Search PubMed⌕ Search

Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 415 records · Page 23Linked to original sources

Glomerular antigens in glomerulonephritis.

Ideas on the immunopathogenesis of glomerulonephritis are evolving to embrace a concept of a dynamic and constantly fluctuating involvement of immune reactants in the production of glomerular inflammation. The glomerulus should be regarded as a template around which the antibody-induced inflammatory events that constitute glomerulonephritis are initiated. Such lesions may be produced by direct antibody attack on glomerular antigens of either intrinsic structural or "planted" type, as discussed in this review, or by the deposition of circulating soluble immune complexes containing extraglomerular antigens. These mechanisms are not mutually exclusive and both may play a role in some situations. Intrinsic glomerular antigens are being increasingly better defined as to site, structure, function, and experimental animal models of spontaneous and induced glomerular injury resulting from direct antibody binding to nonclassic GBM capillary wall antigens are available for study. Similar nonclassic GBM antigens are likely to be found of importance in man. Anti-GBM antibody-induced glomerulonephritis continues to be the best understood example of direct attack on the glomerulus by antibody, and its nephritogenic noncollagenous GBM antigenic constituents are being characterized. The incorporation of extraneous substances as "planted" antigens within glomerular structures is now recognized in experimental animal models, and there is suggestive evidence to support the concept in man. Emphasis needs to be placed on the continuing interplay of free antibody and antigen with deposited reactants which, together with complement components, modulate the quality and quantity of the glomerular immune deposits.

Animals↗

Cellular uptake and intracellular activity of antibiotics against Haemophilus influenzae type b.

The ability of penicillins and chloramphenicol to enter human polymorphonuclear leukocytes (PMNLs) and their antibacterial activity against intracellular Haemophilus influenzae type b were studied. Penicillin was excluded whereas chloramphenicol was concentrated in PMNLs; chloramphenicol uptake was not dependent on PMNL energy and was not competitively inhibited by unlabeled drug. PMNLs that had phagocytized opsonized H. influenzae type b were examined after incubation for 24 hr. In the absences of antibiotics, intact intracellular H. influenzae type b organisms were observed in PMNLs by electron microscopy. These PMNLs contained 10(4.5) colony-forming units (cfu) of H. influenzae type b. Addition of penicillin or ampicillin at four, 20, or 40 times the minimal bactericidal concentration (MBC) decreased this density from 10(4.5) to 10(3.5) cfu. In contrast, addition of chloramphenicol at four times the MBC reduced the density to approximately 100 cfu; at 10 times the MBC it reduced the density to approximately 10 cfu. Thus, lipid-soluble antibiotics such as chloramphenicol are concentrated and are bioactive within PMNLs. Such antibiotics may have a significant advantage at the cellular level.

Adult↗

Piperacillin pharmacokinetics in pediatric patients.

The pharmacokinetics of piperacillin were studied in 15 pediatric patients (age range, 3.3 to 14.3 years). Piperacillin was administered in a dosage of 1.5 +/- 0.4 g/m2 (mean +/- standard deviation) every 4 to 6 h. Peak serum concentrations ranged from 69 to 354 micrograms/ml. The mean elimination half-life was 37.0 +/- 13.3 min, which is shorter than that observed in most adults with normal renal function. The mean elimination half-life in three patients with renal impairment was 60.1 +/- 12.4 min, and the mean ratio of renal clearance to total clearance was 0.57. These results suggest a significant nonrenal elimination of piperacillin. Based on these data, a dosage of 1.5 g/m2 given as a 30-min infusion every 4 h is suggested for children with normal renal function. For patients with renal impairment, the daily dosage could be calculated as follows: corrected dose = normal dose x (0.35 + [0.65 x (ClCr/0.06)]), where ClCr is the creatinine clearance expressed as liters per minute per square meter.

Adolescent↗

Plasma exchange in Goodpasture's syndrome.

