Showing papers in "Annals of the Rheumatic Diseases in 1974"

Proceedings: Functions of the menisci. A preliminary study.

Abstract: There are reasons to believe that one of the most important functions is load-bearing, and this paper presents experimental evidence to demonstrate this and to quantitate the fraction carried by the menisci of the load acting on the joint. Experiments were carried out on young cadaveric knees, at full extension. First the knee was compressed in a universal Instron machine, and the approximation of the condyles, on both sides, was measured. For this two displacement transducers were employed, one on each side of the knee. The armature of the transducer was attached to the femur and the cam to the tibia. Two x y plotters were used to record the load displacement curves on both sides. The load that was applied on the knee was slowly increased by 2 kg. to 100 hg. The menisci were then made redundant by dividing their anterior attachments to the tibiaand the experimentwas repeated. Oncomparing the load displacement curves before and after dividing the meniscal attachments, it was possible to determine the load carried by the menisci. The results showed that they carry a considerable share, the lateral meniscus 70 per cent and the medial meniscus 50 per cent of the load acting on the respective sides of the joint. As a result, the stresses occurring in the knee are low and comparable with those occurring in the hip under the similar conditions of loading. The fact that the menisci have a load-bearing function has other implications. The congruity they add to the joint increases the time of approach of the condylar surfaces to 30 to 60 times its value, based on the assumption that they do not carry load. Previous work has shown this value to be 90 seconds. This means that the bearing surfaces of the joint will not come into contact after long periods ofstandstill. This is a desirable situation as it is known that wear in lubricated bearings takes place during the starting phase, when the surfaces are in contact, and ceases during the running phase, in which the surfaces are separated by a lubricant film. Discussion DR. A. J. PALFREY (London) In my experience there is a good deal of variation in the area of the lateral meniscus. Have you related this to the load transmitted through the meniscus in the individual specimen? Secondly, would you agree that the menisci are virtually inextensible along their length? Thirdly, the surface of the meniscus in a histological preparation is much less smooth than the surface of articular cartilage: is this partly responsible for the long squeeze-ffilm time?

Role of hyaluronic acid in joint lubrication.

Abstract: Hyaluronic acid is the macromolecule which endows synovial fluid with its viscoelastic properties and it is often assumed these properties are important for the lubrication of the tissue surfaces in diarthrodial joints (Barnett, Davies, and MacConaill, 1961). The relationships, if any, that exist between the chemical and physical properties ofsynovial fluid and its lubricating ability, however, have not been determined. Recent in vitro studies concerned with the types of molecules present in synovial fluid which are responsible for the lubrication of the joint tissues have indicated that hyaluronic acid is a good lubricant for the synovial membrane (Radin, Paul, Swann, and Schottstaedt, 1971), but showed that this constituent was not essential for the lubrication of the articular cartilage (Radin, Swann, and Weisser, 1970). After the fractionation of synovial fluid by sedimentation equilibrium centrifugation in a cesium chloride density gradient, it was shown that the articular cartilage lubricating moiety was present in the protein fraction. More recent experiments have confirmed these data and shown that the lubricating moiety is complex and contains peptide and glycopeptide constituents (Swann and Radin, 1972). It thus appears from these in vitro studies that the different types of macromolecular constituents in synovial fluid can function independently in the lubrication of the different types of tissues in the joint. However, these constituents in vivo are intimately associated and the articular lubricating moiety interacts with hyaluronic acid and is retained as a component of the ultrafiltrate residue after the ultrafiltration of the synovial fluid (Swann and Radin, 1972). For this reason it is important to find out if hyaluronic acid has any effect on the lubricating ability of the protein fraction in an articular cartilage system. A well known fact is that the concentration and intrinsic viscosity of hyaluronic acid are both lower in synovial fluid from patients with rheumatoid arthritis (Balazs, Watson, Duff, and Roseman, 1967), but it is not clear whether these changes modify the lubricating properties of the fluid. A characteristic feature of rheumatoid disease is morning stiffness, and a suggestion was made recently that this is caused by a failure in periarticular soft tissue lubrication (Radin and others, 1971). It is also important, therefore, to determine whether the changes in the structure of hyaluronic acid and the composition of synovial fluid in patients with rheumatoid arthritis alters its ability to lubricate synovial tissue. The present experiments were performed in an attempt to answer some of these questions.

