Segmental subepithelial deposits in primary glomerulonephritis: scanning electron microscopic examination of acellular glomeruli

More accurate perception of the structural alterations in glomerular basement membrane (GBM) produced by subepithelial immune complex deposits is possible with a recently adapted technique that uses scanning electron microscopy of acellular material. With this procedure frozen tissue is treated sequentially by osmotic lysis, detergents, and DNase to solubilize both cellular components and immune complex deposits. Four patients with glomerulonephritis (acute postinfectious glomerulonephritis [one patient], segmental membranous glomerulonephritis [two patients], membranoproliferative glomerulonephritis, type III [one patient]) in whom segmental subepithelial deposits were found were studied by this technique; the resulting observations were correlated with the results of routine morphologic studies and a previous study of minimal change disease and diffuse membranous glomerulonephritis. Four types of structural alterations of the subepithelial GBM surface were observed. The differences in lesions observed in the various forms of glomerulonephritis are believed to be related to temporal, quantitative, and qualitative differences in immune complex-mediated glomerular injury.     

Pathologic features of familial visceral myopathy

Familial visceral myopathy is the most common cause of chronic primary (idiopathic) intestinal pseudo-obstruction. We studied four family groups with this disease and found that it has a characteristic morphologic appearance. Grossly, there is segmental dilatation of the alimentary tract, often involving multiple sites and most commonly producing a megaduodenum. Microscopically, the involved areas show a characteristic change consisting of degenerating muscle cells and fibrosis, which may involve the full thickness of the muscularis propria but is often more prominent in or limited to the external layer. Degenerating muscle cells appear pale, poorly defined, and fragmented. As residual thread-like remnants become surrounded by collagen or as muscle cells are destroyed, leaving apparent spaces surrounded by collagen, the longitudinal and circular muscles take on a vacuolated appearance easily recognized at low magnifications. Recognition of this change is greatly facilitated by use of a trichrome stain, and mild lesions may be recognized only with such stains. The nondilated segments of intestine show similar changes but of a less severe degree. Neural and vascular structures are apparently normal. Although the lesion most closely resembles progressive systemic sclerosis, the degenerating muscle cells and vacuolated appearance of the muscle serve to distinguish familial visceral myopathy from the latter entity.     

Where will the resources for the fifth year come from?

Of the approximately 635 residents in each year of pathology training, about 165 are already meeting the Pathology Board's proposed requirement for a fifth year of resident training. The cost of a fifth year of training for the other 470 residents is estimated to be approximately $20 million. Options for avoiding this expense or for finding the funds are discussed. It is concluded that, unless the Board modifies its position, redistribution of the current residency and fellowship slots, without increasing the program size, remains the only feasible alternative.     

Clinical and immunologic evaluation of glutaraldehyde-modified, tyrosine-adsorbed short ragweed extract: a double-blind, placebo-controlled trial

Glutaraldehyde-modified, tyrosine-adsorbed ragweed extract (GTR) is a modification of allergen extract to reduce allergenicity but retain immunogenicity. We evaluated the clinical efficacy and immunologic changes associated with the administration of GTR (16,350 protein nitrogen units) or placebo to a group of 100 atopic subjects with ragweed hay fever. The study was carried out in a double-blind, placebo-controlled fashion. Clinical response was measured by daily symptom diaries. physician evaluations, and patient responses. Changes in ragweed-specific IgE and IgG antibody were evaluated with an amplified enzyme-linked immunosorbent assay (alpha-ELISA) and were compared with measurements by RAST and a protein A-binding assay for IgG antibody. Treatment with GTR resulted in a sixfold increase in blocking IgG antibody and a small increase in IgE-specific antibody. No changes occurred in the placebo treated group. Mild immediate local reactions occurred after 74% of injections, and late-onset local reactions occurred after 62% of injections in the treated group. The placebo-treated group experienced immediate or late local reaction after only 12% of injections. There were two mild late-onset urticarial reactions of a generalized nature in the treatment group. The treatment group experienced significantly fewer symptoms than the placebo group throughout the season (p less than 0.02), although the difference was not dramatic. The results showed that GTR could be safely given in five preseasonal injections, with retained immunogenicity but less potential for generalized reactions. GTR is an improved method of allergy immunotherapy with the potential for clinical benefit when used in a brief preseasonal treatment regimen.     

Inhibition of theophylline clearance by troleandomycin.

