- Email: [email protected]
GASTRIC CANCER AFTER PEPTIC ULCER
1026
.
A fair account of Cuba’s health is not easy to achieve but a review of other sources2,5 would have added to Alwyn Smith’s "Cuban experience", permitting a more factual and less mythical account. Any assessment of Cuba’s health should take into account not only Spanish and American influences but also the Cuban republican
For isoniazid the recommended dose ranged even more widely, from 3 mg/kg to 10-30 mg/kg. A maximum dose was put at 300-500 mg, though most texts did not mention an upper limit. Daily doses ranged from one to four. There was more consistency with ethambutol, 15 mg/kg being preferred. However, "Cecil" and "Alstead and Girdwood" do not recommended ethambutol for children under 13 years old, while H. Jolly’s Diseases of Children recommends this drug for all cases of primary tuberculosis. From one to four daily doses were suggested. Life would be easier for physicians and patients if some unanimity-and sense-were to be brought to bear on this subject.
contribution. Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA
G. J. ARCHER Stepping Hill Hospital, Stockport SK2 7JE
IDENTIFYING TABLETS
CHRISTINE HENDERSON P. M. GRACE
MEDICINE IN CUBA
SIR,-Prof Alwyn Smith’s account (Sept 10, p 616) of a WHO supported conference in Havana last July exalts the Cuban revolutionary health system. He makes no attempt to provide a pluralistic perspective and credits, without qualification, the profound socioeconomic changes which took Cuba into the Soviet bloc for statistical achievements, as if health were a statistical game. Anyone venturing to read, listen to, study, or report on what Cuban physicians claim should first be aware of what they solemnly swear and seem to believe.’ Having sworn to eschew private practice, to work in the rural health service for two years, and to "contribute with our effort, sacrifice and good deed to the betterment of the people"-tenets with which I agree-Cuban doctors also swear: "Third: To push forward the preventive health measures of our country with the new attitude of the proletariat philosophy of medical science: for the good of mankind. Fourth: To keep alive in ourselves a spirit of scientific and political advancement so that we may gain the all too necessary technical qualifications as we become communists ... Fifth: We will be ready to give our scientific help or any other aid to the peoples which are fighting for their national liberation as well as for their economic, political and social independence. Sixth: To defend this heroic socialist and communist Revolution with our lives. We swear this before our people and our highest leader Fidel Castro. We swear it and will maintain these truths anywhere, anyhow, and for whatever reason. Commander in Chief, Order Us! ...
MOTHERLAND OR DEATH! WE SHALL OVERCOME!"
To whom have Cuban physicians pledged fidelity? In pledging themselves unconditionally to be communists they surrender their intellects to the party’s orders in Cuba and elsewhere and obey their commander-in-chief, the host of the Havana conference. What Cuban could be dumb enough to swear to be a communist and then ruffle the beard of the party’s commander-unless he sought the Nobel peace prize? With such a politically inclined data base it is not surprising that Alwyn Smith’s perspective on Cuba’s health care system is a panegyric. There are errors of fact too. Cuba’s pre-revolutionary (1953) infant mortality rate was 32 per 100 000 live births.2The figure of "over 100" supplied to Alwyn Smith was probably a record of the 1800s in precolonial times. A WHO report3noted that Cuba had decreased its infant mortality the least (3%) among more than forty Third World countries. Most countries experienced a decrease in infant mortality from 1951 to 1967 of 20-40%.Cuba came last in this series, but these data are not discussed by Cubans. The environmental "conquests" achieved by the revolution should have included Cuba’s baffling management of the dengue epidemic which started in Cuba in 1976. The spread of this, which was unfortunate for Cuba and the rest of the Caribbean, was brought about by the Cuban government’s denial of an epidemic stemming from the entry from Africa into Cuba4 of type 1 dengue virus, a strain not seen before in the Caribbean.4 1. Trib Med (Cuba) 1966; 26: 47. 2. Diaz-Briquets S. The health revolution in Cuba. Austin: University of Texas Press, 1983. 3. Anon. Fall in infant mortality rates. WHO Chron 1971; 25: 19. 4. Anon. Imported dengue fever, United States, 1982. MMWR 1983; 32: 145-46.