Effect of oral fructose on urate production

Abstract: The oral or intravenous administration of fructose to children results in dramatic rises in both urate and lactate concentrations in serum and an increase in the excretion of uric acid in the urine, findings interpreted as being caused by rapid nucleic acid degradation due to the increased intracellular lactic acidosis in the liver (Perheentupa and Raivio, 1967). As lactate also reduces renal excretion of urate (Yu, Sirota, Halpern, and Gutman, 1967), these authors were unable to assess the relative importance of hepatic and renal factors in the resultant hyperuricaemia, but the increase in the urinary uric acid suggested either a sudden increase in urate production or a shift of urate from an intracellular pool to the extracellular fluid. Moreover, Fox and Kelley (1972) were unable to demonstrate any consistent decrease in the fractional clearance of urate after fructose infusions. Studies in Cebus monkeys have also demonstrated hyperuricaemia and increases in urinary uric acid excretion after infusions of high concentrations of hexoses, fructose having the greatest effect and glucose a lesser effect (Simkin, 1969). This has not been a uniform finding, however, and no significant changes in serum urate concentrations were demonstrated during the 3 hrs after the intravenous administration of 100 g. fructose to ten young adult males (Curreri and Pruitt, 1970). Because of the conflicting evidence, the lack of information concerning the possible mechanism involved and the potential importance in patients with hyperuricaemia, it was decided to compare the effect of diets containing large quantities of either added fructose or glucose on urate metabolism, as reflected by the miscible urate pool and turnover rate and the simultaneous incorporation of glycine into both urinary and produced uric acid.

Quantitation of thermography in arthritis using multi-isothermal analysis. I. The thermographic index.

Abstract: Thermography can be used for the assessment of joint involvement in inflammatory arthritis. Modem thermographic apparatus allows temperature to be measured to within 0-2°C. and simultaneously records the areas involved. It has been demonstrated that thermographic changes in skin temperature over areas of chronic inflammation properly reflect changes in other chemical and cellular processes in rheumatoid arthritis (Ring and Collins, 1970; Collins and Cosh, 1970). The method also agrees with the findings of joint scans after technetium injection (Cosh, Lindsay, Rhys-Davies, and Ring, 1970) and correlates with the intra-articular temperature taken by thermistor probe (Lloyd-Williams, Ring, and Cosh, 1970). Recently Pinder and Ring (1974) have shown that thermographic recordings accurately locate areas of inflamed synovial tissue as shown at synovectomy. The effect of anti-inflammatory compounds on joint inflammation in animals has been quantitated using radiometry (Collins and Ring, 1972). Thermography provides more information about the distribution of temperature. We wish to report a method for the quantitative measurement of joint inflammation in man, using thermography.

Factors affecting urate solubility in vitro.

Abstract: Acute gouty arthritis occurs when crystals of monosodium urate form and deposit in joints and connective tissue. These crystals then provoke the characteristic acute inflammatory response of gout (Seegmiller, 1965), and may accumulate chronically forming gouty tophi. Although deposition of urate crystals from hyperuricaemic body fluids is an essential requirement in the pathogenesis of gout, only a small percentage of hyperuricaemic individuals ever shows clinical signs of gout. The factor or factors predisposing certain hyperuricaemic persons and not others to develop gout are as yet unknown. Thus, it is important for an understanding of the pathogenesis of gout to examine the factors which influence urate solubility and which may ultimately prove to be responsible for the initiation of urate crystal formation. Factors presently known to influence urate solubility include pH, temperature, ionic strength, and the binding of urate to macromolecules, such as plasma proteins and mucopolysaccharides of connective tissue. We have recently published a theoretical discussion offactors influencing urate solubility (Wilcox, Khalaf, Weinberger, Kippen, and Klinenberg, 1972). The present communication summarizes the results of laboratory studies designed to further quantify some parameters of urate solubility in buffers and biological fluids.

Granulocyte-specific antinuclear factors in synovial fluids and sera from patients with rheumatoid arthritis.

