DEC. 29, 1962
`1708
`1708 DEC. 29, 1962 (cid:9)
`
`INTRACRANIAL ANEURYSMS
`INTRACRANIAL ANEURYSMS
`
`BRIJUN
`BRITISH
`MEDICAL JOURNAL
`MEDICAL JOURNAL
`
`the
`National
`Hospital,
`for
`preparing
`all
`Department,
`Department, National Hospital, for preparing all the
`illustrations.
`illustrations.
`
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`H. L. Abrams. Churchill, London.
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`Hassler, 0. (1961). Acta psychiat. scand., Suppl. No. 154.
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`McDonald, C. A., and Korb, M. (1939). Arch. Neurol. Psychiat.
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`S. E. (1936).
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`neurol. Inst. N.Y., 5, 247.
`neurol. Inst. N.Y., 5, 247.
`Meadows, S. P. (1951). " Intracranial Aneurysms" in Modern
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`London
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`Padget, D. H. (1948). Carnegie Contrib. Embryol., 32, 205.
`Padget, D. H. (1948). Carnegie Contrib. Embryol., 32, 205.
`Paterson, J. H., and McKissock, W. (1956). Brain, 79, 233.
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`Rischbieth, R. H. C., duid Bull, J. W. D. (1958). Brit. J. Radiol.,
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`31, 125.
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`- Meadows, S. P., and Taylor, J. (1937). Brain, 60, 52.
`J. clin. Path., 12, 391.
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`Van 't Hofi, W., Hornabrook, R. W., and Marks, V. (1961).
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`Brit. med. J., 2, 1190.
`Brit. med. J., 2, 1190.
`Wolman, L. (1959). Brain, 82, 276.
`Wolman, L. (1959). Brain, 82, 276.
`
`COMPARISON OF CORTICOSTEROID AND SULPHASALAZINE THERAPY IN
`COMPARISON OF CORTICOSTEROID AND SULPHASALAZINE THERAPY IN
`ULCERATIVE COLITIS
`ULCERATIVE COLITIS
`BY
`BY
`GEOFFREY WATKINSON,* M.D., F.R.C.P.
`GEOFFREY WATKINSON,* M.D., F.R.C.P.
`Consultant Physician, York Hospitals, York
`Consultant Physician, York Hospitals, York
`
`S. C. TRUELOVE, M.D., F.R.C.P. (cid:9)
`S. C. TRUELOVE, M.D., F.R.C.P.
`Nuffield Department of Clinical Medicine, (cid:9)
`Nuffield Department of Clinical Medicine,
`Radcliffe Infirmary, Oxford
`Radcliffe Infirmary, Oxford
`
`GERALD DRAPER, B.A.
`GERALD DRAPER, B.A.
`Unit of Biometry, University of Oxford
`Unit of Biometry, University of Oxford
`in the treatment of ulcerative colitis, but it is question-
`No perfect treatment of ulcerative colitis exists.
`Never-
`in the treatment of ulcerative colitis, but it is question-
`No perfect treatment of ulcerative colitis exists. Never-
`able whether they are markedly superior to cortisone in
`theless a number of measures are known to be beneficial
`able whether they are markedly superior to cortisone in
`theless a number of measures are known to be beneficial
`equivalent doses, at any rate so far as can be judged
`in an attack of the disease, and they fall into two main
`equivalent doses, at any rate so far as can be judged
`in an attack of the disease, and they fall into two main
`from comparing published results (Watkinson, 1960).
`On the one hand, certain general medical
`groups.
`from comparing published results (Watkinson, 1960).
`groups. On the one hand, certain general medical
`measures are
`plainly
`beneficial when circumstances
`Another way of using corticosteroids in this disease
`measures are plainly beneficial when circumstances
`Another way of using corticosteroids in this disease
`demand them; the most important ones are correction
`After
`colon.
