W W Buchanan

Precipitating Auto-Antibodies in the Connective Tissue Diseases

In a recent communication we described the occurrence in the serum of patients with Sjogrens disease of two factors which reacted to give precipitates with extracts of various tissues. Evidence was provided that both factors were auto-antibodies (Anderson, Gray, Beck, and Kinnear, 1961b). As Sjogrens disease has close associations with the connective tissue diseases (Heaton, 1959; Bunim, 1961), we thought it of interest to see if autoprecipitins could be detected in patients with connective tissue diseases. This paper describes the detection, in the serum of patients with various connective tissue diseases, of the two auto-antibodies which occur in Sj6grens disease and two additional precipitating antibodies, one of which is an autoantibody to deoxyribonucleic acid.

Liver disease in rheumatoid arthritis and Sjøgren's syndrome. Prospective study using biochemical and serological markers of hepatic dysfunction.

Inter-relationships of biochemical and immunological tests of liver function have been studied in a prospective study of 216 patients with rheumatoid arthritis (RA), 32 patients with Sjogrens syndrome, and 27 patients with the sicca syndrome, and these results have been compared with those obtained 289 patients with osteoarthrosis or with a form of seronegative polyarthropathy. In general the prevalence of abnormalities in serum alkaline phosphatase, bromsulphthalein excretion, smooth muscle antibody, and mitochondrial antibody in the former three groups was higher than in patients with osteoarthrosis. Patients with Sjogrens syndrome with RA had a higher prevalence of abnormalities of bromsulphthalein excretion, salivary duct antibody than patients with the sicca syndrome. Patients with RA had a higher pervalence of rheumatoid factor than those with the sicca syndrome. Patients with a positive smooth muscle or mitochondrial antibody were found to have a higher prevalence of hepatomegaly and splenomegaly, of abnormal liver function tests, of other autoantibodies, and of histological abnromalitis of liver than those in whom these tests were negative.

Liver disease in Sjögren's syndrome and rheumatoid arthritis.

Abstract The prevalence of liver disease in patients with rheumatoid arthritis, Sjogrens syndrome with rheumatoid arthritis, and Sjogrens syndrome without rheumatoid arthritis, has been studied, using mitochondrial antibody as a marker. Clinical and/or biochemical evidence of liver disease was found in 6% of patients with Sjogrens syndrome without rheumatoid arthritis, 1·5% of patients with Sjogrens syndrome and rheumatoid arthritis, and 0·66% with rheumatoid arthritis alone. It is suggested that liver disease is a feature of Sjogrens syndrome.

Otolaryngological Aspects of Sjögren's Syndrome

Twenty-two patients with Sjögrens syndrome uncomplicated by a connective tissue disorder, 31 with Sjögrens syndrome complicated by rheumatoid arthritis, and 21 with rheumatoid arthritis alone were studied with particular reference to changes in the ears and in the upper respiratory and digestive tracts. Epistaxis, soreness and dryness of the throat, dysphagia, and hoarseness were common symptoms, and rhinitis sicca and postcricoid narrowing were not uncommon features of the Sjögren groups. Oesophagoscopy in one patient revealed a web identical to that found in Paterson/Brown Kelly syndrome; none of the patients, however, had an iron-deficiency anaemia or koilonychia. There was an increased frequency of deafness in all groups, and the deafness tended to be conductive in the Sjögren groups and sensorineural in the rheumatoid arthritis group.

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,

Measurement of joint inflammation. A radioisotopic method.

