- Email: [email protected]
Undertreatment of cancer pain
1294
improvement at 4-8 h, and 3 patients described sustained improvement throughout the day. Mazindol had no effect on night sleep. 16 of the 33 patients with the narcoleptic syndrome took clomipramine as well. Side-effects reported by more than 2 patients were as
bradykinin system.’ The absence of reactions with some other (eg, polysulphone) may reside in their lower protein absorption capacity89 or their lower permeability for bacterial derivatives, as suggested by Van Es et al (Jan 12, p 112).
membranes
follows:
Side-effect Nausea
Constipation Palpitations Euphoria Tremor Dizziness Restlessness Nervousness *Numbers of patients
No*
10(4) 13 (7) 8 (6) 3(2) 5 (4) 12(9) 20(8) 6 (4)
Side-effect Headache Difficulty in micturition (males) Rash Impaired sexual drive
Sweating Dry mouth
taking clomipramine shown
m
No*
10(6) 7 (5) 6(3) 10 (10) 16(11) 26(13)
parentheses
Gastrointestinal side-effects were prominent at the start of and the most common reason for drug withdrawal. Mazindol was stopped in 17 patients after 1 day to 2 years of treatment because of side-effects (15) or lack of efficacy (2). Drug withdrawal in 10 of these 17 patients was accompanied by a subjective increase in daytime sleepiness. Clomipramine treatment for cataplexy (combined with mazindol) was associated with weight increase in over half the patients while mazindol alone is associated with weight loss and appetite reduction in only a few subjects with daytime sleepiness despite a persistent central stimulant effect.
treatment
University Department of Neurology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
B. ALVAREZ M. DAHLITZ J. GRIMSHAW J. D. PARKES
1.
Gogerty JH, Penberty C, Iorio LC, Trapold JH. Pharmacological analysis of a new anorectic substance; 5-hydroxy-5-(4’chlorophenyl)-2, 3 dihydro-5H-imidazo(2,1-a) isoindole (mazindol). Arch Int Pharmacodyn 1975; 214: 285-307. 2. Gogerty JH, Trapold JH. Chemistry and pharmacology of mazindol. Triangle 1976; 15: 25-26. 3. Parkes JD, Schachter M. Mazindol in the treatment of narcolepsy. Acta Neurol Scand 1979; 60: 250-54. 4 Vespignani H, Barroche G, Escaillas JP, Weber M. Importance of mazindol in the treatment of narcolepsy. Sleep 1984; 7: 274-75
Anaphylactoid reactions, haemodialysis, and ACE inhibitors SIR,-We have reported anaphylactoid reactions during haemodialysis with AN69 membranes in patients receiving angiotensin converting enzyme (ACE) inhibitors.l Dr Dinarello (Feb 9, p 371) draws attention to a wrong citation of his experimental work, for which we apologise. However, we do not agree that we are confusing acute anaphylactoid shock with gram-negative bacteraemic shock. Although there are no reports on the induction of anaphylactoid reaction by direct introduction of gram-negative products into the circulation, this does not mean that bacterial derivatives could not facilitate such a reaction when covering certain artificial surfaces. Dr Jadoul (Jan 12, p 112), Dr Tielemans (Feb 9, p 370), and their colleagues claim that AN69 membranes can provoke anaphylactoid reactions by themselves, without the need for contaminants originating in the dialysate. Tielemans et al suggest that these reactions are provoked by the negative charge of AN69, leading to an enhanced activation of the kallikrein-bradykinin system.2 We cannot exclude this possibility, but we have never observed it and remain convinced of the additional role of dialysate for two reasons: we never saw a reaction when using the same membranes in a haemofiltration mode and, in all our patients where the "Bioprime rinse method" was used, anaphylactoid reactions were prevented. This method probably decreases the permeability of the membrane for bacterial derivatives, as others have suggested.3 We are not alone in implicating the dialysate.4-t; The way in which bacterial derivatives contribute to anaphylactoid reactions remains to be elucidated. Probably there is a role for negatively charged proteoglycans and endotoxins in activating the kallikrein-
Department of Nephrology, Univeristair Ziekenhuis Gasthuisberg, Herestraat 49,3000 Leuven, Belgium
LUC VERRESEN MARK WAER YVES VANRENTERGHEM PAUL MICHIELSEN
