- Email: [email protected]
ARTERIAL CALCIFICATION AND TOURNIQUETS
1217 2. Wachter H, Fuchs D, Hausen A, et al. Are conditions linked with T-cell stimulation necessary for progressive HTLV-III infection? Lancet 1986; i. 97. 3. Hausen A, Diench MP, Fuchs D, et al. Immunosuppressants in patients with AIDS. Nature 1986, 320: 114. 4. Fuchs D, Hausen A, Reibnegger G, et al. Urinary neopterin evaluation in nsk groups for the acquired immunodeficiency syndrome (AIDS). In Pfleiderer W, Wachter H, Curtius HCh, eds Biochemical and clinical aspects of pteridines: Vol III. Berlin and New York: de Gruyter, 1984: 457-67. 5. Montagnier L, Barré-Sinoussi F, Chermann JC. Possible role of a new type of human T lymphotropic virus in the pathology of AIDS and related syndromes. In: Gnscelli C, Vossen J, eds. Progress in immunodeficiency research and therapy I. Amsterdam: Elsevier Science Publishers, 1984 367-72. 6. Reibnegger G, Fuchs D, Hausen A, Schmutzhard E, Werner ER, Wachter H. Cell-mediated immune activation in malaria is dependent on age and endernicity. Trans Roy Soc Trop Med Hyg (in press). 7. Fuchs D, Hausen A, Kofler M, Kosanowski H, Reibnegger G, Wachter H. Neopterin as an index of immune response in patients with tuberculosis. Lung 1984; 162: 337-46. 8. Biggar RJ, Gngase PL, Melbye M, et al. ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans. Lancet 1985; ii: 520-23. 9. Mann J, Snider DE, Francis H, et al. Association between HTLV-III/LAV infection and tuberculosis in Zaire. JAMA 1986; 256: 346.
ARTERIAL CALCIFICATION AND TOURNIQUETS SIR,—Although accepted surgery,l
established peripheral arterial disease is an contraindication to tourniquet use in orthopaedic the danger of calcified vessels may not always be
appreciated. A 74-year-old
man with gonarthritis was admitted for upper tibial osteotomy. X-rays showed calcification in the popliteal vessels but in the absence of symptoms or signs of vascular insufficiency this was not considered significant. Surgery, in the recommended flexed postitionwas uneventful but, on release of the tourniquet cuff there was no return of circulation. Arteriography revealed a complete block in the popliteal artery proximal to the osteotomy. Despite immediate exploration and removal of fresh thrombus from an ulcerated atheromatous plaque, the limb could not be revascularised and subsequently had to be amputated. Intramural calcification reduces the elasticity of the arterial wall and, if present at the level of the tourniquet cuff, may prevent occlusion of the circulation.3,4However, its presence in proximity to a joint is more sinister since sustained flexion, in the absence of blood flow, is likely to cause kinking and thrombus formation. Such limbs must be handled carefully for, once occlusion of this type of vessel has occurred, reconstructive procedures are difficult and unlikely to succeed.3
Department of Orthopaedic Surgery,
G. B. IRVINE R. N. W. CHAN
Leicester Royal Infirmary, Leicester LE1 5WW
in operations on the knee: a review. J R Soc Med 1982; 75: 31-32. 2. Benjamin A. Double osteotomy. J Bone Joint Surg 1969; 51B: 180. 3. Klenerman L, Lewis JD. Incompressible vessels. Lancer 1976; i: 811-12. 4. Jeyaseelan S, Stevenson TM, Pfitzner J. Tourniquet failure and arterial calcification. Anaesthesia 1981; 36: 48-50. 1. Klenerman L. The tourniquet
USELESS DRUGS?
