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Showing papers in "Annals of the Rheumatic Diseases in 1957"


Journal ArticleDOI
TL;DR: It was concluded that, to ensure maximum uniformity in grading x rays in field surveys and therapeutic trials, all readings should be made by the same observer, preferably at a single session.
Abstract: In a previous study (Kellgren and Bier, 1956), three sets of x rays of the hands were used to assess interand intra-observer differences in interpreting changes of rheumatoid arthritis. Wide disagreement between observers was found, and it was concluded that, to ensure maximum uniformity in grading x rays in field surveys and therapeutic trials, all readings should be made by the same observer, preferably at a single session. The advisability of having a set of standard reference films was also considered.

10,028 citations


Journal ArticleDOI
TL;DR: In this article, a committee of the American Rheumatism Association on diagnostic criteria was formed, with full realization that it would be very difficult to determine the limits of the diagnosis of rheumatoid arthritis.
Abstract: In a disease such as rheumatoid arthritis in which the aetiology is unknown and in which there is no available proof of the diagnosis, a broad description of the disease usually suffices for teaching and for diagnosis in individual cases. When such a method is used for classifying patients for study, however, there is little uniformity in the cases included in any series labelled rheumatoid arthritis (Cobb, Merchant, and Warren, 1955). It is often extremely difficult, therefore, to compare studies from one physician or clinic with those from another-whether the studies relate to prevalence, incidence, manifestations, course, treatment, or other features of the disease. In order to obtain more uniformity in cases listed as rheumatoid arthritis, a committee of the American Rheumatism Association on diagnostic criteria was formed, with full realization that it would be very difficult to determine the limits of the diagnosis \"rheumatoid arthritis\". In view of this difficulty, it seemed wise to classify rheumatoid arthritis in three categories: definite, probable, and possible. In the definite group there should be almost no question that every patient has rheumatoid arthritis and in the probable group the likelihood should be great that every patient has rheumatoid arthritis. These two groups should be used for any study or report of the characteristics, course, and treatment of rheumatoid arthritis. The criteria for the third, the \"possible\" group, are much less rigid and, of necessity, some patients who do not have rheumatoid arthritis may be included in this category. Only by having liberal criteria in this group, however, will it be possible to pick up early and atypical cases which can be followed profitably to learn more of the course and nature of the disease. The inclusion of patients who do not have rheumatoid arthritis will not be serious. Errors in diagnosis will become apparent as the

328 citations


Journal ArticleDOI
TL;DR: It was indicated that standards used so far in grading x-ray changes for rheumatoid arthritis in field surveys in Leigh and South Wales did not differ greatly from the mean values given by physicians and radiologists in Britain.
Abstract: a study was made of interand intra-observer differences in grading hand films for rheumatoid arthritis during the course of therapeutic trials and field surveys. This study indicated that standards used so far in grading x-ray changes for rheumatoid arthritis in field surveys in Leigh and South Wales did not differ greatly from the mean values given by physicians and radiologists in Britain. Before attempting to produce standard films for use in future surveys, it was decided to seek the help of a number of workers in different parts of the world, so that any national bias in assessing such changes could be avoided. Advantage was, therefore, taken of the presence in Toronto of experienced rheumatologists from many countries on the occasion of the XI International Congress of Rheumatic Diseases in June, 1957. During this Congress a series of nineteen hand x-rays with varying degrees of rheumatoid arthritis and osteo-arthrosis were exhibited in the form of a radiological quiz, and members of the Congress were asked to grade these for osteo-porosis and rheumatoid erosions and to give an overall grading for rheumatoid arthritis and osteo-arthrosis (degenerative joint disease). Each of these features was to be graded into five categories: 0 = None

222 citations


Journal ArticleDOI
TL;DR: The impression that the condition might be a clinical entity has grown stronger with continued observation over a period of years, and increasing awareness of the clinical features disclosed that several other such cases were attending the clinics with the presumptive diagnosis of rheumatoid disease.

