solid tumors that initially were subtotally resected, had evidence of tumor recurrence. The only patient with a subtotally resected solid lesion who did not have recurrence received adjuvant chemotherapy. The six patients who had cystic lesions are free of recurrent tumor at 26 to 109 months after surgery. Based on follow-up analysis of the 11 patients, recommendations are proposed for the treatment of primary cerebral neuroblastomas.

Adolescent↗
PubMed1983

Transsphenoidal surgery of intrasellar germinomas. Report of two cases.

Two patients with diabetes insipidus, hypopituitarism, and an enlarged sella turcica underwent a transsphenoidal operation for the treatment of intrasellar germinomas. Successful transsphenoidal treatment of such neoplasms has not been reported previously. The cases indicate that the diagnostic possibility of intrasellar germinoma should be considered in young patients with combined diabetes insipidus and hypopituitarism, even when the sella is markedly expanded.

Adult↗
PubMed1983

Participation of auto-anti-idiotypes in immune complex glomerulonephritis in rabbits.

We report the presence of auto-anti-Id antibodies in the glomerular immune deposits of a rabbit with chronic serum sickness induced by daily i.v. injections of bovine serum albumin. Auto-anti-Id antibodies were also documented in the serum of the same animal during the phase of chronic serum sickness in which immune complex glomerulonephritis develops. These results suggest that auto-anti-Id may normally participate in pathologic reactions and may be one of the mechanisms of potentiation and/or progression of immunopathologic lesions.

Animals↗
PubMed1983

Characterization of anti-tubular basement membrane antibodies in rats.

Autoimmune tubulointerstitial nephritis was induced in Brown-Norway (BN) rats by immunization with bovine (Bov) tubular basement membrane (TBM) in complete Freund's adjuvant. Serum antibodies thus produced reacted to a greater extent with Bov than BN TBM antigens by indirect immunofluorescence and by radioimmunoassay with particulate (P) and collagenase-solubilized (CS) TBM. The quantities of antibodies reactive with CS TBM correlated with the intensity of tubulointerstitial pathologic changes. Antibodies eluted from kidneys reactive with BN TBM by indirect immunofluorescence were 508 times more concentrated in the kidney than in the serum, compared with 15 times for Bov TBM-reactive antibodies. The reactivity of eluted antibodies to P BN TBM was inhibited by 70% after absorption with BN CS TBM. A major CS TBM antigen of 42,000 m.w. was identified by polyacrylamide gel electrophoresis. This antigen was present in both Bov and BN TBM, and may be important in triggering autoantibody formation in this model. Lewis rats immunized under the same conditions produced antibodies reactive with BN TBM by immunofluorescence but failed to develop immune deposits in TBM of their own kidneys. Analysis of serum anti-TBM antibodies in Lewis rats revealed a selective lack of reactivity with either homologous or autologous CS TBM. These results suggest that the ability to make an immune response to one or more elements of CS TBM plays a major role in the development of autoimmune tubulointerstitial nephritis in rats.

Animals↗
PubMed1983

Increased respiratory burst in myeloperoxidase-deficient monocytes.

Studies of the respiratory burst in myeloperoxidase (MPO) deficient monocytes were undertaken to assess the physiologic consequence of the absence of MPO in these cells. As previously demonstrated with neutrophils, MPO-deficient monocytes had a greater initial rate, duration, and total superoxide production in response to phagocytosis of zymosan than did normal monocytes. Introduction of purified eosinophil peroxidase (EPO) into the phagosome by binding the enzyme to the surface of the zymosan particles changed the hypermetabolic characteristics of superoxide production in MPO-deficient cells to more closely resemble normal cells, but had no effect on superoxide generation by the normal monocytes. Further, inactivation of the bound EPO before ingestion restored the supranormal respiratory burst by the MPO-deficient cells. Iodination by MPO-deficient monocytes was significantly depressed as compared to normal monocytes following the ingestion of zymosan (1.9 versus 10.1 nmole I-/10(7) monocytes/30 min; p less than 0.01). In contrast, iodination was markedly augmented in MPO-deficient cells compared to normal cells after ingestion of zymosan coated with EPO (208 versus 70 nmole I-/10(7) monocytes/30 min; p less than 0.005), presumably reflecting the greater amounts of hydrogen peroxide formed by MPO-deficient cells. There were no differences in the levels of endogenous scavengers of reactive oxygen products (catalase, superoxide dismutase, glutathione peroxidase and reductase, and total glutathione) in MPO-deficient and normal monocytes that would account for the enhanced respiratory burst of MPO-deficient cells. These findings support a role for peroxidase in the termination of the respiratory burst of monocytes.

Humans↗
PubMed1983

Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma.

Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.

Adolescent↗
PubMed1983

Anti-idiotype as a probe in the analysis of autoimmune tubulointerstitial nephritis in the Brown Norway rat.

