1130
study period. 3 patients had transient asymptotachyarrhythmias detected only by Holter monitoring. Pergolide was discontinued in 2 patients, but was continued at a lower dose in the third. The significance of these asymptomatic arrhythmias is not clear, and further studies are underway. Lisuride, when added to levodopa, had a marked effect in 15 patients (most of them outpatients), including 7 with on-off re-
the 6-week matic
sponses. The number of hours in which the patients with onoff features could walk increased by 130% (from 3 to 7) during lisuride treatment. In all patients disease severity decreased by
20%. The
mean dose of lisuride was 2.7 mg (range 1-5 mg), and the dose of levodopa (in ’Sinemet’) was reduced by 42% (from 950 to 550 mg). In 5 patients levodopa was discontinued. Lisuride was a more potent anti-parkinsonian agent than levodopa in 3 of these patients, equivalent to levodopa in 1, and less potent in the other. Overall, the combination of lisuride with levodopa appeared synergistic. Adverse effects included reversible mental changes in 3 patients; the drug was discontinued in 1 patient and continued in the other 2 at a lower dose. Two patients were treated at different times with both drugs. 1 patient had a better response on 2.0 mg of pergolide than on 3.0 mg of lisuride, while 1 patient who was unable to tolerate 0.2mg pergolide because of confusion and orthostatic hypotension improved on 3.0 mg lisuride without adverse effects. Pergolide and lisuride are both promising new anti-parkinsonian agents. Pergolide seems to be a potent agent because it was effective in patients with advanced disease. Lisuride seems to induce less orthostatic hypotension and less involuntary movement than does pergolide. The efficacy of both drugs in patients with on-off features may be related to their long duration of action. Pergolide and lisuride seem to be synergistic with levodopa. In the striatum, dopamine activates predominantly the adenyl cyclase linked receptors, while pergolide and lisuride activate the non-adenyl cyclase linked receptors. While the relationship of both receptors to control of Parkinson’s disease is not clear, it is possible that activation of both is necessary for maximum effect.
New York University School of Medicine,
New York, N.Y. 10016, U.S.A.
ABRAHAM N. LIEBERMAN MORTON LEIBOWITZ ANDREAS NEOPHYTIDES MARK KUPERSMITH SIDNEY MEHL DAVID KLEINBERG MICHAEL SERBY MENEK GOLDSTEIN
PRECIPITATION OF ANTIPSYCHOTIC DRUGS IN INTERACTION WITH COFFEE OR TEA
SIR,-The significantly increased consumption of coffee by in mental hospitals’ may weaken the effect of antipsychotic medication. Indeed coffee drinking and intravenous caffeine have been recommended as antiparkinsonian drugs.2 In rats caffeine citrate 10 mg/kg body weight intraperitoneally totally inhibits catalepsy one hour after injection.3 In rats caffeine also induces the microsomal enzyme system.4 The effect
patients
1. Winstead DK. Coffee consumption among
psychiatric inpatients. AmJ Psychiat 1976; 133:1447-50. of FA. differential effects of new pheno2. Freyhan Therapeutic implications thiazine compounds. Am J Psychiat 1959; 115: 577-85. 3. Morpurgo C. Effects of antiparkinson drugs on a phenothiazine induced catatonic reaction. Arch Int Pharmacodyn 1962; 137:84-90. 4. Mitoma C, Sorich TJ, Neubauer SE. The effect of caffeine on drug metabolism. Life Sci 1968; 7: 145-81. 5. Mikkelsen EJ. Caffeine and schizophrenia. J Clin Psychiat 1978; 39: 732-35. 6. Kulhanek F, Linde OK, Meisenberg G. Moegliche interaktionen von Kaffee und Teeloesungen mit Neuroleptika: eine vorlaeufige Mitteilung. Pharmaz
Zeitschrift (in press).
