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PAIN RELIEF AND OTHER EFFECTS FOLLOWING BARBOTAGE
746
CARDIOVASCULAR EFFECTS OF HYPOGLYCÆMIC SULPHONYLUREAS SIR,-The articles in your issue of Feb. 12 (p. 335 and once more raise the possibility that the sulphonylderivatives increase the incidence of myocardial infarction in diabetes. In this regard we should like to draw your attention to two papers 1,2 we published in 1960-61 relating to the effect of tolbutamide on the dog heart-lung preparation. These studies indicate that tolbutamide: (1) increases glucose uptake by the isolated heart-lung preparation; (2) decreases the coronary blood-flow; and (3) depresses the myocardium, causing an increase in atrial pressures and dilatation of the ventricles. These results could be observed with " " physiological concentration of the drug, but were more apparent with higher doses, 2 g. added to the venous reservoir causing severe cardiac failure. In a few experiments with anaesthetised open-chest dogs tolbutamide given intravenously caused a rise of systemic arterial pressure accompanied by an increase in coronary-
338)
p.
urea
artery flow. Several extrapancreatic effects of tolbutamide, including those on the cardiovascular system, have been pointed out. 3,4 Although it is difficult to extrapolate our findings in the denervated heart-lung preparation to the possible clinical effects of prolonged use of tolbutamide, we agree that an extensive investigation of the cardiovascular effects (acute and chronic) of the various sulphonylurea derivatives should be undertaken. University Medical School, Plaza, Chicago, Illinois 60614, A. K. KHACHADURIAN. U.S.A.
Northwestern
sharply to normal in cases of rheumatic polyarthritis where the temperature was raised or could rise temporarily in subacute cases where it was within normal limits)were noted. Speransky noted, too, that greatly enlarged spleens seen in malaria could regress to normal size within 3 weeks of spinal pumping, and that remission lasting 3-5 months occurred in two-thirds of cases of Parkinson’s disease following the introduction by suboccipital puncture into the subarachnoid space of as little as 0-3 ml. of the patient’s blood, either alone or accompanied by lumbar spinal pumping. In other diseases, the efficacy of orally or parenterally administered drugs to which patients had become resistant was also increased by pumping. Speransky’s primary purpose was to disclose the neural component of a pathological process and to show that by intervention through the nervous system (by spinal pumping or by other means) it was possible to alter the course of diseases of widely different aetiology. It is noteworthy, therefore, that the percentage of positive responses to spinal pumping when used for the relief of pain in cancer patients was similar to that obtained in the treatment of fall
salicylate-resistant rheumatic polyarthritis, enlarged spleen in malaria, and other diseases mentioned by Speransky. It is to be hoped that the observations of Lloyd and his colleagues may stimulate a re-evaluation of spinal pumping and other methods described by Speransky in the treatment of diseases for which at present no satisfactory therapy is available. Via Montedoro, 80059 Torre del Greco,
Napoli, Italy.
2300 Children’s
Creighton University Medical School, 2500 California Street, Omaha, Nebraska 68131, H. S. BADEER. U.S.A.
PAIN RELIEF AND OTHER EFFECTS FOLLOWING BARBOTAGE
SIR,-It is encouraging to know that almost 40 years after Speransky published his thought-provoking book,5 Dr. Lloyd and his colleagues (Feb. 12, p. 354) have used barbotage (spinal pumping of cerebrospinal fluid) specifically to relieve severe intractable pain in cancer patients. In seeking an explanation for the mechanism involved, factors other than slight morphological changes in the spinothalamic tract described by Lloyd may need to be considered. Tampering with the cerebrospinal fluid, whether by spinal pumping or by the introduction of various substances into it, can have widespread effects on the physiology of the organism and may arrest or reverse temporarily, or even permanently, the course of many pathological processes, which in current thinking could hardly be attributed to changes in the spinothalamic tract. In acute and subacute rheumatic polyarthritis, whether or not resistant to salicylates and other forms of therapy, spinal pumping led to the rapid relief of pain within 24 hours and to the disappearance of redness, swelling, and stiffness of joints a few days later.5·6 Striking changes were observed in the peripheral vascular system, acneform lesions on the face, neck, and back rapidly disappeared, and paradoxical effects on the body-temperature (which could Khachadurian, A. K., Badeer, H. S. Metabolism, 1960, 9, 890. Khachadurian, A K., Karam, J. D., Badeer, H. S. Archs int. Pharmacodyn. 1961, 132, 42. 3. Wolff, F., Grant, A. New Engl. J. Med. 1971, 284, 915. 4. Roth, J., Prout, T. E., Goldfine, I. D., Wolfe, S. M., Muenzer, J., Grauer, L. E., Marcus, M. L. Ann. intern. Med. 1971, 75, 607. 5. Speransky, A. D. Basis for the Theory of Medicine. Moscow, 1935. 6. Gillman, T., Gillman, J. Am. J. med. Sci. 1946, 211, 448. 1. 2.
