Joseph J. Bunim

The development of malignant lymphoma in the course of Sjögren's syndrome

Abstract Of fifty-eight patients with Sjogrens syndrome followed at the National Institute of Arthritis and Metabolic Diseases, reticulum cell sarcomas developed in three, and lesions resembling Waldenstroms macroglobulinemia in a fourth. These changes were present in lymph nodes and organs exclusive of the salivary and lacrimal glands. These patients have certain clinical and laboratory features in common which distinguish them from patients with the usual benign cases of Sjogrens syndrome. These features include a relatively high incidence of splenomegaly, purpura, vasculitis, leukopenia, lymphopenia and hypogammaglobulinemia. The gamma globulin abnormalities have been investigated by immunoelectrophoretic analysis, ultracentrifugation and fluorescent antibody technics. In one patient, gamma globulin decreased from elevated to markedly low levels; the rheumatoid factor and tissue antibodies disappeared as reticulum cell sarcoma developed. In another patient, lymph nodes were populated with an abnormally large proportion of cells containing 19S macroglobulin, and several cells exhibited unusual intranuclear inclusions which stained positive with periodic acid-Schiff stain. The relationship between connective tissue diseases, gamma globulin abnormalities, thymomas and malignant lymphomas is discussed. The hypothesis is presented that in Sjogrens syndrome the chronic state of immunologic hyperactivity and the proliferation of immunologically competent cells producing abnormal tissue antibodies predispose to the relatively frequent development of malignant lymphoma.

Biochemical, pathologic and clinical aspects of alcaptonuria, ochronosis and ochronotic arthropathy: Review of world literature (1584–1962)

Abstract The biomedical literature on alcaptonuria, ochronosis and ochronotic joint disease, including 604 cases reported from thirty-five countries, is reviewed. The history of the development of our knowledge concerning this hereditary metabolic disorder, from 1584 to 1962, is recapitulated. The nature of the biochemical defect, a deficiency of homogentisic acid oxidase, in alcaptonuria is described and the pattern of genetic transmission traced. The geographic and racial distribution, and the multisystemic clinical manifestations of ochronosis are summarized. The diagnostic features and differential diagnostic considerations are presented. The gross, histopathologic and electron microscopic changes as well as pathogenesis are discussed. The various types of treatment attempted, without success, are mentioned.

Sjögren's syndrome and its relation to connective tissue diseases

Abstract The immunological, clinical, histopathological, radiological, and other laboratory features that characterize Sjogrens syndrome have been described. The description was based on a study of 57 cases of Sjogrens syndrome at the National Institutes of Health, together with numerous reports from the literature. The association with other connective tissue diseases, such as systemic lupus erythematosus and scleroderma, and certain changes which these disorders and Hashimotos thyroiditis share in common with Sjogrens syndrome were discussed. The pathogenetic implication of the unusual frequency of circulating auto-antibodies and of the aggregation of these antibodies among first degree relatives was speculated upon. The answer to this challenging question must await acceptable laboratory evidence which, it is hoped, future studies will produce.

Clinical and Pathological Studies of Joint Involvement in Sarcoidosis

THIS paper deals with a little known form of sarcoidosis in which polyarthritis is a conspicuous or dominant clinical finding. In extensive reviews of the literature on sarcoidosis, articular invol...

Clinical, Pathologic, and Serologic Studies in Sjögren's Syndrome: Combined Clinical Staff Conference at the National Institutes of Health

Excerpt Dr. Joseph J. Bunim: This study on Sjogrens syndrome exemplifies the type of multidisciplinary clinical research for which the facilities and organization of the Clinical Center are especi...

Studies of Pancreatic Function in Sjögren's Syndrome

Excerpt INTRODUCTION Sjogrens syndrome is a chronic, benign, systemic disorder of unknown etiology, involving principally the lacrimal and salivary glands and occasionally other mucus-secreting gl...

Antinuclear and Precipitating Auto-antibodies in Sjögren's Syndrome

The diagnosis of Sjogrens syndrome is usually based on the triad of kerato-conjunctivitis sicca, salivary gland involvement (enlargement and/or xerostomia), and rheumatoid arthritis, but may also be made when any two of these three features are present (Sj6gren, 1943). In addition, the syndrome has been described in patients with systemic lupus erythematosus (Ramage and Kinnear, 1956; Bain 1960), progressive systemic sclerosis (Oblatt, Feher, and Csiky, 1958; Bloch, Bunim, Wohl, and Zvaifler, 1960; Bloch, Wohl, Ship, Oglesby, and Bunim, 1960; Shearn, 1960; Stoltze, Hanlon, Pease, and Henderson, 1960; Bloch and Bunim, 1963), polyarteritis nodosa (Ramage and Kinnear, 1956; Shearn, 1961), and myopathy or polymyositis (Bunim, 1961; Silberberg and Drachman, 1962), any of which may replace rheumatoid arthritis in the diagnostic triad. The sera of patients with Sjogrens syndrome have been found very frequently to contain rheumatoid and antinuclear factors, and precipitating and complement-fixing antibodies reacting with a wide variety of the organs and tissues (Jones, 1958; Heaton, 1959; Bloch and others, 1960a and b; Deicher, Holman, and Kunkel, 1960; Anderson, Gray, Beck, and Kinnear, 1961; Thompson, 1962; Beck, 1963; Bloch and Bunim, 1963; Crews and Whitfield, 1963; Vanselow, Dodson, Angell, and Duff, 1963); in addition,

Effect of acute clinical stress on the levels of hexosamine in serum and its excretion in urine.

The total serum hexosamine 2 level is elevated in many unrelated chronic diseases (1, 2), and in experimental animals following acute injury (3, 4). It is not clear whether this elevation is due to increased production, diminished utilization or merely a shift of tissue hexosamines into the circulation. Since the activity of the adrenal glands is increased in many of these conditions of acute and chronic stress, the role of the adrenal cortex iti sontrclling serum hexosamine levels has been studied. During the course of these studies, it was noted that normal urine contained relatively large amounts of hexosamine, which also increased during conditions of stress. The excretion of hexosamine in the urine in a variety of clinical situations has been measured, therefore, for the purpose of defining factors which alter the rate of its excretion and of correlating excretion levels with changes in serum hexosamine. An ion exchange technique has been applied to urine hydrolysates for the purpose of separating hexosamines from the many chromogens in urine which interfere with the colorimetric determination of hexosamine (5). Previously reported studies on urinary hexosamine have not taken this into account and consequently report erroneously high values (6, 7).

FACTITIOUS DISEASES: CLINICAL STAFF CONFERENCE AT THE NATIONAL INSTITUTES OF HEALTH

Excerpt DR. JOSEPH J. BUNIM: Since the Clinical Center opened in July 1953 we have protested that this is not a diagnostic center, nor is it an institution devoted primarily to the care of patients...

Observations on the use of prednisone in patients with progressive systemic sclerosis (diffuse scleroderma).

Excerpt Both cortisone and corticotropin have been reported as capable of inducing favorable changes in the cutaneous and visceral symptoms of patients with progressive systemic sclerosis.1-6While ...