Abstract: The prevalence of antinuclear factors (ANF) found in sera and synovial fluids (SF) of patients with rheumatoid arthritis (RA) varies from one study to another, chiefly according to the technique used. The importance of sensitivity has been emphasized by Ritchie who found ANF in 89% of undiluted RA sera, employing rat liver as nuclear substrate and an antihuman immunoglobulin conjugate detecting the three main classes of immunoglobulins (Ig) (Ritchie, 1967). As 61 % of normal control sera contained low titres of ANF (<16) a titre of 16 was selected as the upper normal limit. Titres above 16 were found in 32% of the RA sera. The choice of nuclear substrate is also important, since some ANF in RA show limited reactivity (Elling, Graudal, and Faber, 1968). Using human blood leucocytes and an antihuman Ig conjugate these authors found ANF reacting predominantly or solely with polymorphonuclear nuclei in 64% of RA sera and 62% of paired joint fluids. Previous cross absorption experiments on ANF positive RA and systemic lupus erythematosus sera using thyroid and leucocyte nuclei had shown the specificity of granulocyte-specific ANF (GS-ANF) (Elling, 1966). Such antibodies were thus detected in virtually all RA sera and about one-third of systemic lupus erythematosus sera. Most authors have observed a lower incidence of ANF in rheumatoid SF than in sera (Barnett, Bienenstock, and Bloch, 1966; MacSween, Dalakos, Jasani, Boyle, Buchanan, and Goudie, 1968; Cracchiolo and Bamett, 1972; Munthe, 1972). On the other hand, ANF may be present in some SF when absent in the matched sera (Barnett and others, 1966; MacSween and others, 1968; Elling and others, 1968; Cracchiolo and Bamett, 1972; Munthe, 1972), perhaps indicating local production of ANF in the synovial membrane, in the same way as rheumatoid factors (Mellors, Heimer, Corcos, and Korngold, 1959; Hannestad and Mellbye, 1967). The aim of this study was to evaluate a sensitive indirect immunofluorescence technique for determining prevalence and titres of GS-ANF and organnonspecific ANF (ON-ANF) in paired RA and osteoarthrosis (OA) sera and SF using both human leucocytes and thyroid as nuclear substrates, Ig class specific conjugates, and optical equipment giving close to optimal conditions for reading the results. The relative amounts ofANF were judged by titration of the samples.

Quantitative aspects of patello-femoral cartilage fibrillation in Liverpool necropsies.

Abstract: The significance of ageing as a possible factor contributing to the pathogenesis of osteoarthrosis is debatable (Byers, Contepomi, and Farkas, 1970); moreover, the matter may require separate consideration for the hip, knee, and other joints. Necropsy studies of the incidence, natural history, and severity of age-related cartilage lesions in various joints are relevant to this question. Age changes in the hip, knee, and other joints have been studied by Heine (1926), in the knee joint by 0wre (1936) and Bennett, Waine, and Bauer (1942), in the elbow by Goodfellow and Bullough (1967), and in the hip by Byers and others (1970). These previous studies have been based mainly on a qualitative assessment of the state of the articular surfaces, the results being expressed, for example, in terms of a grading system such as that devised by Collins (1949). The present study, in contrast, is based on a quantitative method in which the results are expressed as a percentage of the articular surface area affected by destructive cartilage changes. The patello-femoral component of the knee joint was selected for study by this method, since the slight curvature of the patellar surface makes this articulation suitable for quantitation by a point-counting technique. Previous studies, with the exception of that by Goodfellow and Bullough (1967), mostly seem to have relied mainly on naked-eye inspection of unstained surfaces. The present study, in contrast, was made on surfaces which had been painted with indian ink, since such preparations make cartilage lesions more readily apparent (Bullough and Goodfellow, 1968; Meachim, 1972a) and facilitate point-counting of the various types of surface change. Naked-eye examination was supplemented by stereomicroscopy of the surface and, where indicated, by transmitted light microscopy of tangential surface slices (Meachim, 1972a).

Trial comparing D-penicillamine and gold in rheumatoid arthritis. Preliminary report.

Abstract: The Multicentre Trial Group (1973) showed that penicillamine was superior to placebo in a doubleblind trial against placebo. In this trial penicillamine was compared with gold. There are three reasons why a double-blind trial of penicillamine and gold was not attempted; first, gold is given by injection and penicillamine orally;. secondly, both drugs have distinctive side effects which might 'unblind' the observer; and thirdly, because some side effects are potentially dangerous, it is essential that the physician knows which drug his patient is receiving. For these reasons, the patients were treated by their usual physicians who supervised dosage and documented side effects. Before the trial and at 3-monthly intervals after the start of treatment, the patients were seen by a 'blind' observer from another hospital.

Quantitation of thermography in arthritis using multi-isothermal analysis. II. Effect of nonsteroidal anti-inflammatory therapy on the thermographic index.

Abstract: FIG. la Thermographic indices of acute rheumatoid arthritic knee. Benorylate (8 glday) was given after the first recorded index. The broken line represents the normal range ofthermographic index, with its standard error ofthe mean shown as a vertical bar. (b) Indices of acute rheumatoid arthritic knee. Single intra-articular injection ofprednisolone (Ultracortenol, Ciba) given after first thermogram. Broken line indicates normal index ranges; SEM is shown as a vertical bar

Ankylosing hyperostosis. I. Clinical and radiological features.

