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SCLEROSING SOLUTIONS FOR VARICOSE VEINS
1101 D. Murray Lyon Cases 1 and 2.
respectively
for
permission
to
report
REFERENCES
1. 2. 3. 4.
Critchley, M. : Brain, 1930, liii., 120. Long, E. : Nouv. Icon. de la Salpêtrière, 1908, xxi., 37. Wilson, G. : Arch. Neurol. and Psychiat., 1923, x., 669. Winkelman, N. W. : Ibid., 1924, xii., 241.
SCLEROSING SOLUTIONS FOR VARICOSE VEINS BY J. W.
RIDDOCH, M.C., M.B., F.R.C.S. Edin.
HON. SURGEON TO THE MIDLAND HOSPITAL, BIRMINGHAM
IDEALLY, a solution for sclerosing varicose veins should cause an obliterative endophlebitis over an unlimited length of selected vein without producing any subjective symptoms in the patient. This would entail the use of a chemical which is non-toxic in relatively large quantities and which has a selective effect on endothelium ; and neither of these qualities is likely to be found in any sclerosing agent. In any case it is impossible to imagine the physiopathological processes involved in the conversion of a patent vein into a fibrous cord going on without at least some inconvenience to the patient. But if the gap between these criteria and the results obtained with solutions at present in use may never be bridged, there is little doubt that in time it will be considerably narrowed. Other features of the ideal solution, such as ease of preparation and cheapness, however desirable, must be regarded as of
secondary importance. No attempt will be made here to refer to all the various solutions which have been used by different workers, of which an excellent review is given by McLatchie ; many of them are now of historic interest only. Attention will be confined to agents in common use. Sodium salicylate.-This salt, introduced by Sicard,2 who deserves great credit for consolidating a treatment which is of inestimable benefit to mankind, is the first to have stood the test of time. Used in 20, 30, and 40 per cent. solution, it is dependable in its effects, though in my hands not so certain as quinine. Its disadvantages are : (a) it produces painful cramp immediately after injection, which, though of minor significance to its advocates, appears to be of some importance from the patient’s point of view ; (b) it easily produces sloughs if allowed to escape into the perivenous tissues ; (c) it does not keep well unless dispensed in special iron-free-glass ampoules. Lithium salicylate appears to be comparable to the sodium salt. Sodium chloride, first introduced by Linser,3 is very variable in its effects. I have used it in saturated solution without any effect on the vein, though weaker solutions have at times caused most severe reactions. This salt also causes cramp, and extraescape gives rise to sloughs. Also its use does not appear to be safe from the risks of embolism. Equal parts of 25 per cent. sodium salicylate and 10 per cent. sodium chloride have been used by Meisen.4 I have used various mixtures of these two
venous
salts without being solution combines
impressed by the results ; the disadvantages of
this its
constituents. 1925 Remenovsky and Kantor 5 introduced 50 per cent. glucose, and in the following year
Sugars.-In
Nobl
s
advocated
a
mixture of
glucose
and laevulose.
