1355 decreased exocrine pancreatic and biliary secretions, the that endogenously excreted PP might serve such an in-vivo role was suggested. This hypothesis remains to be tested ; meantime we wish to note that substantial amounts of immunoreactive glucagon and insulin can also be found in human pancreatic exocrine secretions. In patients undergoing cannulation of the major pancreatic duct for diagnostic purposes, we found insulin levels in pancreatic juice ranging from 4 to 1155 U/ml and glucagon concentrations ranging from 192 to 1449 pg/ml. In pancreatic-duct-cannulated dogs, immunoreactive insulin levels rose significantly and glucagon levels dropped during glucose administration. The finding of islet-like peptides in pancreatic exocrine juice is not altogether surprising. Islet cells derive, it is believed, from exocrine ductular cells,9 and in cephalochordates, amphioxus, and mussels, which have no separate islet organ or exocrine pancreas, cells with immunohistochemical properties of insulin-secreting beta and glucagon-secreting alpha cells have been identified in the gastrointestinal mucosa. 10,11 Nevertheless, studies will have to be designed to determine the exact origin of these islet-like peptides in pancreatic juice and to determine what role they play in nutrient metabolism.
VOLUNTEER’S
causes
possibility
Departments of Medicine and Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, U.S.A., and Research Service, V.A. Hospital,
Hines, Illinois
A. M. LAWRENCE R. A. PRINZ E. PALOYAN W. A. KOKAL
OPIATE ANTAGONISM FAILS TO REVERSE HYPNOTIC-INDUCED ANALGESIA
SIR,-Although the endogenous, opiate-like peptides (endorphins) have been implicated in the analgesic mechanism of various treatments, such as placebo,’ acupunctureand nitrous oxide3 their role in hypnotic analgesia is unknown. One single blind study4 indicated that naloxone, a specific opiate antagonist, at a dose of 4 mg intravenously, reversed hypnoticinduced analgesia. However, other reports5.6demonstrated that naloxone in doses of 0.4mg subcutaneously or 0.8-1 mg i.v. failed to alter the hypnotic-induced analgesia. Here, we report the failure of a much higher dose of naloxone (50 mg i.v.) to reduce or abolish hypnotic analgesia. The volunteer, a 22-year-old male, who was susceptible to hypnosis, gave informed consent to the study. He was instructed to rate the pain of the pricks of a 21-gauge needle to the back of his hand as 0 (no feeling), 1 (just touching), 2 (moderately painful pinprick), or 3 (severely painful pinprick). He was hypnotised, and glove analgesia was induced in his left hand. An i.v. injection of either 20 ml physiological saline or naloxone 50 mg in 20 ml water was given over a 10 min period before measurement of pain perception. Neither the volunteer nor the rating physician knew what was being injected. The same procedure was repeated the next day. Pain was rated by the patient in right and left hands every 3 min. The results (see table) indicate that naloxone dose not antagonise hypnotic-induced analgesia, suggesting that endorphins are probably not involved in this type of analgesia. This accords with some reports cited above, but is also consistent with the features of hypnotic-induced analgesia which are different from other types of analgesia in that it can be induced 9. Satake, K., Pairent, F. W., Romero, F. Surg. Gynec. Obstet. 1972, 134, 589. 10. Kataoka, K., Fujita, H. Arch. Histol. Jap. 1974, 36, 401. 11. Fritsch, H. A., VanNoorden, S., Pearse, A. G. Cell Tissue Res. 1976, 165, 365. 1. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 2. Mayer, D. J., Price, D. D., Rafii, A., Barber, J. in Advances in Pain Research and Therapy vol. I: proceedings of First World Congress on Pain (edited by J. J. Bonica and D. Albe-Fessard); p. 751, New York, 1976. 3. Berkowitz, B. A., Ngai, S. H., Finck, A. D. Science, 1976, 194, 967 4. Stephenson, J. B. P. Lancet, 1978, ii, 991. 5. Goldstein, A., Hilgard, E. R. Proc. natn. Acad. Sci. 1975, 72, 2041. 6. Barber, J., Mayer, D.
Pain, 1977, 4, 41.