Abstract: Ankylosing hyperostosis is a condition in which new bone is laid down on the right antero-lateral aspect of the dorsal vertebrae and across the intervertebral spaces forming spurs or bridges. The lumbar and cervical spines, pelvis, hips, and knees may also be involved. There is no single approved name for this condition. Oppenheimer (1942) described 'Calcification and ossification of vertebral ligaments'. Forestier and Rotes-Querol (1950) named it 'senile ankylosing hyperostosis of the spine', but in later works (Forestier and Lagier, 1971) the adjective 'senile' was omitted when the condition was described in younger patients. Smith, Pugh, and Polley (1955) described 'physiologic vertebral ligamentous calcification' and Haijkova, Streda, and Skrha (1965) 'hyperostotic spondylosis'. Beardwell (1969) termed this condition 'ankylosing vertebral hyperostosis' and Julkunen, Heinonen, and Py6rala (1971) referred to 'hyperostosis of the spine'. Bywaters and Forestier (1967) presented a revised system for nomenclature of spinal diseases at the 6th European Congress of Rheumatology. They advised that this condition be named 'ankylosing hyperostosis', and this is the terminology which we have adopted. An association with diabetes mellitus has been shown by several authors, including Boulet and Mirouze, (1954), Hajkova' and others (1965), Bywaters, Doyle, and Oakley (1966), and Ott, Perkovac, and Regehr (1967). Julkunen and others (1971) found an association with diabetes and obesity. Boulet, Serre, and Mirouze (1954) suggested that this condition is due to an increased production of growth hormone occurring when the secretion of gonadal hormones declines, and in fact, Julkunen, Karava, and Viljanen (1966) found six cases of hyperostosis of the spine in 21 acromegalic patients. Beardwell (1969) showed a familial incidence and relationship with tylosis in a Greek Cypriot family. Ott (1953) and Smith and others (1955) considered the disease to be an exaggerated form of osteoarthrosis of the spine. Although many European authors have described the clinical, radiological, and pathological features of ankylosing hyperostosis, there has been no report of a series of patients with this condition from this country. This paper describes the clinical and radiological features of a series of patients seen at various hospitals in the East End of London. Particular reference has been made to the possible association with acromegaly.

Gout and hyperlipidaemia.

Abstract: A number of previous reports have demonstrated an association between gout and hyperlipidaemia (Barlow 1968; Rondier et al 1970).

Depression in rheumatoid disease.

Abstract: In a disease in which the patient is continually subjected to pain and forced to face the probability of increasing deformity and handicap, the occurrence of a depressive reaction might be expected. (Symposium, 1968). It has been suggested that many patients suffering from rheumatoid disease experience a depressive reaction which may materially impede progress and delay rehabilitation (Leading article, 1969). Several studies reported in the literature deal with the psychological profiles and personality traits of patients suffering from rheumatoid arthritis. Thus, Rimon (1969), in a detailed psychological study of 100 female outpatients suffering from rheumatoid arthritis, noted a depressive reaction in 29 during the investigation period. In a psychological study by Robinson, Kirk, and Frye (1971) of patients with rheumatoid arthritis and selected controls with non-painful chronic diseases, it was found that patients with rheumatoid arthritis showed a higher incidence of 'anxiety and depression' when compared with the control subjects. It has also been suggested that any person who suffers from a chronically painful and disabling disease is likely to demonstrate psychological reactions similar to those exhibited by the rheumatoid patients, i.e. 'conflicts in the expression of hostility' and more anxiety and depression. Some support for the plausibility of this 'pain hypothesis' was provided by a recent study by Robinson, Kirk, Frye, and Robertson (1972). In another study (of personality, disease parameters, and medication in RA), Moldofsky and Rothman (1971) found that, in comparison with those who had never received oral corticosteroids, those who had received such drugs were found to be 'less persevering, more depressed, taciturn, complaintive and demanding, dependent and easily upset'. The purpose of the present study has been:

Cell-Mediated Immunity and Resistance to Infection

Abstract: The role of specifically sensitized cells in the reaction to antigenic stimulation has been receiving increasing attention since 1942 when Landsteiner and Chase first demonstrated that tuberculin sensitivity in guinea-pigs could be passively transferred by living peritoneal exudate cells but not by serum antibodies. The current state of knowledge of the nature and function of the cells responsible for this and similar reactions of delayed hypersensitivity is admirably summarized in this recent WHO publication. Despite the compression of a vast amount of factual information into a remarkably small volume, the text is commendably readable and covers far more than the title suggests. In addition to the central theme, namely the characteristics of cell-mediated resistance to various types of infection, ranging from viruses to metazoa, there are useful sections on the aberrant functioning ofcell-mediated immunity, on means of recognizing such aberrant or deficient functions, on autoimmunity, and finally on prophylaxis. As in similar WHO publications, there is a useful bibliography but no half-tone illustrations. The clarity of the exposition makes their absence hardly noticeable and no doubt contributes to the extremely low price. The increasing appreciation of the pathogenic role of immunological reactions in many ofthe rheumatic diseases should tempt many rheumatologists to glance through this book or even to buy it. The immunological novicemay find it hard going but very well worth the effort. L. E. GLYNN

Effects of steroid hormones on human fibroblasts in vitro. I. Glucocorticoid action on cell growth and collagen synthesis.