JOSEPH GILLMAN.
SICKLE-CELL ANÆMIA BEFORE HERRICK SIR,-In 1910, Dr. James Herrick,’ of Chicago, described the first recorded case of sickle-cell anaemia in a Negro student from Grenada in the West Indies. From the striking clinical and hxmatological picture, it may seem surprising that the disease was not recognised before. The answer must be that cases of sickle-cell ansmia were misdiagnosed because the cardinal symptoms of leg ulceration, rheumatism, and jaundice were features common in tropical medical practice. Furthermore, the characteristic red-cell morphology would remain unnoticed because examination of peripheral blood-smears as a diagnostic procedure was unusual before the present century. The condition has been recognised for centuries in West Africa, and Konotey-Ahuluhas drawn attention to the many tribal names referring to this disease. One may assume, therefore, that cases also occurred among American Negroes much earlier than Herrick’s classic description. However, to find these cases in a review of the literature required a feature common to sickle-cell ansmia but unlikely to occur in any other condition. Splenic atrophy is such a factor and has proved useful in identifying two possible early cases of sickle-cell anasmia. In 1898 Hodenpyl 9 described the case of a 32-year-old coloured male patient who presented with pains all over the body, pleuritic symptoms, and jaundice and was noted to have scars on the anterior surfaces of both legs. He died in hospital, and it was recorded that, at necropsy, " notwithstanding careful search, no trace of the spleen was discovered ". The second case,Io reported in 1846, concerned a runaway Negro slave who committed murder, was convicted, executed, and the body " delivered to any surgeon who would demand it ". This man suffered in life from frequent bilious intermittent fevers and was of a 7. 8. 9. 10.
Herrick, J. B. Archs intern. Med. 1910, 6, 517. Konotey-Ahulu, F. I. D. Ghana med. J. 1968, 7, 118. Hodenpyl, E. Med. Record, 1898, 54, 695. Lebby, R. Sth. J. Med. Pharm., Charleston, 1846, 1, 481.
CARDIOVASCULAR EFFECTS OF HYPOGLYCÆMIC SULPHONYLUREAS SIR,-The articles in your issue of Feb. 12 (p. 335 and once more raise the possibility that the sulphonylderivatives increase the incidence of myocardial infarction in diabetes. In this regard we should like to draw your attention to two papers 1,2 we published in 1960-61 relating to the effect of tolbutamide on the dog heart-lung preparation. These studies indicate that tolbutamide: (1) increases glucose uptake by the isolated heart-lung preparation; (2) decreases the coronary blood-flow; and (3) depresses the myocardium, causing an increase in atrial pressures and dilatation of the ventricles. These results could be observed with " " physiological concentration of the drug, but were more apparent with higher doses, 2 g. added to the venous reservoir causing severe cardiac failure. In a few experiments with anaesthetised open-chest dogs tolbutamide given intravenously caused a rise of systemic arterial pressure accompanied by an increase in coronary-
338)
p.
urea
artery flow. Several extrapancreatic effects of tolbutamide, including those on the cardiovascular system, have been pointed out. 3,4 Although it is difficult to extrapolate our findings in the denervated heart-lung preparation to the possible clinical effects of prolonged use of tolbutamide, we agree that an extensive investigation of the cardiovascular effects (acute and chronic) of the various sulphonylurea derivatives should be undertaken. University Medical School, Plaza, Chicago, Illinois 60614, A. K. KHACHADURIAN. U.S.A.
Northwestern
sharply to normal in cases of rheumatic polyarthritis where the temperature was raised or could rise temporarily in subacute cases where it was within normal limits)were noted. Speransky noted, too, that greatly enlarged spleens seen in malaria could regress to normal size within 3 weeks of spinal pumping, and that remission lasting 3-5 months occurred in two-thirds of cases of Parkinson’s disease following the introduction by suboccipital puncture into the subarachnoid space of as little as 0-3 ml. of the patient’s blood, either alone or accompanied by lumbar spinal pumping. In other diseases, the efficacy of orally or parenterally administered drugs to which patients had become resistant was also increased by pumping. Speransky’s primary purpose was to disclose the neural component of a pathological process and to show that by intervention through the nervous system (by spinal pumping or by other means) it was possible to alter the course of diseases of widely different aetiology. It is noteworthy, therefore, that the percentage of positive responses to spinal pumping when used for the relief of pain in cancer patients was similar to that obtained in the treatment of fall
salicylate-resistant rheumatic polyarthritis, enlarged spleen in malaria, and other diseases mentioned by Speransky. It is to be hoped that the observations of Lloyd and his colleagues may stimulate a re-evaluation of spinal pumping and other methods described by Speransky in the treatment of diseases for which at present no satisfactory therapy is available. Via Montedoro, 80059 Torre del Greco,
Napoli, Italy.