195 citations


Journal ArticleDOI
TL;DR: Clinical and pathological changes occurring in the course of rheumatoid arthritis are described and the relationship of these changes to those found in generalized lupus erythematosus is discussed, to the better-defined entities listed briefly above, and to the rarer ill-defined group of published cases not easily accommodated within these diagnostic pigeonholes.
Abstract: Gangrene of the terminal portions of the limbs may be due to obstruction in the peripheral vessels, large or small, or it may be associated with cardiac failure as in rheumatic or ischaemic heart disease (Swan and Henderson, 1951), with ball valve thrombi, or with pulmonary disease (Boulet, Serre, Vedel, Vallat, and Mirouze, 1949; Hejtmancik and Bruce, 1953). In a case of mitral stenosis and gangrene of the limbs and nose, in which I dissected the finger vessels and studied them in detail, no pathological changes were seen: the process had been thought to be one of low output and vasospasm. Obstruction peripherally may be due to primary changes in the blood, as in cryoglobulinaemia (Myerson and Stout, 1955), or to cold agglutination (Stats and Bullowa, 1943), but is more usually due to primary vessel disease, as in polyarteritis nodosa (Taylor and Jacoby, 1949), Buerger's disease, giant cell, or temporal arteritis (Chasnoff and Vorzimer, 1944), to multiple embolization, or to vasospasm, as in Raynaud's disease or crutch arteritis (Stammers, 1954). In scleroderma it seems possible that vessel changes precede the skin sclerosis. Occasionally, however, an unusual type of peripheral arterial obstruction has been found which does not fit easily into any of the above categories (Whiteley and Wilson, 1952). It is the object of this study to describe such clinical and pathological changes occurring in the course of rheumatoid arthritis, and to discuss the relationship of these changes to those found in generalized lupus erythematosus, to the better-defined entities listed briefly above, and to the rarer ill-defined group of published cases not easily accommodated within these diagnostic pigeonholes. Some years ago an account was published of six patients whose early clinical course resembled palindromic rheumatism, but who later showed clinical and radiological signs of rheumatoid arthritis and, in addition, some other curious features, notably cutaneous nodules (Bywaters, 1949). One of these patients (Case 2) later died with gangrene of all four limbs. The present study describes the progress and terminal stages of this case, together with nine other examples of peripheral vascular obstruction (Table, opposite).

160 citations


Journal ArticleDOI
TL;DR: Improvement following treatment in hospital was reasonably well maintained in the majority of patients if subsequent medical and social supervision were adequate and the most important factors in prognosis proved to be the duration of disease on admission, sex, and type of course run up to the time of admission.
Abstract: In a previous communication (Duthie, Thompson, Weir, and Fletcher, 1955), the results of treatment in hospital and the subsequent progress of a group of patients with rheumatoid arthritis were described. At the time of the first report the mean duration of follow-up was 24-4 months. Certain factors which might influence prognosis were considered. It was concluded that improvement following treatment in hospital was reasonably well maintained in the majority of patients if subsequent medical and social supervision were adequate. The most important factors in prognosis proved to be the duration of disease on admission, sex, and type of course run up to the time of admission. Patients admitted within one year of the onset of symptoms fared substantially better than those admitted at a later stage of the disease; the prognosis in males was better than in females; an acute onset followed by

135 citations


Journal ArticleDOI
TL;DR: The objects of this study were to find out the incidence of the permanent deformities occurring in the rheumatoid hand; and to discover which of these deformities were important in everyday function.
Abstract: This is a study of hand deformities in rheumatoid disease: their incidence, their causes, and their effects on function. Three hundred patients with this disease have been examined. There can be no doubt of the importance of hand deformities to the rheumatoid patient, nor of the importance of preventing hand deformities when treating this disease. Consequently it is surprising to find that there are few detailed accounts of these deformities in the literature. Ulnar deviation and its causes have been discussed at length (Fearnley, 1951; Lush, 1952; Vainio and Oka, 1953). Some of the common tendon lesions have been described in detail (Edstrom, 1945; Kellgren and Ball, 1950; Snorrason, 1951; Harris, 1951; Ansell and Bywaters, 1953). Contractures of the intrinsic muscles of the hand due to other causes have been described fully, but there have been few details of this condition as it occurs clinically in rheumatoid disease (Kestler, 1949; Bunnell, 1953, 1955; Harris and Riordan, 1954). Of the remaining deformities, most have at least been mentioned in the literature, but only a few have been described in detail with discussion of their causes. To place the prevention of hand deformities on a sound basis, it is essential to know more about the deformities that occur. The objects of this study were to find out the incidence of the permanent deformities occurring in the rheumatoid hand; and to discover which of these deformities were important in everyday function. Whenever possible the causes of the deformities were recorded.

91 citations


Journal ArticleDOI
TL;DR: The authors' attention was focused sharply on the prevalence of neuropathic disorder as part of rheumatoid arthritic disease, when some 12 months ago four out of eight patients in the ward at one time with rheumatism complained of sensory or motor changes; on examination signs of a peripheral neuropathy were present in all four.
Abstract: Our attention was focused sharply on the prevalence of neuropathic disorder as part of rheumatoid arthritic disease, when some 12 months ago four out of eight patients in the ward at one time with rheumatoid arthritis complained of sensory or motor changes; on examination signs of a peripheral neuropathy were present in all four. This factor altered the symptomatology, treatment, and prognosis quite considerably. Since this time we have seen further cases, and it now appears to be worth reporting them in some detail and discussing their significance. The eleven *cases are listed in the Table. The literature on the subject is very scanty. In the current textbooks of neurology we see occasional references to \"rheumatism\" as a cause of peripheral neuritis, but there is no adequate description to give us greater details. Brain (1951) considers the so-called \"rheumatic\" polyneuritis following exposure to wet and cold to be in all probability the

80 citations


Journal ArticleDOI
TL;DR: Autosuggestion and increased security engendered by contact with the healer can result in an improved mental attitude of faith and hope which can account for improved physiological function, conducive to lessening of symptoms or even to remission of the disease.
Abstract: Medications and procedures reputedly helpful in treating chronic illnesses such as arthritis are multiplying to a degree confusing not only to the lay public but also to physicians. Many or most of drugs have come into use empirically. Remissions, often spontaneous and characteristic of rheumatic disease, may coincide with the taking of some advised substance or the performance of some procedure. Autosuggestion and increased security engendered by contact with the healer can result in an improved mental attitude of faith and hope. This can account for improved physiological function which in its turn is conducive to lessening of symptoms or even to remission of the disease.