of coffee (or caffeine) in schizophrenia is usually discussed in the context of pharmacodynamic or central activity. Searching for possible interactions of antipsychotic drugs with coffee and tea we mixed 5 ml commercially available
phenothiazine drops (’Dapotum’ [‘Moditen Elixir’], fluphenazine 4 mg/ml) and butyrophenone drops (’Haldol’, haloperidol 2 mg/ml) with 5 ml of a standardised solution of coffee or tea made by brewing 10 g of Jakobs coffee or dark Ceylon tea in 200 ml boiling water and filtering the mixture through a ’Selecta’ filter 595 1/2 (Schleicher-Schull). After mixing, milky, flaky precipitates could be seen with the naked eye. Precipitation also occurred with caffeine benzoate or salicylate solutions but not with caffeine hydrochloride. 20 ml of fluphenazine or haloperidol drops were mixed with 20 ml of coffee or tea. The mixtures were centrifuged (tea mixture 5 min at 2000 g, coffee mixture 30 min at 30 000 g). The sediments were washed and centrifuged three times with 20 ml water. Both the sediments and the supernatant solutions contained neuroleptics (Dragendorff’s reagent) but the last sediment contained more than the last wash solution. Thus the precipitate contained the neuroleptic agent. Analysis of the supernatant solutions at dilutions of 1:5 and 1:50 and the sediments at dilutions of 1:10 and 1:100 suggested that about 10% of the drug was precipitated, bound, or otherwise changed in coffee and about 90% in tea. Thin-layer chromatography (’Silicagel G’, running distance 7 or 6 cm in propanol/glacial-acetic-acid/water 5/1/4 and propanol/ethylenediamine/water 5/1/4) showed that the neuroleptics were liberated from the precipitates and had the same Rf values as the controls (0.65 and 0.90 for fluphenazine and haloperidol, respectively). 1 ml from a 20 ml suspension of the precipitate could not be fully dissolved by 1 mol/1 sodium hydroxide, 1
mol/1 hydrochloric acid, or by boiling.
preliminary findings indicate that phenothiazines and butyrophenones interact in vitro with coffee and tea. These
Department of Psychiatry and Psychopharmacology, von Heyden G.m.b.H. Squibb, D-800 Munich 19, West Germany
F. KULHANEK O. K. LINDE G. MEISENBERG
SIR,-Psychiatrists and psychopharmacologists are puzzled the large variation in plasma concentrations of antipsychotic drugs both between patients and within the same patient. Lader’ mentions a 100-fold difference in plasma concentration between individuals taking equivalent doses of chlorpromazine and emphasises the importance of enzyme induction among other possible causes. Hollister2 reports a 5-10 fold variation in plasma concentrations within the same patient under steady state conditions, and Davis3 ascribes these by
differences to variation in absorption, carrier state, metabolism, and excretion. Hollister2states that parenteral administration is 3-4 times as effective as oral administration of anti-
psychotics. In the above letter Dr Kulhanek and his colleagues-who me of their findings and who were encouraged by me to publish them-remind us that in 1959 Freyhan4had observed that intravenous caffeine sodium benzoate acted as a powerful antidote to the parkinsonian symptoms of neuroleptic medication and that Mikkelsen5 has reported two cases where much increased consumption of coffee and tea led to an exacerbation of schizophrenic symptoms. The discovery by Kulhanek et al. that coffee and tea rapidly form highly insoluble precipitates when in contact with fluphenazine and haloperidol could prove
told
1. Lader M. Monitoring plasma concentration of neuroleptics. Pharmakopsychiatric 1976; 9: 170-77. 2. Hollister L. Antipsychotics. In: Clinical pharmacology of psychiatric drugs. 1978: chap 5. 3. Davis, JM. Recent developments in the drug treatment of schizophrenia. Am
J Psychiat 1976; 133:208-14. Freyhan FA. Therapeutic implications of differential effects of new phenothiazine compounds. Am J Psychiat 1959; 115:577-85. 5. Mikkelsen EJ. Caffeine and schizophrenia. J Clin Psychiat 1978; 39:
4.
732-35.