Abstract: Fibroblasts are the predominant cells of connective tissue and their integrity is therefore dependent upon factors which influence the metabolism of these cells. The sensitivity of fibroblasts to anti-inflammatory steroids has been shown by the suppression of collagen and mucopolysaccharide synthesis in vivo (Castor and Baker, 1950; Mancini, Stringa, and Canepa, 1960; Houck, Sharma, Patel, and Gladner, 1968) and in vitro (Castor, 1965), and the inhibition of cell growth in vitro (Grossfeld, 1959; Wellings and Moon, 1961; Berliner and Ruhmann, 1967). During prolonged therapy with anti-inflammatory steroids the inhibition described at a cellular level in vitro is reflected in vivo by an increased susceptibility to skin bruising (West, 1961) and by a decrease in skin thickness (Grahame, 1969). At the site of 'steroid bruising' there is a loss and disorganization of dermal collagen (Scarborough and Shuster, 1960). In order to study the mode of action of antiinflammatory steroids on skin, an in vitro fibroblast culture system has been used, and in this paper the effects of two anti-inflammatory steroids (prednisolone and cortisol) on fibroblast growth and metabolism will be described.

Neutrophil chemotaxis in systemic lupus erythematosus.

Abstract: A high incidence ofinfections in patients with systemic lupus erythematosus (SLE) has frequently been commented upon (Harvey, Shulman, Tumulty, Conley, and Schoenrich, 1954; Jessar, LamontHavers, and Ragan, 1953; Carpenter and Sturgill, 1964; Ropes, 1964) and a recent study has offered some further support for this contention (Staples, Gerding, Decker, and Gordon, 1970). At least part of the explanation for the apparent increase in susceptibility to infections in SLE may be related to the frequent therapeutic use of immunosuppressive agents in these patients. In addition, renal failure, a clinical development associated with a high incidence of infections (Montgomerie, Kalmanson, and Guze, 1968), is common in SLE. Hypocomplementaemia is a frequent finding, particularly when active renal disease is present (Schur and Sandson, 1968) and decreased antibody responses to bacterial antigens have been described (Baum and Ziff, 1969). Granulocytopenia may occur and bone marrow granulocyte reserves have been shown to be diminished (Kimball, Wolff, Talal, Plotz, and Decker, 1973). In some patients phagocytosis has been found to be defective (Brandt and Hedberg, 1969; Orozco, Jasin, and Ziff, 1970). A cellular defect in chemotaxis has been described in a single patient with SLE (Mowat and Baum, 1971a). Another study reported normal neutrophil chemotactic responses, but serum chemotactic activity was not evaluated (Zivkovic and Baum, 1972). In vivo leukocyte migration has been reported to be diminished in patients with SLE (Gewurz, Page, Pickering, and Good, 1967). The current study was undertaken to examine both serum and cellular factors in neutrophil chemotaxis in a group of 23 patients with SLE. Utilizing the in vitro Boyden chamber technique, experiments were designed to evaluate the ability of the patients' serum to generate chemotactic factors and the capacity of the patients' neutrophils to migrate in response to a chemotactic stimulus. Results were correlated with various clinical parameters of disease activity.

Tissue gold levels after chrysotherapy.

Abstract: Although theuseofgoldsalts inthetreatment of rheumatoid arthritis iswell established, themodeof action isstill notknown.Thefinding thatgoldis takenup by synovial tissue macrophages and accumulates inthelysosomes(Persellin andZiff, 1966) hasledtospeculation thatperhaps itacts either by lysosomestabilization, as doeshydrocortisone (Weissmann andThomas, 1963), orbythe inhibition ofthelysosomal enzymes,acidphosphatase, /J-glucuronidase, andcathepsin, asisknownto occurinvitro (Ennis, Granda, andPosner, 1968). These mechanisms would presupposeasite ofaction ofgoldwithin thesynovial membraneandcavity. Yetinformation on thequantitative aspects ofgold deposition inthebodyduring chrysotherapy is scanty, andsuchdataasthere aresuggest thatthe bulkofthegoldbothinman (Gottlieb, Smith, and Smith, 1972) andinanimals (Betrand, Waine, and Tobias, 1948) isselectively concentrated inthelymph nodes, liver, andbonemarrow,withrelatively small concentrations inarticular structures. Thisreport concernsa study oftissue gold concentrations insynovium, striated muscle, bone, and fatinpatients whohavereceived chrysotherapy, and ispartofa larger study setup toattempt todefine those factors whichmightimprove thesuccessrate ofthis formoftherapy.