62 citations


Journal ArticleDOI
TL;DR: The ability of sera from patients with rheumatoid arthritis to potentiate the agglutination of sensitized particulate bodies has been recognized since Cecil, Nicholls, and Stainsby (1931) and has been employed as the basis of a number of clinical tests for the diagnosis of rheumatic arthritis.
Abstract: The ability of sera from patients with rheumatoid arthritis to potentiate the agglutination of sensitized particulate bodies has been recognized since Cecil, Nicholls, and Stainsby (1931) noted the agglutination of certain strains of streptococci by these sera. More recently this property has been employed as the basis of a number of clinical tests for the diagnosis of rheumatoid arthritis. The tests most frequently used are the sensitized sheep cell agglutination, Fraction II agglutination, latex fixation, Rh agglutination, and gamma-globulin precipitation tests. The reaction common to all these tests seems to be the interaction of the rheumatoid factor or factors present in serum with gamma-globulin attached to a particulate body. The particulate body probably acts only as a carrier for the gammaglobulin since it has been demonstrated by Epstein, Johnson, and Ragan (1955) that Fraction II gammaglobulin can form a precipitate with rheumatoid sera directly. This is especially true when the gammaglobulin has previously been altered by heating or a number of other procedures (Franklin, Holman, Mifller-Eberhard, and Kunkel, 1957). Normal human gamma-globulin contains two major ultracentrifugal components. The main one has a sedimentation rate of 7S, while the minor one, which normally makes up from 5 to 10 per cent. of the total gamma-globulin, has a sedimentation coefficient of 19S (Muller-Eberhard, Kunkel, and Franklin, 1956). It has been demonstrated by numerous observers, particularly Svartz and Schlossman (1954) and by Ziff, Brown, Lospalluto, Badin, and McEwen (1956), that the rheumatoid factor is a gamma-globulin and that it can be concentrated in the euglobulin fraction of serum. Since the euglobulin fraction is rich in the minor high molecular weight fraction of gamma-globulin, it seemed

62 citations


Journal ArticleDOI
TL;DR: The present study is concerned with the occurrence of iridocyclitis and other eye manifestations as seen during a period of 7 years at a National Centre for Juvenile Rheumatism.

Journal ArticleDOI
TL;DR: From 1927 to 1955 a series of 174 consecutive cases of brucellosis due to Brucella melitensis was studied at the Barcelona University Medical Clinic of Prof. A. Pedro Pons.
Abstract: From 1927 to 1955 a series of 174 consecutive cases of brucellosis due to Brucella melitensis (sometimes called \"Malta fever\") was studied at the Barcelona University Medical Clinic of Prof. A. Pedro Pons. The duration and intensity of each case varied, but all showed or had shown a stage of acute brucellosis on which the clinical diagnosis was based. The laboratory diagnosis was based on the sero-agglutination, blood culture, intradermal reaction, and, in the latter cases, on the complementfixation test and the test of incomplete antibodies. Osteo-articular signs appeared in 148 cases (85 per cent.). This figure is about the same as that given by other writers who have studied this organism (Cantaloube, 1911; Ruiz Castafieda, 1954; Betoulieres and Maleki, 1948; Rimbaud and Serre, 1947), whereas it is clearly above those obtained by writers studying brucellosis produced by Br. suis (Hardy, 1929, 1937; Harris, 1950), and far above those found by writers studying the disease produced by Br. abortus (Hardy, 1929; Dalrymple-Champneys, 1935, 1950; Sylvest, 1951).

Journal ArticleDOI
TL;DR: The object was to discover whether it is possible to demonstrate in fibrositic areas a lesion of the intercellular and interfibrillar connective tissue.
Abstract: The changes occurring in the muscles of patients suffering from muscular pain owing to fibrositis have been the subject of much discussion. Scientific theories have been chiefly based on objective findings, especially the results of microscopical examinations. Stockman (1920) found hyperplasia of the connective tissue with sero-fibrinous exudation. Microscopy of skeletal muscles with fibrositis supposed to have existed for several years has revealed degenerative changes in the muscle cells and an increase in the number of nuclei (Glogowski and Wallraff, 1951). Other workers (e.g. Schade, 1921; Lange, 1925) have found only normal muscle in biopsy specimens of fibrositic tissue. It is more or less agreed that with some practice it is possible to palpate some abnormality in certain patients but a satisfactory histopathological explanation of the disorder has not yet been found. In the following study one of us (K.J.) has made the clinical examination, especially the palpation, another (P.B.) has carried out chemical analyses by means of an improved technique, and the third author (G.A.-H.) has made microscopic examinations of the same biopsy specimens. Our object was to discover whether it is possible to demonstrate in fibrositic areas a lesion of the intercellular and interfibrillar connective tissue.