1131 be clinically very important. It is remarkable that twentyfive years have passed before this simple observation has been made. Perhaps pharinacologists should look at the interactions between foods and drugs to see if any such combinations inactivate the medication. Readers can convince themselves, as I have done, by adding an elixir of chlorpromazine, haloperidol, fluphenazine, droperidol, promethazine, promazine, or prochlorperazine (or their injectable equivalents) to coffee or tea in a glass and noting the insoluble precipitate. However, when we added trifluoperazine and propranolol to coffee we observed no reaction: if confirmed by a more sensitive technique this observation would provide an interesting contrast to what happened with the other drugs mentioned and could have implications for treatment. Further investigation of this whole area is needed. We have found a note to the effect that a number of normal food substances cause cloudy precipitates when combined with phenothiazines,6 but the authors fail to grasp the implications-that this could render a medication inactive and insoluble and account for differences in blood levels. Dr Kulhanek and his colleagues are to be congratulated. to
Department of Psychiatry, Charing Cross Hospital Medical School, London W6 8RF
STEVEN R. HIRSCH
PROLAMINE SOLUTION TO BLOCK PANCREATIC DUCT
SIR,-Professor Little and his colleagues (Sept. 15,
p.
557)
report their experience of treating chronic alcoholic pancreatitis by duct obstruction with an acrylate glue. Three of six patients had complete pain relief after the instillation of 1-2 ml of alkyl a-cyanoacrylate into the surgically exposed papilla of Vater. The glue set in less than a minute so that the cannula had to be cut off flush with the pancreatic duct opening. We have been using an alcoholic aminoacid solution (prolamine [’Ethibloc’]) for endoscopic duct obstruction. This substance solidifies rapidly, it is microbiologically indifferent, and it disintegrates within 11 days. All patients were scheduled for total pancreatectomy because of intractable pain caused by alcoholic pancreatitis and severe ductal changes on endoscopic retrograde pancreatography. 14 instillations in twelve patients have been done so far. Long-term follow-up shows that six patients are completely free of pain up to 18 months after ductal occlusion. Alcoholic prolamine solution is also routinely instilled in combination with Whipple’s procedure where the tail is occluded. In these cases the resection of the head of the pancreas was necessary because of cysts, duodenal and choledochal stenosis, or occluding concrements in the pancreatic duct. Experience in sixty-five patients with only 1 operative death is encouraging; no relapse of pancreatitis occurred over an observation period of 22 months. In contrast to Little’s patients, all our patients had severely dilated and contorted ducts; the volume instilled varied between 5 and 10 ml. We feel that endoscopic duct obstruction is a complication-free alternative to pancreatic resection, especially in patients who have already undergone subtotal pancreatectomy and still have intractable pain. This method, however, can only be applied if selective cannulation of the pancreatic duct is possible, if the common bileduct shows no stenosis, and if intraductal concretions are excluded. If endoscopic occlusion is technically impossible total pancreatectomy can be avoided in severe pancreatitis by partial duodenopancreatectomy and occlusion of the remaining pancreatic tail.
Some reports of our early experience with this technique appeared in the German literature and elsewhere.’’’
Departments of Medicine and Surgery, University of Erlangen-Nürnberg, 8520 Erlangen, West Germany
have
W. RÖSCH CH. GEBHARDT
SIR,-Subtotal pancreatic transplantation in diabetic patients has been performed using ’Neoprene’ as an occlusive gel for the obstruction of the pancreatic duct. 5.6 In one case of subtotal pancreas transplantation (simultaneously with kidney transplantation) in man we have used an alcoholic solution of aminoacids (prolamine [’Ethibloc’]; Ethicon) as an occlusive gel to obstruct the pancreatic duct. The patient died with functioning graft from cardiac failure on the 10th postoperative day. Post-mortem histological examination of the prolamine-treated pancreatic graft showed: ducts and ductuli filled with amorphic material; necrosis and degeneration of the duct epithelium, but no adjacent inflammatory reaction; slight dilatation and minimal atrophy of the exocrine acini; oedematous islets without signs of inflammation ; cedema in the interstitial tissue with sparse polymorphonuclear and lymphoplasmacytic infiltration and with slight fibrosis; and normal vascularisation. Experimental and clinical studies7.8 show that prolamine solution has some advantages as an occlusion gel. The solution is microbiologically indifferent and it is broken down and resorbed within 2 weeks (i.e., there is no continous foreign stimulus to the tissue); the substance is radio-opaque and so can easily be injected into the pancreas under X-ray control; the oedema that develops is mild; no acute purulent pancreatitis following injection is observed, even in the presence of bacterial contamination of the duct system; and the solution causes atrophy and (mild) fibrosis of the exocrine parenchyma. Occlusion of the pancreatic duct by prolamine in non-diabetic patients with chronic pancreatitis does not lead to diabetes mellitus (observation period more than 2 years). Transplantation Unit, Surgical Department, Klinikum Großhadern; and Institute for Pathology,
W. LAND H. WEITZ
University of Munich, Munich, West Germany
FATAL RESPIRATORY-DISTRESS SYNDROME AND SALICYLATE INTOXICATION IN A TWO-YEAR-OLD
SIR,-Pulmonary oedema associated with salicylate intoxication has occasionally been reported in adults9-12 and older children, but not, to our knowledge, in young children. We have seen a fatal case of accidental salicylate ingestion in a 26-month-old girl. 1. Gebhardt C, Stolte M. Die ausschaltung des exokrinen pankreasparenchyms durch intraductale injektion einer schnell härtenden aminosäurelösung.