RATING OF PAIN UNDER HYPNOSIS WITH GLOVE
ANALGESIA IN THE LEFT HAND FOLLOWING ADMINSTRATION OF
NALOXONE OR PLACEBO
differentially in specific parts of the body, it can be turned off and on abruptly by suggestion (which is not concordant with the release of a substance), and it can remain effective for hours with no development of "tolerance", which is unlike the pattern seen with acupuncture or external opiate administration. The
same above arguments also apply to other mechanisms of analgesia involving the release of a substance, such as cholinomimetic agents (whose analgesic effects are also antagonised by naloxone).7 The mechanism of hypnotic-induced analgesia remains unknown, and could involve an entirely different psychophysiological or neurochemical mechanism. Research into the mechanism of hypnotic-induced analgesia is important, since it could provide insights into the neural mechanism underlying the hypnotic state itself.
Supported by Medical Research Service of the Veterans AdministraCenter, San Diego (MRIS 4576), N.I.M.H. grant 1 P50
tion Medical Tj’3rtQi
m
Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A.
HENRY A. NASRALLAH THOMAS HOLLEY DAVID S. JANOWSKY
PERITONITIS IN PERITONEAL DIALYSIS
SIR,-Peritonitis is
a serious problem in chronic peritoneal The abdominal skin flora, the intestinal flora, and dialysis. contaminated dialysis fluid are generally considered the main sources of infection. 1.2 However, little is known about the rela-
7.
Pedigo, N. W., Dewey, W. L., Harris, L. S. J. Pharmac. exp. Ther. 1975, 193, 845. 1. Black, H. R., Finkelstein, F. O., Lee, R. V. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 115. 2. Kolmos, H. J., Andersen, K. E. H. Scand. J. infect. Dis (in the press). CAUSATIVE MICROORGANISMS AND PROBABLE SOURCES OF PERITONITIS
1356 tive
importance of each of these potential foci. We have analysed 41 consecutive cases of peritonitis in twenty-nine patients with terminal renal failure on peritoneal dialysis with a Tenckhoff catheter and a closed delivery system. The predominant microorganisms were Staphylococcus aureus and coagulase-negative staphylococci and micrococci (see table). In half the cases Staph. aureus was isolated from abdominal wounds and pustules before or coincident with peritonitis. Infections with Enterobacteriaceae, in 3
cases
second-
numerically protracted gram-positive peritonitis, important. We traced infections with Pseudomonas ceruginosa to a- water bath, used to preheat the dialysis fluids to body temperature.2 The preponderance of gram-positive infections, particularly staphylococcal infections, indicates that the abdominal skin flora is the main source of peritonitis. Prophylactic measures should, therefore, concentrate on preventing the abdominal skin flora from invading the peritoneal cavity. Abdominal staphylococcal infections should be treated intensively before implantation of the dialysis catheter. If patients become infected after dialysis has started temporary removal of the catheter
ary
to a
were
less
‘
occur early in the disease process. Platelet activation may activate the coagulation system,6 and platelet activation, possibly by immune complexes,’ could play an important role in initiating the disease process and coagulation changes described in pre-eclampsia. Aspirin inhibits platelet activation, including that induced by antigen-antibody complexes.6 The ingestion of aspirin throughout pregnancy might therefore have been responsible for decrease in pre-eclampsia we found. Platelet participation may be the link between two of the main theories on the pathogenesis of pre-eclampsianamely, the immunological and the haemostatic.
