Alan S. Cohen

A clinical analysis of the course and prognosis of forty-two patients with amyloidosis

Abstract The clinical aspects of systemic amyloidosis in forty-two patients are reviewed, and the presenting manifestations, prognosis, mode of death and certain aspects of particular organ-system involvement are discussed in detail. No categoric differences in the clinical manifestations of amyloid disease were found among patients with primary amyloidosis, myeloma-associated amyloidosis and secondary amyloidosis. The kidney was the major site of involvement in most patients. Sixty per cent excreted more than 4 gm. of protein per day and uremia was the cause of death in 43 per cent. The profile of amyloid renal disease in this series was reviewed. Heart disease was present in 67 per cent of the patients. Our experience with cardiac amyloidosis underscores the problem of digitalis-sensitivity which such patients may present. Amyloid infiltration of the digestive system was responsible for a diversity of clinical manifestations. Among these, bleeding in the gastrointestinal tract was common and occurred in over 50 per cent of the patients. Data are presented which suggest that the prognosis in systemic amyloid disease and in amyloid nephrosis, in particular, may be better than generally believed.

Total and Capillary Fingertip Blood Flow in Raynaud's Phenomenon

Abstract Total (plethysmography) and capillary (radioisotope disappearance rate) fingertip flows were measured in 24 patients with Raynauds phenomenon and compared to 10 normal subjects in a warm room and during reflex sympathetic nerve stimulation by body cooling. Arteriovenous shunt flow was estimated by subtraction of capillary from total flow. Patients with Raynauds phenomenon had a significantly smaller capillary flow in both warm (6.4 vs. 10 ml per 100 g per minute) and cool (4.0 vs. 7.0 ml) rooms than normal subjects. With body cooling, total and arteriovenous shunt flow, but not capillary flow, decreased significantly in normal controls, whereas all three decreased in Raynauds phenomenon. During oral reserpine treatment, 11 patients with Raynauds phenomenon showed a significantly larger capillary flow during warming (8.7 vs. 5.7 ml) and cooling (6.2 vs. 2.8 ml). Patients with Raynauds phenomenon have a smaller finger nutritional (capillary) flow than normal subjects, and this flow decreases s...

Clinical studyAcute infectious arthritis: A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis)☆

The clinical course of 59 patients with acute nongonococcal septic arthritis has been reviewed with special emphasis on the changing bacterial spectrum in recent years. The results of treatment were dependent on various factors, including the specific microbial agent and host defenses. Treatment should include parenteral antibiotics and drainage with needle aspiration, except in hips which should be surgically drained. Successful therapy requires rapid initiation of treatment and ongoing assessment of adequacy of response.

Characterization of the amyloid fibril as a cross-beta protein.

The major component of amyloid is a fibrous protein (1) with a unique organization as seen by high resolution electron microscopy (2). A second component, a pentagonal rod, has been isolated from amyloid deposits and demonstrated to be identical with a circulating a globulia (P-component) (3). This component is distinct from the fibril in its ultrastructure, chemistry, and immunological interactions and constitutes only a minute part of amyloid deposits. In 1960 we obtained an X-ray diffraction powder pattern of an amyloid-rich tissue. In subsequent years improved methods of isolation of amyloid were devised and X-ray diffraction patterns of these more purified preparations were obtained. Results were presented 1 that indicated the presence of a cross-β pattern. The present study was carried out on amyloid fibrils isolated by various techniques to determine whether this molecular structure was consistently present in all preparations, including those freed from the pentagonal unit. Meterials and Methods Amyloid fibrils were obtained from the spleens of patients with primary, secondary, and myelomaassociated amyloidosis and prepared by the following methods: (1) homogenization of whole amyloid-laden spleen, centrifugation and recovery of a top-layer rich in amyloid fibrils (4); (2) sucrose gradient separation of the top-layer specimen to obtain a purer preparation (5); (3) reprecipitation of amyloid fibrils after they had been solubilized in dilute alkali at pH 11.5 (6); (4) a “water-soluble” amyloid prepared after purifying amyloid-laden spleen by exhaustive saline washes followed by homogenization in water (7)

Skin Involvement in Generalized Amyloidosis: A Study of Clinically Involved and Uninvolved Skin in 50 Patients with Primary and Secondary Amyloidosis

A punch or excisional biopsy of the skin was done in 50 patients with generalized amyloidosis: In 46, clinically normal skin, usually the forearm, was biopsied and in four, only cutaneous lesions. Amyloid was seen in the skin of 21 of 38 patients with primary and multiple myeloma-associated amyloidosis. Sixteen of 34 biopsies from clinically uninvolved skin were positive. Five of 12 patients with secondary amyloidosis had amyloid deposits in clinically normal skin. Overall, amyloidosis was definitively diagnosed on skin biopsy examination in 26 patients. A punch biopsy of clinically involved or uninvolved skin is an innocuous, simple procedure with a high diagnostic yield and can be done in an office setting.