A. M. GORDON
I
SIR,-In 1962 Hefferren and colleagues made available an identification guide for solid medications comparable with the ’Tablident’ system you refer to in your Sept 17 editorial. It took up an entire issue of JAMA.6 Based on a ten-digit derivative code, it combined micrometer based measurements, colour variations, shapes, sizes, and so on. In our hands, it took on average more than 10 min to achieve a 56% accuracy and, with white tablets, more than 15 min for a bare 30% accuracy-in large part because the 7 measurement discrimination exceeded the manufacturer’s standard. In 1967 Eli Lilly introduced its ’Identicode’ drug imprinting system, a three-digit alphanumeric code plus the logotype of the manufacturer. With it, we achieved a 98% accuracy in less than 15 s.8,9 The imprint has proven legible and useful even via a gastroscope. As of 1983, 81 of 83 US manufacturers illustrating in the Physician’s Desk Reference used this imprint system. Moreover, some nineteen States, including Washington, California, and New York, have mandated by legislative action and/or governmental rule and regulation that all legend drugs ("trade names" as well as "generics") be imprinted and that the necessary indexing be available. Moreover, most over-the-counter manufacturers are using an imprint technique. In the United States, the ’Poisondex’ microfiche system (used by all regional poison centres and accessible to all health providers via telephone) maintains such an indexing system of the codes. Other State agencies maintain similar indexes, as does the Physician’s Desk Reference itself for its products. While some of our "look alikes" and other "counterfeit" drugs can escape detection via this technique, the imprint strategy would seem far less susceptible to error than the tablident. At a cost of 9 cents per 1000 imprinted capsules, the value seems more than justified for the variety of benefits provided. Consequently, just as I differed with your editorial of 1963,differ with you 20 years later. Is it not time to call for an international drug imprinting system? Department of Pediatrics, University of Washington; and Children’s Orthopedic Hospital and Medical Center, Seattle, Washington 98105, USA
W. O. ROBERTSON
GASTRIC CANCER AFTER PEPTIC ULCER
SIR,-Dr Logan and Professor Langman (Sept 17, p 667) refer to findingithat gastric carcinoma was no more common than predicted in a group of patients (779) followed up for between 15 our
and 32 years after curative peptic ulcer surgery. They find this puzzling in the light of previously reported increases in carcinoma of the gastric remnant and suggest loss to follow-up or dependence on routine death certification as possible reasons for under5. Gordon A. The nutriture of Cubans. In: Mesa-Lago C, ed. Cuban studies. University of Pittsburg, 1983. 6. Hefferren JJ. Identification guide for solid dosage forms. JAMA 1962; 182: 1145-1302. 7. Caldwell JG, Shoman AF, Hurst CB, Robertson WO. Identification of drugs: Use of the JAMA drug identification guide. JAMA 1964; 187: 951. 8. Symonds JK, Robertson WO. Drug identification: Use of coded imprint. JAMA 1967; 199: 664. 9. Robertson KA, Robertson WO. Drug identification by imprint. Clin Toxicol 1974; 7: 83-9. 10. Editorial. Poisoning in the home. Lancet 1963; i 982. 11. McLean Ross AH, Smith MA, Anderson JR, Small WP. Late mortality after surgery for peptic ulcer. N Engl J Med 1982; 307: 519-22.