Periarthritis of the shoulder. Trial of treatments investigated by multivariate analysis.

Abstract: Periarthritis of the shoulder remains one of the commonest rheumatic disorders in general practice. Its pathogenesis is mysterious and its treatment empirical. Suggested treatments have included radiotherapy (Coventry, 1953; Steinbrocker, Neustadt, and Bosch, 1955), ultrasonic therapy (Fransway, 1960), local injections of hydrocortisone (Murnaghan and McIntosh, 1955), heat (Thompson, 1962), short-wave diathermy (Dickson and Crosby, 1932; Levy and Boas, 1938), exercises (Coventry, 1953), gentle traction (Burt, Fletcher, Kininmonth, and Mattingly, 1955), pressure over sensitive points (Levy and Boas, 1938), massage (Thompson, 1962), corticosteroids (Coventry, 1953), ACTH (Solomon, Carp, Berkowitz, Spitzer, Silver, and Steinbrocker, 1951), distension during arthrography (Andren and Lundberg, 1965), injection of trigger point (Travell, Rinzler, and Herman, 1942; Coventry, 1953), and manipulation (Haggart, Dignam, and Sullivan, 1956). The very diversity of these methods casts doubt on the efficacy of any. The present trial was designed to show whether three treatments for periarthritis of the shoulder (namely hydrocortisone to the joint and exercises, hydrocortisone to the bicipital tendon and exercises, and heat and exercises) were superior to an analgesic control. The effect of three different methods of treatment on the shoulder movement of such patients was compared with that of analgesics only. Component analysis was used to determine the significance of the changes in movement.

Destructive arthropathy in chondrocalcinosis articularis.

Abstract: Itisnowwellrecognized thatidiopathic chondrocalcinosis articularis, aswell asbeing associated with acute episodes ofpyrophosphate arthropathy, may lead topremature degenerative changes inthejoints involved. Someworkers havealsomadeoccasional reference tothepresence ofjuxta-articular osteolytic lesions (McCarty, Kohn,andFaires, 1962; Currey, 1970.) Morerecently there havebeenreports of destructive joint changes which canbethecauseof considerable disability (Robinson, 1971;Menkes, Simon,Chouraki, Ecoffet, Amor,andDelbarre, 1973). Fivepatients (4womenand1man), fromaseries of eighty patients withidiopathic chondrocalcinosis seen atKing's College Hospital, havedeveloped asevere destructive arthropathy. Innoneofthemwasthere evidence ofhaemochromatosis orhyperparathyroidism andserological tests forsyphilis andfor rheumatoid factor werenegative. Oneofthefive patients hasrecently developed diabetes mellitus and another hasPaget's disease, although neither ofthese conditions iscausing symptoms. Casereports Patient 1,a75-year-old man,wasfirst seenin1969complaining ofpainandswelling ofbothhandsandpainin theright kneeandneck. Investigations showed anormal erythrocyte sedimentation rate (ESR), anegative WaalerRosetest, andwidespread chondrocalcinosis inradiographs ofhiships, knees, andlumbar spine. Theserum calcium wasinthenormal range butthealkaline phosphatase wasraised at99i.u./litre (normal range30-85), andPaget's disease ofthepelvis wasseenradiologically. Apart fromthechondrocalcinosis there weredegenerative changes inthehips, knees, andspine. Theradiographs of thehandsareinteresting inthattheyshowunusual destructive changes, especially intheright hand(Fig. 1), andfaint calcification ofhyaline cartilage ispresent inthe metacarpophalangeal joint ofthemiddle finger. The destructive change atthisjoint isobvious withcyst formation andcrumbling ofthejoint surface, butmarginal erosions asseeninrheumatoid arthritis arenotpresent. Patient 2,a 69-year-old woman,developed painand swelling oftheleft shoulder. Aneffusion oftheleft shoulder joint wasaspirated andcalcium pyrophosphate crystals

Deforming arthropathy in systemic lupus erthematosus

Abstract: Arthritis is a well-recognized feature ofsystemic lupus erythematosus (SLE), which may be confused with the joint manifestations ofrheumatoid arthritis (Tumulty, 1954). Two recent reviews of the articular disorders of SLE have emphasized that, apart from aseptic necrosis, destructive and deforming arthritis is rare in this disease (Pekin and Zwaifler, 1970; Labowitz and Schumacher, 1971). Arthritis without deformity has indeed been suggested as one of the preliminary American Rheumatism Association criteria for the diagnosis ofSLE (Cohen, Reynolds, Franklin, Kulka, Ropes, Shulman, and Wallace, 1971).

