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.     

Motor vehicle accidents related to psychiatric impairment

To aid in preventing motor vehicle accidents, physicians should be aware of psychiatric factors related to impaired driving ability. Individuals with alcoholism and personality disorders account for much of the increased risk of accidents among the mentally ill. Alcoholics are involved in one third of accidents involving fatalities. Contrary to speculation, less than 5% of such accidents represent suicides. Individuals with antisocial traits and personality also appear to have an important role in motor vehicle accidents. These accidents are often preceded by stressful life events, especially disruption of important relationships. Alcohol and other substances also contribute to accident risk.     

Learned helplessness decreases [3H]imipramine binding in rat cortex

Specific binding of [3H]imipramine decreased in frontal neocortex from rats demonstrating learned helplessness, an animal model of depression. The decrease was in maximal binding but not in affinity for the receptor site. No change in [3H]imipramine binding was found in septum or hippocampus. The receptor changes found in frontal neocortex parallel behavioral and neurochemical changes produced by learned helplessness in this region. These changes are also similar to those found in the frontal neocortex from suicides and in platelets of patients with depression.     

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.     

Suppression of seasonal allergic rhinitis symptoms with daily hydroxyzine.

The effectiveness of hydroxyzine in the suppression of allergic rhinitis symptoms was evaluated using a double-blind, parallel study design during the 1977 ragweed season. Forty-three subjects with positive ragweed skin tests and a history of an exacerbation of symptoms during August and September of the previous two years were randomly assigned to receive either hydroxyzine or placebo. Subjects scored the severity and duration of symptoms in a daily diary and adverse effects were evaluated from a structured interview at two-week intervals. Although drowsiness and dry mouth were frequent initially among the hydroxyzine-treated patients, these minor side effects rapidly disappeared as the dose was slowly increased, and all but one subject tolerated 150 mg/day. Subsequently, during the period of the highest ragweek pollen counts, the hydroxyzine-treated group spent significantly more days free of symptoms or with only mild sneezing, rhinorrhea, and eye symptoms than subjects who took placebo (p less than 0.05). Thus, hydroxyzine appeared to be well tolerated on a continuous daily basis and was effective in suppressing most of the symptoms of seasonal allergic rhinitis. Comparison of hydroxyzine with antihistamines more traditionally used for allergic rhinitis appears warranted.     

Somatic symptoms. A major feature of depression in a family practice

The complaints of depressed patients were investigated in a private, single-physician family practice clinic. Complaints and visits of depressives were compared to those of age- and sex-matched non-depressed controls over a period of 3 years beginning 18 months prior to the diagnosis of depression. Pain, functional and anxiety complaints signalled the onset and paralleled the course of depression. Somatic complaints were a conspicuous mode of presentation in this family practice. These somatic features are not among the usual diagnostic and research criteria for depression (DSM-III, Feighner Criteria and RDC) although they appear to be a major feature in the natural history of depression.     

Can ECT prevent premature death and suicide in ‘schizoaffective’ patients?

Mortality and suicide risks were higher in schizoaffective patients who had not received ECT compared to those having received ECT. The data are from a follow-up study of 74 schizoaffective patients admitted to University of Iowa Psychiatric Hospital between 1934 and 1944; these patients were traced in 1975. Even though the nature of schizoaffective disorder is still unknown, patients who present both schizophrenic and affective features, particularly with suicide risk, may benefit from ECT by lowering their mortality risk.     

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.     

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.     

Effect of erythromycin on theophylline kinetics

The effect of erythromycin base on theophylline kinetics was studied in eight informed, nonsmoking, adult males who received a 15-min infusion of theophylline (aminophylline) 5 mg/kg, prior to (control) and after (experimental) a 7-day course of 1 gm daily ervthromycin base (E-Mycin). Each subject acted as his own control. Multiple serum samples were collected for 24 hr after each dose and were analyzed for theophylline by high-pressure liquid chromatography. The mean ± SD pharmacokinetic parameters for each phase of study were as follows: apparent volume of distribution (L/kg) 0.45 ± 0.05 (control), 0.41 ± 0.05 (experimental); clearance (ml · min/kg) 0.83 ± 0.17 (control), 0.60 ± 0.11 (experimental). elimination half-life (hr) 6.65 ± 1.88 (control), 8.10 ± 1.58 (experimental). Erythromycin significantly affected the elimination half-life and clearance of theophylline (p < 0.05). The apparent volume of distribution was unaffected (p > 0.05). Therefore patients being administered theophylline appear to be at added risk for the development of toxicity when erythromycin is added to the therapeutic regimen.