Journal ArticleDOI
TL;DR: AStock of the present position vis-a-vis rheumatoid arthritis is taken to take stock of the adrenal cortex and its secretions.
Abstract: Steroid research was begun at this Centre 6 years ago in the expectation that it would contribute to our knowledge of the pathogenesis of rheumatoid arthritis. Much has been learnt since then of the secretion and metabolism of the adrenocortical hormones in health and disease. The object of this paper is to take stock of the present position vis-a-vis rheumatoid arthritis. Why should interest have been taken in the adrenal cortex and its secretions when it was already known that cortisone was neither a cure nor a form of replacement therapy for rheumatoid arthritis? The reasons why Philip Hench turned his attention to the adrenal cortex 10 years ago are as valid now as they were then. To-day's reasons may be summarized as follows:

Journal ArticleDOI
TL;DR: Practical experience has shown that the correction of the hyperuricaemia and the associated positive urate balance can most readily be accomplished by the administration of continuous therapy with a uricosuric agent in effective doses.
Abstract: Experience gained during the past 7 years with the prolonged administration of probenecid (Pascale, Dubin, and Hoffman, 1952; Talbott, 1953; Gutman and Yu, 1955; Bartels, 1955; Bauer and Singh, 1957) or of salicylates (Marson, 1953, 1954, 1955) has shown that continuous therapy with a uricosuric agent in effective doses, is the only practical method at present available for preventing the complications and morbidity which occur in patients with chronic gout. Subjective and objective improvement have been recorded in nearly all instances where there has been strict adherence to the therapeutic regimen. Attacks of acute gouty arthritis become progressively less frequent and less severe or may cease entirely; chronic joint pain and stiffness gradually improve; and tophaceous urate deposits gradually shrink in size or may be observed to disappear entirely (Yu and Gutman, 1951; Marson, 1952). The long-term treatment has been directed mainly toward the correction of the hyperuricaemia and reduction of the greatly increased miscible pool of uric acid shown to be present in most patients with established chronic gout (Benedict, Forsham, Roche, Soloway, and Stetten, 1950; Bishop, Rand, and Talbott, 1951; Talbott, 1953; Gutman and Yu, 1955). Although a diet restricted in purines and fat will lower the serum uric acid slightly (Marson, 1953; Gutman and Y%, 1955), dietary restrictions have been only partially successful as a treatment measure (Bauer and Klemperer, 1944; Talbott, 1953; Gutman and Yu, 1955). Practical experience has shown that the correction of the hyperuricaemia and the associated positive urate balance can most readily be accomplished by the administration of

Journal ArticleDOI
TL;DR: A medical practitioner, aged 34, first developed episodic swellings diagnosed as angioneurotic oedema in 1948, but in March, 1950, he developed a polyarthritis, and within a week had deteriorated so much that he was cyanosed despite continuous oxygen therapy.
Abstract: A medical practitioner, aged 34, first developed episodic swellings diagnosed as angioneurotic oedema in 1948. These cleared up, but in March, 1950, he developed a polyarthritis. Attacks of joint swelling were at first intermittent, but after 9 months his symptoms were severe and continuous and subcutaneous nodules appeared on the elbows. In 1951 he treated himself with 100 mg. cortisone acetate daily, with partial remission of his disease. For a few months in 1952 he took 600 mg. daily of phenylbutazone instead, but stopped this because of unfavourable reports. Swelling of the right leg and of the right inguinal lymph nodes developed late in 1952. One of these nodes was removed for histological examination, and Professor R. A. Willis reported that it showed a non-specific reactive hyperplasia. The patient resumed taking cortisone acetate (75 mg. daily) and improved. He first came under supervision at this hospital in November, 1953, when he already showed gross symmetrical swelling and inflammation of the small peripheral as well as of the major limb joints. Large subcutaneous nodules were present in both elbow regions. There was moon face and ankle oedema. Despite these changes he was able to carry on his work as an assistant in a busy general practice. In July, 1954, he developed diarrhoea which persisted for 8 months before clearing up spontaneously. No certain cause for this was found although Giardia lamblia was isolated on one occasion. In May, 1955, the patient developed a productive cough and first noticed dyspnoea on exertion. In August, 1955, his treatment was changed from 125 mg. cortisone to 25 mg. deltacortisone daily. There was an initial "lift" in symptoms, and a transient increase in strength of grip, but no lasting improvement in his arthritis. He began to put on weight. Increasing breathlessness on effort, at first attributed to his increasing weight, soon became his chief disability, and eventually he was unable to continue at work. He was admitted to hospital for further investigation, and within a week had deteriorated so much that he was cyanosed despite continuous oxygen therapy. Antituberculous chemotherapy, given in the hope that the lung shadows seen on x-ray examination might represent an unusual form of tuberculosis, was without effect. Increased amounts of deltacortisone in no way helped him. He died of asphyxia. The only significant previous illness was bilateral lobar pneumonia at the age of 3 years. There was no history of rheumatism in the family, but his mother suffered from various allergic complaints. Laboratory Investigations.-The differential agglutination titre (Ball, 1950) was positive at 1: 128 at 18 hrs in June, 1955. The patient reported that his Mantoux reaction had been positive when he was a student, but no record of this has been kept. In one phase of his disease, the haemoglobin levels fell to 60 per cent., but in the last 6 months of life these levels were normal. The total white cell count was always somewhat elevated at about 13,000 per c.mm. with a normal differential in the last 3 years. The albumin/globulin ratio was reversed at 2 : 4. The erythrocyte sedimentation rate was always elevated. Multiple cultures of the sputum yielded only normal flora. Numerous other examinations of blood and urine were consistently normal.

