heberden society: combined meeting, july...

Annals of the Rheumatic Diseases, 1979, 38, 563-576

Heberden Society: Combined Meeting, July 1979A combined meeting of the Heberden Society, theBritish Association for Rheumatology and Rehabili-tation, and the Section of Rheumatology andRehabilitation of the Royal Society of Medicinewas held at Owen's Park, Manchester, on 12-13July 1979. The meeting consisted of (1) a symposiumon the relevance of contemporary epidemiology toclinical rheumatology; (2) a scientific meetingconsisting of 'free' papers selected by the societies;and (3) demonstrations which were intended toaugment the scientific communications and toemphasise the shared aims and interests of healthprofessionals and medically related industry.

THE SYMPOSIUM

The relevance of contemporary epidemiology toclinical practice in rheumatology. ARC EpidemiologyResearch Unit, University of Manchester (on theoccasion ofthe 25th anniversary of its establishment).Lilienfeld: The epidemiologist attempts to integratedata from diverse disciplines, evaluating the inter-action of these factors relative to time, place andperson.

Lalonde's new perspective: biological and geneticfactors, environmental hazards, life style andbehaviour, health care, and the organisation ofservices.

In considering the health of human populationsfrom these points of view it is customary to followone or more of Morris's approaches to epidemiology:

ClassicalDiagnosis dimensions of disease experienceEtiology seeking causes of health and diseaseHistory changing pattern of disease

RecentSyndromes identifying associationsNatural history completing clinical pictureRisk factors estimating chancesTreatment effectiveness-controlled trials, benefit vs.

risk, etc.efficiency-working ofhealth services

The main presentations at the symposiumreviewed work appertaining to these considerations,with particular emphasis on relevance for clinicalrheumatologists.

Medical characteristics in populations. J. H. Kellgren,Emeritus Professor of Rheumatology. Manchester.Some of the early studies of chronic rheumatic

diseases in populations were described with specialreference to the way in which the features of rheu-matic diseases as observed in populations differfrom those found in patients-especially thoseattending rheumatism clinics. The import of thesefindings on clinical practice and on our understand-ing of rheumatic diseases were diseussed.

Medical characteristics in patients-Identifying syn-dromes and the diagnostic process. Philip H N Wood.ARC Epidemiology Research Unit, University ofManchester.

Sophisticated epidemiological study of rheumaticdisorders is handicapped by a series of genericproblems: events are usually ill-defined; statesexpress themselves in variable ways; methodologyis cumbersome and blunt; disease concepts areunsatisfactory; causal models are obscure; andinformation to set the challenge in perspective hasbeen deficient. The implications of these difficultiesfor research strategies were considered.A key problem is nosological-rheumatic dis-

orders lack a hallmark, a typical feature or test bywhich to identify a specific condition. Associated withthis are difficulties with illness-disease discordanceand heterogeneity. One response has been to assistwith clinical studies of natural history-examiningthe basis on which diagnosis is made, and seekingsyndromes within heterogeneous material (juvenilechronic arthritis is the prime example). Diseaseclassification and nomenclature are also relevant, asis variability in geographical expression.

Illness in context-Behavioural characteristics inpatients and populations. Michael R. Bury. ARCEpidemiology Research Unit, University of Man-chester.

Rheumatology has long been concerned withpsychological and social factors. The pioneeringwork of Sidney Cobb sought to account for theoccurrence of RA by examining the family back-grounds of patients. He pointed to a possible linkbetween types of familial experiences and the onsetof disease. Despite the fact that this work was limitedby its concern with causation, as other workers have

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564 Annals of the Rheumatic Diseases

indicated, interest in psychological and socialaetiology remains. In recent years a wider view hasemerged, focusing on the disabling consequences ofrheumatic disease. Concern has shifted from identi-fying particular 'personality types' to the problemsofchronic illness and rehabilitation, and the resourcesthat individuals are able to call on in adapting todisability. Variations among patients may reflectindividual characteristics, whether in handlingpractical problems or in more sensitive areas such assexual relationships. However, much variation in theconsequences of rheumatic disease may be accountedfor by cultural patterning for example in the reactionto pain. Chronic illness typically involves emotionalproblems and there is a need to complement indi-vidually oriented approaches by those stressingthe social context, especially the family and widersocial network, in which the individual lives.

The challenge for medicine-The consequences ofdisease; impairment, disability, and handicap. Eliza-beth M. Badley. ARC Epidemiology Research Unit,University of Manchester.

When dealing with chronic illness there is usually a

limited potential for medical intervention to abolishor reverse the manifestations of the disease process.The challenge is therefore the amelioration of diseaseconsequences. Individual clinical manifestationsmay give rise to impairment, which in turn can

cause disability. These can then lead to disadvan-tage, or handicap, in all aspects of life.

In assessing the patient the need, then, is to lookbeyond the immediate clinical findings so as to setthem in context. An understanding of the relation-ship between impairment and disability becomesimportant in directing therapy to underlying prob-lems, and also provides the opportunity for thedevelopment of more focused outcome measures. Inparticular, monitoring the functional status ofpatients creates the possibility of evaluation of thelong-term effects of disease-course altering drugs.A more comprehensive view of the impact ofdisease is provided by the concept of handicap,and this can be assessed by a systematic review of thedisadvantage experienced in the different dimensionsof handicap: orientations, physical independence,mobility, occupation, social integration, and eco-

nomic self-sufficiency.

Towards a better future-Medical care and theprovision of services. Alwyn Smith.

Provision of services to meet the needs of a com-

munity is closely analogous to treating an individual

patient; it must depend on the most precise possiblediagnosis of the specific problem or problems, thesetting of specified objectives and the institutionof a continuous monitoring of progress and assess-ment of outcome. Statistical data are as necessaryto the provision of such a standard of service to acommunity as clinical observations are to thetreatment of an individual patient. If the statisticaldata are to be as useful as clinical observationsusually are, doctors must accept responsibility forensuring their quality.

SCIENTIFIC MEETING

The following papers were presented:

HLA typing in seronegative oligoarthritis. C. J.Eastmond, S. M. Rajah, D. Tovey, V. Wright, Leeds.

Peripheral arthritis is a well recognised feature ofseronegative spondarthritis even when the spinaldisease is predominant. The present study wasundertaken to determine (1) if histocompatibility(14LA) typing was of the diagnostic value in thosepatients with seronegative oligoarthritis who lackedspinal and extra-articular features characteristicof this group of diseases, and (2) if HLA B27positive patients had any distinguishing clinicalfeatures when compared with HLA B27 negativepatients.

26 (20 male) consecutive patients with a sero-negative peripheral oligoarthritis were studiedclinically, had an AP pelvic radiograph and wereHLA typed. Patients with definite radiologicalabnormailities of the sacroiliac joints were excluded.Their mean age was 25 * 3 years (range 9-64). Nonehad more than 6 joints affected at once; 18 had two(12 patients) or one (6 patients) only involved. Thelower limb weight bearing joints were most com-monly affected 22 (84 6 %) patients had a synovitisof one or both knees and 7 (26 9%) had low backor buttock pain and stiffness.