1027
representation. It seems unlikely that our lost to follow-up group of 907o could have contributed significantly to the under-reporting of carcinoma. By relying on death certification we have missed the diagnosis of carcinoma in some cases but if, as Logan and Langman state, up to 25% of carcinomas are diagnosed only at necropsy this would not raise our figure for stump cancer by much, to 11or 12 against a predicted value of 10,4for a comparable Scottish
COMPLEMENT ACTIVATION BY UPPER-RESPIRATORY-TRACT BACTERIA ————————————————,—————————————.———————————————
population. Length of follow-up
was probably the important factor. death from carcinoma was 19 years. It is believed that more than 15 years mustlelapse before an increased incidence of gastric remnant carcinoma begins to be seen.12 We may therefore need to wait longer. We agree that greater efforts towards persuading patients to stop smoking would be more beneficial than policies for endoscopic screening. In our experience ulcer patients coming to surgery have not changed over the years.13 80% of patients who undergo highly selective vagotomy smoke and thus any anticipated long-term benefits of this more "physiological" operation are likely to be overshadowed by the complications of addiction to tobacco. A. H. MCLEAN Ross M. A. SMITH Gastric Follow-up Clinic, J. R. ANDERSON Western General Hospital, W. P. SMALL Edinburgh EH4 2XU
Average time
to
COMPLEMENT, HISTAMINE RELEASE, AND TREATMENT OF UPPER-RESPIRATORY-TRACT INFECTIONS
SIR,-Many of the symptoms of upper respiratory tract (URT) infections are similar to those of immediate hypersensitivity (type I allergy) in the same anatomical situation-ie, fever, watering eyes, sneezing, a runny nose, and so on. Since, in type I allergy, these symptoms are associated with the local release of histaminel we wondered if bacteria isolated from the URT might cause the local release of histamine and other vasoactive amines. One possible mechanism is that both pathogenic and normal flora bacteria cleave complement C3 and activate the complement cascade via the alternative or classical pathways. This would cause release of the inflammatory mediators 3C3a and CSF.2Histamine would then be released from mast cells.3 Fifty strains, representing ten species of bacteria known to cause either acute or chronic low-grade opportunistic infections, were isolated from clinical specimens or obtained from the National Type Culture Collection and identified by routine microbiological and serological tests. The bacteria were tested in the presence and absence of chelating agents for their ability to cleave complement proteins and activate complement by the classical and alternative pathways in the presence of fresh human serum. Cleavage of the was complement qualitatively assessed by
proteins immunoelectrophoresis.
Most bacteria associated with the URT (see table) could cleave complement proteins via the alternative pathway. Moreover, the normal human serum used, which was obtained from male and female healthy adult volunteers, contained antibodies to the bacteria studied and permitted complement activation by the classical
pathway also. Although complement activation by bacteria is widespread5 it has not been demonstrated previously that all of the species studied here possess this activity. The potential immunopathological effects which may be elicited by such activity in vivo, especially in individuals predisposed by URT infections, requires further
*included as positive control. FI= fresh isolate; ? = complement activated but mechanism unclear
attention. Furthermore, the ability of URT bacteria to contribute appreciably to the more overt symptoms of URT infections should be considered. Moreover, there would seem to be a place for drugs, inhibiting either local complement activation or vasoactive amine activity in the management of URT infections, particularly in the treatment and control of symptoms. A full table of results for the cleavage of C2, C3, C4 and factor B in NHS, NHS+EDTA and NHS + EGT A + Mg 2 SO 4 is available.
University Department of Immunology, General Infirmary, Leeds LS1 3EX
MEPTAZINOL 13 editorial on meptazinol cites our paper’ but showed that physostigmine reversed the effect of morphine on respiration in pain-free human beings and reversed analgesia and sedation in postoperative patients. This was not so. In the abstract citedl and in two more detailed accounts2,3 physostigmine antagonised sedation and respiratory depression but did not impair the analgesic effect of morphine. physostigmine itself raises the pain threshold in man andinlaboratory animals.5These findings suggest that the respiratory depressant effect of opioids may be associated with a reduction in central cholinergic transmission but that their analgesic effect is not. If the novel analgesic drug meptazinol actually increases central cholinergic transmission, it would serve to explain why this drug is less depressant to respiration than are equi-effective doses of opioid analgesics. Your editorial states that meptazinol, which may increase the release of acetylcholine, does not act like other opioid agonists on the stimulated guineapig ileum. This is not surprising since the depressant effect of opioid on this preparation results from 6 an inhibition of acetylcholine release.