Journal ArticleDOI
TL;DR: Increasing evidence, which substantiates the theory that a susceptibility to the disease is influenced by a genetic factor, is found in families in which parent and offspring, sib pairs, and both members of monozygotic twins have been involved.
Abstract: In recent years the importance of heredity in ankylosing spondylitis has been more widely accepted. Increasing evidence, which substantiates the theory that a susceptibility to the disease is influenced by a genetic factor, is found in families in which parent and offspring, sib pairs, and both members of monozygotic twins have been involved. Most of the reported cases have been brought together in an excellent review by Hersh, Stecher, Solomon, Wolpaw, and Hauser (1950). One of the most interesting family histories is that recorded by Riecker, Neel, and Test (1950), in which five proven cases of spondylitis were found in two generations, and evidence was obtained that the disease was also

Journal ArticleDOI
TL;DR: Clinical experience with prednisone and prednisolone has demonstrated, however, that they share most of the other shortcomings of the older steroids and, according to some investigators, they have seemed to promote such complications as peptic ulcers and ecchymotic skin lesions with greater frequency.
Abstract: During the past few years a concerted effort has been made to develop synthetic derivatives of hydrocortisone and cortisone which would retain their anti-inflammatory activity but would be devoid of certain of their unwanted physiologic effects. Hope that analogues with enhanced therapeutic indices could be synthesized has stemmed from the knowledge that several properties of the naturally occurring hormones may be modified, sometimes selectively, by making changes in their chemical structures. Since 1953 a number of significant innovations have been made in the synthesis of corticosteroid analogues. The first was the introduction, by Fried and Sabo (1953) and Fried (1955), of halogen atoms at the 9th carbon position of the steroid nucleus. The resulting 9-alpha-halogen corticosteroids were in most respects very much more potent than cortisone and hydrocortisone. For example, the potency of 9-alpha-fluorohydrocortisone was found to be ten times that of hydrocortisone with respect to anti-inflammatory, glycogenic, eosinopenic, ACTH-suppressing, and nitrogenwasting activities (Boland, 1955; Liddle, Richard, and Tomkins, 1956). But the electrolyte activity (sodium retention, potassium loss) of the fluoro compound has been found to be at least 125 times that of hydrocortisone, a feature which has precluded its application systemically as an antiphlogistic agent. Another important chemical transformation in the steroid nucleus was the introduction, by Herzog, Nobile, Tolksdorf, Charney, Hershberg, Perlman, and Pechet (1955), of a double bond between carbon atoms 1 and 2 of cortisone and hydrocortisone. The compounds so derived, prednisone and prednisolone, have been found to be approximately four times as potent as their predecessors in anti-inflammatory, glycogenic, ACTH-suppressing, nitrogen-losing, and related properties. However, the 1-dehydro-analogues have exhibited no such increase in electrolyte activity and the partial dissociation of this effect has made them useful therapeutically. Clinical experience with prednisone and prednisolone has demonstrated, however, that they share most of the other shortcomings of the older steroids and, according to some investigators, they have seemed to promote such complications as peptic ulcers and ecchymotic skin lesions with greater frequency (Bunim, Pechet, and Bollet, 1955; Bollet, Black, and Bunim, 1955; Boland, 1956). Hence the quest for more suitable anti-inflammatory steroids has continued. Hogg, Lincoln, Jackson, and Schneider (1955) and Spero, Thompson, Magerlein, Hanze, Murray, Sebek, and Hogg (1956) synthesized a series of methylated corticosteroids. Biologic experiments with these compounds indicated that when a methyl radical was substituted for a hydrogen atom at the second carbon position of the steroid nucleus, the sodium-retaining and potassium-losing effects of 11-hydroxy-corticosteroids were enhanced (Spero and others, 1956; Byrnes, Barnes, Bowman, Dulin, Morley, and Stafford, 1956). But if the methyl grouping were introduced at the 6th carbon position instead, no such increase in electrolyte activity resulted. Preliminary studies in animals with one of the methyl derivatives (6-alpha-methyl-prednisolone) suggested that this compound might have therapeutic promise. Lyster, Barnes, Lund, Meinzinger, and Byrnes (1956) and Glenn, Stafford, Lyster, and Bowman (1957) found the rat-liverglycogen depositing activity of the compound to be sixteen times that of hydrocortisone on oral administration and ten times that of hydrocortisone on subcutaneous administration; the potency ratio of 6-methyl prednisolone to prednisolone was calculated as 3: 1. The anti-inflammatory potency of