platelet changes
Department of Obstetrics University of Leeds,
fluids. should be exchanged with dry-heat incubators. Since the intestinal flora is a relatively rare source of peritonitis non-absorbable intestinal antibiotics, as proposed by Fine,3 are not advisable. Statens
Seruminstitut,
Regional Laboratory, and Department of Nephrology, HANS JØRN KOLMOS Odense University Hospital, KARL ERIK HEMMELØFF ANDERSEN DK-5000 Odense, Denmark EFFECT OF ASPIRIN ON INCIDENCE OF PRE-ECLAMPSIA
SIR,-Goodlin et al.’ have described a patient with recurpre-eclampsia and thrombocytopenia who seemed to benefit from aspirin. The efficacy of aspirin on the progress of pregnancy-associated hypertension has received little attention. Over a period of seven months all 964 primigravida: in their third trimester admitted for antenatal care or for delivery, had a questionnaire administered by one of six carefully instructed midwives, about their intake of aspirin-containing compounds and other non-steroidal anti-inflammatory drugs during pregnancy. Two groups were identified-98 patients who had no history of drug intake during pregnancy and 48 patients who had taken aspirin or aspirin-containing compounds more than rent
once a
fortnight throughout
pregnancy. The
remaining
818
patients had taken other drugs or aspirin infrequently. Preeclampsia was diagnosed if the patient had a sustained increase in diastolic blood-pressure of more than 20 mm HG after 24 weeks’ gestation, having been normotensive when seen in the first trimester. Of the 146 patients studied, 18 (12.3%) had pre-eclampsia-16 (16%) of those who took no aspirin but only 2 (4%) of those who took aspirin frequently throughout pregnancy (Fisher’s exact test, p=0-027S). Evidence is accumulating which suggests that platelet activation is involved in pre-eclampsia.2.3 McKay et al.,4 from animal experiments, suggested that platelet adhesion to endothelium was the first pathological event in pre-eclampsia, and Redman et a1.5 showed that the platelet-count in women with chronic hypertension fell before the onset of superimposed preeclampsia. Both of these studies accord with the concept that ‘
Goodlin, R. C., Haesslein, H. O., Fleming, J. Lancet, 1978, ii, 51. Redman, C. W. G., Allington, M. J., Bolton, F. G., Stirrat, G. M. ibid. 1977, ii, 248. 3. Whigham, K. E., Howie, P. W., Prentice, C. R. M. Br. J. Obstet. Gynœc. 1978, 85, 28. 4. McKay, D. G., Goldenberg, V., Kunnitz, H., Csavossy, I. Archs Path. 1967, 84, 557. 5. Redman, C. W. G., Bonnar, J., Beilin, L. Br. med. J. 1978, i, 467.
1. 2.
Gynæcology,
Leeds LS2 9NG
A. J. CRANDON
Department of Chemical Pathology, University of Leeds
D. M. ISHERWOOD
FETAL SOLVENTS SYNDROME
may be necessary until the lesion has healed. Water baths for
preheating dialysis
and
SIR,-In 1973, the fetal alcohol syndrome was rediscovered by Jones, Smith, and their colleagues.8.9 Dysmorphology attributed to fetal alcohol syndrome usually follows substantial alcohol abuse by the mother during pregnancy,’"’" but we know of no reports of similar presentations in infants born to mothers who have abused solvents while pregnant. We have seen a child born with nearly classic fetal alcohol syndrome to a mother whose major addiction was to solvents (primarily toluene). This 20-year-old primigravida had a 14-year history of daily heavy solvent abuse, and a 3-year history of alcohol intake of about a six-pack of beer weekly. On admission she had ataxia, resting and intention tremors, mild diffuse sensory deficits, short-term memory loss, blunted affect, and poor intellectual functioning compatible with severe solvent and/or alcohol abuse. Hepatic function was normal. Her child was born at term, but small. He was slightly above the 10th percentile in height, at the 10th percentile in weight, and at the 5th percentile in head size. Abnormal features included microcephaly, a flat nasal bridge, hypoplastic mandible, short palpebral fissures, mildly low-set ears, pronounced sacral dimple, sloping forehead, and incoordination of arm movements, with unusual angulation of the left shoulder and elbow. No joint or muscular abnormalities were found on physical examination or X-ray. His suck reflex was poor, and he was jerky on days 2-4, though this improved spontaneously. This case seems no different from reports of fetal alcohol syndrome; however, solvent abuse, rather than alcohol, predominated in this mother’s addiction pattern. Solvent abuse might be totally unrelated to the anomalies observed. On the other hand, could this presentation be a sort of "fetal solvent syndrome" with solvents, such as toluene, being the primary teratogen? Perhaps the solvents damaged the mother’s ability to detoxify alcohol, thus intensifying the risk of fetal alcohol syndrome-but then, equally, alcohol might potentiate a postulated solvent teratogenicity. We know of no reports of fetal damage due to toluene or other solvent abuses, but chronic solvent use after birth is reported to cause brain, bone-marrow, liver, and kidney dysfunction. Department of Psychiatry, School of Medicine, University of Louisville, Louisville, Kentucky 40202, U.S.A.
