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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 541 records · Page 30Linked to original sources

Etiology and pathogenesis of a spontaneous lupus-like syndrome in mice.

Two recently described murine strains, MRL/1 and BXSB, develop a lupus-like syndrome resulting in a 50% mortality by the fifth month of age. Comparison of the immunopathological and virological characteristics of these mice with those of the NZB/NZW F1 mouse reveals several pathogenetic common denominators but no obvious common etiologic factors. In all three kinds of mice, the lupus-like syndrome consists of a fatal immune complex type glomerulonephritis and complete or near complete thymic cortical atrophy plus lymphoid hyperplasia that varies in degree among the three kinds of mice. The nephritic glomeruli contain a concentration of antinuclear antibodies plus varying amounts of stainable gp70. This syndrome is consistently correlated with abnormally elevated serum IgG levels, antinuclear antibodies, anti ds- and ssDNA antibodies, and circulating immune complexes, as well as depressed serum hemolytic complement. Features that differ among the three kinds of mice include: H2 type, anti-lymphocyte antibody, cryoglobulins, T-B cell ratios, sex incidence of disease, vasculitis, and oncornaviral flora. The serum gp70 levels in the three mice also differ considerably, but all are within the range of gp70 levels found in some immunologically normal strains.

Animals↗

Correlations between experimental chemotherapy in the murine glioma and effectiveness of clinical therapy regimens.

Intracerebral murine glioma 26 was used as a model system for evaluating two-drug combinations of antitumor agents, BCNU was combined with either procarbazine, dianhydrogalactitol, or ellipticine. CCNU was combined with procarbazine. All combinations were more active than the individual drugs alone. The most potent combinations achieved 85-100% tumor "cure" at 120 days, with combined toxicity indices of 0.25 (CCNU-procarbazine) to 1.30 (NCNU-dianhydrogalactitol). The experimental data were compared to clinical studies with CCNU, procarbazine, and vincristine, and BCNU-procarbazine.

Animals↗

Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome.

Four patients with rapidly progressive glomerulonephritis and pulmonary hemorrhage (Goodpasture's syndrome) induced by circulating anti-glomerular basement membrane (GBM) antibodies were treated with immunosuppressive agents and varying amounts of plasma exchange. All four patients showed progressive decreases in circulating anti-GBM antibody during therapy. Two patients with established renal failure before therapy showed no improvement in renal function but had a remission from pulmonary disease. In two other patients, renal failure developed early in the course of therapy and required maintenance hemodialysis. Later, their renal function improved coincident with a decrease in circulating anti-GBM antibody. Aggressive measures to reduce the levels of circulating anti-GBM antibody may have a salutory effect on the clinical course of the disease, particularly when undertaken early.

Adolescent↗

Clinical significance of the 1-hour biopsy in renal transplantation.

Biopsy specimens were obtained from 43 transplanted kidneys at the time of excision from the donor but prior to revascularization, and 1 hr after revascularization. Two independent laboratories evaluated specimens by immunofluorescent techniques for the presence of IgM, IgA, IgG, C'3, and fibrin. Results from the two laboratories examined for reproducibility and immunological specificity, and correlated with clinical course. Results show that immunoglobulin deposition seen in the 1-hr renal biopsy specimens is of little significance, because: (1) immunoglobulin deposition was difficult to quantitate reliably, (2) the presence of immunoglobulins did not correlate with clinical course, and (3) the majority of immunoglobulin deposition detected was not immunologically specific, since it was most often either present prior to vascularization or disappeared with vascularization.

Biopsy↗

The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion.