18 patients (14 male) were HLA B27 positive.Two had minor unilateral radiological abnormalitiesof the sacroiliac joints. B27 positive and negativepatients did not significantly differ with respect ofsex ratio, age of onset, number or site of jointsaffected. Five B27 positive patients gave a pasthistory, or subsequently developed, extra-articularfeatures characteristic of seronegative spondarth-ritis, but that did not coincide with the arthritisleading to their ascertainment. Two B27 positivemales had first degree relatives with ankylosingspondylitis.



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Conclusion. (1) HLA typing may be of diagnosticvalue in patients with a seronegative oligoarthritiswhen other features of seronegative spondarthritisare absent. (2) HLA B27 is not associated with any

particular clinical features of the arthritis.

Regional differences of HLA antigens in Behcet'sdisease. H. Yazici, I. Schreuder, H. A. Chamberlain,A. Muftuoglu. Carrahpsa Medical School, Uni-versity of Istanbul, Turkey; University Hospital,Leiden, Holland; University of Leeds MedicalSchool, England.

Marked regional differences are reported in theassociation of Beh9et's syndrome with HLA B5.1 2To evaluate these further we have compared thehistocompatibility antigens of a group of Turkishpatients with a group of English patients in the sametissue typing laboratory (Department of Immuno-haematology, University Hospital, Leiden). Allpatients had ABC loci typing by the NIH techniqueutilising antisera against 37 specificities. Bloodsfrom 52 Turkish controls and 34 English controlswere similarly typed, typing for B5 subgroups aswell as DR typing.Nineteen Turkish and 14 English patients had

DR typing by B cell cytotoxicity utilising antiseraagainst 10 specificities. There were strong associa-tions of B5 and Bw5 1 with the Turkish patients(19/22 vs. 22/52, P<0O01; 18/22 vs. 12/52, P<0 0005respectively). 4/18 English patients and 8/34 Englishcontrols carried B5 and/or its subgroups. HLA B27was raised in the British patients (4/14 vs. 1/34,P<0 05 (corrected)) (ARR 12 v 6).

HLA Istanbul Leeds

Patients Controls Patients Controlsn=22 n=52 n=14 n=34

*B5 19 22 4 6tBw5- 1 18 12 3 4Bw5-2 1 10 1 2B27 1 2 4 1

*Istanbul B5, P<0.01, ARR 8.tlstanbul B5- 1, P<0-0005, ARR 16.

References

I Chamberlain M A. Ann Rheum Dis 1977; 36: 491.2 Yazici H et al. Clin Exp Immunol 1977; 30: 259.

BLA antigens, immunoglobulin and complementstudies in psoriasis and psoriatic arthritis. T. J.Daymond, M. Thompson. Royal Victoria Infirmary,

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Newcastle upon Tyne. J. Bernal, J. Wentzel.Department of Human Genetics, Newcastle Univer-sity.

Genetic and environmental factors have beenimplicated in the aetiology of psoriasis and psoriaticarthritis and HLA antigens are known to be asso-ciated with immune mechanisms. We have studiedHLA antigens, immunoglobulins (Ig), complementfactor levels and 3rd component of complementphenotypes to investigate possible differences bet-ween the two states of the disease. 48 patients withpsoriasis and 60 with psoriatic arthritis (8 withsacroiliitis) were studied. HLA antigen typing wasperformed by lymphocytotoxicity technique. Iglevels, C3c, C4, and C3 activating factor weredetermined by radial immunodiffusion. The slow(S) and fast (F) phenotypes of the 3rd component ofcomplement were isolated by high voltage agarosegel electrophoresis.

Results: there was a statistically significantincrease in HLA B27 in psoriatic arthritis(P<0.025) but in no other HLA antigen; 4/8patients with sacroiliitis were B27 positive. Therewas a statistically significant increase in IgG(P<0.002), IgM (P<0-02) and 04 (P<0-02) inpatients suffering from psoriatic arthritis irrespectiveof whether they were B27 positive or negative.Patients with sacroiliitis had a significant increase inIgG, IgE, and decrease in C3c compared with therest.The distribution of S and F phenotypes was

comparable in both psoriasis and psoriatic arthritis.

Genetics of ankylosing spondylitis. F. E. Nichol,J. C. Woodrow. Department of Medicine, LiverpoolUniversity, England.

Studies of ankylosing spondylitis have been carriedout in HLA B27 positive individuals in populationsamples, in families of patients with the disease andin identical twin pairs.

Radiological evidence of ankylosing spondylitiswas found in 20% of the males and 9% of thefemales in the population samples. In the familystudies of probands with ankylosing spondylitis50% of HLA B27 positive fathers and 5% of HLAB27 positive mothers had ankylosing spondylitis,illustrating the familial aggregation of the disease.However, studies of identical twins showing dis-cordance for the disease suggests an environmentalfactor is necessary for the disease to appear.

Analysis of the data suggests that there is anindependently segregating gene, in addition to HLAB27, which predisposes to ankylosing spondylitis.



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Tienilic acid. Simultaneous regulation of gout andhypertension. J. A. Reardon, J. T. Scott. KennedyInstitute of Rheumatology, London.

A major problem in the management of gout iscontrol of frequently associated hypertension.Increase in serum uric acid with most diureticseither precipitates acute gout attacks or requireslarger, doses of uricosurics or allopurinol.

Tienilic acid, a diuretic with uricosuric properties,has been reported to lower serum uric acid levels inhypertension, but its potential has not been pre-viously assessed in gouty patients.

Maintained on a low-purine diet through the21 days of their admission, 4 patients with gout andhypertension received varying doses of tienilicacid. Detailed measurements were made of urinaryuric acid excretion (collected 4-hourly throughout),serum acid uric (8-hourly) plasma and urine electro-lytes, fluid balance and resting blood pressure (4-hourly).Serum uric acid fell by an average 4 5 mg%

(0-27 mmol/l) to values well within the normalrange. Urinary uric acid altered little with singledaily dosage, but increased significantly with a twicedaily regimen. Reduction in diastolic blood pressurewas seen in all cases producing an average drop of22 mmHg.

Conclusions: (1) Tienilic acid is a potentiallymajor advance in management of the hypertensivegouty patient. (2) Detailed controlled inpatientstudies reveal that twice daily dosage is required forsatisfactory reduction in serum uric acid. (3) Singledaily dosage caused marked fluctuation in serumuric acid and was frequently associated with acutegout attacks, even in the presence of a normalserum urate level.