Journal ArticleDOI
TL;DR: A study of some 3,000 assays in conjunction with the clinical state of the patients concerned leaves no doubt that the anti-rheumatic effects produced by stimulating the adrenal cortex vary directly with the urinary output of 17 KGS and 1 7(OH)CS.
Abstract: The only practical means of maintaining a raised output of steroids from the adrenal cortex is by the daily intramuscular or subcutaneous injection of corticotropin in a medium that delays absorption. The effects produced by such therapy depend upon -the amount by which the daily output of steroids is raised above the starting level and the length of time that the raised level is maintained. The only practical means of measuring the output of the adrenal cortex is by assaying, in 24-hr specimens of urine, the metabolites of the principal hormone cortisol (hydrocortisone). The study reported here covers 4+ years, and is a follow-up of a previous study (West and Newns, 1955). For the first 18 months the metabolites of cortisol were assayed by the "17-ketogenic steroid" (17 KGS) method (Norymberski, Stubbs, and West, 1953) and since then they have been assayed by the "total 17-hydroxycorticosteroid" (17(OH)CS) method (Appleby, Gibson, Norymberski, and Stubbs, 1955). Both assays were developed at this Centre. The results of these two assays do not differ appreciably except in the rare disorders of the adrenal cortex. Consideration of the value and limitations of these assays will be referred to under the heading "Discussion" below but it can be stated at this point that a study of some 3,000 assays in conjunction with the clinical state of the patients concerned leaves no doubt that the anti-rheumatic effects produced by stimulating the adrenal cortex vary directly with the urinary output of 17 KGS and 1 7(OH)CS. There have been many brief reports of the effects produced by corticotropin therapy and not a few describing undesirable effects, but rarely, if ever, 'have these reports included a statement of the level of adrenocortical stimulation achieved or of its duration. In view of the undesirable effects reported, this paper will take account of every


Journal ArticleDOI
TL;DR: Although previous work demonstrated that "moth-eaten" fibres (MEF) were intermediate structures midway between collagen and elastin, the present study shows without doubt that a further range of agents can cause breakdown of these structures to "elastin".
Abstract: Any information on the reaction of the fibrous connective tissue components to various reagents, particularly enzymes, is of interest in the fields of both health and disease. Until some understanding of the normal interrelationships of these structures is reached, no firm attempt to explain pathological findings can be made. Although it is dangerous to extrapolate test-tube results in explanation of changes found in vivo, most of the agents and conditions used in the present study are not too far removed from possible conditions in living mammals. Elastase and hyaluronidase are manufactured in man and recently collagenase activity has been demonstrated in canine pancreatic juice (Ziffren and Hosie, 1955). The mildly alkaline solutions employed could represent a pH value reached in pathological tissue, and most of the experiments were conducted at body temperature. Although previous work (Keech, Reed, and Wood, 1956) demonstrated that \"moth-eaten\" fibres (MEF) were intermediate structures midway between collagen and elastin, the present study shows without doubt that a further range of agents (physical, chemical, enzymatic) can cause breakdown of these structures to \"elastin\". Concurrent experiments on elastin are described, and objections raised to the use of the standard elastin substrate for electron microscopic work.

Journal ArticleDOI
TL;DR: It has previously been observed that Murphy rat lymphosarcoma exudate collected from a tumour-pouch could cause typical proliferative arthritis in one or several joints and such articular changes developed in a few days and were aggravated by adrenalectomy.
Abstract: It has previously been observed that Murphy rat lymphosarcoma (MRLS) exudate collected from a tumour-pouch could cause typical proliferative arthritis in one or several joints (Jasmin and Richer, 1955). Such articular changes developed in a few days and were aggravated by adrenalectomy (Jasmin and Selye, 1955). It is the purpose of this communication to describe these pathological changes with reference to the regulatory action of the adrenocortical hormones. In addition, studies are reported on the inhibitory effect of oxytetracycline and sodium aurothiomalate and the isolation of a micro-organism as the causative agent.