SIR,-Your Aug that
states
we
Furthermore,
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
M. WEINSTOCK
1. Davidson JT, Snir-Mor
2. 12. De Jode LR. Gastric carcinoma following gastroenterostomy and partial gastrectomy. Br J Surg 1961; 48: 512-14. 13. McLean Ross AH, Anderson J, Small WP, Smith MA. After gastrectomy. Br Med J 1981; 282: 1472. 1. Buisseret PD. Allergy. Sci American 1982; 247: 86-97. 2. Muller-Eberhard HJ. Complement. Annu Rev Biochem 1975; 44: 697-724. 3. Brown EJ, Frank MM. Complement activation. Immunol To-day 1981; 2: 129-34. 4. Graber P, Williams CA Jr. Methods immunoelectrophoretique d’analyse de mélanges de substances antigeniques. Biochim Biophys Acta 1953; 10: 193-94. 5. Muller-Eberhard HJ, Schreiber RD. Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol 1980; 29: 2-53.
EILEEN INGHAM G. GOWLAND
I, Weinstock M. Physostigmine as an antagonist in the human subject. Br JPharmacol 1982; 75: 28P. Weinstock M, Davidson JT, Rosin AJ, Schneiden H. Effect of physostigmine on morphine-induced postoperative pain and somnolence. Br J Anaesth 1982; 54:
429-34. 3. Snir-Mor I, Weinstock
M, Davidson JT, Bahar M. Physostigmine antagonizes morphine-induced respiratory depression in human subjects. Anesthesiology 1983;
59: 6-10. 4. Sitaram N, Buchsbaum MS, Gillin JC. Eur 5. Pleuvry BJ, Tobias MA. Comparison
J Pharmacol 1977; 42: 285-91. of the antinociceptive activities of physostigmine, oxotremorine and morphine in the mouse. Br J Pharmacol 1971; 43: 706-14.
6. Cox
BM, Weinstock M. The effect of analgesic drugs on the release of acetylcholine electrically stimulated guinea pig ileum. Br J Pharmacol 1966; 27: 81-92.
from
.
A fair account of Cuba’s health is not easy to achieve but a review of other sources2,5 would have added to Alwyn Smith’s "Cuban experience", permitting a more factual and less mythical account. Any assessment of Cuba’s health should take into account not only Spanish and American influences but also the Cuban republican
For isoniazid the recommended dose ranged even more widely, from 3 mg/kg to 10-30 mg/kg. A maximum dose was put at 300-500 mg, though most texts did not mention an upper limit. Daily doses ranged from one to four. There was more consistency with ethambutol, 15 mg/kg being preferred. However, "Cecil" and "Alstead and Girdwood" do not recommended ethambutol for children under 13 years old, while H. Jolly’s Diseases of Children recommends this drug for all cases of primary tuberculosis. From one to four daily doses were suggested. Life would be easier for physicians and patients if some unanimity-and sense-were to be brought to bear on this subject.
contribution. Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA
G. J. ARCHER Stepping Hill Hospital, Stockport SK2 7JE
IDENTIFYING TABLETS
CHRISTINE HENDERSON P. M. GRACE
MEDICINE IN CUBA
SIR,-Prof Alwyn Smith’s account (Sept 10, p 616) of a WHO supported conference in Havana last July exalts the Cuban revolutionary health system. He makes no attempt to provide a pluralistic perspective and credits, without qualification, the profound socioeconomic changes which took Cuba into the Soviet bloc for statistical achievements, as if health were a statistical game. Anyone venturing to read, listen to, study, or report on what Cuban physicians claim should first be aware of what they solemnly swear and seem to believe.’ Having sworn to eschew private practice, to work in the rural health service for two years, and to "contribute with our effort, sacrifice and good deed to the betterment of the people"-tenets with which I agree-Cuban doctors also swear: "Third: To push forward the preventive health measures of our country with the new attitude of the proletariat philosophy of medical science: for the good of mankind. Fourth: To keep alive in ourselves a spirit of scientific and political advancement so that we may gain the all too necessary technical qualifications as we become communists ... Fifth: We will be ready to give our scientific help or any other aid to the peoples which are fighting for their national liberation as well as for their economic, political and social independence. Sixth: To defend this heroic socialist and communist Revolution with our lives. We swear this before our people and our highest leader Fidel Castro. We swear it and will maintain these truths anywhere, anyhow, and for whatever reason. Commander in Chief, Order Us! ...