CLAIRE TOUTANT STEVEN LIPPMANN
Packham, M. A., Mustard, J. F. Sem. Hœmat. 1971, 8, 30. Pfueller, S., Luscher, E. F. Immunochemistry 1972, 9, 1151. Jones, K. L., and others Lancet, 1973, i, 1267. Jones, K. L., Smith, D. W. ibid. 1973, ii, 999. Hanson, J. W., Jones, K. L., Smith, D. W. J. Am. med. Ass. 1976, 235, 1458. Ouellette, E. M., and others New Engl. J. Med. 1977, 297, 528. National Institute on Alcohol Abuse and Alcoholism, F.D.A. Drug Bull. Fetal Alcohol Syndrome, 1977, 7, 18. 13. Shaywitz, B. A. Drug Ther. 1978, 8, 95.
6. 7. 8. 9. 10. 11. 12.
VOLUNTEER’S
causes
possibility
Departments of Medicine and Surgery, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, U.S.A., and Research Service, V.A. Hospital,
Hines, Illinois
A. M. LAWRENCE R. A. PRINZ E. PALOYAN W. A. KOKAL
OPIATE ANTAGONISM FAILS TO REVERSE HYPNOTIC-INDUCED ANALGESIA
SIR,-Although the endogenous, opiate-like peptides (endorphins) have been implicated in the analgesic mechanism of various treatments, such as placebo,’ acupunctureand nitrous oxide3 their role in hypnotic analgesia is unknown. One single blind study4 indicated that naloxone, a specific opiate antagonist, at a dose of 4 mg intravenously, reversed hypnoticinduced analgesia. However, other reports5.6demonstrated that naloxone in doses of 0.4mg subcutaneously or 0.8-1 mg i.v. failed to alter the hypnotic-induced analgesia. Here, we report the failure of a much higher dose of naloxone (50 mg i.v.) to reduce or abolish hypnotic analgesia. The volunteer, a 22-year-old male, who was susceptible to hypnosis, gave informed consent to the study. He was instructed to rate the pain of the pricks of a 21-gauge needle to the back of his hand as 0 (no feeling), 1 (just touching), 2 (moderately painful pinprick), or 3 (severely painful pinprick). He was hypnotised, and glove analgesia was induced in his left hand. An i.v. injection of either 20 ml physiological saline or naloxone 50 mg in 20 ml water was given over a 10 min period before measurement of pain perception. Neither the volunteer nor the rating physician knew what was being injected. The same procedure was repeated the next day. Pain was rated by the patient in right and left hands every 3 min. The results (see table) indicate that naloxone dose not antagonise hypnotic-induced analgesia, suggesting that endorphins are probably not involved in this type of analgesia. This accords with some reports cited above, but is also consistent with the features of hypnotic-induced analgesia which are different from other types of analgesia in that it can be induced 9. Satake, K., Pairent, F. W., Romero, F. Surg. Gynec. Obstet. 1972, 134, 589. 10. Kataoka, K., Fujita, H. Arch. Histol. Jap. 1974, 36, 401. 11. Fritsch, H. A., VanNoorden, S., Pearse, A. G. Cell Tissue Res. 1976, 165, 365. 1. Levine, J. D., Gordon, N. C., Fields, H. L. Lancet, 1978, ii, 654. 2. Mayer, D. J., Price, D. D., Rafii, A., Barber, J. in Advances in Pain Research and Therapy vol. I: proceedings of First World Congress on Pain (edited by J. J. Bonica and D. Albe-Fessard); p. 751, New York, 1976. 3. Berkowitz, B. A., Ngai, S. H., Finck, A. D. Science, 1976, 194, 967 4. Stephenson, J. B. P. Lancet, 1978, ii, 991. 5. Goldstein, A., Hilgard, E. R. Proc. natn. Acad. Sci. 1975, 72, 2041. 6. Barber, J., Mayer, D.
Pain, 1977, 4, 41.
RATING OF PAIN UNDER HYPNOSIS WITH GLOVE
ANALGESIA IN THE LEFT HAND FOLLOWING ADMINSTRATION OF
NALOXONE OR PLACEBO
differentially in specific parts of the body, it can be turned off and on abruptly by suggestion (which is not concordant with the release of a substance), and it can remain effective for hours with no development of "tolerance", which is unlike the pattern seen with acupuncture or external opiate administration. The
same above arguments also apply to other mechanisms of analgesia involving the release of a substance, such as cholinomimetic agents (whose analgesic effects are also antagonised by naloxone).7 The mechanism of hypnotic-induced analgesia remains unknown, and could involve an entirely different psychophysiological or neurochemical mechanism. Research into the mechanism of hypnotic-induced analgesia is important, since it could provide insights into the neural mechanism underlying the hypnotic state itself.