L, Waer M, Vanrenterghem Y, Michielsen P Angiotensin-convertingenzyme inhibitors and anaphylactoid reactions to high-flex membrane dialysis Lancet 1990; 336: 1360-62. 2. Tielemans C, Madhoun P, Lenears M, Schandene L, Goldman M, Vanherweghem JL. Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int 1990; 38: 982-84 3. Bigazzi R, Atti M, Baldari G. High-permeable membranes and hypersensitivity-like reactions: role of dialysis fluid contamination. Blood Purif 1990; 8: 190-98 4. Man NK, Cianconi, Faivre JM, et al. Dialysis-associated adverse reactions with high flux membranes and microbial contamination of liquid bicarbonate concentrate. Contr Nephrol 1988; 62: 24-34. 5. Montagnac R, Schillinger F, Milcent T, Croix JC Réactions d’hypersensibilité en cours d’hémodialyse. Rôles de la haute perméabilité, de la rétrofiltration et de la contamination bactérienne du dialysat. Néphrologie 1988; 9: 29-32. 6. Bouvier P, Barnouin F, Briat C, Soutif C, Pollini J. Choc anaphylactique en hémodialyse: à propos de deux observations. Néphrologie 1989; 10: 40-41 7. Kozin F, Cochrane CG. The contact activation system of plasma: biochemistry and pathophysiology. In: Gallin JI, Goldstein IM, Snyderman R, eds. Inflammation. basic principles and clinical correlates New York Raven, 1988: 101-20. 8. Martin-Malo A, Mallol J, Castillo D, et al. Factors affecting &bgr;2-microglobulin plasma concentration during hemodialysis Int J Artif Organs 1989; 12: 509-14. 9. Goldman M, Lagmiche M, Dhaene M, Amraoui Z, Thayse C, Vanherweghem JL Adsorption of &bgr;2-microglobulin on dialysis membranes: comparison of different membranes and effects of reuse procedures. Int J Artif Organs 1989; 12: 373-78 1. Verresen
Undertreatment of
cancer
pain
SIR,-Your Round the World correspondent’s comments on undertreatment of cancer pain in Germany (April 13, p 905) and our observations in Turkey are strikingly similar. In Turkey, as in Germany, narcotic analgesics are prescribed by a three-part form (the "red prescription"), which is thoroughly monitored by Ministry of Health officials. Since a prescription for morphine cannot exceed 420 mg (oral) or 125 mg (parenteral), prescriptions have to be frequently repeated, placing another burden on the patient and the family. While investigating the prescription and availability of controlled drugs, we surveyed all of the "red prescriptions" used in the Izmir Province during 1990 (population 2 ’7 million). To our surprise, only 516 people had received a total of 1249 prescriptions for morphine or pethidine. Most of the single orders could be traced to shock-wave lithotripsy clinics and private gynaecologists, and only 124 patients had these drugs prescribed twice or more (range 2-144 in the year, mean 6-9). The estimated cancer incidence rate is at least 200 per 100 000 inhabitants.’ These figures show that only a minority of patients with cancer were taking strong analgesics. The real demand is expected to be much higherZ One of us (M. T.) has followed up 90 cancer patients since 1981 from their definitive diagnoses until death. 28 (31 %) were given narcotic analgesics at some point in their illness, and 8 patients had had narcotics only in the last week of their lives. Some 50% of patients with terminal cancer may experience unendurable pain.3 It may well be true that cancer pain is being inadequately treated in some countries, even though satisfactory means are available.2,4 We may thus be partly responsible for diverting some patients to "alternative" and unscientific remedies. 1440 Sok 6/203, Alsancak, 35220 Izmir, Turkey
MEHMET TUNCA
Pharmacy Department, Provisional Health Directorate, Izmir
JALE YELKEN
Jensen OM, Estève J, Møller H, Renard H Cancer in the European Community and its member states. Eur J Cancer 1990, 26: 1167-256 2. Foley KM The treatment of cancer pain N Engl J Med 1985; 313: 84-95. 3. Ventafridda V, Ripamonti C, Tamburini M, Cassileth RB, De Conno F Unendurable symptoms as prognostic indicators of impending death in terminal cancer patients Eur J Cancer 1990; 26: 1000-01. 4. Breitbart W Psychiatric management of cancer pain Cancer 1989; 63: 2336-42. 1
improvement at 4-8 h, and 3 patients described sustained improvement throughout the day. Mazindol had no effect on night sleep. 16 of the 33 patients with the narcoleptic syndrome took clomipramine as well. Side-effects reported by more than 2 patients were as
bradykinin system.’ The absence of reactions with some other (eg, polysulphone) may reside in their lower protein absorption capacity89 or their lower permeability for bacterial derivatives, as suggested by Van Es et al (Jan 12, p 112).
