Carl M. Pearson

High Association of an HL-A Antigen, W27, with Ankylosing Spondylitis

Abstract The frequencies of 24 HL-A antigens were examined in 40 patients with ankylosing spondylitis, 119 with rheumatoid arthritis, and 66 with gout. No significant deviation from control frequen...

Relapsing polychondritis: prospective study of 23 patients and a review of the literature.

Relapsing polychondritis (RP) is not a totally rare rheumatic disease. We have seen 23 patients from 1960-1975, and there are now a total of 159 reported cases, which form the basis of this study. RP occurs equally in both sexes, and has a maximum frequency in the fourth decade. 2) Empirically defined diagnostic criteria are proposed, to include the most common clinical features: a) Bilateral auricular chondritis b) Nonerosive sero-negative inflammatory polyarthritis c) nasal chondritis d) Ocular inflammation e) Respiratory tract chondritis f) Audiovestibular damage The diagnosis is based primarly upon the unique clinical features, and is quite certain if three or more criteria are present together with histologic confirmation. 3) Fifty percent of patients present with either auricular chondritis or the arthropathy of RP; but with prolonged follow-up, a majority of patients develop four or more of the above mentioned criteria. 4) Approximately 30 percent of patients have a preceding or coexistent rheumatic or autoimmune disease, which can lead to initial diagnostic confusion. 5) Laboratory and radiographic investigations help mainly to rule out other diagnostic possibilities, with no characteristic abnormalities being present in a majority of patients. 6) On follow-up, three-fourths of our patients required chronic corticosteroid therapy with an average dose of 25 mg per day of prednisone. Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases. 7) The mortality rate has been 30 percent in our series and 22 percent in the other 136 reported cases. Of the 29 cases where the cause of death was known, 17 were from respiratory tract involvement and 9 from cardiac valvular or vasculitic involvement, emphasizing the need to search for critical involvement of either of these organ systems in each patient. 8) Detailed reports of selected cases are presented to illustrate the clinical diagnosis and differential diagnosis, and to demonstrate the need for careful prolonged follow-up. 9) Although the etiology remains unknown, there is a frequent association with, and clinical similarity to, other rheumatic diseases. 10) Careful clinicopathological study of our 23 patients leads us to postulate an underying systemic vascultis as an important pathologic mechanism in RP.

Development of Arthritis, Periarthritis and Periostitis in Rats Given Adjuvants.

Summary and Conclusions A reproducible generalized or focal arthritis, synovitis, periostitis and tendonitis has been induced in rats by intracutaneous injections of a Freund-type adjuvant which was most potent when macerated striated muscle tissue was added to the inoculum. The pathogenetic mechanisms underlying the production of these changes is at present unclear.

A metabolic myopathy due to absence of muscle phosphorylase

Abstract Detailed functional and metabolic studies have been conducted in a nineteen year old boy who had a lifelong history of progressive weakness upon usage of exercised muscles and severe cramps if exertion was intense or prolonged. There was no muscular wasting, and strength during initial exercise was normal. The family history was non-contributory. Basal serum lactic and pyruvic acid levels were normal. However, there was no rise following treadmill exercise, in contrast to a transitory but significant rise in controls. Ischemic exercise of the forearm muscles was poorly maintained, and no elevation of lactic or pyruvic acid was noted in the venous return from the arm in contrast to a fourfold increase in control subjects. In the basal state, treadmill exercise at 4 miles per hour (10 degree incline) was limited to about four minutes. Improvement in treadmill exercise tolerance was marked following continuous intravenous infusion of glucose, fructose or lactate but there was no effect from galactose or glycerol. Epinephrine infusion produced a normal hyperglycemic response. Biochemical and histochemical analyses of thigh muscle revealed a fourfold increase in stored glycogen in the muscle and no reliably detectable phosphorylase. Glycolysis in a tissue homogenate, as indicated by lactate production, was markedly reduced. It was raised to near normal intensity by the addition of glucose-1-phosphate or glucose-6-phosphate. The uridine diphosphate glucose pathway for glycogen synthesis was found to be intact. This disorder, originally described by McArdle in 1951, is very rare. The deficiency in phosphorylase appears to be confined solely to the skeletal musculature. Because of the increase in stored muscle glycogen the disorder may be classified as another form of glycogen storage disease.