Sugar solutions have been popular in America, being recommended especially for small veins and, mixed with sodium chloride, for larger varices (McPheeters, Merkert, and Lundblad 7). Invertose and cane-sugar have also been pressed into service. I have no personal experience of sugar solutions, but they have the advantage of being painless on injection and usable in large quantities ; further they do not readily cause sloughs. On the other hand, they appear to be uncertain in their action and by no means free from the danger of causing embolism. Sodium morrhuate.8-This is a combination of sodium with the fatty acids found in cod-liver oil, used in strengths of 5 and 10 per cent. It appears to be rather an indefinite chemical combination, different samples varying considerably in colour. It has been much used of late and has been recommended as a "froth" for small dilated veins found in the skin, the injection of which is liable to be followed by sloughing when some other solutions are used. Except in the case of the smaller veins, I have found sodium morrhuate very disappointing, and in my experience its use has frequently been followed by red and tender swelling of the thrombosed veins which has taken three or four or more weeks to subside. Biegeleisen9 found wide variations in the efficiency of different samples, and has started using a 5 per cent. solution of pure sodium oleate. Quinine.-The use of quinine to produce a therapeutic endophlebitis is due to Génévrier.1o The solution associated with his name consists of 13-3 per cent. neutral quinine hydrochloride with added urethane, the only appreciable effect of the latter being to dissolve the former. In the opinion of many this is the most dependable in common use and I have certainly found it so. It is painless on injection, having no tendency to give rise to cramps, but at times causes rather severe reactions, and if it finds its way outside the vein has a decided tendency to cause sloughing. Minor disadvantages are that it does not keep well unless put up in ampoules and that it tends to crystallise out and therefore has to be warmed before use. Weaker solutions have been employed and I have personally found 5 per cent. quinine hydrochloride the optimum strength for all-round use. Larger amounts of this strength have of course to be injected, the maximum at any sitting being 8 or 9 c.cm., but even with this weaker solution undue reactions sometimes result when considerable lengths of vein are thrombosed. In order to cut out the effect of the acid radicle, quinine alkaloid was used in a number of cases. Quinine-mannitol, consisting of 12 per cent. quinine base dissolved in a solution of mannite, was found to be very poor in producing sclerosis, but when positive results were obtained, reaction was for all practical purposes nil. From this it was concluded that some of the inflammatory results of Genevrier’s solution might be due to the hydrochloric radicle, and that quinine, to be effective, had to be presented in an ionised form. Accordingly another salt was looked for, and quinine lactate was chosen in the hope that the acid radicle in this case, being a normal constituent of the body arising from katabolic processes, would not be so likely to act as an irritant. This salt has been employed in 10 per cent., 15 per cent., and saturated solutions (16-6 per cent.). Since January, 1934, I have used it on 170 new hospital patients apart from giving it to others whose treatment had been started with the hydrochloride, and to private patients.
1102 The average number of injections in a random selection of cases was found to be 11, so that I must have used it in well over 1500 injections. I think therefore I have seen enough of its effects to form definite conclusions as to its value. It appears to be as efficient as Genevrier’s solution, forms a hard adherent clot, and is painless on injection. " Reactions " do occur but on the whole they are less severe than with the hydrochloride, and no case of the severe type of reaction occasionally seen with Genevrier’s solution has come under my notice. On the other hand, it is not uncommon to find fairly large veins becoming thrombosed with a minimum amount of tenderness and subjective discomfort. As a rule it may be safely used for " skin " veins around the ankle and elsewhere without fear of undesirable effects. In legs where nutrition of the tissues is severely affected sloughing may occur if the solution is given extravenously, but the resulting ulcers are very small, and in limbs of good or fair nutrition I have not yet seen an ulcer develop. It rarely causes residual pigmentation along the sclerosed vein. There does not appear to be much point in using the lactate in anything but the saturated solution, so that its preparation is simplicity itself, excess of the powder being added to a bottle of water. The dose of this for each injection varies from 0-25 c.cm. upwards, a full 3 c.cm. being occasionally necessary in large veins. Three c.cm. is as a rule the maximum amount that can be given at one sitting, though some people stand 4 c.cm. without any general effect. The solution has been kept for several weeks without any change in its appearance or sclerosing powers. It may be added here that quinine lactate is also effective in the injection treatment of enlarged bursae and other cavities lined by endothelium. Dr. Felix Smith has kindly carried out experiments on its germicidal powers and these show that it is
self-sterilising. NOTE BY DR. FELIX SMITH
The
efficiency of quinine lactate as an antiseptic tested in the usual way, by its bactericidal action upon streptococci and B. coli. It was found that non-haemolytio streptococci are prevented from growing in bouillon containing 0-5 per cent. and B. coli in bouillon containing 0-85 per cent. of quinine lactate. The same cultures were tested with carbolic acid and this was found to have a bactericidal power only five times that of quinine lactate. The latter is therefore clearly self-sterilising in strengths above 1 per cent.
was
REFERENCES 1. McLatchie, J. D. P. : The Treatment of Varicose Veins by Intravenous Injections, London, 1928. 2. Sicard, J. A. : Congrès. Français de Méd., Paris, October, 1922. 3. Linser, K. : Münch. med. Woch., 1924, lxxi., 515. 4. Meisen, V.: Varicose Veins and Hæmorrhoids, London, 1932. 5. Remenovsky, F., and Kantor, R.: Wien. klin. Woch., 1925, xxxviii., 532. 6. Nobl, G. : Ibid., 1926, xxxix., 1217. 7. McPheeters, H. O., Merkert, C. E., and Lundblad, R. A. : Jour. Amer. Med. Assoc., 1931, xcvi., 1114. 8. Higgins, T. T., and Kittel, P. B. : THE LANCET, 1930, i., 69. 9. Biegeleisen, H. : Surg., Gyn., and Obst., 1933, lvii., 696. 10. Génévrier, J. : Bull. de Soc. de Méd. Milit. de France, 1921, xv., 169 ; Monde Méd., 1922, xxxii., 624.