membranes
follows:
Side-effect Nausea
Constipation Palpitations Euphoria Tremor Dizziness Restlessness Nervousness *Numbers of patients
No*
10(4) 13 (7) 8 (6) 3(2) 5 (4) 12(9) 20(8) 6 (4)
Side-effect Headache Difficulty in micturition (males) Rash Impaired sexual drive
Sweating Dry mouth
taking clomipramine shown
m
No*
10(6) 7 (5) 6(3) 10 (10) 16(11) 26(13)
parentheses
Gastrointestinal side-effects were prominent at the start of and the most common reason for drug withdrawal. Mazindol was stopped in 17 patients after 1 day to 2 years of treatment because of side-effects (15) or lack of efficacy (2). Drug withdrawal in 10 of these 17 patients was accompanied by a subjective increase in daytime sleepiness. Clomipramine treatment for cataplexy (combined with mazindol) was associated with weight increase in over half the patients while mazindol alone is associated with weight loss and appetite reduction in only a few subjects with daytime sleepiness despite a persistent central stimulant effect.
treatment
University Department of Neurology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK
B. ALVAREZ M. DAHLITZ J. GRIMSHAW J. D. PARKES
1.
Gogerty JH, Penberty C, Iorio LC, Trapold JH. Pharmacological analysis of a new anorectic substance; 5-hydroxy-5-(4’chlorophenyl)-2, 3 dihydro-5H-imidazo(2,1-a) isoindole (mazindol). Arch Int Pharmacodyn 1975; 214: 285-307. 2. Gogerty JH, Trapold JH. Chemistry and pharmacology of mazindol. Triangle 1976; 15: 25-26. 3. Parkes JD, Schachter M. Mazindol in the treatment of narcolepsy. Acta Neurol Scand 1979; 60: 250-54. 4 Vespignani H, Barroche G, Escaillas JP, Weber M. Importance of mazindol in the treatment of narcolepsy. Sleep 1984; 7: 274-75
Anaphylactoid reactions, haemodialysis, and ACE inhibitors SIR,-We have reported anaphylactoid reactions during haemodialysis with AN69 membranes in patients receiving angiotensin converting enzyme (ACE) inhibitors.l Dr Dinarello (Feb 9, p 371) draws attention to a wrong citation of his experimental work, for which we apologise. However, we do not agree that we are confusing acute anaphylactoid shock with gram-negative bacteraemic shock. Although there are no reports on the induction of anaphylactoid reaction by direct introduction of gram-negative products into the circulation, this does not mean that bacterial derivatives could not facilitate such a reaction when covering certain artificial surfaces. Dr Jadoul (Jan 12, p 112), Dr Tielemans (Feb 9, p 370), and their colleagues claim that AN69 membranes can provoke anaphylactoid reactions by themselves, without the need for contaminants originating in the dialysate. Tielemans et al suggest that these reactions are provoked by the negative charge of AN69, leading to an enhanced activation of the kallikrein-bradykinin system.2 We cannot exclude this possibility, but we have never observed it and remain convinced of the additional role of dialysate for two reasons: we never saw a reaction when using the same membranes in a haemofiltration mode and, in all our patients where the "Bioprime rinse method" was used, anaphylactoid reactions were prevented. This method probably decreases the permeability of the membrane for bacterial derivatives, as others have suggested.3 We are not alone in implicating the dialysate.4-t; The way in which bacterial derivatives contribute to anaphylactoid reactions remains to be elucidated. Probably there is a role for negatively charged proteoglycans and endotoxins in activating the kallikrein-
Department of Nephrology, Univeristair Ziekenhuis Gasthuisberg, Herestraat 49,3000 Leuven, Belgium
LUC VERRESEN MARK WAER YVES VANRENTERGHEM PAUL MICHIELSEN