Recent studies from this laboratory have revealed that single nephron filtration rate (sngfr) decreases significantly within 1 h of the administration of large doses of complement-fixing antiglomerular basement membrane antibody (AGBM Ab) in plasma-expanded Munich-Wistar rats. This reduction in sngfr was due to decreases in nephron plasma flow (rf) and the glomerular permeability coefficient (LpA) utilizing direct evaluation of all pertinent pressures, flows, and permeabilities. With identical micropuncture techniques, we have determined (a) the respective influences of rpf and LpA upon sngfr by examining the effects of differing doses of AGBM Ab, and (b) the specific effect of complement fixation upon the reduction in sngfr. In normal rats, low dose (1.4 microgram/g body wt) AGBM Ab decreased sngfr from 57.9 +/- 3.4 to 50.8+/- 3.9 nl/min per g kidney wt (kw) (P less than 0.001), and this was due to a 10% reduction in rpf and a decrease in LpA FROM 0.069 +/- 0.014 in control to 0.041 +/- 0.007 nl/s per g kw per mm Hg (P less than 0.02). At the high dose (2.3 microgram/g body wt), sngfr fell dramatically from 58.4 +/- 4.0 to 7.6 +/- 3.8 nl/min per g kw (P less than 0.001), and this effect upon filtration was the result of an 86% reduction in rpf and a decrease in LpA from 0.092 +/- 0.020 to 0.007 +/- 0.004 nl/s per g kw mm Hg (P less than 0.001). Therefore, at lower doses sngfr fell primarily as a result of a 40% reduction in LpA and a 10% decrease in rpf; however, at the high dose massive reductions in both rps and LpA led to the large decrease in sngfr. In complement-depleted rats, receiving identical doses, low-dose AGBM Ab no longer reduced the sngfr, but a reduction in LpA persisted (other factors compensating to maintain sngfr). At the high dose, complement depletion ameliorated the reduction in sngfr (55.1 +/- 2.4 to 37.2 +/- 3.4 nl/min per g kw mm Hg) by nearly eliminating the vasoconstriction but only partially diminished the reduction in LpA (0.097 +/- 0.020 to 0.032 +/- 0.004 nl/s per g kw mm Hg, P less than 0.05). Complement depletion prevented the migration of polymorphonuclear leukocytes (present in larger numbers after the high dose of AGBM Ab) into the capillary and eliminated vasoconstriction. Complement depletion resulted in a lesser effect of high-dose AGBM Ab upon LpA than in normal rats, and this is likely due to lesser polymorphonuclear leukocyte effects upon capillary surface area. The persistent reduction in LpA observed in complement-depleted rats correlated with separation of the endothelial cell from the glomerular basement membrane after AGBM Ab, AGBM Ab diminished glomerular ultrafiltration by decreasing LpA and altering the endothelial surface of the glomerular membrane, and this effect is not totally dependent upon the fixation of complement.

Animals↗

Application of the solid phase C1q and Raji cell radioimmune assays for the detection of circulating immune complexes in glomerulonephritis.

The C1q solid phase and Raji cell radioimmune assays were used to determine the frequency of detectable circulating immune complexes in patients with glomerulonephritis. In this study, 46% of 56 patients with glomerulonephritis had evidence of circulating immune complexes. More important, circulating immune complexes were associated with some, but not other, types of glomerulonephritis. Thus, immune complexes were detected in lupus glomerulonephritis (9/9 patients), rapidly progressive glomerulonephritis (5/6 patients), and acute nephritis (5/6 patients), but not in IgA-IgG glomerulonephritis (0/7 patients), or membranous glomerulonephritis (0/8 patients). The Raji cell radioimmune assay and the C1q solid phase radioimmune assay showed concordance of 79% in the detection of circulating immune complexes. Serial determinations, in general, showed either persistence of a negative or positive result of conversion of positive to negative.

Acute Disease↗

Transsphenoidal microsurgical removal of 250 pituitary adenomas.

In a series of 250 pituitary adenomas, 72 (28.8%) were nonsecreting and 178 (71.2%) produced a hypersecretion syndrome: human growth hormone (83), prolactin (59), and adrenocorticotropic hormone (ACTH) (36). One-fifth had received prior treatment and one-fourth had visual impairment. The technical aspects of the transsphenoidal procedure are given with separate consideration of microadenomas and larger tumors. The results are provided in summary form with emphasis on the favorable outcome following removal of microadenomas. There was one postoperative death, and the complications observed after operation are presented.

Adenoma↗

Coexisting pituitary adenomas and partially empty sellas.

seventeen cases of coexisting secreting pituitary adenomas and partially empty sellas are presented. The location of the cisternal invagination into the sella was not helpful in predicting the location of the tumor. In patients with endocrine indication of a secreting pituitary neoplasm, the finding of a partially empty sella should not contradict the diagnosis.

Adenoma↗

The distribution of nuclear DNA from human brain-tumor cells.

Flow cytometry (FCM) is a technique that measures the quantity of DNA contained in individual nuclei and records a frequency distribution of the DNA content per nucleus in the sampled cell population. Nuclei from a variety of human brain-tumor types were isolated by means of tissue grinding, purified by centrifugation through 40% sucrose (15 minutes at 4000 rpm), fixed with 10% formalin, stained with acriflavin-Feulgen, and analyzed by FCM. Profiles of DNA distribution in histologically benign tumors, such as meningiomas, pituitary adenomas, neuroblastomas, and low-grade astrocytomas, revealed a large diploid population (2C) with a few nuclei in DNA synthesis, as well as a small premitotic population (G2 cells) that contains a 4C DNA complement. In contrast, malignant gliomas, including glioblastomas, consist of more cells in DNA synthesis; these tumor cells show a highly variable distribution of ploidy consisting not only of diploid, and/or aneuploid, but also of triploid, tetraploid, and possibly octaploid populations. Also, a large variability between different regions of each tumor was always observed. In contrast, metastatic brain tumors, despite the fact that they contain a considerable number of cells undergoing DNA synthesis, demonstrate little variability within each individual tumor. The ability to rapidly characterize the cell populations of human brain tumors with FCM may enhance the effectiveness of their clinical management.