Radioactive technetium (99mTc) has been employed in the study of many organs (Harper, Andros, and Lathrop, 1962; Andros, Harper, Lathrop, and McCardle, 1965; Degrossi, Gotta, Olivari, Pecorini, and Chwojnik, 1965; Larson and Nelp, 1965; Davis, Alexander, Witcofski, and Maynard, 1966; Harden, Alexander, and Kennedy, 1967; Irvine, Stewart, McLoughlin, and Tothill, 1967; Tothill and Irvine, 1967). Technetium photoscans (Weiss, Maxfield, Murison, and Hidalgo, 1966) of the joint have been shown to reflect the degree of inflammatory involvement at the time of study and a method of quantitating such scans has been described (Whaley, Pack, Boyle, Dick, Downie, Buchanan, and Gillespie, 1968). The photoscan display system yields a picture of isotope content of the area over a relatively short period of time, however, and the method of quantitation is tedious. Furthermore, a dose of the order of one millicurie of the isotope is required to achieve optimum scans. This is a major disadvantage when repeated measurements are necessary, for example, in clinical trials of therapeutic agents. We considered that continuous external directional counting over the knee joint after the intravenous administration of 99mTc might overcome these difficulties. Thus, we hoped to derive more information from the pattern of uptake than was afforded by a single photoscan and we anticipated that a much lower dose of the isotope would be required. Finally, we hoped that this method would prove simpler to quantitate than the photoscan method.

Pulmonary infection and rheumatoid arthritis

Five of eleven patients with bronchiectasis and/or cystic fibrosis developed a polyarthritis with positive tests for rheumatoid factor. Possible mechanisms of this complication are discussed.

Clinical trial of pentazocine in rheumatoid arthritis. Observations on the value of potent analgesics and placebos.

Severe and chronic pain is a dominant feature in most patients with rheumatoid arthritis. Despite optimum doses of standard analgesic and anti-inflammatory drugs, there are many patients who do not obtain adequate pain relief. Until recently, the use of strong analgesics has been strongly contraindicated, as all such available drugs were classified under the Dangerous Drugs Act (DUdley Hart, 1968). The risk of drug dependence in patients with a chronic disease such as rheumatoid arthritis clearly precludes the use of such drugs except in exceptional circumstances. The development of a new group of narcotic antagonists with a benzomorphan nucleus (Archer, Albertson, Harris, Pierson, Bird, Keats, Telford, and Papadopoulos, 1962) led to the introduction of pentazocine in 1967. When given by intramuscular or subcutaneous injection, 30 mg. pentazocine is approximately equinanalgesic with 10 mg. morphine (British Medical Journal, Todays Drugs, 1970). The W.H.O. Expert Committee on Drug Dependence have passed pentazocine as being safe for use without special controls on three occasions (W.H.O. Technical Reports, 1966, 1969, 1970). It has been widely used for the relief of postoperative pain (Kantor, Sunshine, Laska, Meisner, and Hopper, 1966) in the management of patients with malignant dis-ase (Beaver, Wallenstein, Houde, and Rogers, 1968; Frankendal and Kjellgren, 1971), ischaemic heart (Scott and Orr, 1969) and limb pain (Taylor, 1971), and in obstetric practice (Mitchell, 1963; Filler and Filler, 1966). In two uncontrolled trials (Vignon, Chapuy, and Falconnet, 1969; DavidChausse and Laporte, 1970), it was suggested that injections of pentazocine in doses ranging from 30 to 120 mg. per day were highly effective in patients with a variety of rheumatic diseases. The marketing of an oral preparation in 1969 made it possible to consider the use of pentazocine as a practical possibility in the long-term management of rheumatoid arthritis, although it was found to be only one-third as effective as the parenteral preparation on clinical assessment (Beaver, 1968) and on monitoring blood levels (Beckett, Taylor, and Kourounakis, 1970). In considering the use of pentazocine for the treatment of rheumatoid arthritis, it is unlikely that it would be an effective form of therapy on its own. It possesses no anti-inflammatory or antipyretic activity (Sterling Winthrop Laboratories, Unpublished observations). Fremont-Smith and Bayles (1965) showed that even large doses of pethidine were less effective than salicylates in relieving symptoms in active rheumatoid arthritis, and it is generally accepted that, if adequate analgesia is to be obtained, drugs combining peripheral anti-inflammatory, analgesic, and antipyretic effects must be employed (Winter, 1966; Drug Ther. Bull., 1966). In this paper, we report the results of a doubleblind cross-over trial in which oral pentazocine and identical placebo tablets were given to patients who were receiving standard and stable regimes of nonsteroidal analgesic anti-inflammatory drugs but were obtaining inadequate relief of pain.

