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.     

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.     

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.     

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.     

Somatic complaints -- harbinger of depression in primary care

The pattern of patient visits and type of complaints relating to depressive illness was investigated in a University family practice clinic. Complaints and visits of depressives were compared to those made by age and sex-matched controls over 6 time periods which spanned a period of 2 years starting 6 months prior to the diagnosis of depression. Functional, pain, anxiety, and social complaints appeared to parallel the course of the depression, rising before the diagnosis of depression and returning to control levels 15-18 months after the depression was diagnosed. Somatic complaints were a prominent part of the depressive presentation.     

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.     

Symptoms as predictors of response to amitriptyline and nortriptyline: The plasma level variable

Data collected to define therapeutic plasma levels for amitriptyline and nortriptyline were re-analyzed to test endogenous and non-endogenous symptoms as response predictors while controlling for plasma level variable. The selection criteria limited the range of historical predictors. Initial symptom quality was not predictive of outcome for the entire group of 44 patients or for the 27 with therapeutic plasma levels. Delusions were not associated with poor outcome. The authors conclude that historical components of the endogenous—non-endogenous distinction (e.g., premorbid personality, stability of symptoms over time, quality of remissions) may be more important as response predictors.     

Treatment of unipolar depression accompanied by delusions. ECT versus tricyclic antidepressant--antipsychotic combinations

A retrospective chart study conducted to compare the effectiveness of ECT to tricyclic antidepressant--antipsychotic combination therapy in the treatment of psychotic major depressive disorder. A favorable treatment response occurred in 86% of the ECT-treated patients and 42% of the antidepressant--antipsychotic-treated patients. Depressive symptoms showed improvement in all ECT-treated patients but only 50% of the tricyclic antidepressant--antipsychotic-treated patients. It was concluded that a significantly better treatment response can be expected in delusional depressed patients if treated with ECT rather than a tricyclic antidepressant--antipsychotic drug combination.     

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.     

Should ‘non-Feighner schizophrenia’ be classified with affective disorder?

Narrow definitions of schizophrenia increase homogeneity at the expense of leaving unclassified many patients with shizophrenic symptoms. Family history and follow-up studies indicate that many such patients ought to be classified with those having affective disorders. This study determines morbid risks for affective disorder and schizophrenia in first degree relatives of patients with chart but not research diagnoses of schizophrenia. Comparisons with morbid risk figures for relatives of individuals satisfying research criteria for depression, mania or schizophrenia indicate that the 'non-Feighner schizophrenia' group is probably too heterogenous to be classified entirely as affective disorder or as schizophrenia.     

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.     

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.     

Treatment of unipolar depression following electroconvulsive therapy. Relapse rate comparisons between lithium and tricyclics therapies following ECT.

A restrospective chart study and follow-up telephone interviews were used to compare the relapse rates of unipolar depressives who had received either lithium or tricyclics following ECT. The results showed no difference between the two treatment groups. The literature on ECT was reviewed in the light of the results from the present study. We concluded that ECT followed by either lithium or a tricyclic antidepressant is a more effective treatment for unipolar depression than ECT alone.     

Pulmonary changes induced by frontal EMG training

Earlier research suggested that the effects of facial muscle tension changes on other responses are not widespread but limited to a rather narrow set of pulmonary events. Further evidence in support of the specificity of the facial muscle-pulmonary relationship was provided in the present study by monitoring changes in several responses as a function of muscle tension training. Feedback training for increases and decreases in muscle tension at both facial and limb muscle sites was given to adult males. The effects of these manipulations on PEFR, RR, and HR were examined. Increases in facial muscle tension resulted in PEFR decreases whereas increases in limb muscle tension did not. Decreases in facial muscle tension were not observed as a function of training and no PEFR changes resulted from these conditions. Neither RR nor HR were related to the facial EMG changes observed during feedback training. These observations demonstrated the specificity inherent in the relationship between facial muscle tension and PEFR. and lent support to the hypothesis that these two responses are linked reflexively.     