SIR,—We agree with Dr Laporte and Dr Capella (Oct 11, p 853) that
innocuous but
disagree with their labelling of cinnarizine, flunarizine, co-dergocrine, and citicoline as "mass placebos ... useless drugs not even mentioned in most pharmacological textbooks". That they are not panaceas is obvious, but all these drugs have recognised therapeutic virtues (albeit perhaps not those they are usually prescribed for). All four drugs are cited in "Martindale" (1982) and the first three are in "Goodman not
all
placebos
are
we
and Gilman" (1985). Cinnarizine has antihistaminic properties; flunarizine is a calcium antagonist effective in the treatment of migraine (like other calcium
antagonists); co-dergocrine (or dihydroergotoxin, or ergoloid mesylate) is one of the few drugs shown to be effective in the treatment of senile demential and has been approved for that use by the US Food and Drug Administration; citicoline is effective in the treatment of parkinsonism and post-traumatic coma.2 That these drugs are widely misused is probable, but they are not placebos (ie, agents devoid of pharmacological activity) or useless. Their misuse could be cured by better education of the prescribers
in
clinical and fundamental, and by more careful of commercial claims of efficacy. Banning these "placebos" would simply result in the prescription of other, perhaps less innocuous drugs. What is needed may be better education of the public that drugs will not cure everything under the sun and that a visit to a doctor should not necessarily result in the prescription of a drug. This could relieve doctors of some of the pressure to
pharmacology,
assessment
prescribe. Urging the banning of drugs to suppress an "invitation spinal-reflex prescription" is like urging the suppression
to
of automobiles to avoid automobile accidents. It is a final admission of a loss of hope in the power of teaching, which we do not share. Centre de Pharmacovigilance, Centre Hospitalier Regional, 76800 Saint-Etienne-du-Rouvray, France
N. MOORE C. SALIGAUT F. BOISMARE
1. Editorial. Ergot for dementia? Lancet 1984; ii: 1313-14. 2. Zappia, et al, eds. Novel biochemical, pharmacological and clinical aspects of citydinediphosphocholine. Amsterdam: Elsevier, 1985.
SIR,-During the past few months, The Lancet has published several reports on depressive and parkinsonian reactions to flunarizine. Dr Laporte and Dr Capella now question the therapeutic usefulness of flunarizine and cinnarizine, among other drugs, and focus on their side-effects. Yet the therapeutic activity of the two drugs (for example, in migraine, vertigo, and cerebrovascular disease) is well documented. How important, therefore, are the side-effects? 3250 ambulatory patients treated with 10-20 mg flunarizine daily for various diseases, have been observed in our centres. The incidence of the side-effects (depressive and extrapyramidal disorders) was 0-5%. For patients over 65, the incidence varied between 1-5% with 10 mg and 7-5% with 20 mg (mostly Parkinson-like-total incidence 47 %). Furthermore, we have seen patients with correctly treated Parkinson’s disease to whom the general practitioner had prescribed 10-20 mg daily of flunarizine. Within 15-30 days, there was a 25% worsening strictly of akinetic type; within 2-3 months after discontinuation of the treatment, scores returned to normal. Such a phenomenon could be explained in terms of the experimental data showing an in-vitro inhibition of K-induced dopamine release from rat striatal slices by flunarizine and other calcium antagonists. On the other hand, ageing brain is characterised by a progressive reduction of the dopaminergic neurons, up to a limit of 20-25 % (threshold for the onset of motor symptoms). It is not surprising, therefore, that elderly patients with flunarizine occasionally report such symptoms after long-term treatment. However, in our hands, discontinuation of treatment is always followed by a complete reversal of the adverse reactions. Department of Neurological Sciences and Extrapyramidal Research Centre, University of Rome "La Sapienza"
ALESSANDRO AGNOLI
Isututo Scientifico Mondino
and Extrapyramidal Research Centre, University of Pavia, Italy
GIUSEPPE NAPPI
SIR,-Without any valid arguments, Dr Laporte and Dr Capella dismiss the drug flunarizine as useless. This statement cannot be taken seriously. Several thousands of sufferers from common and classic migraine have benefited from the drug, despite the side effects. Several double-blind cross-over studies have proven that this compound is superior to placebo and comparable with some generally accepted drugs for prophylaxis of migraine. 1-4 St Lucas Hospital, 1061 AE Amsterdam, Netherlands
B.