Pathology of the dorsal spine in ankylosing hyperostosis.

Abstract: SELECTION OF SPECIMENS Dorsal spines were removed from twenty subjects at postmortem examination. They were judged to have AH on the basis of the presence of syndesmophytes in the form of bony flanges or bridges situated predominantly on the right anterolateral aspect of the bodies of two or more vertebrae, and the absence of previous clinical findings or other spinal pathology which could account for these features. Radiographs of the dorsal spines taken during life and post-mortem were examined independently by a radiologist and a rheumatologist who confirmed the diagnosis of AH in all the cases included in this study. The twenty cases ofAH used in this study were selected from about 500 autopsies where one of us (B.V.-R.) was personally able to examine the spine in each case, and excluded from the study were about ten other cases of AH where removal of the spine was not possible for a variety of reasons. The overall incidence of AH in patients coming to autopsy at The London Hospital is therefore in the region of 6 %. The twenty subjects comprised eleven males of mean age 66 years (range 58-77 years) and nine females of mean age 71 years (range 53-87 years). Details of the age, sex, extent of the dorsal spine affected, and the principal cause of death in each subject are shown in Table I.

Double-blind cross-over comparison of indomethacin, flurbiprofen, and placebo in ankylosing spondylitis.

Abstract: Preliminary studies of flurbiprofen, a newly introduced anti-inflammatory agent, have shown that it exerts some anti-inflammatory and analgesic effects in man when compared with placebo and is relatively well tolerated (Chalmers, Cathcart, Kumar, Dick and Buchanan, 1972). The purpose of this paper is to compare the effects of flurbiprofen, indomethacin, and placebo under double-blind conditions in a group of patients with ankylosing spondylitis.

Measurement of spinal mobility.

Abstract: In the assessment of deterioration or improvement in spinal stiffness it is important to have a measure of spinal range of movement which is reproducible, little subject to observer error, and takes only a short time to perform. In a study ofpatients with ankylosing spondylitis by one of us (FDH), which has continued since 1946, measurements by existing techniques were at first unsatisfactory and unreliable. After 3 years, however, Dunham (1949) reported the use of his spondylometer and since 1950 this has been in constant use in our clinic. We have now records of spondylometry using this instrument over a period of 23 years and have found it reliable, quick, and

Withdrawal of Allopurinol in Patients with Gout

Abstract: A few years ago the possibility was raised that allopurinol therapy might lead to the incorporation of abnormal genetic material into cell nuclei. Another potential hazard was suggested by the finding of crystals of allopurinol and oxypurinol in muscle biopsy specimens from patients taking allopurinol. It subsequently appears that the first eventuality does not in fact occur and that the second is of no clinical significance. At the time, however, it was thought to be reasonable to determine the effect of discontinuing allopurinol therapy in gout patients who were not over-producers of uric acid and whose renal function was not impaired.

Comparison of ultrasound and positive contrast arthrography in the diagnosis of popliteal and calf swellings.

Abstract: Popliteal cysts have for long been recognized as a not uncommon accompaniment ofchronic arthritis of the knee joint (Adams, 1840; Baker, 1877), and in recent years there have been frequent reports of their occurrence in patients with rheumatoid arthritis (Meyerding and Van Demark, 1943; Harvey and Corcos, 1960; Maudsley and Arden, 1961; and Hall and Scott, 1966). Detailed pressure studies by Jayson and Dixon (1970) have supported the view that a valvular mechanism is responsible for their formation and persistence, and it has been claimed that they may protect the knee joint from excessive damage (Genovese, Jayson, and Dixon, 1972). Attempts at removal of these cysts frequently lead to their recurrence, or to fistula formation (Bennett, Hughes, Bywaters, and Holt, 1972), so that anterior synovectomy may be the treatment of choice for large cysts which are causing symptoms (Jayson, Dixon, Kates, Pinder, and Coomes, 1972). A recognized complication of such cysts is rupture into the calf simulating a deep vein thrombosis (Tait, Bach, and Dixon, 1965; Myles, 1971). Genovese and others (1972), in 36 rheumatoid knees, found that only four out of ten popliteal cysts could be detected on clinical examination, but it is well known that such cysts can readily be shown by arthrography. Arthrography of the knee is generally a safe examination, but does involve the patient in some discomfort and there is a possibility that infection may be introduced. We have therefore been investigating the possibility of using an ultrasound scanning machine to produce an image of the posterior aspect of the knee and calf.