OVERCROWDED UNIVERSITIES IN HOLLAND.-We learn from Bru.’Celles-médical that the Netherlands Government have set up a commission, consisting of University professors and other well-known persons, to see what can be done to remedy the excessive entry of students at the Dutch universities and to limit the number of
diplomas granted.
Climical and Laboratory Notes SUBACUTE RHEUMATISM DUE TO A PNEUMOCOCCUS BY NAJIB
FARAH, M.D.
FORMERLY INSTRUCTOR IN THE AMERICAN SCHOOL OF MEDICINE, BEIRUT
IN previous papers1I have endeavoured to establish the pneumococcus as a primary causal agent in acute rheumatism. While awaiting the results of further investigations I propose to report an interesting case of subacute rheumatism, due to pneumococcal infection, which has been under my care for the past ten years. CLINICAL RECORD
The patient, aged 40, is an expert agriculturist; he has four children, all healthy, but two of them with enlarged tonsils. There is no history of syphilis, gonorrhoea, malaria, dysentery, or tuberculosis. He has never had pneumonia or rheumatism ; but repeated sore-throats necessitated removal of the tonsils at the age of 17, and he has had similar attacks since then, though not so severe or
frequent.
In February, 1924, when 31 years of age, he had a bad sore-throat complicated by bronchitis. In April, about 50 days later, there was a sudden onset of subacute articular rheumatism in the right knee with fever ranging from 37° to 38° C. (985° to 100-5° F.) for a few days. The joint was red, swollen, and tender, the swelling being mostly due to effusion, but partly to peri-articular oedema. No other joint was implicated; nothing abnormal was found in the heart; the throat was slightly red. I prescribed a gargle and salicylates internally, with oil of wintergreen over the knee-joint. The pain was soon relieved and the inflammation abated within three weeks with total resolution, the joint resuming its normal aspect. In July, 1924, without any complaint of sore-throat, the left knee was suddenly involved in the same way. The temperature rarely exceeded 38° C. ; no abnormality could be detected elsewhere, and the heart appeared undamaged. Salicylates were again prescribed, and within 20 days recovery was complete. A stock vaccine was given, and also injections of colloidal sulphur by a practitioner in Cairo with the object of preventing a recurrence. In December, 1925, he had a sore-throat, and three days later the right knee-joint was affected in the same fashion as before, again with slight fever ; later the inflammation migrated to the left wrist. Intravenous injections of iodaseptine were given, with salicylates internally. The patient was soon relieved and had no more attacks for about a year. In February, 1927, however, after a slight initial sore-throat the right knee was again implicated, being also relieved by salicylates. The patient refused intravenous medication and, worried by these relapses, consulted several other practitioners, who prescribed various remedies. From that time until February, 1933, there were further occasional attacks of the same kind; more or less mild; migrating from one joint to another ; occasionally preceded by sore-throat or coryza ; involving sometimes the ankles, the knees, the wrists and fingers, and sometimes the shoulder-joints, occasionally being localised in two or even three joints at the same time. The patient was always relieved by salicylates, and once the inflammation had subsided the joints resumed their normal aspect. On Feb. 24th an attack more generalised than the others, with an initial temperature of 37’80 C. (100° F.), came on. The manifestations were the same except that there was no sore-throat. This time, however, six joints were involved simultaneously-the ankles, the knees, the right wrist, and the right metatarso-phalangeal of the index. 1 Presse méd. d’Égypte, August 1st, 1933, p. 231; and before the Society of Tropical Medicine and Hygiene of Egypt on Nov. 3rd, 1933, and Feb. 2nd, 1934 (Compt. rend., 1933-34, i., 4, 26, and 145).
respectively
for
permission
to
report
REFERENCES
1. 2. 3. 4.