J. J.
ANSINK
BJJ, Danby M, Oosterveld WJ, Shimsheimer RJ, Caers LI, Amery WK. Flunarizine, the vestibular system and migraine. Cephalalgia 1985, 5: 205-10. 2. Louis P A double-blind placebo-controlled prophylactic study of flunarizine (Sibelium) in migraine. Headache 1981; 21: 235-39. 3. Sorensen PS, Hansen K, Olesen J. A placebo-controlled, double-blind, cross-over trial of flunarizine in common migraine. Cephalalgia 1986; 6: 7-14. 4. Rascol A, Montastruc JL, Rascol O. Flunarizine vs pisotifen: a double-blind study in the prophylaxis of migraine. Headache 1986; 26: 83-85 1. Ansink
ARTERIAL CALCIFICATION AND TOURNIQUETS SIR,—Although accepted surgery,l
established peripheral arterial disease is an contraindication to tourniquet use in orthopaedic the danger of calcified vessels may not always be
appreciated. A 74-year-old
man with gonarthritis was admitted for upper tibial osteotomy. X-rays showed calcification in the popliteal vessels but in the absence of symptoms or signs of vascular insufficiency this was not considered significant. Surgery, in the recommended flexed postitionwas uneventful but, on release of the tourniquet cuff there was no return of circulation. Arteriography revealed a complete block in the popliteal artery proximal to the osteotomy. Despite immediate exploration and removal of fresh thrombus from an ulcerated atheromatous plaque, the limb could not be revascularised and subsequently had to be amputated. Intramural calcification reduces the elasticity of the arterial wall and, if present at the level of the tourniquet cuff, may prevent occlusion of the circulation.3,4However, its presence in proximity to a joint is more sinister since sustained flexion, in the absence of blood flow, is likely to cause kinking and thrombus formation. Such limbs must be handled carefully for, once occlusion of this type of vessel has occurred, reconstructive procedures are difficult and unlikely to succeed.3
Department of Orthopaedic Surgery,
G. B. IRVINE R. N. W. CHAN
Leicester Royal Infirmary, Leicester LE1 5WW
in operations on the knee: a review. J R Soc Med 1982; 75: 31-32. 2. Benjamin A. Double osteotomy. J Bone Joint Surg 1969; 51B: 180. 3. Klenerman L, Lewis JD. Incompressible vessels. Lancer 1976; i: 811-12. 4. Jeyaseelan S, Stevenson TM, Pfitzner J. Tourniquet failure and arterial calcification. Anaesthesia 1981; 36: 48-50. 1. Klenerman L. The tourniquet
USELESS DRUGS?
SIR,—We agree with Dr Laporte and Dr Capella (Oct 11, p 853) that
innocuous but
disagree with their labelling of cinnarizine, flunarizine, co-dergocrine, and citicoline as "mass placebos ... useless drugs not even mentioned in most pharmacological textbooks". That they are not panaceas is obvious, but all these drugs have recognised therapeutic virtues (albeit perhaps not those they are usually prescribed for). All four drugs are cited in "Martindale" (1982) and the first three are in "Goodman not
all
placebos
are
we
and Gilman" (1985). Cinnarizine has antihistaminic properties; flunarizine is a calcium antagonist effective in the treatment of migraine (like other calcium
antagonists); co-dergocrine (or dihydroergotoxin, or ergoloid mesylate) is one of the few drugs shown to be effective in the treatment of senile demential and has been approved for that use by the US Food and Drug Administration; citicoline is effective in the treatment of parkinsonism and post-traumatic coma.2 That these drugs are widely misused is probable, but they are not placebos (ie, agents devoid of pharmacological activity) or useless. Their misuse could be cured by better education of the prescribers
in
clinical and fundamental, and by more careful of commercial claims of efficacy. Banning these "placebos" would simply result in the prescription of other, perhaps less innocuous drugs. What is needed may be better education of the public that drugs will not cure everything under the sun and that a visit to a doctor should not necessarily result in the prescription of a drug. This could relieve doctors of some of the pressure to
pharmacology,
assessment
prescribe. Urging the banning of drugs to suppress an "invitation spinal-reflex prescription" is like urging the suppression
to
of automobiles to avoid automobile accidents. It is a final admission of a loss of hope in the power of teaching, which we do not share. Centre de Pharmacovigilance, Centre Hospitalier Regional, 76800 Saint-Etienne-du-Rouvray, France
N. MOORE C. SALIGAUT F. BOISMARE
1. Editorial. Ergot for dementia? Lancet 1984; ii: 1313-14. 2. Zappia, et al, eds. Novel biochemical, pharmacological and clinical aspects of citydinediphosphocholine. Amsterdam: Elsevier, 1985.