Journal ArticleDOI
TL;DR: After an initial decrease in the medullary reticulo-endothelial hyperplasia, the electrophoretic pattern and the sero-agglutinating titres returned to normal (Berglund, Nordenson, and Glhagen, 1951).
Abstract: Hyperglobulinaemia is a fundamental characteristic of rheumatoid arthritis, and is also found in other collagen diseases. It is said to demonstrate the hyperactivity of the reticulo-endothelial system shown by the hyperplasia of its medullary elements (Marmont, 1948; Curletto and Magistretti, 1949). In the course of studying this hyperglobulinaemia by paper electrophoresis, an increase has been observed in the alpha and gamma globulin fractions (Olhagen, 1952; Wallis, 1950; Ropes, Perlmann, Kaufman, and Bauer, 1954; Jacqueline, de Traverse, and Besson, 1954; Hunt and Trew, 1954), or in the beta-gamma globulin fractions (Layani, Bengui, and de Mende, 1952). An increase in the alpha-2 globulin is considered to be characteristic of the first phase of rheumatoid disease, associated with inflammatory-exudative changes; an increase in gamma globulin generally appears later, together with a reactionary fibrosis (Olhagen, 1952; Ropes and others, 1954; Layani and others, 1952; Jacqueline and others, 1954). In exceptionally serious cases, a conspicuous increase in the gamma globulin fraction and a moderate increase in the alpha globulin fraction (Olhagen, 1952), or a persistently raised gamma-l globulin (Layani and others, 1952), have been observed. During the hormone therapy of rheumatoid arthritis, a decrease has been noted in the alpha globulins (particularly alpha-2), and especially in the gamma globulins in cases which were progressing favourably (Wallis, 1950; Villa, Ballabio, and Sala, 1953; Layani and others, 1952; Ropes and others, 1954). After an initial decrease in the medullary reticulo-endothelial hyperplasia, the electrophoretic pattern and the sero-agglutinating titres returned to normal (Berglund, Nordenson, and Glhagen, 1951). Similar electrophoretic changes

Journal ArticleDOI
TL;DR: Investigations were started at the King Gustaf V Research Institute into the haemagglutinating factor that induces the reaction in rheumatoid arthritis and positive results were obtained with the type of modification of the sheep cell test.
Abstract: Shortly after Rose, Ragan, Pearce, and Lipman (1948) had published their paper on the agglutination of sensitized sheep cells in rheumatoid arthritis, investigations were started at the King Gustaf V Research Institute into the haemagglutinating factor that induces the reaction. The first reports of our experiments, presented by Svartz and Schlossmann (1949) and Svartz (1951a, b; 1952), were mainly concerned with the importance of removing the heterophil haemagglutinins which almost invariably exist in human serum, before carrying out the principal reaction. Similar observations were published by Sulkin, Pike, and Coggeshall (1952). The first attempts to absorb heterophil haemagglutinins had been made by Meyer (1922). Schlossmann and I have obtained positive results with our type of modification of the sheep cell test in 85 to 90 per cent. of cases of rheumatoid arthritis (Schlossmann and Svartz, 1950). The test was considered positive when the titre was I : 64 or higher. The frequency of positive reactions varied somewhat from one period to another depending on the nature of the cases tested. The more cases of active rheumatoid arthritis are included in a series the higher will be the percentage of positive reactions. But purely technical factors also influence the results. The sheep cells must be fresh and the amboceptor suitable, and the results should be read on two occasions: first when the

Journal ArticleDOI
TL;DR: The immunologic reactivity of a group of young healthy subjects as homogeneous is observed and it is inferred that this particular hyperreactivity was primary or secondary in character.
Abstract: an altered immunologic reactivity, different of that of normal controls (Creger, Choy, and Rantz, 1951; Miller, Kibrick, and Massell, 1953; Quinn, Seastone, and Dickie, 1953; Kuhns and McCarty, 1954), but the results of their experiments proved mostly negative or inconclusive. A convincing proof of this altered reactivity seems to have been furnished only after attention had been focused on incomplete antibody, as shown, for example, in our previously reported experiments applying single non-streptococcal immunizing impulses (Wagner and Rejholec, 1955; Padovcovi, Rejholec, Suda, Mal', and Wagner, 1956). The assumption of increased immunologic reactivity appearing thus corroborated, the next problem we faced was whether this particular hyperreactivity was primary or secondary in character. In the latter case it would be a sequela of the past rheumatic disease; in the former, viz. if it had been present in the subject before the onset of rheumatic fever, it might be inferred that it had a bearing on the pathogenic mechanism of this disease. In order to elucidate this question we adopted the following procedure. The immunologic reactivity of a group of young healthy subjects as homogeneous

Journal ArticleDOI
TL;DR: The term "rheumatoid" refers to the fact thatitismost frequently detected intheserum of individuals having rheumatoids arthritis; it is alsofound in about half of patients withdisseminated lupus erythematosus and from patients withother connective tissue diseases.
Abstract: FromtheRheumatic Disease Group oftheDepartment ofMedicine, andtheMetabolic UnitforResearch in Arthritis andAllied Diseases, University ofCalifornia School ofMedicine, SanFrancisco, California Theterm"rheumatoid factor" (R.F.) hasbeen applied tothesubstance orsubstances intheserum ofmostindividuals havingrheumatoid arthritis which combines with immuneglobulins orsubstances closely associated withimmuneglobulins. Theterm "rheumatoid" refers tothefactthatitismost frequently detected intheserumofindividuals having rheumatoid arthritis; itisalsofoundin aboutonethird toonehalfofpatients withdisseminated lupus erythematosus andinsomesera frompatients withother connective tissue diseases