Chirurg 1978; 49:428. 2. Gebhardt C, Stolte M. Pankreasgang-okklusion durch injektion einer schnell härtenden animosäurelösung. Langenbecks Arch Chir 1978; 346: 149. 3. Rösch W, Phillip J, Gebhardt C. Endoscopic duct obstruction in chronic pancreatitis. Endoscopy 1979; 10:43. 4. Gall FP, Gebhardt C. Ein neues konzept in der chirurgie der chronischen pankreatitis: Rezidivverhütung durch gangokklusion und erhaltung des magens. Dtsch Med Wschr 1979; 104: 1003. 5. Dubernard JM, Traeger J, Neyra P, Touraine G-L, Devonec M, BlancBrunat N, Ruitton A. Une nouvelle méthode de préparation du greffon pancréatique en vue de la transplantation. Chirurgie 1978; 104: 242. 6. Traeger J, Dubernard JM, Touraine J-L, Neyra P, Malik MC, Pelissard C, Ruitton A. Pancreatic transplantation in man: A new method of pancreas preparation and results on diabetes correction. Transp Proc 1979; 11: 331. 7. Gebhardt C, Stolte M. Pankreasgang-okklusion durch injektion einer schnellhärtenden aminosäurelösung. Langenbecks Arch Chir 1978; 149: 149. 8. Gebhardt C, Stolte M. Die ausschaltung des exkretorischen pankreasparenchyms durch intraductale injektion einer schnell härtenden aminosäurelösung. Chirurg 1978; 49: 428. 9. Davis PR, Burch RE. Pulmonary edema and salicylate intoxication. Ann Intern Med 1974; 80: 553-54. 10. Hrnicek G, Skelton J, Miller WC. Pulmonary edema and salicylate intoxication. JAMA 1974; 230: 866-67. 11. Tashima CK, Rose M. Pulmonary edema and salicylates. Ann Intern Med.
1974; 81: 274. PG, Hague JR. Observations on phenothiazine ing agents. Am J Psychiat 1964; 120: 1000-02.
6. Lever
concentrates
and dilut-
12. Sørensen SC. Adult
respiratory-distress syndrome
Lancet 1979; i: 1025.
in
salicylate intoxication.