MOTHERLAND OR DEATH! WE SHALL OVERCOME!"
To whom have Cuban physicians pledged fidelity? In pledging themselves unconditionally to be communists they surrender their intellects to the party’s orders in Cuba and elsewhere and obey their commander-in-chief, the host of the Havana conference. What Cuban could be dumb enough to swear to be a communist and then ruffle the beard of the party’s commander-unless he sought the Nobel peace prize? With such a politically inclined data base it is not surprising that Alwyn Smith’s perspective on Cuba’s health care system is a panegyric. There are errors of fact too. Cuba’s pre-revolutionary (1953) infant mortality rate was 32 per 100 000 live births.2The figure of "over 100" supplied to Alwyn Smith was probably a record of the 1800s in precolonial times. A WHO report3noted that Cuba had decreased its infant mortality the least (3%) among more than forty Third World countries. Most countries experienced a decrease in infant mortality from 1951 to 1967 of 20-40%.Cuba came last in this series, but these data are not discussed by Cubans. The environmental "conquests" achieved by the revolution should have included Cuba’s baffling management of the dengue epidemic which started in Cuba in 1976. The spread of this, which was unfortunate for Cuba and the rest of the Caribbean, was brought about by the Cuban government’s denial of an epidemic stemming from the entry from Africa into Cuba4 of type 1 dengue virus, a strain not seen before in the Caribbean.4 1. Trib Med (Cuba) 1966; 26: 47. 2. Diaz-Briquets S. The health revolution in Cuba. Austin: University of Texas Press, 1983. 3. Anon. Fall in infant mortality rates. WHO Chron 1971; 25: 19. 4. Anon. Imported dengue fever, United States, 1982. MMWR 1983; 32: 145-46.
A. M. GORDON
I
SIR,-In 1962 Hefferren and colleagues made available an identification guide for solid medications comparable with the ’Tablident’ system you refer to in your Sept 17 editorial. It took up an entire issue of JAMA.6 Based on a ten-digit derivative code, it combined micrometer based measurements, colour variations, shapes, sizes, and so on. In our hands, it took on average more than 10 min to achieve a 56% accuracy and, with white tablets, more than 15 min for a bare 30% accuracy-in large part because the 7 measurement discrimination exceeded the manufacturer’s standard. In 1967 Eli Lilly introduced its ’Identicode’ drug imprinting system, a three-digit alphanumeric code plus the logotype of the manufacturer. With it, we achieved a 98% accuracy in less than 15 s.8,9 The imprint has proven legible and useful even via a gastroscope. As of 1983, 81 of 83 US manufacturers illustrating in the Physician’s Desk Reference used this imprint system. Moreover, some nineteen States, including Washington, California, and New York, have mandated by legislative action and/or governmental rule and regulation that all legend drugs ("trade names" as well as "generics") be imprinted and that the necessary indexing be available. Moreover, most over-the-counter manufacturers are using an imprint technique. In the United States, the ’Poisondex’ microfiche system (used by all regional poison centres and accessible to all health providers via telephone) maintains such an indexing system of the codes. Other State agencies maintain similar indexes, as does the Physician’s Desk Reference itself for its products. While some of our "look alikes" and other "counterfeit" drugs can escape detection via this technique, the imprint strategy would seem far less susceptible to error than the tablident. At a cost of 9 cents per 1000 imprinted capsules, the value seems more than justified for the variety of benefits provided. Consequently, just as I differed with your editorial of 1963,differ with you 20 years later. Is it not time to call for an international drug imprinting system? Department of Pediatrics, University of Washington; and Children’s Orthopedic Hospital and Medical Center, Seattle, Washington 98105, USA
W. O. ROBERTSON