Critchley, M. : Brain, 1930, liii., 120. Long, E. : Nouv. Icon. de la Salpêtrière, 1908, xxi., 37. Wilson, G. : Arch. Neurol. and Psychiat., 1923, x., 669. Winkelman, N. W. : Ibid., 1924, xii., 241.
SCLEROSING SOLUTIONS FOR VARICOSE VEINS BY J. W.
RIDDOCH, M.C., M.B., F.R.C.S. Edin.
HON. SURGEON TO THE MIDLAND HOSPITAL, BIRMINGHAM
IDEALLY, a solution for sclerosing varicose veins should cause an obliterative endophlebitis over an unlimited length of selected vein without producing any subjective symptoms in the patient. This would entail the use of a chemical which is non-toxic in relatively large quantities and which has a selective effect on endothelium ; and neither of these qualities is likely to be found in any sclerosing agent. In any case it is impossible to imagine the physiopathological processes involved in the conversion of a patent vein into a fibrous cord going on without at least some inconvenience to the patient. But if the gap between these criteria and the results obtained with solutions at present in use may never be bridged, there is little doubt that in time it will be considerably narrowed. Other features of the ideal solution, such as ease of preparation and cheapness, however desirable, must be regarded as of
secondary importance. No attempt will be made here to refer to all the various solutions which have been used by different workers, of which an excellent review is given by McLatchie ; many of them are now of historic interest only. Attention will be confined to agents in common use. Sodium salicylate.-This salt, introduced by Sicard,2 who deserves great credit for consolidating a treatment which is of inestimable benefit to mankind, is the first to have stood the test of time. Used in 20, 30, and 40 per cent. solution, it is dependable in its effects, though in my hands not so certain as quinine. Its disadvantages are : (a) it produces painful cramp immediately after injection, which, though of minor significance to its advocates, appears to be of some importance from the patient’s point of view ; (b) it easily produces sloughs if allowed to escape into the perivenous tissues ; (c) it does not keep well unless dispensed in special iron-free-glass ampoules. Lithium salicylate appears to be comparable to the sodium salt. Sodium chloride, first introduced by Linser,3 is very variable in its effects. I have used it in saturated solution without any effect on the vein, though weaker solutions have at times caused most severe reactions. This salt also causes cramp, and extraescape gives rise to sloughs. Also its use does not appear to be safe from the risks of embolism. Equal parts of 25 per cent. sodium salicylate and 10 per cent. sodium chloride have been used by Meisen.4 I have used various mixtures of these two
venous
salts without being solution combines
impressed by the results ; the disadvantages of
this its
constituents. 1925 Remenovsky and Kantor 5 introduced 50 per cent. glucose, and in the following year
Sugars.-In
Nobl
s
advocated
a
mixture of
glucose
and laevulose.
Sugar solutions have been popular in America, being recommended especially for small veins and, mixed with sodium chloride, for larger varices (McPheeters, Merkert, and Lundblad 7). Invertose and cane-sugar have also been pressed into service. I have no personal experience of sugar solutions, but they have the advantage of being painless on injection and usable in large quantities ; further they do not readily cause sloughs. On the other hand, they appear to be uncertain in their action and by no means free from the danger of causing embolism. Sodium morrhuate.8-This is a combination of sodium with the fatty acids found in cod-liver oil, used in strengths of 5 and 10 per cent. It appears to be rather an indefinite chemical combination, different samples varying considerably in colour. It has been much used of late and has been recommended as a "froth" for small dilated veins found in the skin, the injection of which is liable to be followed by sloughing when some other solutions are used. Except in the case of the smaller veins, I have found sodium morrhuate very disappointing, and in my experience its use has frequently been followed by red and tender swelling of the thrombosed veins which has taken three or four or more weeks to subside. Biegeleisen9 found wide variations in the efficiency of different samples, and has started using a 5 per cent. solution of pure sodium oleate. Quinine.