study period. 3 patients had transient asymptotachyarrhythmias detected only by Holter monitoring. Pergolide was discontinued in 2 patients, but was continued at a lower dose in the third. The significance of these asymptomatic arrhythmias is not clear, and further studies are underway. Lisuride, when added to levodopa, had a marked effect in 15 patients (most of them outpatients), including 7 with on-off re-
the 6-week matic
sponses. The number of hours in which the patients with onoff features could walk increased by 130% (from 3 to 7) during lisuride treatment. In all patients disease severity decreased by
20%. The
mean dose of lisuride was 2.7 mg (range 1-5 mg), and the dose of levodopa (in ’Sinemet’) was reduced by 42% (from 950 to 550 mg). In 5 patients levodopa was discontinued. Lisuride was a more potent anti-parkinsonian agent than levodopa in 3 of these patients, equivalent to levodopa in 1, and less potent in the other. Overall, the combination of lisuride with levodopa appeared synergistic. Adverse effects included reversible mental changes in 3 patients; the drug was discontinued in 1 patient and continued in the other 2 at a lower dose. Two patients were treated at different times with both drugs. 1 patient had a better response on 2.0 mg of pergolide than on 3.0 mg of lisuride, while 1 patient who was unable to tolerate 0.2mg pergolide because of confusion and orthostatic hypotension improved on 3.0 mg lisuride without adverse effects. Pergolide and lisuride are both promising new anti-parkinsonian agents. Pergolide seems to be a potent agent because it was effective in patients with advanced disease. Lisuride seems to induce less orthostatic hypotension and less involuntary movement than does pergolide. The efficacy of both drugs in patients with on-off features may be related to their long duration of action. Pergolide and lisuride seem to be synergistic with levodopa. In the striatum, dopamine activates predominantly the adenyl cyclase linked receptors, while pergolide and lisuride activate the non-adenyl cyclase linked receptors. While the relationship of both receptors to control of Parkinson’s disease is not clear, it is possible that activation of both is necessary for maximum effect.
New York University School of Medicine,
New York, N.Y. 10016, U.S.A.
ABRAHAM N. LIEBERMAN MORTON LEIBOWITZ ANDREAS NEOPHYTIDES MARK KUPERSMITH SIDNEY MEHL DAVID KLEINBERG MICHAEL SERBY MENEK GOLDSTEIN
PRECIPITATION OF ANTIPSYCHOTIC DRUGS IN INTERACTION WITH COFFEE OR TEA
SIR,-The significantly increased consumption of coffee by in mental hospitals’ may weaken the effect of antipsychotic medication. Indeed coffee drinking and intravenous caffeine have been recommended as antiparkinsonian drugs.2 In rats caffeine citrate 10 mg/kg body weight intraperitoneally totally inhibits catalepsy one hour after injection.3 In rats caffeine also induces the microsomal enzyme system.4 The effect
patients
1. Winstead DK. Coffee consumption among
psychiatric inpatients. AmJ Psychiat 1976; 133:1447-50. of FA. differential effects of new pheno2. Freyhan Therapeutic implications thiazine compounds. Am J Psychiat 1959; 115: 577-85. 3. Morpurgo C. Effects of antiparkinson drugs on a phenothiazine induced catatonic reaction. Arch Int Pharmacodyn 1962; 137:84-90. 4. Mitoma C, Sorich TJ, Neubauer SE. The effect of caffeine on drug metabolism. Life Sci 1968; 7: 145-81. 5. Mikkelsen EJ. Caffeine and schizophrenia. J Clin Psychiat 1978; 39: 732-35. 6. Kulhanek F, Linde OK, Meisenberg G. Moegliche interaktionen von Kaffee und Teeloesungen mit Neuroleptika: eine vorlaeufige Mitteilung. Pharmaz
Zeitschrift (in press).
of coffee (or caffeine) in schizophrenia is usually discussed in the context of pharmacodynamic or central activity. Searching for possible interactions of antipsychotic drugs with coffee and tea we mixed 5 ml commercially available
phenothiazine drops (’Dapotum’ [‘Moditen Elixir’], fluphenazine 4 mg/ml) and butyrophenone drops (’Haldol’, haloperidol 2 mg/ml) with 5 ml of a standardised solution of coffee or tea made by brewing 10 g of Jakobs coffee or dark Ceylon tea in 200 ml boiling water and filtering the mixture through a ’Selecta’ filter 595 1/2 (Schleicher-Schull). After mixing, milky, flaky precipitates could be seen with the naked eye. Precipitation also occurred with caffeine benzoate or salicylate solutions but not with caffeine hydrochloride. 20 ml of fluphenazine or haloperidol drops were mixed with 20 ml of coffee or tea. The mixtures were centrifuged (tea mixture 5 min at 2000 g, coffee mixture 30 min at 30 000 g). The sediments were washed and centrifuged three times with 20 ml water. Both the sediments and the supernatant solutions contained neuroleptics (Dragendorff’s reagent) but the last sediment contained more than the last wash solution. Thus the precipitate contained the neuroleptic agent. Analysis of the supernatant solutions at dilutions of 1:5 and 1:50 and the sediments at dilutions of 1:10 and 1:100 suggested that about 10% of the drug was precipitated, bound, or otherwise changed in coffee and about 90% in tea. Thin-layer chromatography (’Silicagel G’, running distance 7 or 6 cm in propanol/glacial-acetic-acid/water 5/1/4 and propanol/ethylenediamine/water 5/1/4) showed that the neuroleptics were liberated from the precipitates and had the same Rf values as the controls (0.65 and 0.90 for fluphenazine and haloperidol, respectively). 1 ml from a 20 ml suspension of the precipitate could not be fully dissolved by 1 mol/1 sodium hydroxide, 1
mol/1 hydrochloric acid, or by boiling.
