RESEARCH ON RHEUMATIC DISEASES OR
"WHAT'S COOKIN' AT BATH?" BY
G. D. KERSLEY,
It
was
within the
Royal
National
T.D., D.L., M.D., F.R.C.P.
Hospital
for Rheumatic Diseases that the
resea[j,e
unit, whose activities are to be reviewed here, began its existence in 1949hospital had been famous, and had been engaged in research, for many years
t>e c0tf
that. Before the last war, it was the Mecca of students of rheumatic disesase over the world. It is the oldest spa hospital in the world, and was the first to specia entirely in rheumatic diseases. ^ti The Hospital's history begins with the opening of the subscription list by Beau ser in 1723. Ralph Allen provided the stone, and John Wood the Elder gave his ^ as architect, free. In 1742 the hospital was opened for 150 patients from p, City of Bath, under the name of "The Hospital or Infirmary at Bath", with Dr. (of Bath Oliver Biscuit fame) as the first physician and Mr. Pierce as the first After this, among the subscriptions received one of special interest was of mi
*
w
22
G. D. KERSLEY
sampling are essential, and neither the patient nor the assessor should know the dr^S the patient is taking. Every effort must be made to neutralize possible psychology factors. Statistical analysis of the data is essential. The assessor should be the for each recording?preferably a research fellow of senior registrar grade?but t 0 over-all welfare of the patients must remain the responsibility of a physician who, t ethical and humanitarian grounds, must be prepared to put the patient before project and withdraw him from the trial, noting the reason for withdrawal, if he thn1
saflj
it is to the patient's advantage. The first major clinical trial was concerned with the effects of Rheumatic patients in a carefully controlled series were given various dosages X-ray therapy, and in the control group the patients were laid on a couch W1
2
radiotherapy^ -tjs
the current being turned on. It was found that those with rheumatoid arthi"1 received no benefit, about 50 percent of osteo-arthritics had some temporary ameh? V tion of symptoms, and that 95 per cent of those with ankylosing spondylitis one greatly improved, the benefit lasting in the majority of patients for at least The medium range of dosage, about 1,200 roentgen units, was found the most suita This investigation was carried out before the leukaemia dangers of radio-therapy f been discovered, but now the knowledge that radiography increases the chance developing leukaemia about seventeen-fold must be considered before it is especially as it is so frequently required in spondylitics in the comparatively can age groups. However, this treatment still appears justifiable where severe pain be relieved by other methods. {r During this same period a second clinical trial was carried out on the use of benefit in the in osteo-arthritis. It was found that some articular .
y0^ .
injections of increased mobility and reduction of pain produced by "novocaine", saline or lactic needling of the joint.
slight
was
produced
acid.
to an extent
in^y
equal
to
^ j
The control group suffered
jjy
A considerable amount of work 4> 5- 6> 7- was carried out on the anaemia associated with rheumatoid arthritis. It seemed that there were many factors ?neither deficient absorption, blood loss, changes in iron binding, nor haemodn s could explain the anaemia. Parenteral iron improved a large proportion of Pa c0m' resistant to iron by mouth. Cobalt assisted in a few resistant cases but gastric jg plications were frequent. Bone marrow findings were equivocal. It seems
uStjved
in?.Ot|0ji
Pr?0jetic
that deficient iron absorption, excessive iron requirements, and some haemop y abnormality all played their part in the anaemia of rheumatoid arthritis. To this be added the small repeated blood losses due to aspirin treatment, probably is cant except when long continued in the menstruating woman, whose safety mai& reduced. f 0ut? 0 Projects still in progress consist of investigation of the uricosuric treatment an evaluation of antimalarial drugs in rheumatoid arthritis, further work on the ^ ^ ment of anaemia with iron, and the use of long-acting steroid injections, not yet market, in order to determine their dosage, length of action, and likely value there is the complication of peptic ulceration. In the antimalarial trial a series of patients suffering from rheumatoid ar ^jgh lwas given plaquenil, camoquin, and control tablets for alternating periods ^ percentage of patients enjoyed suppression of symptoms with the antimalafi3 the margin between toxicity and therapeutic benefit was very small, and one developed agranulocytosis as a result of camoquin treatment. Temporary Pv ^ $ corneal opacities were common. It was felt that this group of drugs might with justification in a limited number of cases where safer, simpler measu dP ineffective, provided careful supervision is maintained. For some three years now a series of fifty patients with gout has been foh? jjjflj clinically and biochemically while under treatment with a number of increase uric acid excretion 19> 20. These consist of aspirin in large doses, pr? -
^rU^len3c'
RESEARCH ON RHEUMATIC DISEASES
"longacid" (or jbcnernid"), Aspirin cheap, eXln'.')"b