2300 Children’s
Creighton University Medical School, 2500 California Street, Omaha, Nebraska 68131, H. S. BADEER. U.S.A.
PAIN RELIEF AND OTHER EFFECTS FOLLOWING BARBOTAGE
SIR,-It is encouraging to know that almost 40 years after Speransky published his thought-provoking book,5 Dr. Lloyd and his colleagues (Feb. 12, p. 354) have used barbotage (spinal pumping of cerebrospinal fluid) specifically to relieve severe intractable pain in cancer patients. In seeking an explanation for the mechanism involved, factors other than slight morphological changes in the spinothalamic tract described by Lloyd may need to be considered. Tampering with the cerebrospinal fluid, whether by spinal pumping or by the introduction of various substances into it, can have widespread effects on the physiology of the organism and may arrest or reverse temporarily, or even permanently, the course of many pathological processes, which in current thinking could hardly be attributed to changes in the spinothalamic tract. In acute and subacute rheumatic polyarthritis, whether or not resistant to salicylates and other forms of therapy, spinal pumping led to the rapid relief of pain within 24 hours and to the disappearance of redness, swelling, and stiffness of joints a few days later.5·6 Striking changes were observed in the peripheral vascular system, acneform lesions on the face, neck, and back rapidly disappeared, and paradoxical effects on the body-temperature (which could Khachadurian, A. K., Badeer, H. S. Metabolism, 1960, 9, 890. Khachadurian, A K., Karam, J. D., Badeer, H. S. Archs int. Pharmacodyn. 1961, 132, 42. 3. Wolff, F., Grant, A. New Engl. J. Med. 1971, 284, 915. 4. Roth, J., Prout, T. E., Goldfine, I. D., Wolfe, S. M., Muenzer, J., Grauer, L. E., Marcus, M. L. Ann. intern. Med. 1971, 75, 607. 5. Speransky, A. D. Basis for the Theory of Medicine. Moscow, 1935. 6. Gillman, T., Gillman, J. Am. J. med. Sci. 1946, 211, 448. 1. 2.
JOSEPH GILLMAN.
SICKLE-CELL ANÆMIA BEFORE HERRICK SIR,-In 1910, Dr. James Herrick,’ of Chicago, described the first recorded case of sickle-cell anaemia in a Negro student from Grenada in the West Indies. From the striking clinical and hxmatological picture, it may seem surprising that the disease was not recognised before. The answer must be that cases of sickle-cell ansmia were misdiagnosed because the cardinal symptoms of leg ulceration, rheumatism, and jaundice were features common in tropical medical practice. Furthermore, the characteristic red-cell morphology would remain unnoticed because examination of peripheral blood-smears as a diagnostic procedure was unusual before the present century. The condition has been recognised for centuries in West Africa, and Konotey-Ahuluhas drawn attention to the many tribal names referring to this disease. One may assume, therefore, that cases also occurred among American Negroes much earlier than Herrick’s classic description. However, to find these cases in a review of the literature required a feature common to sickle-cell ansmia but unlikely to occur in any other condition. Splenic atrophy is such a factor and has proved useful in identifying two possible early cases of sickle-cell anasmia. In 1898 Hodenpyl 9 described the case of a 32-year-old coloured male patient who presented with pains all over the body, pleuritic symptoms, and jaundice and was noted to have scars on the anterior surfaces of both legs. He died in hospital, and it was recorded that, at necropsy, " notwithstanding careful search, no trace of the spleen was discovered ". The second case,Io reported in 1846, concerned a runaway Negro slave who committed murder, was convicted, executed, and the body " delivered to any surgeon who would demand it ". This man suffered in life from frequent bilious intermittent fevers and was of a 7. 8. 9. 10.
Herrick, J. B. Archs intern. Med. 1910, 6, 517. Konotey-Ahulu, F. I. D. Ghana med. J. 1968, 7, 118. Hodenpyl, E. Med. Record, 1898, 54, 695. Lebby, R. Sth. J. Med. Pharm., Charleston, 1846, 1, 481.