Steroid osteoporosis-where does all the calcium go?R. Amos, V. Wright. Leeds and Harrogate.A patient with rheumatoid arthritis (RA) on corti-costeroids (steroids) was turned down for hipreplacement on the basis of severe arterial diseasecharacterised by extensive calcification. The patternof calcification was typical of Monckeberg's medialarteriosclerosis (MMA), a benign disorder clini-cally and radiologically distinct from atheroma. Thestriking changes in the index patient prompted amore thorough investigation of the subject.The presence of MMA has been sought in pelvic

radiographs in 273 patients with a variety of dis-orders (see Table). In 109 consecutive admissionsto a rheumatology hospital, where pelvic radio-graphs were available, MMA was seen in 7; all 7

were rheumatoid patients who had been receivinglong-term steroid therapy. Ninety-one patientsattending the Mineral Metabolism Unit at LeedsGeneral Infirmary were reviewed; MMA was pre-sent in 14 patients and was strongly associated withsevere osteoporosis whether or not steroid induced.The relationship to steroid therapy was less strongin a group of patients with severe chronic renalfailure attending a renal unit for dialysis or followingrenal transplantation. In itself MMA represents abenign complication of steroid therapy though itmay indicate the presence of significant bone disease.

TableDiagnosis No of Patients Mean age- Mean No.

patients years duration withMale Female (range) of steroid MMA

therapyyears(range)

RA long-term steroids 26 5 21 62 8 7

(42-83) (2-21)RA-nosteroids 23 6 17 58 - 0

(27-76)OA and AS-no steroids 60 23 37 61 - 0

(19-95)Steroids forvariousdisorders 62 23 39 57 9 10

(24-81) (1-28)Spinalosteoporosisno steroids 29 7 22 63 - 4

(37-77)Chronic renalfailure(a) Onsteroids 37 27 10 34 3 7

(18-62) (3/12-8)(b) Nosteroids 36 26 10 38 - 2

(16-58)

EULAR study of adverse reactions (ARs) to D-penicillamine (D-P). A. G. L. Kay (for the StandingCommittee on International Clinical Studies).ARC Epidemiology and Guy's Arthritis ResearchUnits, Guy's Hospital, London SEl.

Many types of AR to D-P have been reported sincethe drug has been used in the treatment of rheu-matoid arthritis and allied conditions. 63 centres in17 member countries monitored 2694 patientstreated with D-P between 1 September 1977 and1 March 1979. All ARs severe enough to requiredrug withdrawal were reported. The patients weredivided into 2 groups: (1) a prospective sample ofall 1410 patients who started to take D-P on or after1 September 1977 and (2) 1284 patients alreadytaking D-P at the beginning of the study period.



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18% of group (1) and 9% of group (2) had thedrug withdrawn because of an AR. 65% of allgroup (1) ARs occurred during the first 3 months oftreatment when skin rashes, taste impairment, andgastrointestinal disturbances were most common.Renal and haemopoietic abnormalities tended topresent later. Multiple ARs were common, less so inthose developing renal or haemopoietic compli-cations. Two patients died, 1 with multiple pulmonaryabscesses, hemiparesis, and thrombocytopenia, andthe other of septicaemia with marrow failure.

It is concluded that a substantial number of seriousARs occur in association with the administration ofD-P. Early ARs are more frequent, but seriousreactions may occur after many months of treat-ment. (Note: These are provisional figures, as datastill being received).

Comparison of gold, penicilamine, and levamisole intreatment of rheumatoid arthritis. H. A. Capell,J. A. N. Rennie, P. J. Rooney, D. Spencer, W. C.Dick.Recent multicentre studies12 have compared dif-ferent dose regimens of levamisole in the treatmentof patients with rheumatoid arthritis. In view of thepotential benefit and toxicity of this drug we con-sider that data comparing levamisole at differentdoses with established second-line drugs are urgentlyrequired.

Seventy-five patients were randomly allocated totreatment with either gold, penicillamine, or leva-misole. The dose of levamisole was 150 mg/day on3 consecutive days each week and gold and peni-cillamine were given in conventional dosage. Clinicaland laboratory assessments were done at 3 and 6months.Of the 25 patients who commenced each drug,

16 remained on gold at the end of 6 months com-pared with 18 on penicillamine and 9 on levamisole.There was no significant difference in the overallclinical and laboratory response of these patients.Four patients in the levamisole group, all of whomhad responded well, developed leucopenia comparedwith one patient on gold. There was a more rapiddrop-out rate on levamisole 3 days/week than in aprevious study from this centre using levamisole 7days/week3.The place of levamisole in the treatment of

patients with rheumatoid arthritis requires con-tinuing careful evaluation.

References1 Multicentre Study Group. J Rheumatol 1978; 5: Suppl

4, 5-10.s Multicentre Study Group. Lancet 1978; 2: 1007-1012.3 El-Ghobarey et al. Q JMed 1978; 47: 385-400.

A long-term trial comparing ICI 55897 (Clozic) andpenicilamine in rheumatoid arthritis. D. Y. Bulgen,B. L. Hazleman, A. M. Mowat, A. G. Mowat.Adenbrooke's Hospital, Cambridge, and NuffieldOrthopaedic Centre, Oxford.

This new compound inhibits the chronic phase ofadjuvant arthritis in rats but is essentially devoid ofboth acute anti-inflammatory and analgesic activityin animal studies. These properties promptedstudies in rheumatoid arthritis.

Forty patients with classical or definite rheumatoidarthritis who were taking stable doses of NSAIDbut required more specific therapy were treated witheither penicillamine or ICI 55897 at 100 mg or 300mg daily for a period of 6 months. Clinical assess-ments suggested that ICI 55897 was effective, but lessso than penicillamine. Laboratory data showed asimilar fall in ESR and acute phase proteins in allgroups. Side effects in patients taking 100 mg ICI55897 daily were nil, suggesting that this drug couldprovide a safer alternative to gold and penicillamine.

Treatnent of fibrosing alveolitis with penicilamineand methotrexate. D. G. I. Scott, R. C. Bucknall,P. A. Bacon. Royal National Hospital for Rheu-matic Diseases.

Fibrosing alveolitis (FA) is a well recognised com-plication of rheumatoid arthritis (RA) and otherconnective tissue diseases and is thought to relateto circulating immune complexes. Conventionaltreatment with corticosteroids has been disappointingso alternative drugs, including immunosuppressants,are now being used. The response to penicillamine,which is known to effect systemic RA and immunecomplexes has not been well documented.

Penicillamine was given to 9 patients with FAfollowed over a period ranging from 5 months to4 years. Clinical assessment, chest radiographs andpulmonary function tests were performed before andat regular intervals during treatment. Methotrexatewas given to 3 patients with FA, followed over aperiod ranging from 10 months to 2 years andsimilarly studied.

Penicillamine had little overall effect (Table).By contrast methotrexate resulted in symptomaticimprovement in all 3 patients, radiographic improve-ment in 2, and significant improvement of lungfunction in 1 (Table 1). Some improvement incarbon monoxide transfer occurred in all 3 patientscompared with improvement of 3 patients treatedwith penicillamine and deterioration in 6. Two of thepatients treated with methotrexate had deterioratedduring previous treatment with penicillamine and 1



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Table Treatment offibrosing alveolitis with penicillamineand methotrexate1. D-penicillamine 2. Methotrexate

Diagnosis Sympt CXR PFT Diagnosis Sympt CXR PFT

Sclero- MCTD + 0 0derma + + + DM +1+ ++ +

MCTD - 0 0 RA + ++ 0RA 0 0 0RA - -RA 0 0 0RA 0 0 0RA + + 0RA - - 0RA 0 0 0

Key - Worse; 0=No change; + Improved: + + Much improved.

patient had failed to respond to large doses ofprednisolone and azathioprine.