The effect of troleandomycin, a macrolide antibiotic, on theophylline elimination was examined in eight patients with chronic asthma. Clearance from serum was reduced by 50 +/- 6% (mean +/- SD) during administration of 250 mg troleandomycin four times daily. Reduction of clearance persisted to a lesser degree in one of these patients examined while receiving 250 mg troleandomycin daily. An increase in serum theophylline concentration can thus result from initiating troleandomycin in asthmatic patients receiving continuous treatment with theophylline. This may be at least a partial explanation for the apparent benefit of troleandomycin in chronic asthma and also suggests that possibility of inducing theophylline toxicity, including seizures, as was observed in one of the patients in this study.     

Evaluation of a program for the pharmacologic management of children with asthma

An evaluation of a program used for the pharmacologic management of asthma was conducted by a retrospective chart review of patients seen by the Pediatric Allergy and Pulmonary Service at the University of Iowa. A scheme for drug selection based on pharmacologic and physiologic principles had been used to determine the medication requirements needed to attain specified therapeutic goals. Explicit criteria, defined prior to the review, were used to confirm the diagnosis, characterize the patients as chronically or intermittently symptomatic, and grade the disease by severity prior to the initiation of therapy. Of the 25 patients with intermittent symptoms, none of the patients with the 2 least severe grades of asthma required more than as-needed bronchodilators for control of symptoms while 80% of the patients in the 2 more severe grades required corticosteroids (p = 0.002). Among the 172 patients with chronic symptoms, a single noncorticosteroid prophylactic drug (usually theophylline in optimal doses) was the final management requirement for nearly 90% of the 27 patients in the 2 least severe grades of chronic asthma, for 70% of 129 patients in grade III, and in only 30% of the 16 patients in grade IV, the most severe grade (p < 0.001). This method for evaluating a pharmacologic management program has implications both for physician education and identification of patients used in drug trials.     

Cutaneous and nasal allergic responses in ragweed hay fever: lack of clinical and histopathologic correlations with late phase reactions.

The present study was designed to test the hypotheses that late cutaneous and nasal responses to allergen in patients with ragweed hay fever were human correlates of cutaneous basophil hypersensitivity, and that late responses in the nose and skin reflect similar pathogenesis. Forty-seven patients with ragweed hay fever were studied during a ragweed season for peripheral basophilia and clinical patterns reflecting late responses. Provocative nasal challenge, skin testing, and biopsy were carried out subsequently in 21 of the same patients during the winter months. Conclusions were as follows: (1) no histologic features distinguish positive from negative late skin reactions at 24 hr in patients with immediate wheal-and-flare responses; (2) cutaneous basophil hypersensitivity, i.e., tissue basophilia, is not a distinguishing feature of late skin responses in ragweed pollenosis; (3) seasonal peripheral basophilia was not found; (4) late responses in the nose were difficult to document objectively and did not correlate with late skin reactions; and (5) lymphocyte responses to antigen failed to correlate with late responses in either the nose or the skin.     

Antigen-specific densensitization in a rabbit model of acute hypersensitivity pneumonitis

Rabbits that had been prepared to develop acute alveolitis after aerosol challenge with simple protein antigens did not develop chronic alveolitis but rather gradually recovered despite continued challenge. Immunologic accompaniments of waning disease were compared in this model to those associated with intravenous injections of antigen causing "desensitization." We also studied the effects of aerosol challenge prior to systemic immunization, antigen specificity, and the duration of desensitization by aerosolized and intravenous antigen. We found that repeated aerosol or intravenous challenges produced antigen-specific desensitization in this model, and the effect lasted several weeks. Prior exposure to aerosolized antigen was not protective. Neither aerosol nor intravenous desensitization maneuvers abrogated antigen-specific lymphocyte blastogenesis, although an early transient fall did occur. Humoral responses were boosted. These findings suggest that chronic alveolitis is prevented in this model by specific desensitization, without the induction of true tolerance or of nonspecific anergy. Such immunoregulation may result from development of antigen-specific blockade or blocking factors (e.g., lymphokines), antigen-antibody complexes, or suppressor cells affecting specific effector cells. Evaluation of these mechanisms may have implications for diagnosis and prognosis in human hypersensitivity pneumonitis.     

Ultrastructural studies of acute hypersensitivity pneumonitis in rabbits

Acute experimental hypersensitivity pneumonitis in rabbits was studied using scanning and transmission electron microscopy. Scanning electron microscopy reveals the three-dimensional architecture of lesion localization, alveolar cellular filling, and scptal thickening, which typify this animal model. Transmission electron microscopy has identified the macrophage as the dominant cell filling alveolar spaces with variable numbers of lymphocytes and granulocytes. Septal thickening is also accompanied by increased cellularity involving septal cells and fewer numbers of other mononuclear and polymorphonuclear cells. No evidence of proliferating alveolar lining cells was found.