Rabbit antibodies specific for the idiotype (Id) of autoantibodies to tubular basement membrane (TBM) eluted from kidneys of Brown Norway rats with tubulointerstitial nephritis (TIN) were used to analyze the immune response to TBM antigens at the humoral and cellular levels. These antibodies appeared to recognize Id determinants associated with the antigen combining site on the anti-TBM Id as well as on splenic lymphocytes. However, efforts to detect Id-positive cells in the interstitial infiltrates of kidneys with TIN failed. In contrast, in vivo injection of anti-Id serum before immunization with TBM resulted in a) significant selective suppression of antibodies to the autologous collagenase-solubilized TBM moiety but not to antigenic determinants of the intact TBM nor to those of heterologous TBM, and b) a corresponding decrease of TIN. These results suggest that anti-Id antibodies of this type can be useful as a probe for further dissecting the pathogenetic mechanisms underlying these complex autoimmune responses.

Animals↗
PubMed1983

Apparent meningococcemia: clinical features of disease due to Haemophilus influenzae and Neisseria meningitidis.

To determine the etiology of apparent meningococcemia, all cases of sepsis with coagulopathy, purpura, and/or adrenal hemorrhage (Waterhouse-Friderichsen syndrome) with and without shock occurring over a 12-year period were reviewed. A total of 42 cases were identified; 30 cases were caused by Neisseria meningitidis and 12 cases were caused by Haemophilus influenzae. Compared with patients with disease caused by H influenzae, patients with meningococcal disease were older, more often male, more often contracted the disease in winter-spring, and had a longer duration of antecedent symptoms; however, none of these differences was statistically significant. All patients were febrile (greater than 38 degrees C) and appeared toxic. Similar proportions in each group had shock and disseminated intravascular coagulopathy at the time of admission. Ten of 12 patients with H influenzae infection compared with 15/30 (P less than .05) with meningococcal infection were lethargic or comatose at the time of admission. Nine of 12 patients with H influenzae infection died compared with 5/30 with meningococcal disease (P less than .005); the mean time from onset of symptoms to death with H influenzae infection (20.7 +/- 11.4 [SE] hours) was significantly shorter (P less than .05) than with meningococcal infection (120 +/- 74.4 hours). Children with clinical signs of sepsis and with purpura, petechiae, or coagulopathy may have N meningitidis or H influenzae as etiologic agents. Initial antibiotic therapy should be directed against these pathogens.

Age Factors↗
PubMed1982

Clonogenicity of multiple populations of human glioma cells in vitro sorted by DNA content.

Malignant human gliomas have a highly variable distribution of cell nuclei, consisting of diploid and/or other populations in terms of nuclear DNA content. In order to study in vitro clonogenicity of each population, dissociated or cultured human glioma cells were stained with 20 microM/ml of Hoechst 33342 dye (which stains viable DNA with minimal cell kill), and were sorted sterile into separate populations, based on specific nuclear DNA content, for clonogenicity assay. The colony-forming efficiency (CFE) of tumor cells plated immediately after disaggregation of the biopsy specimens ranged from 0.0044 to 0.149%, and the CFEs increased dramatically with successive passages (to 5 to 40%). The CFEs of the individual populations sorted according to DNA content were similar within individual tumors. These results suggest not only that malignant gliomas are composed of multiple populations in terms of DNA content, but also that each of these populations contain clonogenic cells. The morphologic structure of cells within and among colonies did not appear to relate to DNA content.

Adult↗
PubMed1982

Age-related chemosensitivity of stem cells from human malignant brain tumours.

After radiation therapy and chemotherapy for malignant glioma, patients aged 50 or under survive longer than patients over 50. Data from Brain Tumor Study Group trials show that, without treatment, these age groups have similar survival; therefore unperturbed tumour growth does not account for the difference. Sixteen consecutive patients with malignant glioma were studied, half of whom were less than or equal to 50 years of age; none had been treated before initial surgery, and all were subsequently treated with radiation and chemotherapeutic agents (in all but two patients, with nitrosoureas). Median survival of those aged greater than 50 was less than or equal to 50 years was 54 + weeks whereas that of those aged greater than 50 was 37 weeks. The longer survival for younger patients could not be attributed to tumour type, size, or location, pretreatment Karnofsky status, or mode of treatment. In-vitro sensitivity testing of clonogenic cells obtained from biopsy specimens showed that tumour cells from seven of eight patients aged less than or equal to 50 years were sensitive to 1,3-bis (2-chloroethyl)-1-nitrosourea (greater than 40% cell kill at clinically achievable concentrations) compared with only one patient with sensitive cells out of eight older patients. Patient age was inversely correlated with in-vitro cell kill, and patients with sensitive cells were significantly younger than those with resistant cells. Therefore influence of age on survival after treatment of malignant gliomas is probably due to inherent differences in the sensitivity of clonogenic cells to radiation and/or chemotherapeutic agents.

Age Factors↗
PubMed1982

Polyamine levels in CSF from patients with pituitary tumors or nonneoplastic pituitary disease.

Cerebrospinal fluid polyamine determinations were performed in 21 patients harboring pituitary tumors and six patients with nonneoplastic pituitary disease. Although CSF putrescine levels were significantly elevated in some patients harboring tumors, other patients showed no elevation. Polyamine levels did not correlate with tumor size, as assessed by the presence or absence of suprasellar extension. Data on patients harboring nonneoplastic pituitary disease were variable. Compared with other findings from this laboratory on the use of polyamine levels for the diagnosis and management of other brain tumors, these findings suggest that CSF polyamine levels will not have a significant diagnostic role in the treatment of patients suspected to have pituitary disease.

Acromegaly↗