Methotrexate may be a useful treatment of severe

FA complicating connective tissue diseases andwarrants further investigation.

Quantitation of polymorphonuclear (PMN) motilityin rheumatic diseases. G. B. Howe, K. V. Swettenham,H. L. F. Currey. Bone and Joint Research Unit,The London Hospital Medical College.

Different techniques of measuring PMN motilityhave given inconsistent results. We have studied themovement of PMN through Micropore filters usingimage analysis (Quantimet). This allows projectionof a microscopic image on to a television screen

and, with appropriate cell staining the instrument'reads' the proportion of the field occupied bystained cells in focus. This focusing on the upper

surface of the filter and then moving stepwise downthrough the full thickness of the filter provides a

profile of cell density distribution through a cylin-drical core of the filter. Automation and a linkedcomputer allow rapid analysis of repeated measure-

ments.

Conclusions. (1) 80% of cells remain within thefirst 60 ,um of the filter at 20 minutes. However, a

small fraction of cells penetrate the filter much more

rapidly, some to drop off the lower surface by 1 hour.(2) Filter thickness varies grossly (90-280 V,mwithin one batch with a stated thickness of 150 ,um± 15%). (3) These considerations indicate thatcalculations based on filter surface counts areunreliable. Leading front measurements after 20minute incubations give more reproducible resultsand correlate well with indices based on measure-ment of total cell movement. (4) Data obtained usingimage analysis make it possible to differentiatebetween total and subpopulation differences.

Polymorphonuclear (PMN) function in rheumatoidarthritis (RA) with and without neutropenia. G. B.Howe, J. N. Fordham, K. A. Brown, H. L. F.Currey. Bone and Joint Research Unit, The LondonHospital Medical College.

PMN functions were studied in 29 normal controlsand 25 patients with RA, of whom 9 had persistingneutropenia (mostly with splenomegaly, i.e., Felty'ssyndrome).With a modified Boyden chamber (3 um Micro-

pore filters) cell migration was measured by theleading front method after 20 minutes' incubation.Both random and directed locomotion were normalin patients with RA alone but significantly impairedin those with RA plus neutropenia. Directed migra-tion was tested in the presence of serum, and all RAsera supported migration as efficiently as did normalserum, suggesting that this impaired migrationreflected a cellular defect. Analysis of the data bycomputer-linked image analysis (Quantimet) showedthat this slowing of the leading front measurementwas due to an overall showing of all cells rather thandepletion of a more mobile subset.

Patients with RA alone had a significant neutro-philia compared with normal controls. Studies ofPMN adhesiveness using nylon fibre columns'showed the proportions of adhesive to nonadhesivecells to be the same between all 3 groups. Analysis ofPMN electrophoretic mobility between these groupsshowed that all patients with RA had a decrease inthe proportion of cells with a high surface chargewhen compared with normals. Changes in cellmigration correlated neither with cell adhesivenessnor with electrophoretic mobility.

ReferenceMacGregor R B, Spagnuolo P-J, Lentnek A L. N EnglJ Med 1974; 291: 642.

The incidence of RANA antibodies in rheumatoidarthritis. K. C. Ng, K. A. Brown, J. D. Perry, E. J.Holborow. Bone and Joint Research Unit, LondonHospital Medical College, London El 2AD.

Alspaugh et al.1 reported that two-thirds of sero-positive rheumatoid patients possess an antibodywhich gives characteristic immunofluorescent stain-ing ofan antigen termed rheumatoid arthritis nuclearantigen (RANA) present in EB virus transformedhuman B lymphoblastoid cell lines. We repeatedtheir findings using Tan's prototype serum forRANA, and have obtained definite positive tests forantibody against RANA with sera from 32 (84%)of 38 seropositive rheumatoid patients and weaklypositive tests in 7 (26%) out of 27 normal subjects.



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A cell line lacking the EB virus genome was negativewith all sera tested. All tests were done on codedsera without knowledge of the diagnosis. Sera werealso examined for knownEB virus antibodies, namelyVCA (viral capsid antigen) and EBNA (Epstein-Barr nuclear antigen). We have confirmed thatRANA antibodies are independent of these knownEB virus antibodies.

ReferenceAlspaugh M A, Jenson F C, Rabin H, Tan E M. Lympho-cytes transformed by Epstein-Barr virus. J Exp Med1978; 147: 1018.

Significance of humoral immunity to native type IIcollagen in the chronic inflammatory arthritides.R. B. Clague, M. J. Shaw, P. J. L. Holt. DepartmentofRheumatology, University of Manchester MedicalSchool, Manchester.

Serum IgG and IgM antibody levels to native typen collagen were measured in patients with classical/rheumatoid arthritis, Still's disease, ankylosingspondylitis and seronegative polyarthritis associatedwith psoriasis. The results are shown in the Table.The highest levels were found in RA and Still'sdisease. The 6 patients with elevated TgG antibodylevels in the ankylosing spondylitic group all hadassociated peripheral joint disease.Tn the patients with RA, there was a highly

significant correlation (P<O001) between IgGand IgM antibody levels to native type 11 collagen.Higher IgG and IgM antibody levels were found tonative type I collagen, than native type I collagen.Adsorption studies with denatured and nativecollagens as well as rabbit IgG, confirmed thespecificity of the antibodies to native type II col-lagen. Most patients with elevated levels had hadtheir arthritis for 4-8 years. The highest levelswere associated with severe erosive disease. Similarantibody levels were obtained using bovine, humanor rat native type II collagens.

It is suggested that measurement of antibodylevels to native collagen, especially type 1, may bea useful marker of erosive disease. Sequentialstudies on patients are in progress and it is hoped toreport these at the meeting.

Table Incidence ofelevated IgG and IgM antibodylevels to native type II collagen

Rheumatoid Still's Ankylosing Psoriaticarthritis disease spondylitis arthritis

Numbers ingroup 33 28 20 14

IgG 13 14 6 0IgM 19 10 1 1

A possible common ancestry for collagen aA andaB chains. Robert A. Brown, Jacqueline B. Weiss.Department of Rheumatology, University ofManchester.

It is known that at least 4 genetically distinct formsof collagen exist in the connective tissues. Three ofthese have been completely characterised and thefourth-basement membrane collagen type IV-hasbeen clearly identified.'A new form of collagen consisting of highly

glycosylated a chains has been found in rheumatoidand nonrheumatoid infiammed synovial membranesas well as from membranes of normal joints.2 Thereare at present 2 postulated structures for this newcollagen either a single molecular association(cA[oCB]2) or two separate molecular forms [xA]3and [oB]3.34The cyanogen bromide peptide patterns which we

have obtained support the concept of separatemolecular forms. At the same time they show evi-dence for common ancestry of the two ox chains.We further suggest that a third a chain [ocC] may beassociated with them and derive from the same source.