Astrocytoma↗

Pituitary adenomas in childhood and adolescence.

This report describes a group of 25 children and adolescents with biopsy-proven pituitary adenomas. They were found in 33% of patients encountered in our recent study of 74 parasellar tumor detected in patients under 20 years old. Earlier detection accounts for this apparent increase in frequency. This interpretation is supported by the rarity of signs of intracranial hypertension at presentation, as well as decreased incidence and severity of visual failure. More than 70% of patients have evidence of pituitary hypersecretion at presentation. Increased awareness of these endocrinological signs as well as improved hormonal assays facilitate both diagnosis and management. Hypopituitarism is rare; the important exception is suppression of gonadotrophic function that is known to occur early in the natural history of intrasellar pituitary adenomas. The low incidence of suprasellar and extrasellar extension is documented by both radiographic and operative findings. Transsphenoidal resection was employed in 92% of patients, with an estimated total resection in 73% of cases. Follow-up studies show a high quality of survival; no patient has severe neurological deficit and less than half of them require replacement therapy. The recurrence rate is 8%. Our findings do not support a previous report that pituitary adenomas in this age group are frequently extrasellar and invasive.

Adenoma↗

Postoperative epidural hematoma as a complication of anterior cervical discectomy. Report of three cases.

In three cases, anterior cervical discectomy was complicated by acute postoperative paraplegia secondary to epidural hematomas at the operative sites. Prompt evacuation of the hematomas was followed by recovery in each instance. The source of bleeding was an arterial arcade that may be encountered during the course of removing the posterior longitudinal ligament. As a result of this experience, the authors suggest steps to be taken to avoid this uncommon complication.

Cervical Vertebrae↗

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Adolescent↗

Management of recurrent CSF rhinorrhea of the middle and posterior fossa.

The authors review 39 patients with cerebrospinal fluid (CSF) leaks originating from the middle or posterior fossa. They evaluate the usefulness of preoperative investigative procedures, including cisternal radionuclide scanning and the deliberate increase of intracranial pressure. The results in this series emphasize the important role that abnormal CSF dynamics play in the recurrence of problematic cases of rhinorrhea or otorrhea. The following guidelines are recommended by the authors on the basis of their recent experience: 1) if hydrocephalus is present, if the cisternogram is abnormal, or if the CSF leak is intermittent and slight, the initial treatment should be insertion of a lumboperitoneal shunt; 2) if the leak is localized in the sellar or parasellar area, a transsphenoidal approach to obliterate the leak is advised; 3) if the CSF leak originates through a dural opening into the middle ear, an intracranial repair is indicated.

Adolescent↗

Chemotherapy of recurrent medulloblastoma with combined procarbazine, CCNU, and vincristine.

Seventeen patients with recurrent medulloblastoma were treated with a combination of three drugs: procarbazine, CCNU, and vincristine (PCV). Tumor recurrence was documented at varying periods following surgery and radiotherapy. Among 16 evaluable patients, ten showed a response to PCV on the basis of subjective neurological improvement and a decrease in tumor size by radiological criteria. Five patients were designated as having stable disease on the basis of no change in neurological status and tumor size. One patient showed uninterrupted progression of disease. The median time to progression for all patients was 45 weeks. Significnat myelotoxicity, exacerbated by prior spinal irradiation, compromised therapy. After an initial response, it was often necessary to reduce the higher doses of CCNU and procarbazine that caused concomitant bone-marrow toxicity; as a consequence of the lowered doses, tumor progression was then frequently observed. The authors conclude that PCV is an effective form of palliative therapy for recurrent medulloblastoma.

Adolescent↗

Intrasellar cysticercosis presenting as a pituitary tumor: successful transsphenoidal cystectomy with preservation of pituitary function.

A 42-year-old woman from El Salvador presented with arthralgias and headache. She was found to have an enlarged sella with an intrasellar mass. Transsphenoidal exploration of the sella revealed a cysticercus. The cyst was removed and normal pituitary function was retained. Review of the literature showed three previously reported confirmed or suspected cases of intrasellar cysticercosis: in two, the diagnosis was made at autopsy; in the third, a patient with hypopituitarism, intrasellar cysticercosis was suspected in life but never confirmed histologically. Transsphenoidal cystectomy successfully treated our patient without compromise of pituitary function and is recommended for similar cases.

Adult↗