preliminary findings indicate that phenothiazines and butyrophenones interact in vitro with coffee and tea. These
Department of Psychiatry and Psychopharmacology, von Heyden G.m.b.H. Squibb, D-800 Munich 19, West Germany
F. KULHANEK O. K. LINDE G. MEISENBERG
SIR,-Psychiatrists and psychopharmacologists are puzzled the large variation in plasma concentrations of antipsychotic drugs both between patients and within the same patient. Lader’ mentions a 100-fold difference in plasma concentration between individuals taking equivalent doses of chlorpromazine and emphasises the importance of enzyme induction among other possible causes. Hollister2 reports a 5-10 fold variation in plasma concentrations within the same patient under steady state conditions, and Davis3 ascribes these by
differences to variation in absorption, carrier state, metabolism, and excretion. Hollister2states that parenteral administration is 3-4 times as effective as oral administration of anti-
psychotics. In the above letter Dr Kulhanek and his colleagues-who me of their findings and who were encouraged by me to publish them-remind us that in 1959 Freyhan4had observed that intravenous caffeine sodium benzoate acted as a powerful antidote to the parkinsonian symptoms of neuroleptic medication and that Mikkelsen5 has reported two cases where much increased consumption of coffee and tea led to an exacerbation of schizophrenic symptoms. The discovery by Kulhanek et al. that coffee and tea rapidly form highly insoluble precipitates when in contact with fluphenazine and haloperidol could prove
told
1. Lader M. Monitoring plasma concentration of neuroleptics. Pharmakopsychiatric 1976; 9: 170-77. 2. Hollister L. Antipsychotics. In: Clinical pharmacology of psychiatric drugs. 1978: chap 5. 3. Davis, JM. Recent developments in the drug treatment of schizophrenia. Am
J Psychiat 1976; 133:208-14. Freyhan FA. Therapeutic implications of differential effects of new phenothiazine compounds. Am J Psychiat 1959; 115:577-85. 5. Mikkelsen EJ. Caffeine and schizophrenia. J Clin Psychiat 1978; 39:
4.
732-35.
1131 be clinically very important. It is remarkable that twentyfive years have passed before this simple observation has been made. Perhaps pharinacologists should look at the interactions between foods and drugs to see if any such combinations inactivate the medication. Readers can convince themselves, as I have done, by adding an elixir of chlorpromazine, haloperidol, fluphenazine, droperidol, promethazine, promazine, or prochlorperazine (or their injectable equivalents) to coffee or tea in a glass and noting the insoluble precipitate. However, when we added trifluoperazine and propranolol to coffee we observed no reaction: if confirmed by a more sensitive technique this observation would provide an interesting contrast to what happened with the other drugs mentioned and could have implications for treatment. Further investigation of this whole area is needed. We have found a note to the effect that a number of normal food substances cause cloudy precipitates when combined with phenothiazines,6 but the authors fail to grasp the implications-that this could render a medication inactive and insoluble and account for differences in blood levels. Dr Kulhanek and his colleagues are to be congratulated. to
Department of Psychiatry, Charing Cross Hospital Medical School, London W6 8RF
STEVEN R. HIRSCH
PROLAMINE SOLUTION TO BLOCK PANCREATIC DUCT
SIR,-Professor Little and his colleagues (Sept. 15,
p.