References1 Miller E J. Mol Cell Biochem 1976; 13: 165-192.2 Brown R A, Shuttleworth C A, Weiss J B. Biochem BiophysRes Commu 1978; 80: 866-872.

3 Bentz H, Backinger G R, Kuhn K. Eur J Biochem 1979;92: 563-572.

4 Rhodes R K, Miller E J. Biochemistry 1978; 17: 3442-3448.

Further studies on diagnostic criteria for poly-myalgia rheumatica. H. A. Bird, W. Esselinckx,A. St. J. Dixon, A. G. Mowat, P. H. N. Wood.

An earlier presentation to the Heberden Society in1978 reported the performance of diagnosticcriteria for polymyalgia rheumatica (PMR) in 263patients who were thought unequivocally to besuffering from this condition. We also mentionedthat 70 patients who might possibly have had PMRwere also being studied.

These patients with possible PMR have now beenfollowed up after an interval of approximately 3years. Their clinical status has been assessed, themost likely diagnosis of their original problem hasbeen reviewed in retrospect, and the discriminatoryperformance of the proposed criteria originallyfulfilled has been analysed.Our proposed criteria were not applied in the

possible cases in our original analysis. It is encour-aging that, of those fulfilling 3 criteria, the responseto a therapeutic test with prednisolone providedvery good discrimination. In the largest series of



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cases from one centre, of 15 with 3 criteria 8 had apositive steroid test and all had PMR; 4 had anegative test and on review had RA or OA; and in3 in whom the test was not done the diagnosisremained uncertain.We have also explored the value of less stringent

models, requiring the presence of only 2 criteriaif there was also a response to prednisolone. Onceagain the results in those with possible PMR wereencouraging, although reanalysis of our originaldata from this point of view does not support theidea that the minimal number of criteria might bereduced other than in very specific circumstances.

Longitudinal studies of circulating immune complexesand acute phase reactants in polymyalgia rheumaticaand giant cell arteritis. J. Park, J. G. Jones, B. L.Hazleman. Addenbrooke's Hospital, Cambridge.

The relationship between acute phase reactants,immune complexes, and disease activity was studiedin 108 patients with polymyalgia rheumatica and/orgiant cell arteritis.The erythrocyte sedimentation rate (ESR) is the

acute phase reactant commonly measured. However,it can be unreliable as an indicator of diseaseactivity. Other acute phase reactants measured wereC-reactive protein (CRP), xc antitrypsin, orosomu-coid, and haptoglobin. Jmmune complexes weremeasured by the polyethyleneglycol precipitationcomplement consumption assay.144% of an active untreated group (21 patients)

had increased levels of immune complexes whereas23 of an inactive group (49 patients) were raised.They were increased in patients with arteritis.

Detailed longitudinal studies revealed a goodcorrelation between CRP, ESR, and disease activity.It is concluded that the additional measurements ofimmune complexes and acute phase reactants are nobetter at reflecting fluctuations in disease activitythan the ESR.

Reference1 Harkiss G D, Brown D C. Clin Exp Immunol 1979; 3.

The prognosis and management of polymyaWarheumatica (PMR). J. G. Jones, B. L. Hazleman.Addenbrooke's Hospital, Cambridge.

PMR is considered a benign disease by some' whileothers2 think it is a more serious illness whichrequires similar treatment to giant cell arteritis.The progress of 85 patients with PMR who pre-sented to a district general hospital has been studiedin an attempt to study this relationship.

Thirty-eight patients had PMR alone, 14 develop-ed PMR and GCA within one month. Five patientspresented with GCA and then developed PMR and28 patients developed symptoms of GCA afterpresenting with PMR (PMR to GCA). The meaninterval from onset ofPMR to onset of symptoms ofGCA was 1 year (1 month-9 years).Twenty-two patients (25%) developed some

cerebral or visual complication (see Table). 15 ofthese patients were in the PMR-GCA group. Sevenpatients developed complications while on corti-costeroids.

Table Cerebral and visual complications in 22 patientswith PMRPermanent loss of vision 6Temporary loss of vision 7Permanent lateral rectus palsy 1Transient third nerve palsy ITransient diplopia 4Transient visual blurring 5Meteorism 1Hemiparesis 4Vertebrobasilar ischaemia 1Vertigo 2Deafness I

Several patients had more than one complication.

All but 6 patients were treated with corticosteroids.Nine patients were able to stop treatment but theremainder still require therapy.

In this group of patients PMR appears to resultin potentially serious complications in 25% ofpatients. Low doses of steroids did not alwaysprevent these side effects occurring.

References

1 Ettlinger R E et al. Ann Rev Med 1978; 29: 15.2 Hamilton C R et al. Medicine 1971; 50: 1.

Is idiopathic pulmonary hypertension (IPH) aconnective tissue disease? P. J. L. Holt, R. B. Clague,F. C. Hay, L. J. Nineham, E. G. Wade. UniversityDepartment of Rheumatology and Cardiology,Manchester Royal Infirmary, Manchester andImmunology Department, Middlesex Hospital,London.

Previous papers have suggested that IPH mayrepresent one of the connective tissue diseases.Twenty-five patients have been studied. In nonewas there clinical features of systemic disease and inparticular no evidence of rheumatoid disease, SLEor systemic sclerosis. Two patients had a positiveRose-Waaler titre and none had raised anti-DNAantibodies. Thirteen patients with chronic heartdisease and pulmonary hypertension and 10 patients



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with congenital heart disease and hypertensionwere examined. A high incidence of immunologicalabnormalities was found (see Table). The auto-antibodies found in the various conditions differed:in IPH they were mainly antinuclear and anti-thymic; smooth muscle antibodies were only foundin patients with congenital heart disease; the patientswith rheumatic heart disease had a mixture of auto-antibodies. Small quantities of circulating immunecomplexes were found in all groups.

Table Number ofpatients with raised valuesIgA IgG IgGRF IgMRF Auto-

antibodies

IPH 25 7 8 16 8 17*SPH 13 9 8 6 5 4CHD 10 5 3 0 0 2

All these 17 patients had two auto-antibodies. IgGRF and IgM RFby radioimmunoassay. IPH=idiopathic pulmonary hypertension.SPH=secondary pulmonary hypertension. CHD=congenital heartdisease.

Rheumatoid factors of both IgG and IgM typewere raised in patients with both IPH and hyper-tension secondary to rheumatic heart disease butnot when congenital heart disease was the cause ofpulmonary hypertension. From these studies noclinical evidence of a generalised systemic disease,such as is found in the unusual types of connectivetissue disease has been found in IPH. But there isstrong evidence of an immunological basis for thisdisease, and this may offer hope of a method oftreatment for this usually fatal disease.

OA-Should the patient lose weight? Elvet E. Smith,Philip N. H. Wood, ARC Epidemiology ResearchUnit, University of Manchester.