Localized Amyloidosis of the Head and Neck and Upper Aerodigestive and Lower Respiratory Tracts

Seven cases of localized amyloidosis limited to structures of the head and neck and upper aerodigestive and lower respiratory tracts evaluated and treated at Boston University Hospitals in a recent 7-year period were reviewed. Negative Congo red staining of abdominal adipose aspiration biopsy or rectal biopsy specimens established that the amyloidosis was not systemic. Localized amyloidosis occurred in discrete masses in a variety of sites in the aerodigestive tract including the orbit, nasopharynx, lips, floor of mouth, tongue, larynx, and tracheobronchial tree. Five patients required surgical excision because of significant airway obstruction or organic dysfunction. Amyloid deposits completely excised with the carbon dioxide laser have not recurred, though other amyloid masses may appear elsewhere within the same organ or region. Amyloidosis may occur primarily or secondarily to other disease states. Localized amyloidosis has not been chemically identified but is usually defined by the absence of systemic features. While rare, amyloidosis must be recognized and understood by the otolaryngologist head and neck surgeon to allow appropriate diagnostic and therapeutic planning.

Acute arthritis caused by gram-negative bacilli: a clinical characterization.

ACUTE ARTHRITIS CAUSED BY GRAM-NEGATIVE BACILLI: A CLINICAL CHARACTERIZATION DON GOLDENBERG;KENNETH BRANDT;EDGAR CATHCART;ALAN COHEN; Medicine

The epidemiology of AL and AA amyloidosis

The limited available epidemiological information on AL amyloidosis suggests that there may be differences between population-based studies and case series data with respect to variables such as age and racial patterns. Much more work in this area is required before specific aetiologic hypotheses can be tested. Most available data to approximate the epidemiology of AA amyloidosis are derived from autopsies. Most patients with AA amyloidosis die from causes other than amyloidosis, therefore mortality data based on death certificates is of limited value in AA amyloidosis. Case ascertainment in autopsy studies may be difficult due to the frequent lack of adequate histological controls. Establishment of registries for both AL and AA amyloidosis would facilitate epidemiological research in these disorders.

Tuberculous arthritis: A report of two cases with review of biopsy and synovial fluid findings☆

Two cases of tuberculous arthritis with synovial fluid findings are presented, and the major series with culture results and synovial fluid analyses are reviewed. Synovial fluid cultures are positive for tuberculosis in almost 80 per cent of proved cases. Specimens obtained by open synovial biopsy are positive by histology or culture in over 90 per cent of proved cases. Little experience with closed needle biopsy has been published. About one-fifth of the patients with tuberculous arthritis will have a positive synovial fluid acid-fast smear for tubercle bacilli. The tuberculous synovial effusion invariably has an elevated protein level, fair to poor mucin clot formation and usually a low joint fluid sugar level. The synovial fluid white cell count is usually in the range of 10,000 to 20,000 cells/mm3, but it varies widely. Most fluids exhibited a predominance of polymorphonuclear leukocytes. The importance of bacteriologic or histologic study of the synovial fluid and membrane in establishing the diagnosis is emphasized. In general, this disease is different from tuberculous involvement of serous membranes both in the frequency of positive cultures and in the difference in cellular response.

Immunoglobulins and amyloidosis: An immunologic study of sixty-two patients with biopsy-proved disease

Abstract Immunoglobulin abnormalities have been studied in sixty-two patients with biopsy-proved amyloidosis. In ten of eleven cases associated with well defined lymphoproliferative disorders the patients were found to have M-components in their serum or urine. A similar abnormality was demonstrable in seven of fourteen cases of primary amyloidosis, but M-components were not present in the serum or urine of eight patients with localized amyloidosis, six patients with hereditary amyloidosis and twenty-three patients with secondary amyloid disease. Despite the absence of M-components in the majority of patients, nonspecific immunoglobulin abnormalities (elevated or depressed serum levels of immunoglobulins G, A and M) were frequently encountered in patients with secondary amyloidosis as well as in patients with idiopathic disease and lymphoproliferative disorders. These results suggest that immune mechanisms may be involved in the pathogenesis of human amyloidosis.