G Nuki

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.

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.

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.

Penicillin allergy in rheumatoid arthritis. With special reference to Sjogren's syndrome.

An increased prevalence of penicillin allergy has been noted in certain connective tissue disorders, in particular polyarteritis nodosa (Rose and Spencer, 1957) and systemic lupus erythematosus (Harvey, Shulman, Tumulty, Conley, and Schonerich, 1954). There is, to our knowledge, no reported study of the prevalence of penicillin allergy in rheumatoid arthritis, although an increased prevalence has been observed in patients with Sj0grens syndrome, including those individuals with co-existing rheumatoid arthritis (Bloch, Buchanan, Wohl, and Bunim, 1965).

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.

Effect of Glyvenol (CIBA) on pain and on capillary resistance in rheumatoid arthritis.

It antagonizes a number of pharma active substances, including histamine, acetylcholine, angiotensin, bradykinin, an It decreases the speed of leucocyte migrati the Arthus reaction and passive cutaneo laxis, and can prevent the fatal outcome lactic shock in experimental anima corticosteroids, however, it does not inhit production nor does it affect complemen As these students showed Glyvenol t( quite unusual combination of anti-inflarm other pharmacological properties with toxicity in animal experiments, we thc interest to study the effect of the drug with rheumatoid arthritis and in particul in them on capillary resistance.

Cellular immune mechanisms in rheumatoid arthritis and Sjögren's syndrome.

The immune responses to 2, 4-dinitrochlorobenzene (DNCB) and old tuberculin (OT) were studied in four groups of patients in addition to controls: sicca syndrome, Sjogrens syndrome complicated by rheumatoid arthritis, and seropositive and serone-.Jtive rheamatoid arthritis. Patients with seropositive rheimatoid arthritis and patients with rheumatoid arthritis complicated by Sjogrens syndrome demonstrated a diminished ability to become sensitized to DNCB, whereas normal responses were found in the other two groups. Testing with OT, on the other hand, revealed normal responses in patients in all groups except the sicca syndrome group, which showed diminished sensitivity. Analysis of the RNA/DNA content of the peripheral blood lymphocytes revealed elevated values in those groups of patients with diminished DNCB responsiveness, whereas normal ratios were found in the other clinical groups. The mean diameter of the peripheral lymphocytes was closely related to the RNAJDNA ratio, which suggests that patients having elevated RNA/DNA ratios have a higher proportion of circulatino lymphocytes of the large type, presumably lymphocytes committed in response to some antigenic stimulus. It is concluded that cutaneous anergy to DNCB may be due to a functional depletion of thymic dependent lymphocytes.

Follow-up studies on synovectomy of the knee in rheumatoid arthritis.

145 patients who had had unilateral synovectomy of the knee for rheumatoid arthritis were studied. The duration of follow-up after operation ranged from 6 months to 5 years. Before operation and at the time of follow-up each patient was assessed with regard to the status of the knee and to his general health. The assessment consisted of a subjective enquiry about knee and other general articular symptoms, an objective evaluation of the knee, and a general assessment based on examination of the other joints. 83 per cent. of subjects considered that the operation had been successful, and this subjective assessment was supported by a significant reduction in knee joint symptoms such as pain at rest and in motion, and stiffness, and a general improvement in functional grade. Objective corroboration of local improvement was found in the significant reduction of synovial hypertrophy, effusion, and knee joint tenderness on pressure, and generally by a marked reduction in the articular index of joint tenderness. In this group also there was a significant fall in the erythrocyte sedimentation rate. The remaining 17 per cent. who claimed that the operation had been unsuccessful showed no improvement in the knee symptoms, deterioration in functional capacity, and no change in the general articular index. There was significant improvement in the objective evaluation of the operated knee with reduction of synovial hypertrophy, effusion, and local tenderness, but this was much less than in the successful group, and in addition the erythrocyte sedimentation rate remained unchanged. In view of these findings, the authors consider that the postoperative course of a synovectomized joint depends on the evolution of the rheumatoid disease in general, namely that a successful synovectomy is probably the result of spontaneous remission of the disease process. There is no evidence from the present study to support the suggestion that synovectomy per se can influence the course of rheumatoid process.

Liver palms in rheumatoid arthritis.

Liver palms or palmar erythema are well recognized as a clinical feature of hepato-cellular disease (Sherlock, 1968). They have also been recorded in many other conditions, such as pregnancy, chronic febrile states, leukaemia, thyrotoxicosis, and rheumatoid arthritis (Copeman, 1964; Ragan, 1966; Sherlock, 1968). In the last-named disease the prevalence of palmar erythema has not been, to our knowledge, ascertained. In this paper we report a study of palmar erythema in 144 patients with rheumatoid arthritis, in whom we have studied the relationship of palmar erythema to the clinical and laboratory features of the disease.

Observations on the clinical outcome and recovery of hypothalamo-pituitary-adrenal axis function after complete withdrawal of long-term corticosteroid therapy in patients with rheumatoid arthritis.

normal are between 20 and 50 mg./100 ml. serum. Quantitative determinations were made in cases of degenerative joint disease, inflammatory arthropathy (rheumatoid arthritis, psoriatic arthropathy, collagenoses, etc.) and during attacks of various other rheumatological diseases. The results, which are difficult to interpret at this stage, seem to indicate an increase in serum caeruloplasmin, particularly in inflammatory arthropathies. This is not surprising in view of the alpha I glycoprotein changes.