A patient presenting with pain in the knees andevidence of osteoarthrosis (OA) is usually advised toreduce weight. The scientific basis for this adviceis particularly the work of Kellgren and Lawrence,1who demonstrated a relationship between assess-ments of obesity and the overall severity of radio-graphic changes in OA. However, the associationis not observed in all populations, and some clini-cians have expressed doubts about the link.

In order to explore this association further wehave reviewed data from a larger sample-theoriginal report was based on those aged 55-64, andcohort effects might have been observed. Theradiographs were reread so as to distinguish bet-ween osteophytosis and evidence of joint damagein the different compartments of the knee. Obesitywas assessed by the more sensitive Quetelet's (Q)index (weight . height2).

Because different observations have been madeone would expect the results to differ also. Just as thepattern of distribution with age is different betweenosteophytosis and joint narrowing, so their relation-ship with degrees above or below the Q index meanfor age varies as well. When the differences betweenmedial and lateral compartments are taken intoaccount the associations become far more complex.Although dispatching a patient with one problem,painful knees, after inflicting a second problem,dieting, may promote relief of symptoms, the aetio-logical significance of obesity in regard to OA kneesis far from straightforward.

Reference

Kellgren J H, Lawrence J S. Ann Rheum Dis 1958; 17:388.

Measurement ofquadriceps muscle wasting. A. Young,I. Hughes, P. Russell, M. J. Parker. Oxford Rehabili-tation Research Unit.

It is difmcult to obtain an objective measure of thesize of an individual muscle. In a needle biopsy studyof quadriceps wasting following lower leg fractureand subsequent knee immobilisation 1 measurementsofmuscle fibre size suggested that quadriceps wastingmight sometimes be much greater than would beexpected from anthropometric estimates of fat-free thigh volume.

Grey-scale ultrasonography can produce an imageof the quadriceps muscle from which it is possibleto measure its cross-sectional area (CSA). Thebetween-days coefficient of variation for quadricepsCSA (at mid-thigh) in 14 legs of 7 subjects eachscanned on 4 days was reduced to 4 * 0% by averag-ing 4 scans on each day.

Bilateral scans at the mid-thigh level were usedto measure the severity of quadriceps wasting inotherwise healthy adult patients with at least 2 cmdiscrepancy in thigh circumference following uni-lateral knee immobilisation or injury. Quadricepswasting as demonstrated by the scans was consist-ently more severe than the disparity in thigh cross-sectional area at the same level or the disparityin anthropometric estimates of fat-free thigh volume.The extent to which measurements of thigh cir-cumference may underestimate the severity ofquadriceps wasting must be recognised if clinicalmeasurements are to be correctly interpreted.

Reference

Sargeant A J, Davies C T M, Edwards R H T, MaunderC, Young A. Clin Sci Molec Med 1977; 52: 337-342.



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Profile of rheumatic disabilities. Elizabeth M. Badley,Michael R. Bury, Philip H. N. Wood. AREpidemiology Research Unit, Manchester.

A lengthy enumeration of disabilities present can bedaunting for all concerned. For research purposesGuttmann scaling has been used for simplification,with the assumption that activities can be ordered sothat inability to perform one would imply inabilitywith those further up the scale. However, thisempirical approach offers little to the clinical team-they cannot avoid all the diverse individual prob-lems and the implication that each need should bemet.The interrelationship between various disabilities

can be approached in other ways. We have studiedthe range of disabilities in individuals with RA,OA, and back troubles, using these as models forpolyarticular, monarticular, and spinal involvemeniin the light of clusters of activities identified pre-viously.1 Comparison between the groups highlightedthe dominant influences of age and sex and of fea-tures associated with these, such as living alone.After allowing for these we have explored theinterdependence of different disabilities.The patterns of disabilities were much as would be

expected on the basis of clinical experience and thefeatures of the underlying conditions. However, theattempt to display regularities in these relationshipshas proved instructive. The results suggest ways inwhich the process of assessment might be simplified,with potential implications for clinical practice as wellas research.

Reference1 Badley E M, Lee J, Wooh P H N. Rheumatol Rehabil

1979; 18: 105.

Antirheumatic drug treatment of outpatients: atolerance study. A. Kay, R. Jacoby, M. I. V. Jayson.University of Bristol and the ARC Epidemiologyand Guy's Arthritis Research Units, Guy's Hospital,London SEl.

A pilot study suggested that discontinuation of drugtreatment was common among rheumatic patients.119 (3 Y.) of the patients attending the rheumatologyclinics at Bristol Royal Infirmary, between 1 April1976 and 1 February 1977, had their drug therapyadded to or changed. There were 49 males and71 females, mean age 47 years: two-thirds of thepatients were receiving treatment for rheumatoidarthritis or other inflammatory arthropathies.The patients were registered and the details of

their drug treatment recorded. Within 3 months ofstarting the new treatment (index drug(s)) eachpatient was submitted to a written questionnaire:clinic follow-up of treatment outcome was also main-tained for 1 year.

123 index drugs were prescribed and by the endof the year only 36 (29%) of them were still beingtaken. 41 of the drugs had been stopped during thefirst 3 months nearly half of these because of theadverse effects. Eight drugs accounted for over 90%of index prescribing: corticosteroids were not used.The drugs most commonly used were indomethacin,ibuprofen, and naproxen. Half the patients on goldand penicillamine and a quarter of those on indo-methacin developed adverse reactions.

Observations made in one rheumatology clinicshowed adverse reactions to be the commonestcause of drug withdrawal. The range of drugs usedwas small.

Survival in rheumatoid arthritis. John E. Zlosnik,Philip H. N. Wood, ARC Epidemiology ResearchUnit, Manchester.

An earlier 20 year follow-up of 189 Harrogatepatients with RA1 demonstrated that in both sexesand at all ages mortality was higher than in thegeneral population of England, and that this wascorrelated with the initial grade of functionalimpairment However, deaths from the individualcauses were too few to establish satisfactorily anyexcess or deficit of particular diseases.

Because of the theoretical interest of positivelyand negatively associated conditions (includingsuggested deficits of myocardial infarction andexcesses of infection and renal disease), an attempthas been made to augment these data by 20 yearfollow-up of 252 Hammersmith patients (Bywaters)and 307 Edinburgh patients (Duthie).The results permit calculation of the degree of

under-reporting of RA on death certificates, whichallows overall prevalence estimates to be generatedfrom routine mortality statistics. The generallyreduced chances of survival in RA were confirmed,as were various features associated with an unfavour-able outcome.Even with this large series of cases there is

difficulty in assessing the significance of the asso-ciation of certain causes of death (e.g., suicide).This material is useful as a reference standard forcomparison with groups of patients, either withparticular features or submitted to various forms oftreatment. The most important limitation is thatthis experience is not representative of today's



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patients, but this is unavoidable and importantlessons can nevertheless be learned.

Reference1 Benn R T, Wood P H N. Br JPrev Soc Med 1972; 26: 60.