-The use of quinine to produce a therapeutic endophlebitis is due to Génévrier.1o The solution associated with his name consists of 13-3 per cent. neutral quinine hydrochloride with added urethane, the only appreciable effect of the latter being to dissolve the former. In the opinion of many this is the most dependable in common use and I have certainly found it so. It is painless on injection, having no tendency to give rise to cramps, but at times causes rather severe reactions, and if it finds its way outside the vein has a decided tendency to cause sloughing. Minor disadvantages are that it does not keep well unless put up in ampoules and that it tends to crystallise out and therefore has to be warmed before use. Weaker solutions have been employed and I have personally found 5 per cent. quinine hydrochloride the optimum strength for all-round use. Larger amounts of this strength have of course to be injected, the maximum at any sitting being 8 or 9 c.cm., but even with this weaker solution undue reactions sometimes result when considerable lengths of vein are thrombosed. In order to cut out the effect of the acid radicle, quinine alkaloid was used in a number of cases. Quinine-mannitol, consisting of 12 per cent. quinine base dissolved in a solution of mannite, was found to be very poor in producing sclerosis, but when positive results were obtained, reaction was for all practical purposes nil. From this it was concluded that some of the inflammatory results of Genevrier’s solution might be due to the hydrochloric radicle, and that quinine, to be effective, had to be presented in an ionised form. Accordingly another salt was looked for, and quinine lactate was chosen in the hope that the acid radicle in this case, being a normal constituent of the body arising from katabolic processes, would not be so likely to act as an irritant. This salt has been employed in 10 per cent., 15 per cent., and saturated solutions (16-6 per cent.). Since January, 1934, I have used it on 170 new hospital patients apart from giving it to others whose treatment had been started with the hydrochloride, and to private patients.
1102 The average number of injections in a random selection of cases was found to be 11, so that I must have used it in well over 1500 injections. I think therefore I have seen enough of its effects to form definite conclusions as to its value. It appears to be as efficient as Genevrier’s solution, forms a hard adherent clot, and is painless on injection. " Reactions " do occur but on the whole they are less severe than with the hydrochloride, and no case of the severe type of reaction occasionally seen with Genevrier’s solution has come under my notice. On the other hand, it is not uncommon to find fairly large veins becoming thrombosed with a minimum amount of tenderness and subjective discomfort. As a rule it may be safely used for " skin " veins around the ankle and elsewhere without fear of undesirable effects. In legs where nutrition of the tissues is severely affected sloughing may occur if the solution is given extravenously, but the resulting ulcers are very small, and in limbs of good or fair nutrition I have not yet seen an ulcer develop. It rarely causes residual pigmentation along the sclerosed vein. There does not appear to be much point in using the lactate in anything but the saturated solution, so that its preparation is simplicity itself, excess of the powder being added to a bottle of water. The dose of this for each injection varies from 0-25 c.cm. upwards, a full 3 c.cm. being occasionally necessary in large veins. Three c.cm. is as a rule the maximum amount that can be given at one sitting, though some people stand 4 c.cm. without any general effect. The solution has been kept for several weeks without any change in its appearance or sclerosing powers. It may be added here that quinine lactate is also effective in the injection treatment of enlarged bursae and other cavities lined by endothelium. Dr. Felix Smith has kindly carried out experiments on its germicidal powers and these show that it is
self-sterilising. NOTE BY DR. FELIX SMITH
The
efficiency of quinine lactate as an antiseptic tested in the usual way, by its bactericidal action upon streptococci and B. coli. It was found that non-haemolytio streptococci are prevented from growing in bouillon containing 0-5 per cent. and B. coli in bouillon containing 0-85 per cent. of quinine lactate. The same cultures were tested with carbolic acid and this was found to have a bactericidal power only five times that of quinine lactate. The latter is therefore clearly self-sterilising in strengths above 1 per cent.
was
REFERENCES 1. McLatchie, J. D. P. : The Treatment of Varicose Veins by Intravenous Injections, London, 1928. 2. Sicard, J. A. : Congrès. Français de Méd., Paris, October, 1922. 3. Linser, K. : Münch. med. Woch., 1924, lxxi., 515. 4. Meisen, V.: Varicose Veins and Hæmorrhoids, London, 1932. 5. Remenovsky, F., and Kantor, R.: Wien. klin. Woch., 1925, xxxviii., 532. 6. Nobl, G. : Ibid., 1926, xxxix., 1217. 7. McPheeters, H. O., Merkert, C. E., and Lundblad, R. A. : Jour. Amer. Med. Assoc., 1931, xcvi., 1114. 8. Higgins, T. T., and Kittel, P. B. : THE LANCET, 1930, i., 69. 9. Biegeleisen, H. : Surg., Gyn., and Obst., 1933, lvii., 696. 10. Génévrier, J. : Bull. de Soc. de Méd. Milit. de France, 1921, xv., 169 ; Monde Méd., 1922, xxxii., 624.