Polymyositis and dermatomyositis: combined methotrexate and corticosteroid therapy.

Abstract Twenty-two patients with polymyositis and dermatomyositis were treated with combined prednisone and intravenous methotrexate when moderate to high-dose cortisone alone was ineffective in c...

Cyclophosphamide Therapy in Wegener's Granulomatosis

Abstract Four adults suffering from Wegeners granulomatosis, each with extensive pulmonary and Central-nervous-system involvement and lesser degrees of renal disease and sinusitis, were treated wi...

Experimental joint disease

Abstract Examples of a few forms of human articular disease can be found in other species. So far, however, it has been impossible to discover naturally occurring or induced models of the common and devastating joint diseases of man such as rheumatoid arthritis, Reiters disease and analogous conditions. For several years studies have been conducted on a disease which can be induced in rats after the simple injection of a water-in-oil adjuvant which contains killed tubercle bacilli, or the Wax D fraction therefrom, as the active factor. The joints are affected in an acute migratory and polyarticular fashion, a chronic arthritis may ensue, and the histopathology resembles that found in Reiters disease or rheumatoid arthritis. Lesions of the eye, genitalia and skin also occur in some animals. Studies have nearly eliminated infection as a causative factor. Almost all of the results point to adjuvant disease as representing an experimentally induced hypersensitivity disease. Since prior injection of lipopolysacchardies (endotoxins) or concurrent injection of protein antigens can inhibit the disease there is a good possibility that a unique form of hypersensitivity, which is related to but not identical with delayed hypersensitivity, is pathogenetically involved When the mechanisms which underlie this disease process are more clearly understood it may be possible to explain in a more rational fashion certain perplexing human articular syndromes to which adjuvant disease bears an obvious resemblance.

Muscle membrane potentials in episodic adynamia

Abstract 1. 1. In vivo measurements of membrane potentials of human muscles (M. vastus med,; nerve block anaesthesia) have been performed in a healthy young man, a patient with periodic paralysis and a patient with episodic Adynamia (e.A.) Control measurements were performed in rats. 2. 2. The resting potentials of striated muscles of rats under general anaesthesia were − 79.9 ± 73.3 mV. In the healthy man (without general anaesthesia) the mean value was −87.4 ± 8.9 mV and in the patient with periodic paralysis it was −85.6 ± 6.1 mV in a free interval. During the attempt to provoke a paralytic attack in this patient the average dropped to −77.1 ± 8.2 mV, whereas the serum K + fell from 4.25 to 3.17 mequiv./1. The questionable significance of this slight drop of membrane potential is discussed. 3. 3. In the patient with e.A. the resting potential, even in the free interval, (serum K + 3.75 mequiv./l) was only −68.5 ± 5.9 mV. During an induced attack, with a rise in serum potassium to 6.9 mequiv./l, the average value dropped to −46.3 ± 6.6 mV and during a spontaneous attack, with a serum potassium of 5.24 mequiv./l, the mean value was −51.5 ± 6.3 mV. 4. 4. The significance of the results is discussed. The pathogenetic mechanism of e.A. can be explained by a disturbance of sodium permeability of muscle membranes.

A calcium-activated neutral protease in normal and dystrophic human muscle

Abstract Human skeletal muscle homogenate was found to degrade casein-yellow substrate slowly at neutral pH. This protease activity was maximally stimulated by 1 mM Ca 2+ . A significant increase in the level of Ca 2+ -activated neutral protease was found specifically in muscle of five patients with Duchenne dystrophy and one patient with the Becker form of X-linked dystrophy.

Catalase, superoxide dismutase, glutathione reductase and thiobarbituric acid-reactive products in normal and dystrophic human muscle

The level of thiobarbituric acid-reactive products and the specific activities of catalase and glutathione reductase were significantly higher in muscles from patients with major forms of muscular dystrophies over those of control subjects. Superoxide dismutase activity was not altered in dystrophic muscles. These findings indicate the occurrence in human dystrophic muscles of an increased level of lipid peroxidation and the possible activation of certain enzymes that could conceivably inhibit lipid peroxidation in vivo.