Radioisotope study of small joint inflammation in rheumatoid arthritis.

Radioactive technetium (9QmTc), introduced into nuclear medicine in 1964 (Harper, Beck, Charleston, and Lathrop, 1964), has been used to visualize many organs (McCready, 1967), including the thyroid gland (Andros, Harper, Lathrop, and McCardle, 1965), the salivary glands (Harden, Hilditch, Kennedy, Mason, Papadopoulos, and Alexander, 1967b), the stomach (Harden, Alexander, and Kennedy, 1967a; Irvine, Stewart, McLoughlin, and Tothill, 1967), the liver (Sorensen and Archambault, 1963), the brain (Davis, Alexander, Witcofski, and Maynard, 1966), the placenta (Larson and Nelp, 1965), and the joints (Weiss, Maxfield, Murison, and Hidalgo, 1966; Alarc6n-Segovia, Trujeque, Tovar, and Adame, 1967; Whaley, Pack, Boyle, Dick, Downie, Buchanan, and Gillespie, 1968; McCarty, Polcyn, and Collins, 1970a; McCarty, Polcyn, Collins, and Gottschalk, 1970b). Technetium scintiphotography of finger and wrist joints and knees in rheumatoid arthritis has shown increased uptake in the joints which reflected the degree of inflammatory involvement at the time of study (Weiss and others, 1966; Alarcon-Segovia and others, 1967; McCarty and others, 1970a), and Whaley and others (1968) have described a technique for quantitating the joint scintiphotographs. Scintiphotography of joints has the major disadvantage of requiring doses of the order of over one millicurie of 99mTc to obtain adequate contrast between inflamed and normal joints (Whaley and others, 1968; McCarty and others, 1970a) and quantitation of the scintiphotographs is tedious and time-consuming. Recently, Dick, Neufeld, Prentice, Woodburn, Whaley, Nuki, and Buchanan (1970) have reported a method of quantitation in the knee joint based upon the uptake of 99mTc by the joint as measured by continuous external directional counting after the intravenous administration of approximately 40 uci of the isotope. This method was shown to be reproducible when repeat measurements were made within 24 hrs, to reflect differences between normal and inflamed joints affected by rheumatoid arthritis, and to be capable of reflecting the effects of intra-articular injection of corticosteroids (Dick and others, 1970). In this paper we describe similar studies carried out on the proximal interphalangeal joints.

Corticosteroid-induced hypothalamo-pituitary-adrenal axis suppression. Prospective study using two regimens of corticosteroid therapy.

Long-term oral corticosteroid therapy leads to suppression of the hypothalamo-pituitary-adrenal (HPA) axis (Paris, 1961; Treadwell, Savage, Sever, and Copeman, 1963; Jasani, Boyle, Greig, Dalakos, Browning, Thompson, andBuchanan, 1967). Much work has been done on the influence of the regimen of corticosteroid administration on this suppression. Harter, Reddy, and Thorn (1963) have presented evidence that administration of oral corticosteroid in a single dose given every other day leads to substantially less adrenal suppression than that which occurs with a regimen giving divided doses of corticosteroid over the same period. The doses used in this study were not physiological; that is to say patients received doses of prednisone or prednisolone-equivalent ranging from 20 to 40 mg. daily. Grant, Forsham, and DiRaimondo (1965) have shown that a daily morning dose of 8 mg. Triamcinolone administered to normal subjects over a period of 8 days does not lead to lasting adrenal suppression. Nichols, Nugent, and Tyler (1965) have demonstrated virtually complete suppression of the secretion of cortisol by the adrenal gland for a period of 24 hours following the administration of a physiological dose of corticosteroid (0 5 mg. dexamethasone) given at midnight. The same amount given at 8 a.m. or 4 p.m. caused only temporary suppression of cortisol secretion. In the present study we have compared the effect of two regimens of corticosteroid administration on