OVERCROWDED UNIVERSITIES IN HOLLAND.-We learn from Bru.’Celles-médical that the Netherlands Government have set up a commission, consisting of University professors and other well-known persons, to see what can be done to remedy the excessive entry of students at the Dutch universities and to limit the number of
diplomas granted.
Climical and Laboratory Notes SUBACUTE RHEUMATISM DUE TO A PNEUMOCOCCUS BY NAJIB
FARAH, M.D.
FORMERLY INSTRUCTOR IN THE AMERICAN SCHOOL OF MEDICINE, BEIRUT
IN previous papers1I have endeavoured to establish the pneumococcus as a primary causal agent in acute rheumatism. While awaiting the results of further investigations I propose to report an interesting case of subacute rheumatism, due to pneumococcal infection, which has been under my care for the past ten years. CLINICAL RECORD
The patient, aged 40, is an expert agriculturist; he has four children, all healthy, but two of them with enlarged tonsils. There is no history of syphilis, gonorrhoea, malaria, dysentery, or tuberculosis. He has never had pneumonia or rheumatism ; but repeated sore-throats necessitated removal of the tonsils at the age of 17, and he has had similar attacks since then, though not so severe or
frequent.
In February, 1924, when 31 years of age, he had a bad sore-throat complicated by bronchitis. In April, about 50 days later, there was a sudden onset of subacute articular rheumatism in the right knee with fever ranging from 37° to 38° C. (985° to 100-5° F.) for a few days. The joint was red, swollen, and tender, the swelling being mostly due to effusion, but partly to peri-articular oedema. No other joint was implicated; nothing abnormal was found in the heart; the throat was slightly red. I prescribed a gargle and salicylates internally, with oil of wintergreen over the knee-joint. The pain was soon relieved and the inflammation abated within three weeks with total resolution, the joint resuming its normal aspect. In July, 1924, without any complaint of sore-throat, the left knee was suddenly involved in the same way. The temperature rarely exceeded 38° C. ; no abnormality could be detected elsewhere, and the heart appeared undamaged. Salicylates were again prescribed, and within 20 days recovery was complete. A stock vaccine was given, and also injections of colloidal sulphur by a practitioner in Cairo with the object of preventing a recurrence. In December, 1925, he had a sore-throat, and three days later the right knee-joint was affected in the same fashion as before, again with slight fever ; later the inflammation migrated to the left wrist. Intravenous injections of iodaseptine were given, with salicylates internally. The patient was soon relieved and had no more attacks for about a year. In February, 1927, however, after a slight initial sore-throat the right knee was again implicated, being also relieved by salicylates. The patient refused intravenous medication and, worried by these relapses, consulted several other practitioners, who prescribed various remedies. From that time until February, 1933, there were further occasional attacks of the same kind; more or less mild; migrating from one joint to another ; occasionally preceded by sore-throat or coryza ; involving sometimes the ankles, the knees, the wrists and fingers, and sometimes the shoulder-joints, occasionally being localised in two or even three joints at the same time. The patient was always relieved by salicylates, and once the inflammation had subsided the joints resumed their normal aspect. On Feb. 24th an attack more generalised than the others, with an initial temperature of 37’80 C. (100° F.), came on. The manifestations were the same except that there was no sore-throat. This time, however, six joints were involved simultaneously-the ankles, the knees, the right wrist, and the right metatarso-phalangeal of the index. 1 Presse méd. d’Égypte, August 1st, 1933, p. 231; and before the Society of Tropical Medicine and Hygiene of Egypt on Nov. 3rd, 1933, and Feb. 2nd, 1934 (Compt. rend., 1933-34, i., 4, 26, and 145).