GASTRIC CANCER AFTER PEPTIC ULCER
SIR,-Dr Logan and Professor Langman (Sept 17, p 667) refer to findingithat gastric carcinoma was no more common than predicted in a group of patients (779) followed up for between 15 our
and 32 years after curative peptic ulcer surgery. They find this puzzling in the light of previously reported increases in carcinoma of the gastric remnant and suggest loss to follow-up or dependence on routine death certification as possible reasons for under5. Gordon A. The nutriture of Cubans. In: Mesa-Lago C, ed. Cuban studies. University of Pittsburg, 1983. 6. Hefferren JJ. Identification guide for solid dosage forms. JAMA 1962; 182: 1145-1302. 7. Caldwell JG, Shoman AF, Hurst CB, Robertson WO. Identification of drugs: Use of the JAMA drug identification guide. JAMA 1964; 187: 951. 8. Symonds JK, Robertson WO. Drug identification: Use of coded imprint. JAMA 1967; 199: 664. 9. Robertson KA, Robertson WO. Drug identification by imprint. Clin Toxicol 1974; 7: 83-9. 10. Editorial. Poisoning in the home. Lancet 1963; i 982. 11. McLean Ross AH, Smith MA, Anderson JR, Small WP. Late mortality after surgery for peptic ulcer. N Engl J Med 1982; 307: 519-22.
1027
representation. It seems unlikely that our lost to follow-up group of 907o could have contributed significantly to the under-reporting of carcinoma. By relying on death certification we have missed the diagnosis of carcinoma in some cases but if, as Logan and Langman state, up to 25% of carcinomas are diagnosed only at necropsy this would not raise our figure for stump cancer by much, to 11or 12 against a predicted value of 10,4for a comparable Scottish
COMPLEMENT ACTIVATION BY UPPER-RESPIRATORY-TRACT BACTERIA ————————————————,—————————————.———————————————
population. Length of follow-up
was probably the important factor. death from carcinoma was 19 years. It is believed that more than 15 years mustlelapse before an increased incidence of gastric remnant carcinoma begins to be seen.12 We may therefore need to wait longer. We agree that greater efforts towards persuading patients to stop smoking would be more beneficial than policies for endoscopic screening. In our experience ulcer patients coming to surgery have not changed over the years.13 80% of patients who undergo highly selective vagotomy smoke and thus any anticipated long-term benefits of this more "physiological" operation are likely to be overshadowed by the complications of addiction to tobacco. A. H. MCLEAN Ross M. A. SMITH Gastric Follow-up Clinic, J. R. ANDERSON Western General Hospital, W. P. SMALL Edinburgh EH4 2XU
Average time
to
COMPLEMENT, HISTAMINE RELEASE, AND TREATMENT OF UPPER-RESPIRATORY-TRACT INFECTIONS
SIR,-Many of the symptoms of upper respiratory tract (URT) infections are similar to those of immediate hypersensitivity (type I allergy) in the same anatomical situation-ie, fever, watering eyes, sneezing, a runny nose, and so on. Since, in type I allergy, these symptoms are associated with the local release of histaminel we wondered if bacteria isolated from the URT might cause the local release of histamine and other vasoactive amines. One possible mechanism is that both pathogenic and normal flora bacteria cleave complement C3 and activate the complement cascade via the alternative or classical pathways. This would cause release of the inflammatory mediators 3C3a and CSF.2Histamine would then be released from mast cells.3 Fifty strains, representing ten species of bacteria known to cause either acute or chronic low-grade opportunistic infections, were isolated from clinical specimens or obtained from the National Type Culture Collection and identified by routine microbiological and serological tests. The bacteria were tested in the presence and absence of chelating agents for their ability to cleave complement proteins and activate complement by the classical and alternative pathways in the presence of fresh human serum. Cleavage of the was complement qualitatively assessed by
proteins immunoelectrophoresis.