The clinical course and levels of anti-glomerular basement membrane (GBM) antibody were compared in 20 patients with Goodpasture's syndrome treated with plasma exchange and immunosuppression (8 patients), immunosuppression alone (4 patients) or no specific therapy (8 patients). There was a more rapid fall in the level of anti-GBM antibody and pulmonary hemorrhage was less protracted in the 8 patients treated with plasma exchange and immunosuppression. In this group, 1 patient who presented with severe renal failure showed a marked improvement of renal function and there was no progression of disease in the 4 with milder renal involvement. 2 of the 4 patients treated with immunosuppression alone, and only 2 of the 8 patients who received no specific therapy, maintained normal renal function. In the group which received no specific therapy, 1 of the 6 patients who progressed to renal failure had mild renal involvement initially. There was a significant correlation between the level of anti-GBM antibody and the severity of the morphological changes seen at renal biopsy but not between the level of anti-GBM antibody and the severity of lung hemorrhage. The course and outcome of the disease in those patients not treated, or treated with immunosuppression alone, was better than that described in early reports of this disease, while those patients with plasma exchange and immunosuppression fared even better. An adequately stratified controlled trial of immunosuppression and plasma exchange versus immunosuppression alone is in order.

Adolescent↗

Role for endogenous and acquired peroxidase in the toxoplasmacidal activity of murine and human mononuclear phagocytes.

Oxygen products generated by the respiratory burst of mononuclear phagocytes are microbicidal to intracellular pathogens including Toxoplasma gondii. The toxicity of one of these products, H(2)O(2), is markedly amplified by the granule peroxidase of circulating phagocytes in the presence of a halide. Eosinophil peroxidase (EPO) binds firmly to the surface of T. gondii and such organisms remain viable as determined by vital staining, uptake of 2-deoxyglucose, and survival and replication in human fibroblasts. They are, however, rapidly killed by the addition of H(2)O(2) and iodide under conditions in which control organisms are unaffected. We have used EPO bound to T. gondii to explore the role of peroxidase in the toxoplasmacidal activity of mononuclear phagocytes. Resident mouse peritoneal macrophages lack a granule peroxidase and have a weak respiratory burst; toxoplasma survive and replicate within these cells. However, these cells acquire significant toxoplasmacidal activity, as assessed microscopically and by the inhibition of uracil uptake, when organisms are coated with EPO before ingestion, an effect which is decreased by the hemeprotein inhibitors, aminotriazole and azide. EPO on the surface of Toxoplasma does not increase their ingestion by macrophages or the associated respiratory burst. Monocytes from patients with hereditary myeloperoxidase deficiency have a significant toxoplasmacidal defect that is abolished when EPO-coated organisms are used. In contrast, the toxoplasmacidal defect of monocytes from chronic granulomatous disease patients is unaffected by surface-bound EPO. In these studies, replication of surviving intracellular organisms varied inversely with the magnitude of the respiratory burst: replication was greatest in fibroblasts, slightly less in resident macrophages, and least in monocytes; it was significantly greater in chronic granulomotous disease than in normal or myeloperoxidase-deficient monocytes. These studies support a role for oxygen products and endogenous peroxidase in the optimal killing of T. gondii by monocytes and demonstrate that peroxidase-negative phagocytes can utilize peroxidase on the surface of ingested organisms to augment microbicidal activity.

Animals↗

Cushing's syndrome: problems in management.

CS comprises a group of disorders characterized by hypercortisolism. The variety of causes--pituitary-dependent CS (CD), adrenal tumor, and the ectopic ACTH syndrome--necessitates a variety of therapies--surgical, radiotherapeutic, and medical. Once a specific diagnosis is made, specific therapy can be instituted. Although some controversy persists regarding treatment, particularly that of CD, for most patients it is straightforward. However, in our experience with more than 60 patients, therapeutic dilemmas can arise in a number of circumstances, e.g. the patient with the radiologically normal sella or recurrent CD after adrenalectomy. In addition, the treatment of such conditions as the large ACTH-producing pituitary tumor, Nelson's syndrome, the malignant ectopic ACTH syndrome, and adrenal carcinoma is not entirely satisfactory. Our approach to these problems is illustrated by seven cases, and we emphasize that the proper management of CS requires both correct diagnosis and the logical application of all available therapies.

ACTH Syndrome, Ectopic↗

Chiasmal apoplexy. Report of four cases.