The long-term management of early rheumatoidarthritis. R. Million, J. H. Kellgren, P. H. Poole,M. I. V. Jayson. Department of Rheumatology,University of Manchester.We have completed a long-term study over 10 yearscomparing 2 different philosophies of treatment forearly definite and classical arthritis. In the first(group I) the patients were kept mobile avoidingrest and splintage but using nonsteroidal anti-inflammatory drugs (NSAID), specific antirheu-matic agents, and the responsible administrationof systemic prednisolone up to 20 mg/day. Thesecond (group II) received conservative treatmentwith rest, splints, NSAID, and specific antirheumaticagents but excluding the use of systemic steroids. Ifthe disease was inadequately controlled the patientswere transferred to a common regimen involvingboth forms of treatment. 103 patients were entered(53 group I, 50 group II). After 10 years only 24remained in group I (9 on steroids, mean dose 9 5mg/day) and 22 in group H. Thirty-seven patients inall received steroid therapy.

In the majority of parameters the patients remain-ing in group I were better than in group II and inseveral of these the differences achieved statisticalsignificance. Seven of the group I patients died (2steroid related, 0 disease related) and 8 of group II(0 disease related 1 treatment related). Four patients,2 from each group, suffered vertebral body collapse,but all had severe disease, had failed the initialtreatment programmes, and were in the finalcommon regime. Other side effects of treatment werecomparable in the 2 groups. The patients who failedthe 2 regimens ended up receiving similar forms oftreatment. At the end of 10 years the clinical andlaboratory parameters in these patients were verysimilar.We conclude that maintenance of physical

activity combined with the responsible use of steroidswhen necessary may be regarded as a useful form oftreatment in early rheumatoid arthritis.

Unusual collagenase and gelatinase enzymes inimmature pig intervertebral discs. Ian Tomlinson,M. I. V. Jayson, Jacqueline B. Weiss. RheumaticDiseases Centre, University of Manchester.A collagenase capable of attacking the helical

portion of the collagen molecule has been demon-strated from day 1 in both annulus and nucleus of pigintervertebral disc. Unlike normal mammaliancollagenases this enzyme is not inhibited by EDTA.On the contrary concentrations of 5 mM EDTAand over actually enhance the activity. The enzymeis present in the free form but it can be activated bymersalyl, suggesting it is also present as an enzymeinhibitor complex. When EDTA and mersalyl areadded together to the incubation mixture, the acti-vation by mersalyl is further enhanced.Enzymes capable of acting on a gelatin substrate

are also present in the annulus of discs from day onebut cannot be detected in the nucleus of corres-ponding discs. These enzymes are always presentin the active form and treatment with mersalyltends to mildly inhibit. Treatment with EDTAactivates one of those enzymes and inhibits another.

Identification of collagenase and other neutralproteinases in human intervertebral discs. S. K. A.Sedowofia, I. Tomlinson, M. I. V. Jayson, Jac-queline B. Weiss. Rheumatic Diseases Centre,University of Manchester.Collagenolytic enzymes have been directly extractedfrom human intervertebral disc by a method whichpartially denatures the collagen matrix.1 Theseenzymes have been detected and identified in crudemixtures by means of an assay system which employsspecific substrates carrying a tritium label.2At least 2 neutral proteinases in addition to

collagenase have been detected. The collagenaseis inhibited by EDTA but not to any significantextent by cysteine. It is present in a free form as wellas in an enzyme-inhibitor complex which can beactivated by mersalyl. In contrast other thiolblocking agents such as PCMB inhibit the enzymeslightly. A neutral proteinase with high activityagainst a gelatin substrate is present in free as wellas in a zymogen form but is not apparently presentas an enzyme inhibitor complex.Free endogenous inhibitors of neutral porteinase

activity have also been demonstrated in disc tissue.

ReferencesWeeks J C, Halme J, Woessner J F. Biochem BiophysActa 1976; 445: 205-214.

2 Weiss J B, Sedowofia K A, Jones C. In: Viidik A,Vuust J, eds. The Biology of Collagen. New York:Academic Press, in press.

Is there an autoimmune basis for lumbar disc disease?M. De Silva, B. Hazleman, M. Ward, J. Park,I. Dixon. Addenbrooke's Hospital and StrangewaysLaboratories, Cambridge.



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After embryological development the nucleus pul-posus (NP) is enclosed within the annulus fibrosus(AF) and from an immunological viewpoint has beenconsidered to be a sequestered antigen. Rupture ofthe AF and posterior longitudinal ligament occursin the prolapsed intervertebral disc (IV) syndrome,exposing the NP to immunocompetent cells. Severalauthors have considered autoimmunity as a pos-sible aetiological factor1 in lumbar disc disease, andothers believe that autoimmunity could contribute tothe chronicity of symptoms.2 If valid, these conceptscould have important diagnostic therapeutic andprognostic implications.The purpose of our study was to investigate the

possible existence of an autoimmune basis. Twentypatients with prolapsed lumbar IV discs withpositive myelograms, who were subsequentlytreated surgically and an equal number of age andsex-matched controls were studied. Soluble antigenswere prepared from JV discs obtained from a freshyoung human cadaver. Lymphocyte transformation,immunoglobulin quantitation, C-reactive proteinand ESR were performed. Our results showed nosignificant differences in any of the above indicesbetween patients and controls. We were unableto confirm by our methods the existence of anautoimmune basis for intervertebral disc disease.References

Naylor A. The biophysical and biochemical aspects ofintervertebral disc herniation and degeneration. AnnR Coil Surg Engl 1962; 31: 91.

2 Gertzbein S T, Tait J H, Devlin S R. Clin Orthop 1977;123: 149-154.

Annular tears in the dorsolumbar spine (D10-L5).R. C. Hilton, J. Ball, R. T. Benn. Department ofRheumatology, University of Manchester and HopeHospital, Salford.The distribution and severity of anterior andposterior annular tears in the dorsolumbar spinehave been studied in 52 female and 65 male post-mortem spines (aged 13-96 yr) using sagittal slabsof the discs and vertebral bodies. The findings werecorrelated with angular sagittal mobility.

Results: (1) The number of cases with tears inmultiple discs increases with age but exceptionsto this trend occur in both young and elderly spines.(2) Correlation coefficients indicate that anteriorand posterior tears at L4 and L5 do not predict tearsat other levels. At L3 and above significantly posi-tive correlations occur between multiple disc levelsparticularly posteriorly. (3) The severity pattern foranterior and posterior annular tears differs withrespect to age in cases >50 yr. the mean anteriortear score rises sharply from L5 to peak at L2 and

Li in both sexes; in contrast the mean posteriortear score falls from L4 to Li in this age group. (4)The increase in severity of anterior tears corres-ponds with increased mobility in L4-L1 discs from50-70 yr. In contrast mobility of the L5 disc fallsprogressively with age.

Conclusions. The data are compatible with 2factors causing tears posteriorly one affecting L4 andL5 in young adults, and a second operating at alater age and promoting widespread disc involve-ment. The increased prevalence and severity ofanterior tears (and the associated increase inmobility) in the upper lumbar region in the middleaged and elderly may be a pathogenic factor in backpain for this age group.