"urelim"),
"anturan"
(G.28.315)
23 and zoxazolamine
but in large doses it is depressing and is a gastric irritant; is satisfactory in about 80 per cent of cases but produces toxic symptoms in remainder. "Longacid" is very similar in its effect. "Anturan" is more powerful and virtually non-toxic. Zoxazolamine appears to run "anturan" a fairly close as t^ie uricosuric agent of choice. Apart from aspirin, all these uricosuric agents te ri to stir attacks up gouty during the first six weeks of administration, but from ^ ?ywards the attacks become less severe and less frequent, and any interval *S reduced. During these first six weeks therefore colchicine should be administ regularly, and butazolidin may be given in addition for two days at a time to c0m any severe attacks. Aspirin inhibits the effects of the other drugs, but the is
^ern^"
svMp6
reir.-
er are complementary to each other. Long-term and regular administration 1Cosur*c agents is essential to their effectiveness. They appear to have no significant effe ?n has K een P^asma cholesterol levels or prothrombin times, a possible drawback that su??ested by some cardiologists. Their use has revolutionized the treatment and a Pr?gnosis of severe gout. 1 fr"orn research work carried out on its own initiative, the Unit has been Part for the past five years in various multi-centre trials organized by the ^esearch Council, Empire Rheumatism Council, and Nuffield Foundation. Ve.to ten centres in the country may work on the same project, using the same crjt by a central committee, and the results are assessed by one medical stati 1Clan" The first trial showed that in the long run little more benefit was to be e*De e* from cortisone than from aspirin22. Prednisolone however produced Co le long-term benefit including less deterioration as seen on consecutive X_ra therapy produce definite amelioration at the end of a year's follow-up, effects of a course of 1 gm. was compared with that of o-oi mgm. 24. These t^als are still being continued to assess long-term results and toxic reactions. Sa^ before, with the change in ownership of the unit a temporary iron curtain Was is becr- ?PPed between the fundamental and clinical research. A chink in this curtain to appear in that clinical research facilities may be available in the rebuilt hosr,jt Medical Research Council may help with some of these, thus bringing -an
"WHAT'S COOKIN' AT BATH?" BY
G. D. KERSLEY,
It
was
within the
Royal
National
T.D., D.L., M.D., F.R.C.P.
Hospital
for Rheumatic Diseases that the
resea[j,e
unit, whose activities are to be reviewed here, began its existence in 1949hospital had been famous, and had been engaged in research, for many years
t>e c0tf
that. Before the last war, it was the Mecca of students of rheumatic disesase over the world. It is the oldest spa hospital in the world, and was the first to specia entirely in rheumatic diseases. ^ti The Hospital's history begins with the opening of the subscription list by Beau ser in 1723. Ralph Allen provided the stone, and John Wood the Elder gave his ^ as architect, free. In 1742 the hospital was opened for 150 patients from p, City of Bath, under the name of "The Hospital or Infirmary at Bath", with Dr. (of Bath Oliver Biscuit fame) as the first physician and Mr. Pierce as the first After this, among the subscriptions received one of special interest was of mi
*
w
22
G. D. KERSLEY
sampling are essential, and neither the patient nor the assessor should know the dr^S the patient is taking. Every effort must be made to neutralize possible psychology factors. Statistical analysis of the data is essential. The assessor should be the for each recording?preferably a research fellow of senior registrar grade?but t 0 over-all welfare of the patients must remain the responsibility of a physician who, t ethical and humanitarian grounds, must be prepared to put the patient before project and withdraw him from the trial, noting the reason for withdrawal, if he thn1
saflj
it is to the patient's advantage. The first major clinical trial was concerned with the effects of Rheumatic patients in a carefully controlled series were given various dosages X-ray therapy, and in the control group the patients were laid on a couch W1
2
radiotherapy^ -tjs
the current being turned on. It was found that those with rheumatoid arthi"1 received no benefit, about 50 percent of osteo-arthritics had some temporary ameh? V tion of symptoms, and that 95 per cent of those with ankylosing spondylitis one greatly improved, the benefit lasting in the majority of patients for at least The medium range of dosage, about 1,200 roentgen units, was found the most suita This investigation was carried out before the leukaemia dangers of radio-therapy f been discovered, but now the knowledge that radiography increases the chance developing leukaemia about seventeen-fold must be considered before it is especially as it is so frequently required in spondylitics in the comparatively can age groups. However, this treatment still appears justifiable where severe pain be relieved by other methods. {r During this same period a second clinical trial was carried out on the use of benefit in the in osteo-arthritis. It was found that some articular .