L, Waer M, Vanrenterghem Y, Michielsen P Angiotensin-convertingenzyme inhibitors and anaphylactoid reactions to high-flex membrane dialysis Lancet 1990; 336: 1360-62. 2. Tielemans C, Madhoun P, Lenears M, Schandene L, Goldman M, Vanherweghem JL. Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int 1990; 38: 982-84 3. Bigazzi R, Atti M, Baldari G. High-permeable membranes and hypersensitivity-like reactions: role of dialysis fluid contamination. Blood Purif 1990; 8: 190-98 4. Man NK, Cianconi, Faivre JM, et al. Dialysis-associated adverse reactions with high flux membranes and microbial contamination of liquid bicarbonate concentrate. Contr Nephrol 1988; 62: 24-34. 5. Montagnac R, Schillinger F, Milcent T, Croix JC Réactions d’hypersensibilité en cours d’hémodialyse. Rôles de la haute perméabilité, de la rétrofiltration et de la contamination bactérienne du dialysat. Néphrologie 1988; 9: 29-32. 6. Bouvier P, Barnouin F, Briat C, Soutif C, Pollini J. Choc anaphylactique en hémodialyse: à propos de deux observations. Néphrologie 1989; 10: 40-41 7. Kozin F, Cochrane CG. The contact activation system of plasma: biochemistry and pathophysiology. In: Gallin JI, Goldstein IM, Snyderman R, eds. Inflammation. basic principles and clinical correlates New York Raven, 1988: 101-20. 8. Martin-Malo A, Mallol J, Castillo D, et al. Factors affecting &bgr;2-microglobulin plasma concentration during hemodialysis Int J Artif Organs 1989; 12: 509-14. 9. Goldman M, Lagmiche M, Dhaene M, Amraoui Z, Thayse C, Vanherweghem JL Adsorption of &bgr;2-microglobulin on dialysis membranes: comparison of different membranes and effects of reuse procedures. Int J Artif Organs 1989; 12: 373-78 1. Verresen
Undertreatment of
cancer
pain
SIR,-Your Round the World correspondent’s comments on undertreatment of cancer pain in Germany (April 13, p 905) and our observations in Turkey are strikingly similar. In Turkey, as in Germany, narcotic analgesics are prescribed by a three-part form (the "red prescription"), which is thoroughly monitored by Ministry of Health officials. Since a prescription for morphine cannot exceed 420 mg (oral) or 125 mg (parenteral), prescriptions have to be frequently repeated, placing another burden on the patient and the family. While investigating the prescription and availability of controlled drugs, we surveyed all of the "red prescriptions" used in the Izmir Province during 1990 (population 2 ’7 million). To our surprise, only 516 people had received a total of 1249 prescriptions for morphine or pethidine. Most of the single orders could be traced to shock-wave lithotripsy clinics and private gynaecologists, and only 124 patients had these drugs prescribed twice or more (range 2-144 in the year, mean 6-9). The estimated cancer incidence rate is at least 200 per 100 000 inhabitants.’ These figures show that only a minority of patients with cancer were taking strong analgesics. The real demand is expected to be much higherZ One of us (M. T.) has followed up 90 cancer patients since 1981 from their definitive diagnoses until death. 28 (31 %) were given narcotic analgesics at some point in their illness, and 8 patients had had narcotics only in the last week of their lives. Some 50% of patients with terminal cancer may experience unendurable pain.3 It may well be true that cancer pain is being inadequately treated in some countries, even though satisfactory means are available.2,4 We may thus be partly responsible for diverting some patients to "alternative" and unscientific remedies. 1440 Sok 6/203, Alsancak, 35220 Izmir, Turkey
MEHMET TUNCA
Pharmacy Department, Provisional Health Directorate, Izmir
JALE YELKEN
Jensen OM, Estève J, Møller H, Renard H Cancer in the European Community and its member states. Eur J Cancer 1990, 26: 1167-256 2. Foley KM The treatment of cancer pain N Engl J Med 1985; 313: 84-95. 3. Ventafridda V, Ripamonti C, Tamburini M, Cassileth RB, De Conno F Unendurable symptoms as prognostic indicators of impending death in terminal cancer patients Eur J Cancer 1990; 26: 1000-01. 4. Breitbart W Psychiatric management of cancer pain Cancer 1989; 63: 2336-42. 1