Supported by Medical Research Service of the Veterans AdministraCenter, San Diego (MRIS 4576), N.I.M.H. grant 1 P50
tion Medical Tj’3rtQi
m
Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla, California 92093, U.S.A.
HENRY A. NASRALLAH THOMAS HOLLEY DAVID S. JANOWSKY
PERITONITIS IN PERITONEAL DIALYSIS
SIR,-Peritonitis is
a serious problem in chronic peritoneal The abdominal skin flora, the intestinal flora, and dialysis. contaminated dialysis fluid are generally considered the main sources of infection. 1.2 However, little is known about the rela-
7.
Pedigo, N. W., Dewey, W. L., Harris, L. S. J. Pharmac. exp. Ther. 1975, 193, 845. 1. Black, H. R., Finkelstein, F. O., Lee, R. V. Trans. Am. Soc. artif. intern. Organs, 1974, 20, 115. 2. Kolmos, H. J., Andersen, K. E. H. Scand. J. infect. Dis (in the press). CAUSATIVE MICROORGANISMS AND PROBABLE SOURCES OF PERITONITIS
1356 tive
importance of each of these potential foci. We have analysed 41 consecutive cases of peritonitis in twenty-nine patients with terminal renal failure on peritoneal dialysis with a Tenckhoff catheter and a closed delivery system. The predominant microorganisms were Staphylococcus aureus and coagulase-negative staphylococci and micrococci (see table). In half the cases Staph. aureus was isolated from abdominal wounds and pustules before or coincident with peritonitis. Infections with Enterobacteriaceae, in 3
cases
second-
numerically protracted gram-positive peritonitis, important. We traced infections with Pseudomonas ceruginosa to a- water bath, used to preheat the dialysis fluids to body temperature.2 The preponderance of gram-positive infections, particularly staphylococcal infections, indicates that the abdominal skin flora is the main source of peritonitis. Prophylactic measures should, therefore, concentrate on preventing the abdominal skin flora from invading the peritoneal cavity. Abdominal staphylococcal infections should be treated intensively before implantation of the dialysis catheter. If patients become infected after dialysis has started temporary removal of the catheter
ary
to a
were
less
‘
occur early in the disease process. Platelet activation may activate the coagulation system,6 and platelet activation, possibly by immune complexes,’ could play an important role in initiating the disease process and coagulation changes described in pre-eclampsia. Aspirin inhibits platelet activation, including that induced by antigen-antibody complexes.6 The ingestion of aspirin throughout pregnancy might therefore have been responsible for decrease in pre-eclampsia we found. Platelet participation may be the link between two of the main theories on the pathogenesis of pre-eclampsianamely, the immunological and the haemostatic.
platelet changes
Department of Obstetrics University of Leeds,
fluids. should be exchanged with dry-heat incubators. Since the intestinal flora is a relatively rare source of peritonitis non-absorbable intestinal antibiotics, as proposed by Fine,3 are not advisable. Statens
Seruminstitut,
Regional Laboratory, and Department of Nephrology, HANS JØRN KOLMOS Odense University Hospital, KARL ERIK HEMMELØFF ANDERSEN DK-5000 Odense, Denmark EFFECT OF ASPIRIN ON INCIDENCE OF PRE-ECLAMPSIA
SIR,-Goodlin et al.’ have described a patient with recurpre-eclampsia and thrombocytopenia who seemed to benefit from aspirin. The efficacy of aspirin on the progress of pregnancy-associated hypertension has received little attention. Over a period of seven months all 964 primigravida: in their third trimester admitted for antenatal care or for delivery, had a questionnaire administered by one of six carefully instructed midwives, about their intake of aspirin-containing compounds and other non-steroidal anti-inflammatory drugs during pregnancy. Two groups were identified-98 patients who had no history of drug intake during pregnancy and 48 patients who had taken aspirin or aspirin-containing compounds more than rent
once a
fortnight throughout
pregnancy. The
remaining
818
patients had taken other drugs or aspirin infrequently. Preeclampsia was diagnosed if the patient had a sustained increase in diastolic blood-pressure of more than 20 mm HG after 24 weeks’ gestation, having been normotensive when seen in the first trimester. Of the 146 patients studied, 18 (12.3%) had pre-eclampsia-16 (16%) of those who took no aspirin but only 2 (4%) of those who took aspirin frequently throughout pregnancy (Fisher’s exact test, p=0-027S). Evidence is accumulating which suggests that platelet activation is involved in pre-eclampsia.2.3 McKay et al.,4 from animal experiments, suggested that platelet adhesion to endothelium was the first pathological event in pre-eclampsia, and Redman et a1.5 showed that the platelet-count in women with chronic hypertension fell before the onset of superimposed preeclampsia. Both of these studies accord with the concept that ‘
Goodlin, R. C., Haesslein, H. O., Fleming, J. Lancet, 1978, ii, 51. Redman, C. W. G., Allington, M. J., Bolton, F. G., Stirrat, G. M. ibid. 1977, ii, 248. 3. Whigham, K. E., Howie, P. W., Prentice, C. R. M. Br. J. Obstet. Gynœc. 1978, 85, 28. 4. McKay, D. G., Goldenberg, V., Kunnitz, H., Csavossy, I. Archs Path. 1967, 84, 557. 5. Redman, C. W. G., Bonnar, J., Beilin, L. Br. med. J. 1978, i, 467.