Computed tomography of the lumbar spine. N. M.Antoun, I. Isherwood, K. H. Nilsen, M. I. V.Jayson. Departments of Diagnostic Radiology andRheumatology, University of Manchester.Computed tomography (CT) is an x-ray transmissiontechnique providing transaxial sections approxi-mately 1 cm in thickness. The method permits thedemonstration of spinal topographical anatomyagainst a detailed background of paravertebralstructures and body cavity organs. In particular itenables precise identification of apophyseal jointsto be made together with their relationship to thespinal canal and the intervertebral foraminae. Over3000 patients have been investigated on the EMICT5005 General Purpose Scanner in the Depart-ment of Diagnostic Radiology, University ofManchester Medical School, since 1976. The spinehas been imaged in all patients but particularattention has been directed to some 300 patientspresenting with spinal disorders. Computer assistedmyelography with a water-soluble contrast medium(metrizamide) has been employed in the demon-stration of neural tissue and the pathological pro-cesses affecting it. The movement of metrizamidein neural tissue has been explored. Current researchis directed towards the value of higher resolution andreduced section thickness in the demonstration ofneutral tissue without contrast medium. The appli-cation of the technique in the study of a variety ofstructural disorders will be discussed and illustratedCT is particularly valuable in identifying and locali-sing spinal canal stenosis and apophyseal jointdisease. The digital nature of the image allows accessto the quantitative study of trabecular bone. Theanatomical configuration of the spine together withrestricted section thickness at present place con-straints on the role of CT as a screening procedurein the investigation of spinal disorders.



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DEMONSTRATIONS

The mouth in connective tissue disease. Derek Chis-holm, Gabriel Donald. Glasgow Dental School andDepartment of Medical Illustration, WesternInfirmary, Glasgow.

Soft tissue release of hips and knees in juvenilechronic arthritis. M. Swann, N. Rowden, B. M.Ansell, D. Macauley. Juvenile Rheumatism Unit,Canadian Red Cross Memorial Hospital, Taplow,Berks.

Conservative treatment of the hip in juvenile chronicarthritis. M. Swann, B. M. Ansell. Juvenile Rheu-matism Unit, Canadian Red Cross MemorialHospital, Taplow, Berks.

Amyloidosis in juvenile chronic arthritis. B. M. Ansell,A. Howard, M. Gwyther. Clinical Research Centre,Northwick Park Hospital, Harrow, Middlesex.

Hind foot involvement in juvenile chronic arthritis.B. M. Ansell, A. B. Kinnier Wilson. JuvenileRheumatism Unit. Canadian Red Cross MemorialHospital and Clinical Research Centre, WatfordRoad, Harrow.

The adolescent learning to live with arthritis. JuvenileRheumatism Unit, Canadian Red Cross MemorialHospital, Taplow, Maidenhead.

Frequency of chondrocalcinosis of the knees andavascular necrosis of the femoral heads in gout.J. T. Scott, A. Stockman, L. G. Darlington. KennedyInstitute of Rheumatology, London.

The Northwick cervical collar. S. A. Peskett, K.Laming, R. Roberts, B. M. Ansell, D. S. Smith.Division ofRheumatology, Northwick Park HospitalHarrow, Middlesex.

ARC national cash register of less common rheu-matic diseases. Hilary Hill, W. Carson Dick, PhilipH. N. Wood, Verna Wright.

Postgraduate aids in rheumatology. J. Ferguson.WB Pharmaceuticals Ltd., Bracknell, Berks.

Processing results from a medical survey. April Kay,Clinical Section, David Hewitt, Data ProcessingSection; ARC Epidemiology Research Unit, Univer-sity of Manchester.

Fibrogenesis imperfecta ossium-the seventh case.J. Ball, J. Denton, W. van't Hoff, C. Jones, A. J.McCall. North Staffs Royal Infirmary and Depart-ment of Rheumatology, Manchester University.

The surveillance of work factors in relationship tolow back pain in industry. J. A. D. Anderson, B. J.Sweetman, P. Kiernan. Department of CommunityMedicine, Guy's Hospital, London.

The action of drugs on the release of prostaglandinsand lysosomal enzymes from stimulated mouseperitoneal macrophages. N. Skeldon, L. Steele.Research Department, Boots Company Limited,Nottingham.

Impairment, disability, and handicap. Philip H. N.Wood, Elizabeth M. Badley, Michael R. Bury.ARC Epidemiology Research Unit, University ofManchester.

Gout-A historical disease. M. S. Dixon. MedicalDivision of the Wellcome Foundation Ltd.

Adverse drug reactions to pyrazole drugs. P. D.Fowler. Medical Department, Geigy Pharma-ceuticals.

A neutral collagenolytic system from inflamedsynovial membranes. Jacqueline B. Weiss, S. K. A.Sedowofia, C. Jones. Department of Rheumatology,University of Manchester.

Angiogenesis and its relevance to inflammatoryarthritis. Robert A. Brown, Jacqueline B. Weiss.Department of Rheumatology, University of Man-chester.References

I Folkman J. Sci Am 1978; 59-73.2 Philips P, Kumor S. Int J Cancer 1979; 23: 82-88.

Intra- and periarticular injection techniques. MedicalDepartment, Upjohn Limited.



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576 Annals of the Rhleumatic Diseases

Computerised diagnostic index. David Hewitt,Premlata Gandhi, Karla Brabbins. Data ProcessingSection, ARC Epidemiology Research Unit, Uni-verisity of Manchester.

Needle biopsy of muscle in clinical practice. R. H. T.Edwards,' C. A. Maunder,2 J. M. Round,' C. M.Wiles,' A. Young.3 'University College HospitalMedical School, 2Jerry Lewis Muscle ResearchCentre, Hammersmith Hospital, and 30xfordRehabilitation Research Unit.

Epidemiological Services. ARC EpidemiologyResearch Unit, University of Manchester.

Human immunity to native type HI collagen inhuman arthritis. R. B. Clague, M. J. Shaw, P. J. L.Holt. Department of Rheumatology, ManchesterRoyal Infirmary.

Humoral immunity in native type II collagen-induced arthritis in the rat. Keith Morgan, Roy B.Clague, Mary J. Shaw, P. J. Lennox Holt. Depart-

ment of Rheumatology, University of ManchesterMedical School, Oxford Road, Manchester M139PT.

Intra-articular therapy and arthritis: Suggestedtechniques of injection for Lederspan (triamcinolonehexacetonide). Medical Department, Lederle Labo-ratories, Fareham Road, Gosport, Hampshire.

Rheumatoid arthritis: A patient's viewpoint. G. Poole,E. W. Paice. Stoke Mandeville Hospital, Aylesbury.

Arthritis and everyday life. Michael R. Bury. ARCEpidemiology Research Unit, University of Man-chester.

Everyday life of children with arthritis. Gerald Beales.Department of Rheumatology, University of Man-chester.

Designing a field survey.ARC Epidemiology ResearchUnit, University of Manchester.



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