`the
`to
`apply them topically
`demand them ; the most important ones are correction
`to
`is
`is to apply them topically to the colon. After
`of dehydration and electrolyte deficiencies, blood trans-
`results
`encouraging
`studies had given
`of dehydration and electrolyte deficiencies, blood trans-
`preliminary
`preliminary studies had given encouraging results
`fusions to combat loss of blood, a nutritious diet
`controlled
`1957) two independent
`fusions to combat loss of blood, a nutritious diet
`1956,
`(Truelove,
`(Truelove, 1956, 1957) two independent controlled
`containing ample protein to minimize wasting, and
`therapeutic trials employing a " double-blind " technique
`containing ample protein to minimize wasting, and
`therapeutic trials employing a " double-blind " technique
`vitamin supplements to guard against deficiencies. On
`yielded unequivocal evidence that this form of treatment
`vitamin supplements to guard against deficiencies. On
`yielded unequivocal evidence that this form of treatment
`the other hand, a large number of drugs have been
`was beneficial (Truelove, 1958; Watkinson, 1958).
`the other hand, a large number of drugs have been
`was beneficial (Truelove, 1958 ; Watkinson, 1958).
`employed because of some evidence that they may bring
`employed because of some evidence that they may bring
`These two methods of using corticosteroids can be
`These two methods of using corticosteroids can be
`the attack swiftly to an end. We know of only two
`the attack swiftly to an end. We know of only two
`combined, and there is evidence that this enhances the
`combined, and there is evidence that this enhances the
`types of therapeutic agent for which there is strong
`types of therapeutic agent for which there is strong
`therapeutic effect (Truelove, 1960).
`therapeutic effect (Truelove, 1960).
`evidence that they promote the chance of rapid termina-
`evidence that they promote the chance of rapid termina-
`tion of the attack.
`They are the corticosteroids and
`tion of the attack. They are the corticosteroids and
`sulphasalazine respectively.
`sulphasalazine respectively.
`
`Corticosteroid Treatment
`Corticosteroid Treatment
`Shortly after the discovery by Hench et al. (1949) of
`Shortly after the discovery by Hench et al. (1949) of
`the
`beneficial symptomatic actions of cortisone
`in
`the beneficial symptomatic actions of cortisone in
`rheumatoid arthritis, reports began to appear of the
`rheumatoid arthritis, reports began to appear of the
`use of this agent and of A.C.T.H. in ulcerative colitis.
`use of this agent and of A.C.T.H. in ulcerative colitis.
`The early reports were conflicting, but a large-scale
`The early reports were conflicting, but a large-scale
`controlled
`therapeutic
`trial
`showed that
`cortisone
`controlled therapeutic trial showed that cortisone
`increased the chance of clinical remission within six
`increased the chance of clinical remission within six
`weeks of starting medical treatment (Truelove and
`weeks of starting medical treatment (Truelove and
`Witts, 1954, 1955). A second therapeutic trial showed
`Witts, 1954, 1955). A second therapeutic trial showed
`that A.C.T.H. was similar to cortisone in the treatment
`that A.C.T.H. was similar to cortisone in the treatment
`of first attacks but was superior to cortisone in relapses
`of first attacks but was superior to cortisone in relapses
`of established disease, although at the price of more
`of established disease, although at the price of more
`complications of therapy (Truelove and Witts, 1959).
`complications of therapy (Truelove and Witts, 1959).
`The newer corticosteroids have been extensively used
`The newer corticosteroids have been extensively used
`Medicine, Leeds University,
`*Formerly Senior Lecturer in
`*Formerly Senior Lecturer in Medicine, Leeds University,
`during the time when most of this study was being made.
`during the time when most of this study was being made.
`
`Sulphasalazine Treatment
`Sulphasalazine Treatment
`Sulphasalazine was first used for the treatment of
`Sulphasalazine was first used for the treatment of
`ulcerative colitis by Svartz, who has written a number
`ulcerative colitis by Svartz, who has written a number
`of articles on its use (Svartz, 1942, 1948, 1954, 1956,
`of articles on its use (Svartz, 1942, 1948, 1954, 1956,
`physician who has
`Another Scandinavian
`1960).
`1960). Another Scandinavian physician who has
`advocated its use is Lagercrantz (1949, 1955), who has
`advocated its use is Lagercrantz (1949, 1955), who has
`employed it extensively in children with the disease.
`employed it extensively in children with the disease.
`About 1950 the drug began to be used in America, under
`About 1950 the drug began to be used in America, under
`the name of "azopyrin," which was later changed to
`the name of " azopyrin," which was later changed to
`" asulfidine," and many favourable reports have come
`" asuffidine," and many favourable reports have come
`from physicians there (Morrison, 1952, 1953; Bargen,
`from physicians there (Morrison, 1952, 1953 ; Bargen,
`1955; Moertel and Bargen, 1959).
`1955 ; Moertel and Bargen, 1959).
`Sulphasalazine (" salazopyrin") is an azo-compound
`Sulphasalazine (" salazopyrin ") is an azo-compound
`Like other acid
`of salicylic acid and sulphapyridine.
`of salicylic acid and sulphapyridine. Like other acid
`for
`affinity
`a pronounced
`has
`azo-compounds,
`it
`azo-compounds, it has a pronounced affinity for
`connective tissue, as has been shown by fluorescent
`connective tissue, as has been shown by fluorescent
`It is a brown powder which
`microscopy (Svartz, 1960).
`microscopy (Svartz, 1960). It is a brown powder which
`is prescribed in the form of tablets, each containing
`is prescribed in the form of tablets, each containing
`0.5 g., for oral use. For an acute attack of ulcerative
`0.5 g., for oral use. For an acute attack of ulcerative
`colitis it is usually employed in a dose of 1-2 g. four
`colitis it is usually employed in a dose of 1-2 g. four
`
`

`

`DEC. 29, 1962
`DEC. 29, 1962 (cid:9)
`
`DEC. 29, 1962
`
`ULCERATIVE COLITIS
`ULCERATIVE COLITIS
`
`COLITIS
`
`BRrrISH
`BRITISH (cid:9)
`MMICAL JOUM-UL
`MEDICAL JOURNAL
`
`1709
`1709
`
`Random Allocation of Treatments to Patients
`Random Allocation of Treatments to Patients
`Each patient from Oxford was paired with another
`Each patient from Oxford was paired with another
`from Oxford and patients from Leeds were similarly
`from Oxford and patients from Leeds were similarly
`paired together.
`Treatments were allocated randomly
`paired together. Treatments were allocated randomly
`at each centre, using a method of restricted randomiza-
`at each centre, using a method of restricted randomiza-
`tion which ensured that at no time did the number of
`tion which ensured that at no time did the number of
`patients having had one treatment greatly exceed the
`patients having had one treatment greatly exceed the
`number having had the other.
`This was achieved by
`number having had the other. This was achieved by
`preparing in advance a treatment allocation sheet in
`preparing in advance a treatment allocation sheet in
`which each treatment was randomly assigned to patients
`which each treatment was randomly assigned to patients
`in such a way that each successive group of six patients
`in such a way that each successive group of six patients
`contained three patients on one treatment and three on
`contained three patients on one treatment and three on
`the other. The physicians were of course not aware of
`the other. The physicians were of course not aware of
`the sequence of treatments on these lists.
`the sequence of treatments on these lists.
`
`Results
`Results
`Two separate charts were used in recording the
`Two separate charts were used in recording the
`progress of the trial. The patients in each pair were
`progress of the trial. The patients in each pair were
`compared separately on clinical and on sigmoidoscopic
`compared separately on clinical and on sigmoidoscopic
`criteria and the results plotted on Figs. 1 and 2 respec-
`criteria and the results plotted on Figs. 1 and 2 respec-
`tively in those cases where the pairs were "untied"
`tively in those cases where the pairs were " untied "
`according to the appropriate criterion.
`Results from
`according to the appropriate criterion. Results from
`Oxford and Leeds were taken together and plotted in
`Oxford and Leeds were taken together and plotted in
`
`o‘6
`
`20 (cid:9)
`
`10
`
`c S
`
`c
`_. wCp E
`Y
`*w
`O
` 2
`
`s
`
`nc
`
`. E
`'a 2 • 0.
`U 0.
`.0;
`.'20X
`unber of
`tO
`2
`to
`0
`Number of
`10
`40 44 untied pairs
`2~~~~~0
`40 44 untied pairs
`0 .s
`0-
`.0 0 -
`an ytmccriotri hrp ismoetliel
`ha 5p
`'0
`-10
`t: -10 0ii-
`• Y
`w E
`.2, —20
`..
`O .E
`O z
`iG. 1.-Sequential analysis chart showing that combined topical
`Fla. 1.—Sequential analysis chart showing that combined topical
`and systemic cortacosteroid therapy is more likely than suipha-
`and systemic corticosteroid therapy is more likely than sulpha-
`salazine to induce rapid symptomatic remissions.
`salazine to induce rapid symptomatic remissions.
`
`ot
`
`;
`
`o 0
`
`zF
`
`Number of
`Number of
`,untied pairs
`40 44 untied pairs
`
`Oible
`
`ScCwE c
`_- W
`O ;
`0
`20
`w
`20
`• g 20
`v
`0
`O• N 10
`,-
`_
`_
`0 .0
`• 0.
`OU
`
`0, 5 C•N
`oc
`a O0.
`0'
`g v.
`:!
`c- 0
`N >o -io
`-10
`0
`Oa
`Y E
`C C -20
`.0 —20 (cid:9)
`2
`
`1
`O
`0
`
`0 o
`
`O 0z
`
`O • 6
`
`FIG. 2.-Sequential analysis chart showing that combined topical
`Fin. 2.—Sequential analysis chart showing that combined topical
`and systemic corticosteroid therapy is more likely than sulpha-
`and systemic corticosteroid therapy is more likely than sulpha-
`salazine
`to bring about early reduction
`in colonic mucosal
`salazine to bring about early reduction in colonic mucosal
`inflammation as judged by the sigmoidoscopic appearances.
`inflammation as judged by the sigmoidoscopic appearances.
`
`Occasional patients can tolerate larger
`times a day.
`times a day. Occasional patients can tolerate larger
`doses of up to 12 g. a day in divided doses.
`doses of up to 12 g. a day in divided doses.
`A considerable
`number
`patients
`of
`experience
`A considerable number of patients experience
`vomiting with the larger doses. Less common, but more
`vomiting with the larger doses. Less common, but more
`serious, toxic effects are fever, drug rashes, and blood
`serious, toxic effects are fever, drug rashes, and blood
`dyscrasias.
`dyscrasias.
`
`Present Study
`Present Study
`The main object of this study was to compare
`The main object of this study was to compare
`combined topical and systemic corticosteroid therapy
`combined topical and systemic corticosteroid therapy
`with sulphasalazine in terms of their efficacy in cutting
`with sulphasalazine in terms of their efficacy in cutting
`short an attack of ulcerative colitis.
`short an attack of ulcerative colitis.
`Dosages.-Combined corticosteroid therapy consisted
`Dosages.—Combined corticosteroid therapy consisted
`of oral prednisolone 5 mg. four times a day and a nightly
`of oral prednisolone 5 mg. four times a day and a nightly
`rectal drip of 100 mg. of hydrocortisone succinate
`rectal drip of 100 mg. of hydrocortisone succinate
`sodium in solution. The rectal drip was prepared by
`sodium in solution. The rectal drip was prepared by
`dissolving one hydrocortisone (" ef-Cortelan solution ")
`dissolving one hydrocortisone (" ef-Cortelan solution ")
`tablet in approximately 150 ml. of tap-water.
`Sulpha-
`tablet in approximately 150 ml. of tap-water. Sulpha-
`salazine treatment consisted in the administration of
`salazine treatment consisted in the administration of
`0.5-g. tablets in a dose of 2 g. four times a day for the
`0.5-g. tablets in a dose of 2 g. four times a day for the
`first week, followed by 1 g. four times a day for the
`first week, followed by 1 g. four times a day for the
`second.
`second.
`Selection of Cases.-The cases were all examples of
`Selection of Cases.—The cases were all examples of
`classical ulcerative colitis but without complications
`classical ulcerative colitis but without complications
`which might demand other types of therapy.
`All were
`which might demand other types of therapy. All were
`suffering from a frank attack of the disease at the time
`suffering from a frank attack of the disease at the time
`of admission to the therapeutic trial.
`of admission to the therapeutic trial.
`Assessment of Effect of Therapy..-The effects of
`Assessment of Effect of Therapy.—The effects of
`therapy were assessed on clinical and sigmoidoscopic
`therapy were assessed on clinical and sigmoidoscopic
`(a) Clinical Assessment: At the end of two
`evidence.
`evidence.
`(a) Clinical Assessment : At the end of two
`weeks' treatment those patients who were completely
`weeks' treatment those patients who were completely
`symptom-free were classed as successes. All others were
`symptom-free were classed as successes. All others were
`to achieve a rapid clinical
`classed as having failed
`classed as having failed to achieve a rapid clinical
`remission.
`Sigmoidoscopic
`(b)
`The
`Responses:
`(b) Sigmoidoscopic Responses: The
`remission.
`beginning
`sigmoidoscopic
`the
`of
`appearances
`at
`sigmoidoscopic appearances at the beginning of
`treatment were graded according to the criteria we
`treatment were graded according to the criteria we
`have used in previous therapeutic trials.
`At the end
`have used in previous therapeutic trials. At the end
`of two weeks' treatment sigmoidoscopy was repeated
`of two weeks' treatment sigmoidoscopy was repeated
`and a definite improvement was classed as a successful
`and a definite improvement was classed as a successful
`(In the case of the Leeds
`sigmoidoscopic response.
`sigmoidoscopic response. (In the case of the Leeds
`patients these sigmoidoscopic assessments were made
`patients these sigmoidoscopic assessments were made
`by an independent observer, Professor J. C. Goligher.)
`by an independent observer, Professor J. C. Goligher.)
`
`The Statistical Method
`The Statistical Method
`The sequential method of Armitage (1957) was used.
`The sequential method of Armitage (1957) was used.
`The essential feature of sequential methods is that the
`The essential feature of sequential methods is that the
`sample size depends on the results obtained as the trial
`sample size depends on the results obtained as the trial
`progresses, and is not decided in advance as is the case
`progresses, and is not decided in advance as is the case
`with classical statistical tests.
`with classical statistical tests.
`The patients were paired, one patient in each pair
`The patients were paired, one patient in each pair
`receiving corticosteroids and the other sulphasalazine.
`receiving corticosteroids and the other sulphasalazine.
`The results for those pairs in which one treatment was
`The results for those pairs in which one treatment was
`successful according to an agreed criterion and the other
`successful according to an agreed criterion and the other
`was not (the " untied pairs ") were plotted on a chart
`was not (the " untied pairs ") were plotted on a chart
`as shown in Figs. 1 and 2.
`If one treatment is superior
`as shown in Figs. 1 and 2. If one treatment is superior
`the plotted line will tend towards either the upper or
`the plotted line will tend towards either the upper or
`the lower boundary. The trial is halted when it reaches
`the lower boundary. The trial is halted when it reaches
`one of these boundaries or the central one. When this
`one of these boundaries or the central one. When this
`occurs we may make one of the following assertions:
`occurs we may make one of the following assertions :
`(1) Upper boundary is reached: corticosteroid therapy
`(1) Upper boundary is reached : corticosteroid therapy
`is superior.
`(2) Lower boundary is reached: sulpha-
`is superior. (2) Lower boundary is reached: sulpha-
`salazine is superior.
`(3) Central boundary is reached:
`salazine is superior. (3) Central boundary is reached:
`no difference between treatments.
`no difference between treatments.
`The combined probability of (1) or (2) occurring if
`The combined probability of (1) or (2) occurring if
`there is in fact no difference between the treatments
`there is in fact no difference between the treatments
`is 0.05-that is, we were making a significance test at
`is 0.05—that is, we were making a significance test at
`the conventional 5% level.
`the conventional 5% level.
`
`

`

`DEC. 29, 1962
`1710
`1710 DEC. 29, 1962 (cid:9)
`
`ULCERATIVE COLITIS
`ULCERATIVE COLITIS
`
`B PrSH
`ftRrrtsin
`MEDICAL JOURNAL
`MEDICAL JOURNAL
`
`chronological order as determined by the date of entry
`chronological order as determined by the date of entry
`into the trial of the second patient of the pair.
`into the trial of the second patient of the pair.
`It will be observed that on the sigmoidoscopic criterion
`It will be observed that on the sigmoidoscopic criterion
`in favour of corticosteroids was obtained
`a result
`a result in favour of corticosteroids was obtained
`comparatively early. However, the trial was continued
`comparatively early. However, the trial was continued
`until a result was obtained on the clinical criterion also.
`until a result was obtained on the clinical criterion also.
`This also showed a difference in favour of corticosteroids.
`This also showed a difference in favour of corticosteroids.
`The completed sequential analysis charts show whether
`The completed sequential analysis charts show whether
`one treatment is superior to another but give little idea
`one treatment is superior to another but give little idea
`of the proportion of successful treatments owing to the
`of the proportion of successful treatments owing to the
`The overall
`fact that "tied pairs" are not charted.
`fact that " tied pairs " are not charted. The overall
`results for the two treatments tested are given in the
`results for the two treatments tested are given in the
`Table.
`Table.
`Percentage of Rapid Clinical and Sigmoidoscopic Responses in
`Percentage of Rapid Clinical and Sigmoidoscopic Responses in
`Two Treatment Groups at End of Two-weeks Trial Period
`Two Treatment Groups at End of Two-weeks Trial Period
`Sigmoidoscopic Results
`Clinical Results
`Sigmoidoscopic Results
`Clinical Results
`~~~~~~~~No.
`No.
`Showing
`No. of
`Showing
`No. of
`Patients Sigmoidoscopic
`Patients
`Sigmoidoscopic
`Improvement
`Improvement
`45 (78%)
`45 (78%)
`26 (43%)
`26 (43%)
`
`Treatment
`Treatment
`
`Treatment
`No. of
`
`of No.
`Patients
`Patients
`
`No. in
`No. in
`Remission
`Remission
`
`Combined corticosteroids
`Combined corticosteroids
`..
`..
`Sulphasalazine
`Sulphasalazine (cid:9)
`.. (cid:9)
`..
`
`58
`58
`60*
`60*
`
`44 (76%)
`44 (76%)
`31(52%)
`31 (52%)
`
`58
`58
`60*
`60*
`
`* Includes two patients admitted to the trial in the closing stages who had
`* Includes two patients admitted to the trial in the closing stages who had
`not yet been paired with corticosteroid-treated patients when the sequential
`not yet been paired with corticosteroid-treated patients when the sequential
`analysis brought the trial to an end.
`analysis brought the trial to an end.
`
`Complications of the Disease During the Trial Period
`Complications of the Disease During the Trial Period
`These were few, and consisted of the following.
`These were few, and consisted of the following.
`disease
`the
`Corticosteroid group: In one instance
`Corticosteroid group : In one instance the disease
`pursued a fulminating course and the patient was
`pursued a fulminating course and the patient was
`brought to emergency colectomy. Sulphasalazine group:
`brought to emergency colectomy. Sulphasalazine group :
`Two patients developed colitic arthritis, but there was
`Two patients developed colitic arthritis, but there was
`One patient showed
`improvement during treatment.
`improvement during treatment. One patient showed
`evidence of severe malnutrition and abnormal liver
`evidence of severe malnutrition and abnormal liver
`function'
`function!
`
`9
`
`20
`20
`8
`8
`9
`2
`2
`I
`1
`1
`1
`
`Complications of Therapy
`Complications of Therapy
`patients had negligible
`The corticosteroid-treated
`The corticosteroid-treated patients had negligible
`complications-one patient suffering from nausea and
`complications—one patient suffering from nausea and
`anorexia attributed to treatment.
`anorexia attributed to treatment.
`The sulphasalazine group showed a high incidence of
`The sulphasalazine group showed a high incidence of
`side-effects
`of
`symptoms which were attributed
`to
`side-effects (cid:9) of
`to (cid:9)
`symptoms (cid:9) which (cid:9) were (cid:9) attributed (cid:9)
`treatment, namely:
`treatment, namely :
`...
`Nausea
`Nausea ..
`..
`Vomiting
`Vomiting
`General malaise (often including headaches)
`General malaise (often including headaches)
`Drug rashes ..
`Drug rashes (cid:9)
`..
`Drowsiness
`.. (cid:9)
`..
`Drowsiness (cid:9)
`Paraesthesiae of limbs
`.. (cid:9)
`Paraesthesiae of limbs
`Some patients had more than one of these symptoms.
`Some patients had more than one of these symptoms.
`It can be seen that nausea, vomiting, and general
`It can be seen that nausea, vomiting, and general
`malaise were common. These effects were usually relieved
`malaise were common. These effects were usually relieved
`when the dose was reduced to 4 g. daily, but occasional
`when the dose was reduced to 4 g. daily, but occasional
`patients required even further reduction to eliminate
`patients required even further reduction to eliminate
`them.
`them.
`Two examples of drug rashes occurred. One patient
`Two examples of drug rashes occurred. One patient
`had a macular eruption which developed 10 days after
`had a macular eruption which developed 10 days after
`starting sulphasalazine and disappeared a few days after
`starting sulphasalazine and disappeared a few days after
`stopping it. The second suffered from a generalized
`stopping it. The second suffered from a generalized
`scarlatiniform rash in the second week of treatment,
`scarlatiniform rash in the second week of treatment,
`the rash disappearing soon after the sulphasalazine was
`the rash disappearing soon after the sulphasalazine was
`stopped.
`stopped.
`There were no examples of dangerous complications
`There were no examples of dangerous complications
`such as severe blood dyscrasias.
`such as severe blood dyscrasias.
`
`Discussion
`Discussion
`This trial has shown that, as judged by the proportion
`This trial has shown that, as judged by the proportion
`of attacks of ulcerative colitis which are rapidly checked,
`of attacks of ulcerative colitis which are rapidly checked,
`combined topical and systemic corticosteroid treatment
`combined topical and systemic corticosteroid treatment
`
`at a dosage level which appears to be virtually free from
`at a dosage level which appears to be virtually free from
`side-effects is superior to sulphasalazine in full dosage.
`side-effects is superior to sulphasalazine in full dosage.
`First,
`Several points are immediately worth making.
`Several points are immediately worth making. First,
`it can be taken that sulphasalazine is a useful agent in
`it can be taken that sulphasalazine is a useful agent in
`ulcerative colitis. When dummy treatments have been
`ulcerative colitis. When dummy treatments have been
`used by us in the past, the results have been bad and
`used by us in the past, the results have been bad and
`a negligible proportion of patients so treated have
`a negligible proportion of patients so treated have
`achieved a rapid clinical remission (Truelove, 1958;
`achieved a rapid clinical remission (Truelove, 1958 ;
`In the present study it required the
`Watkinson, 1958).
`Watkinson, 1958). In the present study it required the
`admission of a large number of patients into the trial
`admission of a large number of patients into the trial
`before combined corticosteroid treatment emerged as the
`before combined corticosteroid treatment emerged as the
`Secondly, the present
`significantly better treatment.
`significantly better treatment. Secondly, the present
`trial probably underestimates the difference between
`trial probably underestimates the difference between
`therapy.
`combined corticosteroid and sulphasalazine
`combined corticosteroid and sulphasalazine therapy.
`The corticosteroids were used in a relatively low dose
`The corticosteroids were used in a relatively low dose
`which has become a standard out-patient regime at
`which has become a standard out-patient regime at
`Oxford because of its safety when used for short periods
`Oxford because of its safety when used for short periods
`of only a few weeks, whereas patients ill enough to be
`of only a few weeks, whereas patients ill enough to be
`admitted to hospital are usually treated with double the
`admitted to hospital are usually treated with double the
`dosage employed in the trial. By contrast, the dose of
`dosage employed in the trial. By contrast, the dose of
`sulphasalazine was ill-tolerated by many of the patients,
`sulphasalazine was ill-tolerated by many of the patients,
`so that it can be inferred that it was being employed
`so that it can be inferred that it was being employed
`at or near to its maximum dose. Thirdly, corticosteroids
`at or near to its maximum dose. Thirdly, corticosteroids
`and sulphasalazine can be combined. This combination
`and sulphasalazine can be combined. This combination
`has appeared to us to be a useful one in our ordinary
`has appeared to us to be a useful one in our ordinary
`clinical practice, but additional controlled trials will be
`clinical practice, but additional controlled trials will be
`necessary to settle the issue.
`necessary to settle the issue.
`Every controlled therapeutic trial has its limitations
`Every controlled therapeutic trial has its limitations
`because only a few points can be firmly settled in a single
`because only a few points can be firmly settled in a single
`trial. We must therefore emphasize that the present
`trial. We must therefore emphasize that the present
`study merely shows that combined corticosteroid treat-
`study merely shows that combined corticosteroid treat-
`ment is better than sulphasalazine for rapidly checking
`ment is better than sulphasalazine for rapidly checking
`Extrapolation from these
`an attack of the disease.
`an attack of the disease. Extrapolation from these
`to embrace treatment over more prolonged
`results
`results to embrace treatment over more prolonged
`periods of time would be wrong. The need for caution
`periods of time would be wrong. The need for caution
`controlled
`results of a
`can be illustrated by the
`can be illustrated by the results of a controlled
`therapeutic