Studies on synovial fluid lymphocytes in rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is a systemic disease in which the major lesion is a chronic inflammation of the synovial membrane, with a characteristic though not pathognomonic histology. Rheumatoid activity in the synovial membrane may lead to the production of an increased amount of synovial fluid which in active cases is often richly cellular with polymorphs, monocyte-like cells, or lymphocytes predominating. The aetiology of the condition is unknown but the presence in many cases of serum rheumatoid factor, and often of increased circulating immunoglobulin and other auto-antibodies, has for long suggested involvement of the immune system. Lymphocytes are known to be closely involved in immune responses leading to graft or tumour rejection, antibody production, and delayed hypersensitivity, and it seemed prudent therefore to study their characteristics in the peripheral blood of controls and RA cases and in synovial effusions occurring in patients with RA, seropositive or negative. Lymphocytes may be identified as thymic-derived (T) or bone marrow-derived (B) cells. Both are involved as effectors ofimmune responses, though the former are especially concerned with the expression of cell mediated immunity, i.e. delayed hypersensitivity, and the latter as the precursors of plasma cells producing circulating antibodies. T cells are also important as helper cells in the response to antigensthough co-operation with other cells in all these immune processes is likely. Human T cells do not differ morphologically from B cells by ordinary light microscopy. Electron microscopy reveals differences in surface conformation (Polliack, Lampen, Clarkson, De Harven, Bentwich, Siegal ,and Kunkel, 1973). T cells may be detected by their ability to form rosettes with sheep red cells (Lay, Mendes, Bianco, and Nussenzweig, 1971; Jondal, Holm, and Wigzell, 1972; Papamichail, Holborow, Keith, and Currey, 1972). Additionally, they respond to the mitogen phytohaemagglutinin (PHA) more readily than B cells (Greaves, Owen, and Raff, 1973). B cells may be distinguished from T cells by the presence of surface immunoglobulins (Papamichail, Brown, and Hol-

Spontaneous rupture of the liver in systemic lupus erythematosus.

Abstract: The commonest cause of rupture of the liver in this the patient improved through a period of intensive care. country is severe blunt trauma to the abdomen, She subsequently deteriorated, became increasingly particularly in road traffic accidents. Though rupture icteric, and developed a staphylococcal septicaemia. She either spontaneously or after minimal trauma may suffered a cardiac arrest on her 14th postoperative day occur in malarious areas, such an occurrence is rare and died 24 hours later. in.masrios areas,tsuchnanhoccurrenceeisfrar The resected lobe of liver measured 23 x 15 x 9 cm, in Brita A case is reported in which rupture Of the and had a subcapsular haematoma measuring 22 x 13 x liver occurred as an apparently spontaneous event. 0cm. The whole specimen weighed 1,350 g (Fig. 1).

Follow-up study of 100 cases of juvenile rheumatoid arthritis.

Abstract: Although juvenile rheumatoid arthritis (JRA) was first described by Cornil (1864) and by Still (1897), the paediatrician often encounters aetiological, diagnostic, and prognostic problems. The purpose of the present follow-up study is to review our experience of this disease in recent years in an attempt to add to our knowledge of its natural history and in particular to clarify the long-term prognosis of JRA and the factors affecting it. As far as we can ascertain the previous review articles in Britain on JRA were published by Colver (1937), Ansell and Bywaters (1959), and Schlesinger, Forsyth, White, Smellie, and Stroud (1961). To-day most would agree that Still's disease is but one part of a larger spectrum of rheumatoid disease in adults and children (Bywaters, 1971; Calabro and Marchesano, 1967), although age at onset still seems to be an important factor in its presentation and evolution.

Digest of data on the rheumatic diseases. 5. Morbidity in industry, and rheumatism in general practice.

Abstract: (1) Data on sickness and injury incapacity for work in Great Britain in 1969-1970 from the Department of Health and Social Security (DHSS) Annual Report 1971, and from Digest of Statistics analysing Certificates of Incapacity, June, 1968-May, 1969, supplemented by further details supplied by the Department. (2) Data on handicapped persons on the General Classes Registers of local authorities in England and Wales at December 31, 1970, from the same sources. (3) Data on Registered Disabled Persons at April 20, 1970, from the Employment and Productivity Gazette, November 1970, supplemented by further details supplied by the Department of Employment and Productivity (DEP). (4) Mortality data from the Registrar General's Statistical Review of England and Wales and the Annual Report of the Registrar General for Scotland, both for the year 1970. (5) Data on handicapped persons and on rheumatism in general practice derived from a variety of published