1. 2.
Gynæcology,
Leeds LS2 9NG
A. J. CRANDON
Department of Chemical Pathology, University of Leeds
D. M. ISHERWOOD
FETAL SOLVENTS SYNDROME
may be necessary until the lesion has healed. Water baths for
preheating dialysis
and
SIR,-In 1973, the fetal alcohol syndrome was rediscovered by Jones, Smith, and their colleagues.8.9 Dysmorphology attributed to fetal alcohol syndrome usually follows substantial alcohol abuse by the mother during pregnancy,’"’" but we know of no reports of similar presentations in infants born to mothers who have abused solvents while pregnant. We have seen a child born with nearly classic fetal alcohol syndrome to a mother whose major addiction was to solvents (primarily toluene). This 20-year-old primigravida had a 14-year history of daily heavy solvent abuse, and a 3-year history of alcohol intake of about a six-pack of beer weekly. On admission she had ataxia, resting and intention tremors, mild diffuse sensory deficits, short-term memory loss, blunted affect, and poor intellectual functioning compatible with severe solvent and/or alcohol abuse. Hepatic function was normal. Her child was born at term, but small. He was slightly above the 10th percentile in height, at the 10th percentile in weight, and at the 5th percentile in head size. Abnormal features included microcephaly, a flat nasal bridge, hypoplastic mandible, short palpebral fissures, mildly low-set ears, pronounced sacral dimple, sloping forehead, and incoordination of arm movements, with unusual angulation of the left shoulder and elbow. No joint or muscular abnormalities were found on physical examination or X-ray. His suck reflex was poor, and he was jerky on days 2-4, though this improved spontaneously. This case seems no different from reports of fetal alcohol syndrome; however, solvent abuse, rather than alcohol, predominated in this mother’s addiction pattern. Solvent abuse might be totally unrelated to the anomalies observed. On the other hand, could this presentation be a sort of "fetal solvent syndrome" with solvents, such as toluene, being the primary teratogen? Perhaps the solvents damaged the mother’s ability to detoxify alcohol, thus intensifying the risk of fetal alcohol syndrome-but then, equally, alcohol might potentiate a postulated solvent teratogenicity. We know of no reports of fetal damage due to toluene or other solvent abuses, but chronic solvent use after birth is reported to cause brain, bone-marrow, liver, and kidney dysfunction. Department of Psychiatry, School of Medicine, University of Louisville, Louisville, Kentucky 40202, U.S.A.
CLAIRE TOUTANT STEVEN LIPPMANN
Packham, M. A., Mustard, J. F. Sem. Hœmat. 1971, 8, 30. Pfueller, S., Luscher, E. F. Immunochemistry 1972, 9, 1151. Jones, K. L., and others Lancet, 1973, i, 1267. Jones, K. L., Smith, D. W. ibid. 1973, ii, 999. Hanson, J. W., Jones, K. L., Smith, D. W. J. Am. med. Ass. 1976, 235, 1458. Ouellette, E. M., and others New Engl. J. Med. 1977, 297, 528. National Institute on Alcohol Abuse and Alcoholism, F.D.A. Drug Bull. Fetal Alcohol Syndrome, 1977, 7, 18. 13. Shaywitz, B. A. Drug Ther. 1978, 8, 95.
6. 7. 8. 9. 10. 11. 12.