Most bacteria associated with the URT (see table) could cleave complement proteins via the alternative pathway. Moreover, the normal human serum used, which was obtained from male and female healthy adult volunteers, contained antibodies to the bacteria studied and permitted complement activation by the classical
pathway also. Although complement activation by bacteria is widespread5 it has not been demonstrated previously that all of the species studied here possess this activity. The potential immunopathological effects which may be elicited by such activity in vivo, especially in individuals predisposed by URT infections, requires further
*included as positive control. FI= fresh isolate; ? = complement activated but mechanism unclear
attention. Furthermore, the ability of URT bacteria to contribute appreciably to the more overt symptoms of URT infections should be considered. Moreover, there would seem to be a place for drugs, inhibiting either local complement activation or vasoactive amine activity in the management of URT infections, particularly in the treatment and control of symptoms. A full table of results for the cleavage of C2, C3, C4 and factor B in NHS, NHS+EDTA and NHS + EGT A + Mg 2 SO 4 is available.
University Department of Immunology, General Infirmary, Leeds LS1 3EX
MEPTAZINOL 13 editorial on meptazinol cites our paper’ but showed that physostigmine reversed the effect of morphine on respiration in pain-free human beings and reversed analgesia and sedation in postoperative patients. This was not so. In the abstract citedl and in two more detailed accounts2,3 physostigmine antagonised sedation and respiratory depression but did not impair the analgesic effect of morphine. physostigmine itself raises the pain threshold in man andinlaboratory animals.5These findings suggest that the respiratory depressant effect of opioids may be associated with a reduction in central cholinergic transmission but that their analgesic effect is not. If the novel analgesic drug meptazinol actually increases central cholinergic transmission, it would serve to explain why this drug is less depressant to respiration than are equi-effective doses of opioid analgesics. Your editorial states that meptazinol, which may increase the release of acetylcholine, does not act like other opioid agonists on the stimulated guineapig ileum. This is not surprising since the depressant effect of opioid on this preparation results from 6 an inhibition of acetylcholine release.
SIR,-Your Aug that
states
we
Furthermore,
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
M. WEINSTOCK
1. Davidson JT, Snir-Mor
2. 12. De Jode LR. Gastric carcinoma following gastroenterostomy and partial gastrectomy. Br J Surg 1961; 48: 512-14. 13. McLean Ross AH, Anderson J, Small WP, Smith MA. After gastrectomy. Br Med J 1981; 282: 1472. 1. Buisseret PD. Allergy. Sci American 1982; 247: 86-97. 2. Muller-Eberhard HJ. Complement. Annu Rev Biochem 1975; 44: 697-724. 3. Brown EJ, Frank MM. Complement activation. Immunol To-day 1981; 2: 129-34. 4. Graber P, Williams CA Jr. Methods immunoelectrophoretique d’analyse de mélanges de substances antigeniques. Biochim Biophys Acta 1953; 10: 193-94. 5. Muller-Eberhard HJ, Schreiber RD. Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol 1980; 29: 2-53.
EILEEN INGHAM G. GOWLAND
I, Weinstock M. Physostigmine as an antagonist in the human subject. Br JPharmacol 1982; 75: 28P. Weinstock M, Davidson JT, Rosin AJ, Schneiden H. Effect of physostigmine on morphine-induced postoperative pain and somnolence. Br J Anaesth 1982; 54:
429-34. 3. Snir-Mor I, Weinstock
M, Davidson JT, Bahar M. Physostigmine antagonizes morphine-induced respiratory depression in human subjects. Anesthesiology 1983;
59: 6-10. 4. Sitaram N, Buchsbaum MS, Gillin JC. Eur 5. Pleuvry BJ, Tobias MA. Comparison
J Pharmacol 1977; 42: 285-91. of the antinociceptive activities of physostigmine, oxotremorine and morphine in the mouse. Br J Pharmacol 1971; 43: 706-14.
6. Cox
BM, Weinstock M. The effect of analgesic drugs on the release of acetylcholine electrically stimulated guinea pig ileum. Br J Pharmacol 1966; 27: 81-92.
from