Unpredictability of theophylline saliva measurements in chronic obstructive pulmonary disease

The use of saliva as an indirect, non-invasive method of theophylline plasma level measurement was evaluated in 23 older men with chronic obstructive pulmonary disease and numerous concurrent medical problems. Simultaneously collected plasma and saliva samples were obtained on two or more occasions and analyzed for theophylline concentration by the Schack and Waxler spectrophotometric method. The mean (± SD) plasma:saliva ratio for 84 sample sets was 1.6 (± 0.5) with the saliva concentration averaging 64.8% (± 20.8%) of the plasma concentration. Multiplying a randomly chosen plasma:saliva ratio from each patient by the saliva concentration of a second randomly selected observation resulted in a predicted plasma concentration that differed by more than 20% of the measured concentrations for 16 of the 23 patients. Thus, use of saliva theophylline measurements obtained by the Schack and Waxler method to adjust dosage regimens cannot be recommended in these patients.     

Light and immunofluorescent study of the Arthus reaction in the rabbit lung

A localized Arthus reaction was produced in the lung of sensitized rabbits by delivery of antigen into a lower lobe bronchus using a method of selective bronchial catheterization under fluoroscopy. The rabbits were sensitized with bovine immunoglobulin G (B-IgG) in incomplete Freund's adjuvant (IFA) to produce precipitating antibody without classic delayed hypersensitivity. Pulmonary histopathology was studied at intervals following antigen challenge, using light and immunofluorescent microscopy. Gross lesions peripheral to the lower lobe bronchus receiving antigen were found within 12 hr. Subsequent necrosis resulted in a dense scar by 6 wk. Microscopically, early lesions were typified by localized bronchitis, bronchiolitis, alveolitis, and vasculitis with exuberant exudates containing predominantly polymorphonuclear leukocytes. Extensive focal necrosis was present by 72 hr. Immunofluorescent studies revealed the presence of B-IgG, rabbit IgG, and complement (C3) in and around bronchi, bronchioles, alveoli, and vessels. No granulomatous lesions were found, and proliferation of alveolar lining cells was not detected in these studies. Thus, the lung can participate in an acute Arthus reaction following local antigen challenge in systemically sensitized animals. The pathology more closely resembles a necrotizing bacterial pneumonia than an interstitial or hypersensitivity pneumonitis under the conditions of this experimental system. Implications for human disease are speculative.     

Dermal hypersensitivity to schistosome cercariae in rhesus monkeys during immunization and challenge : I. Complex hypersensitivity reactions of a well-immunized monkey during the challenge

Complex dermal hpersensitivity reactions induced by the challenge infection with Schistosoma japonicum cercariae were observed in a rhesus monkey that had been immunized six times with cercariae exposed to high doses of x-irradiation and had been proved to have acquired a solid resistance against subsequent challenge infection. Macroscopically, three hypersensitivity reactions—reaginic whealing reaction, Arthus reaction, and delayed hypersensitivity reaction—appeared in sequence after the cercarial application. Results of microscopic examinations of sections prepared from biopsies of skin samples taken serially correlated in general with those of the macroscopic examinations. In the Arthus reaction, however, neither intravascular thrombi nor vascular fibrinoid necrosis was found, and the predominant cells in the perivascular infiltrate were not neutrophils but eosinophils. Pending further investigation, the Arthus reaction, previously so designated because of the macroscopic features noted, is temporarily designated an Arthus-like reaction. Most of the migrating schistosomula derived from the challenge cercariac seemed to be destroyed in the dermis as well as in the epidermis at about 12 hours after the challenge. Discussions of the true nature of the present “Arthus-like reaction” with special speculation on the possible role of IgE antibody in this reaction, the possible production of eosinophil chemotactic factor by the lymphocytes, and the schistosomulicidal effect of the eosinophils are presented.     

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.     

Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis.

A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis.