Acta Medica Scandinavica. Vol. CX, fasc. VI, 1942.
`Acta Medica Scandinavica. Vol. CX, fasc. VI, 1942.
`Acta Medica Scandinavica. Vol. CX, fasc. VI, 1942.
`
`(From the Medical Service, Karolinska Sjukhuset, Stockholm. Chief:
`(From the Medical Service, Karolinska Sjukhuset, Stockholm. Chief:
`(From the Medical Service, Karolinska Sjukhuset, Stockholm. Chief:
`Professor N. Svartz).
`Professor N. Svartz).
`Professor N. Svartz).
`
`Salazopyrin, a new sulfanilamide preparation.
`Salazopyrin, a new sulfanilamide preparation.
`Salazopyrin, a new sulfanilamide preparation.
`A. Therapeutic Results in Rheumatic Polyarthritis. B. Thera-
`A. Therapeutic Results in Rheumatic Polyarthritis. B. Thera-
`A. Therapeutic Results in Rheumatic Polyarthritis. B. Thera-
`peutic Results in Ulcerative Colitis. C. Toxic Manifestations in
`peutic Results in Ulcerative Colitis. C. Toxic Manifestations in
`peutic Results in Ulcerative Colitis. C. Toxic Manifestations in
`Treatment with Sulfanilamide Preparations.
`Treatment with Sulfanilamide Preparations.
`Treatment with Sulfanilamide Preparations.
`By
`BY
`By
`NANNA SVARTZ.
`NANNA SVARTZ.
`NANNA SVARTZ.
`(Submitted for publication March 23rd, 1942).
`(Submitted for publication March 23rd, 19/42).
`(Submitted for publication March 23rd, 1942).
`
`A. Therapeutic Results in Rheumatic Polyarthritis.
`A. Therapeutic Results in Rheumatic Polyarthritis.
`A. Therapeutic Results in Rheumatic Polyarthritis.
`For about four years I have been engaged in experiments on the
`For about four years I have been engaged in experiments on the
`For about four years I have been engaged in experiments on the
`treatment of rheumatic polyarthritis with combinations of sulfa-
`treatment of rheumatic polyarthritis with combinations of sulfa-
`treatment of rheumatic polyarthritis with combinations of sulfa-
`nilamide and salicyl preparations. As I have several times pointed
`nilamide and salicyl preparations. As I have several times pointed
`nilamide and salicyl preparations. As I have several times pointed
`out, the earlier known sulfanilamide preparations are active in the
`out, the earlier known sulfanilamide preparations are active in the
`out, the earlier known sulfanilamide preparations are active in the
`socalled septic forms of arthritis, but not in the common rheuma-
`socalled septic forms of arthritis, but not in the common rheuma-
`socalled septic forms of arthritis, but not in the common rheuma-
`tic forms.
`tic forms.
`tic forms.
`At first my experiments concerned the question of whether
`At first my experiments concerned the question of whether
`At first my experiments concerned the question of whether
`medication with both salicyl and sulfanilamide preparations at the
`medication with both salicyl and sulfanilamide preparations at the
`medication with both salicyl and sulfanilamide preparations at the
`same time affects rheumatic polyarthritis. These experiments
`same time affects rheumatic polyarthritis. These experiments
`same time affects rheumatic polyarthritis. These experiments
`yielded no tangible results, however.
`yielded no tangible results, however.
`yielded no tangible results, however.
`The next phase in the series of investigations consisted of
`The nest phase in the series of investigations consisted of
`The next phase in the series of investigations consisted of
`attempts to produce chemical compounds between salicyl prepara-
`attempts to produce chemical compounds between salicyl prepara-
`attempts to produce chemical compounds between salicyl prepara-
`tions on the one hand and sulfanilamide or sulfapyridine on the
`tions on the one hand and sulfanilamide or sulfapyridine on the
`tions on the one hand and sulfanilamide or sulfapyridine on the
`other. These experiments were first conducted by the writer alone,
`other. These experiments were first conducted by the writer alone,
`other. These experiments were first conducted by the writer alone,
`but later in collaboration with A. B. Pharmacia, where the chemists,
`but later in collaboration with A. B. Pharmacia, where the chemists,
`but later in collaboration with A. B. Pharmacia, where the chemists,
`Civil Engineer E. Askelof and Dr. Phil. H. Willstaedt produced
`Civil Engineer E. Askelof and Dr. Phil. H. Willstaedt produced
`Civil Engineer E. Askelof and Dr. Phil. H. Willstaedt produced
`different combinations of salicyl and sulfanilamide preparations
`different combinations of salicyl and sulfanilamide preparations
`different combinations of salicyl and sulfanilamide preparations
`
`Ex. 1058 - Page 1
`
`

`

`578
`578
`NANNA SVARTZ.
`NAlVNA SVARTZ.
`578
`NANNA SVARTZ.
`for the later investigations. One of these preparations, salicylazosul-
`for the later investigations. One of these preparations, salicylazosul-
`for the later investigations. One of these preparations, salicylazosul-
`fapyridine or acidum p- (benzolsulfonyl-[amino- a-pyridine1)-azo-
`fapyridine or acidum p- (benzolsulfonyl-[amino- a-pyridine])-azo-
`fapyridine or acidum p- (benzolsulfonyl-[amino- a-pyridine])-azo-
`salicylicum, was found to possess remarkable qualities. It is now
`salicylicum, was found to possess remarkable qualities. It is now
`salicylicum, was found to possess remarkable qualities. It is now
`in the market under the name salazopyrin.
`in the market under the name salazopyrin.
`in the market under the name salazopyrin.
`The preparation in question has shown a definite effect in
`The preparation in question has shown a definite effect in
`The preparation in question has shown a definite effect in
`certain cases of rheumatic polyarthritis. It is by no means generally
`certain cases of rheumatic polyarthritis. I t is by no means generally
`certain cases of rheumatic polyarthritis. It is by no means generally
`active in this disorder, however. For instance, its effect often fails
`active in this disorder, however. For instance, its effect often fails
`active in this disorder, however. For instance, its effect often fails
`t o appear in patients in whom the disease has been present for
`to appear in patients in whom the disease has been present for
`to appear in patients in whom the disease has been present for
`many years. But if the disease is still in an active stage, the treat-
`many years. But if the disease is still in an active stage, the treat-
`many years. But if the disease is still in an active stage, the treat-
`ment often yields good results in cases of this type too. The effect on
`ment often yields good results in cases of this type too. The effect on
`ment often yields good results in cases of this type too. The effect on
`polyarthritis of short duration is also varying. Of two apparently
`polyarthritis of short duration is also varying. Of two apparently
`polyarthritis of short duration is also varying. Of two apparently
`similar cases, one may be affected remarkably quickly, the other
`similar cases, one may be affected remarkably quickly, the other
`similar cases, one may be affected remarkably quickly, the other
`extremely slowly or not at all. The reason for the variations in
`extremely slowly or not at all. The reason for the variations in
`extremely slowly or not at all. The reason for the variations in
`effect is still unclear.
`effect is still unclear.
`effect is still unclear.
`In the case reports will he given a short account of some cases
`In the case reports will he given a short account of some cases
`In the case reports will he given a short account of some cases
`of polyarthritis treated with salazopyrin (the preparation is made
`of polyarthritis treated with salazopyrin (the preparation is made
`of polyarthritis treated with salazopyrin (the preparation is made
`up in tablet form with 0.5 g salicylazosulfapyridine in each.)
`up in tablet form with 0.5 g salicylazosulfapyridine in each.)
`up in tablet form with 0.5 g salicylazosulfapyridine in each.)
`A short summary of the cases described on pages 590-595
`A short summary of the cases described on pages 590-595
`A short summary of the cases described on pages 590-595
`is given in table 1.
`is given in table 1.
`is given in table 1.
`From this table and the case reports it will appear that
`From this table and the case reports it will appear that
`From this table and the case reports it will appear that
`salicylazosulfapyridine has shown an indubitable and good effect
`salicylazosulfapyridine has shown an indubitable and good effect
`salicylazosulfapyridine has shown an indubitable and good effect
`in these cases of polyarthritis.
`in these cases of polyarthritis.
`in these cases of polyarthritis.
`The cases were selected from my material and represent patients
`The cases were selected from my material and represent patients
`The cases were selected from my material and represent patients
`who reacted rapidly or favorably to the treatment. The reason why
`who reacted rapidly or favorably to the treatment. The reason why
`who reacted rapidly or favorably to the treatment. The reason why
`I have not presented the whole material is, that it is not yet possible
`I have not presented the whole material is, that it is not yet possible
`I have not presented the whole material is, that it is not yet possible
`to evaluate the results in a great part of it. As pointed out introduc-
`to evaluate the results in a great part of it. As pointed out introduc-
`to evaluate the results in a great part of it. As pointed out introduc-
`torily, however, it must be admitted that in certain cases, parti-
`torily, however, it must be admitted that in certain cases, parti-
`torily, however, it must be admitted that in certain cases, parti-
`cularly markedly chronic ones, the treatment often has little if any
`cularly markedly chronic ones, the treatment often has little if any
`cularly markedly chronic ones, the treatment often has little if any
`effect. In other cases an improvement does occur, but not until
`effect.
`In other cases an improvement does occur, but not until
`effect. In other cases an improvement does occur, but not until
`after two to three months of treatment.
`after two to three months of treatment.
`after two to three months of treatment.
`During medication with salazopyrin the blood always contains
`During medication with salazopyrin the blood always contains
`During medication with salazopyrin the blood always contains
`free sulfapyridine and acetylsulfapyridine in greatly varying con-
`free sulfapyridine and acetylsulfapyridine in greatly varying con-
`free sulfapyridine and acetylsulfapyridine in greatly varying con-
`centration. With the usual dosage (2 tablets five or six times daily)
`centration. With the usual dosage (2 tablets five or six times daily)
`centration. With the usual dosage (2 tablets five or six times daily)
`the sulfapyridine content in the blood is generally not greater
`the sulfapyridine content in the blood is generally not greater
`the sulfapyridine content in the blood is generally not greater
`than 1-2 mg per cent. The sulfapyridine content is thus consider-
`than 1-2 mg per cent. The sulfapyridine content is thus consider-
`than 1-2 mg per cent. The sulfapyridine content is thus consider-
`ably lower than is usual with therapeutically active sulfapyridine
`ably lower than is usual with therapeutically active sulfapyridine
`ably lower than is usual with therapeutically active sulfapyridine
`treatment.
`treatment.
`treatment.
`Salicylazosulfapyridine is a brown-yellow azo compound which
`Salicylazosulfapyridine is a brown-yellow azo compound which
`Salicylazosulfapyridine is a brown-yellow azo compound which
`is difficult to dissolve in water. It is admittedly somewhat soluble in
`is difficull t o dissolve in water. It is admittedly somewhat soluble in
`is difficult to dissolve in water. It is admittedly somewhat soluble in
`
`Ex. 1058 - Page 2
`
`(cid:9)
`(cid:9)
`

`

`SALAZOPYRIN, A N E W S U L F A N I L A M I D E PREPARATION.
`
`SALAZOPYRIN, A NEW SULFANILAMIDE PREPARATION. SALAZOPYRIN, A NEW SULFANILAMIDE PREPARATION.
`Table 1.
`
`Table 1. Table 1.
`Sed. rate
`
`Sed. rate Sed. rate
`at begin-
`
`at begin- at begin-
`ning of
`
`ning of ning of
`treatmen
`
`treatment treatment
`
`--
`
`jed. rate
`
`Sed. rate Sed. rate
`it endof
`
`at end of at end of
`treat-
`
`treat- treat-
`ment
`
`ment ment
`
`579
`
`579 579
`
`_~
`
`Joint troubles a t end 01
`
`Joint troubles at end of Joint troubles at end of
`treatment
`
`treatment treatment
`
`Patient
`
`Patient Patient
`
`~~
`
`Duration of
`
`Duration of Duration of
`disease
`
`disease disease
`
`Salazopyrin medica-
`
`Salazopyrin medica - Salazopyrin medica -
`tion
`
`tion tion
`
`___---
`25 mm
`
`25 mm 25 mm
`
`50 mm
`
`50 mm 50 mm
`
`~
`
`~
`
`i5-40 mn
`Insignificant
`12 mm
`1. Lisa J.
`Oct. '40 to Feb. '41
`Recurrent poly
`
`Oct. '40 to Feb. '41 35-40 mm 12 mm Insignificant Oct. '40 to Feb. '41 35-40 mm 12 mm Insignificant
`
`
`1. Lisa J. 1. Lisa J.
`Recurrent poly- Recurrent poly-
`arthr. since 1933
`born 1906
`
`arthr. since 1933. arthr. since 1933.
`
`born 1906 born 1906
`Continuous sincc
`
`Continuous since Continuous since
`_ _ _ - _ - - _ - - _ - - - - - -
`- _ _ _ _
`1939.
`
`1939. 1939.
`_ _ _ _ - - - _ _ _ _
`_ _ _ _ _ _ _ _
`1 '/z yr.
`Mild in one knee
`NOV. '4O-J~ly '41
`7 mm
`2. Ingrid A.
`
`7 mm Mild in one knee 7 mm Mild in one knee
`
`Nov. '40—July '41 Nov. '40—July '41
`
`
`
`2. Ingrid A. 2. Ingrid A. 1 3/2 yr. 1 3/2 yr.
`_ - - _ _ - - - _ _ _ _ _ - _ _ _ _ - - - - - -
`(about 1000 tablets)
`born 1896
`_ _ _ _ _ _ _ _ _ _ _ _ _ _ - _ _ _ _
`
`(about 1000 tablets) (about 1000 tablets)
`_ _ _ _
`. - - - .- - _ _ -
`
`born 1896 born 1896
`No symptoms
`3. Bengt L.
`108 mm
`17 mm
`Feb.-July
`2-3 weeks
`1941
`
`108 mm 17 mm No symptoms 108 mm 17 mm No symptoms
`
`Feb.—July 1941 Feb.—July 1941
`
`
`
`3. Bengt L. 3. Bengt L. 2-3 weeks 2-3 weeks
`. _ _ _ .. - _ - - - - - - - - - - -
`born 1900
`_ _ _ _ _ -
`_ _ _ _ _ _ _ _
`- - _ _ _
`
`born 1900 born 1900
`_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
`Irreparable changes in on
`Since 1937
`6 mm
`May-Oct.,
`33 mm
`i. Eiiiar G.
`1941
`
`6 mm Irreparable changes in one 6 mm Irreparable changes in one
`
`May—Oct., 1941 May—Oct., 1941
`
`33 mm 33 mm
`
`Since 1937 Since 1937
`
`4. Einar G. 4. Einar G.
`knee. No other symptom
`born 1897
`_ _ _ _ _ -
`
`knee. No other symptoms knee. No other symptoms
`
`born 1897 born 1897
`1 mo. (Apr.-May
`No symptoms
`40 mm
`10 mm
`Autumn 1940
`5 . Elsa A.
`
`40 mm 10 mm No symptoms 40 mm 10 mm No symptoms
`
`1 (cid:9) mo. (Apr.—May 1 (cid:9) mo. (Apr.—May
`
`Autumn 1940 Autumn 1940
`
`5. Elsa A. 5. Elsa A.
`1941)
`born 1910
`____------_------
`
`1941) 1941)
`_ _ _ _ _
`
`born 1910 born 1910
`_ _ _ _ _ _ - _ _ _ _ _ _ - - - - -
`Swelling in 2 metacarpc
`23 mm
`86 mm
`6. Ebba R.
`Aug. '41--March
`'42
`March 1940
`
`Aug. '41--March '42 86 mm 23 mm Swelling in 2 metacarpo- Aug. '41--March '42 86 mm 23 mm Swelling in 2 metacarpo-
`
`March 1940 March 1940
`
`6. Ebba R. 6. Ebba R.
`phalangeal joints. Treal
`born 1888
`
`phalan ge al joints. (cid:9) Treat- phalan ge al joints. (cid:9) Treat-
`
`born 1888 born 1888
`- - _ __ _ _ - _ - _ _ _ _ _ _ _ -
`ment continuing
`
`ment continuing ment continuing
`. . . . . . . . . . . . . . . . . . . . . . . .
`- - - _.
`_ _ _ _ _ _ ~ .
`No symptoms
`121 mm
`13 mm
`
`N O ~ . '40-Jan.
`Nov. 1940
`'41
`7. Stig J.
`
`Nov. '40—Jan. '41 121 mm 13 mm No symptoms Nov. '40—Jan. '41 121 mm 13 mm No symptoms
`
`Nov. 1940 Nov. 1940
`
`7. Stig J. 7. Stig J.
`born1917
`- _ _ _ - _ - _ _ _ _ - - - ._ - -
`.. _ _ _
`
`born 1917 born 1917
`_ _ _ _ _ _ _ _ _ - - - - -
`Moderate swelling in fe1
`110 mm
`32 mm
`8. Olof H.
`Recurrent poly-Apr.-May
`1941
`
`110 mm 32 mm Moderate swelling in few 110 mm 32 mm Moderate swelling in few
`
`8. Olof H. 8. Olof H.
`
`Apr.—May 1941 Apr.—May 1941
`
`Recurrent (cid:9) poly- Recurrent (cid:9) poly-
`finger joints.
`arthr. since 1933
`born 1894
`
`finger joints. finger joints.
`
`arthr. since 1933 arthr. since 1933
`
`born 1894 born 1894
`No symptoms
`20 mm
`u Olof H.
`Recurrence Oct. 20/10-20/11
`'41
`
`20 mm No symptoms 20 mm No symptoms
`
`,i (cid:9) Olof H. ,i (cid:9) Olof H.
`
`20/10-20/11 '41 20/10-20/11 '41
`
`Recurrence (cid:9) Oct. Recurrence (cid:9) Oct.
`born 1894
`1941
`_ _ _ _ _ _ _ _ _ _ _ _ _ _----_-
`
`1941 1941
`
`born 1894 born 1894
`. . . . . . . . . . . . . . . . . . . . . . . . . .
`---
`_ . _ _ _ _ _ _ _
`Consider.
`improvement
`16 mm
`42 mm
`9. Ingrid S.
`3 weeks. (0ct.-Nov
`March 1940
`
`improvement. improvement.
`
`42 mm 16 mm Consider. (cid:9)42 mm 16 mm Consider. (cid:9)
`
`
`March 1940 March 1940
`3 weeks. (Oct.—Nov. 3 weeks. (Oct.—Nov.
`
`9. Ingrid S. 9. Ingrid S.
`born 1911
`1941)
`
`1941) 1941)
`
`born 1911 born 1911
`_ _ - _ _ _ _ _
`_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ - - - -
`No symptoms
`12 mm
`Oct. 41-Febr.
`30 mm
`1927
`194:
`10.AitridH.
`
`Oct. 41—Febr. 1942 30 mm 12 mm No symptoms Oct. 41—Febr. 1942 30 mm 12 mm No symptoms
`
`10. Astrid H. 10. Astrid H.
`
`1927 1927
`born 1907
`__---
`_ _ _ _ _ _ _ _ _ _ _ - - - ---
`_ _ _ _ _
`
`born 1907 born 1907
`Consider. improvement.
`16 mm
`47 mm
`11. Erik. K.
`1930
`
`47 mm 16 mm Consider. improvement. 47 mm 16 mm Consider. improvement.
`
`
`11. Erik. (cid:9) K. 1930 1930 11. Erik. (cid:9) K.
`
`born 1880
`
`born 1880 born 1880
`
`- - - - _ _ _
`
`2 mos. (Sept.-Nov
`
`2 mos. (Sept.—Nov. 2 mos. (Sept.—Nov.
`1941)
`
`1941) 1941)
`
`concentrated acid, but insoluble in dilute. The alkaline salts are,
`
`concentrated acid, but insoluble in dilute. The alkaline salts are, concentrated acid, but insoluble in dilute. The alkaline salts are,
`unlike the original preparation, fairly easily soluble. Salicylazosul-
`
`unlike the original preparation, fairly easily soluble. Salicylazosul-unlike the original preparation, fairly easily soluble. Salicylazosul-
`fapyridine is excreted partly in undecomposed form with the urine.
`
`fapyridine is excreted partly in undecomposed form with the urine. fapyridine is excreted partly in undecomposed form with the urine.
`If the urine is alkaline it takes on an orange-yellow color on medi-
`
`If the urine is alkaline it takes on an orange-yellow color on medi-If the urine is alkaline it takes on an orange-yellow color on medi-
`cation with salazopyrin. No discoloration appears in acid urine.
`
`cation with salazopyrin. No discoloration appears in acid urine. cation with salazopyrin. No discoloration appears in acid urine.
`
`Ex. 1058 - Page 3
`
`(cid:9)
`(cid:9)
`

`

`580
`580
`N AN N A SNTATITZ.
`N A N N A SVARTZ.
`580
`N AN N A SNTATITZ.
`The immediate relief from pain secured with the usual salicyl
`The immediate relief from pain secured with the usual salicyl
`The immediate relief from pain secured with the usual salicyl
`preparations is generally not obtained with salazopyrin. — Thus
`preparations is generally not obtained with salazopyrin. - Thus
`preparations is generally not obtained with salazopyrin. — Thus
`it is at first often necessary to allow patients accustomed to salicyl
`it is at first often necessary to allow patients accustomed to salicyl
`it is at first often necessary to allow patients accustomed to salicyl
`preparations to continue taking them. If salicyl preparations are
`preparations to continue taking them. If salicyl preparations are
`preparations to continue taking them. If salicyl preparations are
`stopped entirely, patients who are used to them often consider that
`stopped entirely, patients who are used to them often consider that
`stopped entirely, patients who are used to them often consider that
`the disease has become worse after the beginning of the salazopyrin
`the disease has become worse after the beginning of the salazopyrin
`the disease has become worse after the beginning of the salazopyrin
`medication.
`medication.
`medication.
`A suitable dose of salazopyrin (the preparation is made by
`A suitable dose o€ salazopyrin (the preparation is made by
`A suitable dose of salazopyrin (the preparation is made by
`A. B. Pharmacia, Stockholm) for adults is two tablets four to six
`A. B. Pharmacia, Stockholm) for adults is two tablets four to six
`A. B. Pharmacia, Stockholm) for adults is two tablets four to six
`times a day. The intervals between the doses should not, even in
`times a day. The intervals between the doses should not, even in
`times a day. The intervals between the doses should not, even in
`the night, exceed about eight hours. The medication should be con-
`the night, exceed about eight hours. The medication should be con-
`the night, exceed about eight hours. The medication should be con-
`tinued for weeks or months. Several of our patients have taken
`tinued for weeks or months. Several of our patients have taken
`tinued for weeks or months. Several of our patients have taken
`approximately one thousand tablets. If the condition appears to
`approximately one thousand tablets.
`If the condition appears t o
`approximately one thousand tablets. If the condition appears to
`be stationary and the sedimentation rate has become normal or
`be stationary and the sedimentation rate has become normal or
`be stationary and the sedimentation rate has become normal or
`remained the same for a long period, the dose may be reduced to one
`remained the same for a long period, the dose may be reduced to one
`remained the same for a long period, the dose may be reduced to one
`tablet three to six times a day. With this smaller dose the patient
`tablet three to six times a day. With this smaller dose the patient
`tablet three to six times a day. With this smaller dose the patient
`may possibly be able to start working again. It is not suitable, on
`may possibly be able to start working again. It is not suitable, on
`may possibly be able to start working again. It is not suitable, on
`the other hand, for the patient to move about too much during the
`the other hand, for the patient to move about too much during the
`the other hand, for the patient to move about too much during the
`first stage of the treatment. Rest in bed is preferable at the be-
`first stage of the treatment. Rest in bed is preferable at the be-
`first stage of the treatment. Rest in bed is preferable at the be-
`ginning of the cure.
`ginning of the cure.
`ginning of the cure.
`It may be mentioned that the form of chemotherapy under dis-
`It may be mentioned that the form of chemotherapy under dis-
`It may be mentioned that the form of chemotherapy under dis-
`cussion had a good effect in several cases of polyarthritis in which
`cussion had a good effect in several cases of polyarthritis in which
`cussion had a good effect in several cases of polyarthritis in which
`gold therapy yielded negative results.
`gold therapy yielded negative results.
`gold therapy yielded negative results.
`As in all forms of treatment, relapses may occur following sala-
`As in all forms of treatment, relapses may occur following sala-
`As in all forms of treatment, relapses may occur following sala-
`zopyrin therapy also, a few examples of which we have already
`zopyrin therapy also, a few examples of which we have already
`zopyrin therapy also, a few examples of which we have already
`seen. These relapses have, however, been remarkably easily influen-
`seen. These relapses have, however, been remarkably easily influen-
`seen. These relapses have, however, been remarkably easily influen-
`ced by a new period of treatment.
`ced by a new period of treatment.
`ced by a new period of treatment.
`
`B. Therapeutic Results in Ulcerative Colitis.
`B. Therapeutic Results in Ulcerative Colitis.
`B. Therapeutic Results in Ulcerative Colitis.
`As previously mentioned, salazopyrin is not only active in poly-
`As previously mentioned, salazopyrin is not only active in poly-
`As previously mentioned, salazopyrin is not only active in poly-
`arthritis but in certain other infections also, particularly ulcerative
`arthritis but in certain other infections also, particularly ulcerative
`arthritis but in certain other infections also, particularly ulcerative
`colitis.
`colitis.
`colitis.
`An account will now be given of the results secured with sala-
`An account will now he given of the results secured with sala-
`An account will now be given of the results secured with sala-
`zopyrin medication in ulcerative colitis.
`zopyrin medication in ulcerative colitis.
`zopyrin medication in ulcerative colitis.
`In earlier publications Kallrli r and I described our experi-
`In earlier publications Kallncr and I described our experi-
`In earlier publications Kallm r and I described our experi-
`ments on the treatment of ulcerative colitis with sulfapyridine and
`ments on the treatment of ulcerative colitis with sulfapyridine and
`ments on the treatment of ulcerative colitis with sulfapyridine and
`pointed out that exceedingly good results were achieved. We also
`pointed out that excecdingly good results were achieved. We also
`pointed out that exceedingly good results were achieved. We also
`
`Ex. 1058 - Page 4
`
`(cid:9)
`(cid:9)
`

`

`58 1
`581
`S A L A Z O P Y R I N , A N E W S U L F A N I L A M I D E P R E P A R A T I O N .
`SALAZOPYRIN, A NEW SULFANILAMIDE PREPARATION.
`581
`SALAZOPYRIN, A NEW SULFANILAMIDE PREPARATION.
`remarked that the preparation was not universally effective in the
`remarked that the preparation was not universally effective in the
`remarked that the preparation was not universally effective in the
`disorder in question.
`disorder in question.
`disorder in. question.
`I have since reported, in Nordisk Medicin 1941, for example,
`I have since reported, in. Nordisk Medicin 1941, for example,
`I have since reported, in. Nordisk Medicin 1941, for example,
`that even better results have been obtained with salazopyrin than
`that even better results have been obtained with salazopyrin than
`that even better results have been obtained with salazopyrin than
`with sulfapyridine and that some cases which did not become free
`with sulfapyridine and that some cases which did not become free
`with sulfapyridine and that some cases which did not become free
`of symptoms with sulfapyridine rapidly improved with salazopyrin.
`of symptoms with sulfapyridine rapidly improved with salazopyrin.
`of symptoms with sulfapyridine rapidly improved with salazopyrin.
`Neither is, salazopyrin effective however in all forms of ulcerative
`Neither is, salazopyrin effective however in all forms of ulcerative
`Neither is, salazopyrin effective however in all forms of ulcerative
`colitis.
`colitis.
`colitis.
`A few cases of ulcerative colitis will be described on page 15
`A few cases of ulcerative colitis will be described on page 15
`A few cases of ulcerative colitis will be described on page 15
`and further to illustrate the action of salazopyrin in this disorder.
`and further to illustrate the action of salazopyrin in this disorder.
`and further to illustrate the action of salazopyrin in this disorder.
`The temperature charts of these cases are reproduced here in the
`The temperature charts of these cases are reproduced here in the
`The temperature charts of these cases are reproduced here in the
`text to give a rapid survey of the effect of salazopyrin.
`text to give a rapid survey of the effect of salazopyrin.
`text to give a rapid survey of the effect of salazopyrin.
`A horizontal stretch signifies gruel-thin, a slanting stretch
`A horizontal stretch signifies gruel-thin, a slanting stretch
`A horizontal stretch signifies gruel-thin, a slanting stretch
`srrnisolid and a vertical stretch a solid evacuation. An enema is
`semisolid and a vertical stretch a solid evacuation. An enema is
`semisolid and a vertical stretch a solid evacuation. An enema is
`indicated by a cross.
`indicated by a cross.
`indicated by a cross.
`Treatment with salazopyrin has given excellent results in many
`Treatment with salazopyrin has given excellent results in many
`Treatment with salazopyrin has given excellent results in many
`cases of ulcerative colitis. This form of chemotherapy is worthy of
`cases of ulcerative colitis. This form of chemotherapy is worthy of
`cases of ulcerative colitis. This form of chemotherapy is worthy of
`trial in every case of ulcerative colitis. In relatively few cases is the
`trial in every case of ulcerative colitis. In relatively few cases is the
`trial in every case of ulcerative colitis. In relatively few cases is the
`treatment entirely ineffectual.
`In severe cases the administration
`treatment entirely ineffectual. In severe cases the administration
`treatment entirely ineffectual. In severe cases the administration
`of vitamins often hastens recovery.
`of vitamins often hastens recovery.
`of vitamins often hastens recovery.
`
`C. Toxic Manifestations.
`C. Toxic Manifestations.
`C. Toxic Manifestations.
`Toxic manifestations are often completely lacking with salazo-
`Toxic manifestations are often completely lacking with salazo-
`Toxic manifestations are often completely lacking with salazo-
`Fyrin medication.
`pyrin medication.
`pyrin medication.
`Nausea and vomiting appear very seldom. Particularly a t the
`Nausea and vomiting appear very seldom. Particularly at the
`Nausea and vomiting appear very seldom. Particularly at the
`beginning of the cure, the patients do sometimes complain of poor
`beginning of the cure, the patients do sometimes complain of poor
`beginning of the cure, the patients do sometimes complain of poor
`appetite.
`appetite.
`appetite.
`Cyanosis is, as we know, an exceedingly common symptom with
`Cyanosis is, as we know, an exceedingly common symptom with
`Cyanosis is, as we know, an exceedingly common symptom with
`sulfanilamide and sulfapyridine medication. As shown by Svartz
`sulfanilamide and sulfapyridine medication. As shown by Svartz
`sulfanilamide and sulfapyridine medication. As shown by Svartz
`and Kallner, the cyanosis which appears in connection with the use
`and Kaliner, the cyanosis which appears in connection with the use
`and Kaliner, the cyanosis which appears in connection with the use
`of sulfanilamjde preparations does not depend on the formation
`of sulfanilamide preparations does not depend on the formation
`of sulfanilamide preparations does not depend on the formation
`It i s due to the amide
`of methemoglobin or sulfhemoglobin.
`of methemoglobin or sulfhemoglobin. It is due to the amide
`of methemoglobin or sulfhemoglobin. It is due to the amide
`component of the sulfonamide preparations becoming combined wifh
`component of the sulfonamide preparations becoming combined with
`component of the sulfonamide preparations becoming combined with
`hemoglobin. Kallner will in the near future present further investiga-
`hemoglobin. Kaliner will in the near future present further investiga-
`hemoglobin. Kallner will in the near future present further investiga-
`tions on this question. He is of the opinion that the cyanosis
`tions on this question. He is of the opinion that the cyanosis
`tions on this question. He is of the opinion that the cyanosis
`is due to a combination between the sulfonamide preparations
`is due to a combination between the sulfonamide preparations
`is due to a combination between the sulfonamide preparations
`and carbhemoglobin.
`and carbhemoglobin.
`and carbhemoglobin.
`
`Ex. 1058 - Page 5
`
`(cid:9)
`(cid:9)
`

`

`mem-mum
`
`
`
`isrAMT261iMA
`
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`
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`6 (cid:9)
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`ar Im
`wr IVZ/
`
`oh:fier.: a_
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`R A N N A SVARTZ.
`'ZIUVAS VNINVII
`'ZIIIVAS VNI/sIVU
`
`58 2
`
`IsZ)
`00
`Cn
`
`Fig. 3. Case of Ulcerative colitis treated with
`Fig. 3. Case of Ulcerative colitis treated with
`mommommummommommumm
`mommummommummommom
`nommummenmemnsimmummm
`nomnrammenmemnommmummm
`
`9 '5
`a,
`2 Y
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`
`salazopyrin.
`salazopyrin.
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`LI
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`ai
`E
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`_ (cid:9)
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`
`
`
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`
`tam IN/
`tam 18B/
`
`Fig. 2. Case of Ulcerative colitis treated with
`Fig. 2. Case of Ulcerative colitis treated with
`IIIMMEIMMUMMEMEMMEMEMMMIll
`WAIMMOMMOMEMMEMMEMMEMMIII
`IMIMMWEMMMEMEMMEMMEMMOM
`!IUMAKMMaMMUMMTIMMEMMEMM
`1-7 (cid:9)
`
`salazopyrin.
`salazopyrin.
`
`•(cid:9)
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`:272MMMORDOMMOOMminntinnnunn
`=E2IMMOOMMOMMDMntinnnumn
`,44 (cid:9)
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`
`tft (cid:9)
`
`•
`
`• (cid:9)
`
`• (cid:9)
`
`' (cid:9)
`
`Fig. 1. Case of Ulcerative colitis treated with salazopyrin.
`Fig. 1. Case of Ulcerative colitis treated with salazopyrin.
`
`II II II II II I I I/ II II II II II II II I
`II 11 II n ll I (cid:9)
`II II ll U II II it II I
`
`I (cid:9)
`
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`_/ II II /I. II
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`
`= (cid:9)
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`
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`
`.04
`
`2.
`2.
`
`31 7.
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`
`27 28 29. 30.
`27
`28. 29. 30.
`
`30. 21 22. 23. 24.25. 36.
`20. 21
`22. 23. 24 25.26.
`
`79
`79.
`
`76.
`16 M M
`
`77
`
`75.
`15.
`
`74%
`77. m 13. 74.
`
`73.
`
`9 22 n 72.
`
`7.
`7. e. 9. io.
`
`a.
`
`