Four patients with chiasmal syndromes were found to have intrachiasmal hematomas. Computerized tomography scans showed high-density suprasellar masses in all cases. Cryptic vascular anomalies were presumed to be responsible for spontaneous bleeding into the chiasm in three of the cases. In the remaining case, hemorrhage was due to an occult optic glioma. Surgical evacuation of clotted blood resulted in improved visual function in three of the four cases.

Adolescent↗

Lymphocytic adenohypophysitis of pregnancy simulating a pituitary adenoma: a distinct pathological entity. Report of two cases.

Diffuse lymphocytic infiltration of the adenohypophysis occurring in temporal relation to pregnancy was found in two patients, each of whom had an intrasellar mass with suprasellar extension that caused compression of the optic chiasm. The pathology and etiology of this lesion is discussed. This entity should be considered when evaluating patients with a pituitary mass lesion that presents in temporal association to pregnancy, particularly if there is evidence of hypopituitarism rather than a hypersecreting, endocrine-active adenoma.

Adenoma↗

Transsphenoidal microsurgical removal of growth hormone-secreting pituitary adenomas. A review of 137 cases.

A series of 137 patients with growth hormone (GH)-secreting pituitary adenomas were treated by transsphenoidal surgery during a 10-year period. Group A comprised patients for whom this surgery was the first therapeutic interventions, and Group B included those who underwent the surgery after previous therapeutic intervention. The results were analyzed considering preoperative and postoperative endocrinological, neurological, ophthalmological, and neuroradiological data. Remission was defined as clinical response and a normal postoperative GH level, and partial remission at clinical response and postoperative reduction of the GH level by more than 50%. Any other result was considered failure. The mean follow-up period was 37.1 months; follow-up review was achieved in all the patients. Among the 102 patients in Group A, remission was achieved in 80 (78%) patients with transsphenoidal surgery alone, and in an additional 16 (16%) after postoperative irradiation (combined response rate, 94%). All failures and patients with partial remission had preoperative GH levels of more than 50 ng/ml and suprasellar extension of the tumor. There were no deaths; 8% of patients had minor surgical morbidity; 5% had new hypopituitarism postoperatively. Of patients subsequently irradiated, 71% developed hypopituitarism. Among the 35 patients in Group B, remission was achieved in 26 (74%), partial remission was obtained in two (6%), and seven (20%) were considered treatment failures. There were no deaths, and the morbidity rate was 14%; 66% of patients had hypopituitarism postoperatively. Of the eight patients who had received prior irradiation only, seven (88%) went into remission. All failures and partial responders had preoperative GH levels greater than 40 ng/ml; 56% had suprasellar extension. These results confirm the efficacy of the transsphenoidal approach for the treatment of GH-secreting pituitary adenomas.

Adenoma↗

Medial occipital arteriovenous malformations. Surgical treatment.

In a consecutive operative series of 115 intracranial arteriovenous malformations (AVM's), 16 occupied the medial occipital region. Typically, the patients with medial occipital AVM's presented with bleeding often accompanied by homonymous visual field deficit, or with migrainous headache. The malformations were supplied principally by branches of the posterior cerebral artery. Through an occipital craniotomy, a surgical approach along the junction of the falx and tentorium provided access to the arteries feeding the AVM and facilitated excision of the malformation. There were no deaths in the series. The incidence of visual field deficit after the operation varied, but in only five cases was the visual field worsened postoperatively. All patients who had a history of intractable headache were cured or improved after surgery. These lesions are favorably situated for surgical treatment.

Adult↗

Computerized tomography of a sellar spine. Case report.

A presumed developmental variant of the dorsum sellae was found in a patient undergoing evaluation for a suspected pituitary adenoma. An initial computerized tomography (CT) scan suggested a suprasellar mass; however, high-resolution CT with reformations clearly revealed the mass to be the pituitary gland, which was deformed and displaced upward by an osseous spine projecting from the dorsum sellae. The radiographic appearance and etiology of this anomaly are discussed. Neurosurgeons and neuroradiologists should be aware of this anomaly when evaluating a patient for pituitary adenoma.

Adult↗