SIR,-During the past few months, The Lancet has published several reports on depressive and parkinsonian reactions to flunarizine. Dr Laporte and Dr Capella now question the therapeutic usefulness of flunarizine and cinnarizine, among other drugs, and focus on their side-effects. Yet the therapeutic activity of the two drugs (for example, in migraine, vertigo, and cerebrovascular disease) is well documented. How important, therefore, are the side-effects? 3250 ambulatory patients treated with 10-20 mg flunarizine daily for various diseases, have been observed in our centres. The incidence of the side-effects (depressive and extrapyramidal disorders) was 0-5%. For patients over 65, the incidence varied between 1-5% with 10 mg and 7-5% with 20 mg (mostly Parkinson-like-total incidence 47 %). Furthermore, we have seen patients with correctly treated Parkinson’s disease to whom the general practitioner had prescribed 10-20 mg daily of flunarizine. Within 15-30 days, there was a 25% worsening strictly of akinetic type; within 2-3 months after discontinuation of the treatment, scores returned to normal. Such a phenomenon could be explained in terms of the experimental data showing an in-vitro inhibition of K-induced dopamine release from rat striatal slices by flunarizine and other calcium antagonists. On the other hand, ageing brain is characterised by a progressive reduction of the dopaminergic neurons, up to a limit of 20-25 % (threshold for the onset of motor symptoms). It is not surprising, therefore, that elderly patients with flunarizine occasionally report such symptoms after long-term treatment. However, in our hands, discontinuation of treatment is always followed by a complete reversal of the adverse reactions. Department of Neurological Sciences and Extrapyramidal Research Centre, University of Rome "La Sapienza"
ALESSANDRO AGNOLI
Isututo Scientifico Mondino
and Extrapyramidal Research Centre, University of Pavia, Italy
GIUSEPPE NAPPI
SIR,-Without any valid arguments, Dr Laporte and Dr Capella dismiss the drug flunarizine as useless. This statement cannot be taken seriously. Several thousands of sufferers from common and classic migraine have benefited from the drug, despite the side effects. Several double-blind cross-over studies have proven that this compound is superior to placebo and comparable with some generally accepted drugs for prophylaxis of migraine. 1-4 St Lucas Hospital, 1061 AE Amsterdam, Netherlands
B.
J. J.
ANSINK
BJJ, Danby M, Oosterveld WJ, Shimsheimer RJ, Caers LI, Amery WK. Flunarizine, the vestibular system and migraine. Cephalalgia 1985, 5: 205-10. 2. Louis P A double-blind placebo-controlled prophylactic study of flunarizine (Sibelium) in migraine. Headache 1981; 21: 235-39. 3. Sorensen PS, Hansen K, Olesen J. A placebo-controlled, double-blind, cross-over trial of flunarizine in common migraine. Cephalalgia 1986; 6: 7-14. 4. Rascol A, Montastruc JL, Rascol O. Flunarizine vs pisotifen: a double-blind study in the prophylaxis of migraine. Headache 1986; 26: 83-85 1. Ansink