Journal ArticleDOI
TL;DR: It is noted that the pain in acute Heberden's nodes increases rapidly in severity during short periods of arterial occlusion and that this increase is immediately relieved when the circulation is restored, and the chemical nature of the gelatinous material in these cysts is of some theoretical interest.
Abstract: Since Heberden (1803) wrote about digitorum nodi, these nodes on the terminal interphalangeal joints have been considered to comprise a distinct form of joint disease, which in later years has been classified as a form of osteo-arthritis. Stecher (1955), in an excellent summary of his extensive researches, distinguished the occasional posttraumatic node from the more common idiopathic nodes which he concludes are genetically determined. Although Stecher is of the opinion that Heberden's nodes are not associated with similar joint changes in other parts of the body, this view is not universally accepted (Kellgren and Moore, 1952) and recent radiological surveys of samples of the general population have shown a highly significant association between Heberden's nodes and radiological signs of osteo-arthritis in other joints (Kellgren, 1956). This communication is solely concerned with the pathogenesis of Heberden's nodes and presents no new evidence on the controversy about Heberden's nodes and generalized osteo-arthritis. Heberden's nodes usually develop slowly and painlessly over many years, but in some patients the process had a rapid evolution so that massive bony outgrowths may develop in a single year. The formation of such acute nodes is accompanied by much spontaneous pain and the development of small cystic swellings over the dorsum of the joint. These swellings occasionally burst to discharge clear gelatinous material. It seems probable that this gelatinous material is in some way connected with the pathogenesis of the nodes and the mechanism of pain production in such cases. In a previous study (Addis, Jepson, and Kellgren, 1950) and in later observations, we have noted that the pain in acute Heberden's nodes increases rapidly in severity during short periods of arterial occlusion and that this increase is immediately relieved when the circulation is restored. After the evacuation of the contents of such a cyst, the node gradually becomes painless. The chemical nature of the gelatinous material in these cysts is of some theoretical interest, and we have therefore studied material obtained from four typical cases of acute Heberden's nodes.

Journal ArticleDOI
TL;DR: It is possible that tests of capillary resistance are a measure of haemostatic mechanisms other than those primarily involved in haemorrhagic disorders, and this conception might explain the frequently anomalous results of such tests in patients with purpura.
Abstract: For more than 50 years, tests of \"capillary resistance\" have been used to measure the facility with which petechiae may be produced experimentally, mainly with a view to detecting latent purpuric tendencies. Hare and Miller (1951) listed the many different methods which have been evolved, and assessed the merits and demerits of techniques in general use. \"Pressure\" tests, such as the snake venom test, have been used more extensively than any other method and can be defined in two broad categories. In \"positive pressure\" tests, the arm is constricted by a sphygmomanometer, the number of petechiae appearing in response to venous engorgement of the forearm serving as an index of capillary resistance. \"Negative pressure\" tests require apparatus consisting of a vacuum pump, a manometer, and a suction cup which can be applied to the skin. The pressure of air in the system is reduced to a predetermined level for a period, and the number of petechiae thus produced in the underlying skin, in relation to the magnitude and duration of the negative pressure applied, is used as a measure of capillary resistance. While it is unlikely that all the different modifications of these tests measure the same biological properties, suction or \"negative pressure\" techniques have an advantage over other procedures in that tests can be repeated in an individual at intervals of a few hours and can be used to measure, for example, the influence of substances the administration of which may produce rapid and transient changes in capillary resistance. It has been customary to regard the expressions \"capillary resistance\" and \"capillary fragility\" as interchangeable, but it should be noted that \"increased resistance\" is equivalent to \"diminished fragility\" and vice versa. Although these tests were originally introduced to facilitate the study of haemorrhagic diseases, the results of investigations in this field have been somewhat conflicting. In a review of the subject of capillary resistance tests in scurvy, Munro, Lazarus, and Bell (1947) concluded that most investigators had failed to demonstrate a significant relationship between capillary strength and ascorbic acid reserves assessed by chemical methods. Nevertheless, Scarborough (1953) observed reasonably good correlation between depletion of ascorbic acid and the level of capillary resistance in otherwise normal subjects. In other haemorrhagic disorders, capillary resistance appeared to be unrelated to the bleeding time, the coagulation time, or the number of thrombocytes (Hare and Miller, 1951). In thrombocytopenic purpura, however, Elliott (1938), Elliott and Whipple (1940), and Robson (1949) found evidence of a consistent relationship between capillary resistance and the \"bleeding tendency\". It is possible that tests of capillary resistance are a measure of haemostatic mechanisms other than those primarily involved in haemorrhagic disorders, and this conception might explain the frequently anomalous results of such tests in patients with purpura. The available evidence indicates that the maintenance of normal levels of resistance may depend upon the integrity of the perivascular connective tissue; histological studies of petechiae induced by suction applied to normal skin have revealed fragmentation of elastic fibres in the vicinity of haemorrhages without evidence of damage to capillary endothelium (Peck, Rosenthal, and Erf, 1937). The low capillary resistance found in premature, but otherwise normal, infants has been attributed to under-development of the connective tissues around cutaneous blood vessels (Hare and Miller, 1951). From experimental evidence, Zweifach (1955) concluded that increased capillary fragility may be a consequence of a disturbance in the structure of the connective tissue sheath of small cutaneous vessels. The foregoing therefore suggests that tests of capillary resistance