y0^ .
injections of increased mobility and reduction of pain produced by "novocaine", saline or lactic needling of the joint.
slight
was
produced
acid.
to an extent
in^y
equal
to
^ j
The control group suffered
jjy
A considerable amount of work 4> 5- 6> 7- was carried out on the anaemia associated with rheumatoid arthritis. It seemed that there were many factors ?neither deficient absorption, blood loss, changes in iron binding, nor haemodn s could explain the anaemia. Parenteral iron improved a large proportion of Pa c0m' resistant to iron by mouth. Cobalt assisted in a few resistant cases but gastric jg plications were frequent. Bone marrow findings were equivocal. It seems
uStjved
in?.Ot|0ji
Pr?0jetic
that deficient iron absorption, excessive iron requirements, and some haemop y abnormality all played their part in the anaemia of rheumatoid arthritis. To this be added the small repeated blood losses due to aspirin treatment, probably is cant except when long continued in the menstruating woman, whose safety mai& reduced. f 0ut? 0 Projects still in progress consist of investigation of the uricosuric treatment an evaluation of antimalarial drugs in rheumatoid arthritis, further work on the ^ ^ ment of anaemia with iron, and the use of long-acting steroid injections, not yet market, in order to determine their dosage, length of action, and likely value there is the complication of peptic ulceration. In the antimalarial trial a series of patients suffering from rheumatoid ar ^jgh lwas given plaquenil, camoquin, and control tablets for alternating periods ^ percentage of patients enjoyed suppression of symptoms with the antimalafi3 the margin between toxicity and therapeutic benefit was very small, and one developed agranulocytosis as a result of camoquin treatment. Temporary Pv ^ $ corneal opacities were common. It was felt that this group of drugs might with justification in a limited number of cases where safer, simpler measu dP ineffective, provided careful supervision is maintained. For some three years now a series of fifty patients with gout has been foh? jjjflj clinically and biochemically while under treatment with a number of increase uric acid excretion 19> 20. These consist of aspirin in large doses, pr? -
^rU^len3c'
RESEARCH ON RHEUMATIC DISEASES
"longacid" (or jbcnernid"), Aspirin cheap, eXln'.')"b
"urelim"),
"anturan"
(G.28.315)
23 and zoxazolamine
but in large doses it is depressing and is a gastric irritant; is satisfactory in about 80 per cent of cases but produces toxic symptoms in remainder. "Longacid" is very similar in its effect. "Anturan" is more powerful and virtually non-toxic. Zoxazolamine appears to run "anturan" a fairly close as t^ie uricosuric agent of choice. Apart from aspirin, all these uricosuric agents te ri to stir attacks up gouty during the first six weeks of administration, but from ^ ?ywards the attacks become less severe and less frequent, and any interval *S reduced. During these first six weeks therefore colchicine should be administ regularly, and butazolidin may be given in addition for two days at a time to c0m any severe attacks. Aspirin inhibits the effects of the other drugs, but the is
^ern^"
svMp6
reir.-
er are complementary to each other. Long-term and regular administration 1Cosur*c agents is essential to their effectiveness. They appear to have no significant effe ?n has K een P^asma cholesterol levels or prothrombin times, a possible drawback that su??ested by some cardiologists. Their use has revolutionized the treatment and a Pr?gnosis of severe gout. 1 fr"orn research work carried out on its own initiative, the Unit has been Part for the past five years in various multi-centre trials organized by the ^esearch Council, Empire Rheumatism Council, and Nuffield Foundation. Ve.to ten centres in the country may work on the same project, using the same crjt by a central committee, and the results are assessed by one medical stati 1Clan" The first trial showed that in the long run little more benefit was to be e*De e* from cortisone than from aspirin22. Prednisolone however produced Co le long-term benefit including less deterioration as seen on consecutive X_ra therapy produce definite amelioration at the end of a year's follow-up, effects of a course of 1 gm. was compared with that of o-oi mgm. 24. These t^als are still being continued to assess long-term results and toxic reactions. Sa^ before, with the change in ownership of the unit a temporary iron curtain Was is becr- ?PPed between the fundamental and clinical research. A chink in this curtain to appear in that clinical research facilities may be available in the rebuilt hosr,jt Medical Research Council may help with some of these, thus bringing -an