557)
report their experience of treating chronic alcoholic pancreatitis by duct obstruction with an acrylate glue. Three of six patients had complete pain relief after the instillation of 1-2 ml of alkyl a-cyanoacrylate into the surgically exposed papilla of Vater. The glue set in less than a minute so that the cannula had to be cut off flush with the pancreatic duct opening. We have been using an alcoholic aminoacid solution (prolamine [’Ethibloc’]) for endoscopic duct obstruction. This substance solidifies rapidly, it is microbiologically indifferent, and it disintegrates within 11 days. All patients were scheduled for total pancreatectomy because of intractable pain caused by alcoholic pancreatitis and severe ductal changes on endoscopic retrograde pancreatography. 14 instillations in twelve patients have been done so far. Long-term follow-up shows that six patients are completely free of pain up to 18 months after ductal occlusion. Alcoholic prolamine solution is also routinely instilled in combination with Whipple’s procedure where the tail is occluded. In these cases the resection of the head of the pancreas was necessary because of cysts, duodenal and choledochal stenosis, or occluding concrements in the pancreatic duct. Experience in sixty-five patients with only 1 operative death is encouraging; no relapse of pancreatitis occurred over an observation period of 22 months. In contrast to Little’s patients, all our patients had severely dilated and contorted ducts; the volume instilled varied between 5 and 10 ml. We feel that endoscopic duct obstruction is a complication-free alternative to pancreatic resection, especially in patients who have already undergone subtotal pancreatectomy and still have intractable pain. This method, however, can only be applied if selective cannulation of the pancreatic duct is possible, if the common bileduct shows no stenosis, and if intraductal concretions are excluded. If endoscopic occlusion is technically impossible total pancreatectomy can be avoided in severe pancreatitis by partial duodenopancreatectomy and occlusion of the remaining pancreatic tail.
Some reports of our early experience with this technique appeared in the German literature and elsewhere.’’’
Departments of Medicine and Surgery, University of Erlangen-Nürnberg, 8520 Erlangen, West Germany
have
W. RÖSCH CH. GEBHARDT
SIR,-Subtotal pancreatic transplantation in diabetic patients has been performed using ’Neoprene’ as an occlusive gel for the obstruction of the pancreatic duct. 5.6 In one case of subtotal pancreas transplantation (simultaneously with kidney transplantation) in man we have used an alcoholic solution of aminoacids (prolamine [’Ethibloc’]; Ethicon) as an occlusive gel to obstruct the pancreatic duct. The patient died with functioning graft from cardiac failure on the 10th postoperative day. Post-mortem histological examination of the prolamine-treated pancreatic graft showed: ducts and ductuli filled with amorphic material; necrosis and degeneration of the duct epithelium, but no adjacent inflammatory reaction; slight dilatation and minimal atrophy of the exocrine acini; oedematous islets without signs of inflammation ; cedema in the interstitial tissue with sparse polymorphonuclear and lymphoplasmacytic infiltration and with slight fibrosis; and normal vascularisation. Experimental and clinical studies7.8 show that prolamine solution has some advantages as an occlusion gel. The solution is microbiologically indifferent and it is broken down and resorbed within 2 weeks (i.e., there is no continous foreign stimulus to the tissue); the substance is radio-opaque and so can easily be injected into the pancreas under X-ray control; the oedema that develops is mild; no acute purulent pancreatitis following injection is observed, even in the presence of bacterial contamination of the duct system; and the solution causes atrophy and (mild) fibrosis of the exocrine parenchyma. Occlusion of the pancreatic duct by prolamine in non-diabetic patients with chronic pancreatitis does not lead to diabetes mellitus (observation period more than 2 years). Transplantation Unit, Surgical Department, Klinikum Großhadern; and Institute for Pathology,
W. LAND H. WEITZ
University of Munich, Munich, West Germany
FATAL RESPIRATORY-DISTRESS SYNDROME AND SALICYLATE INTOXICATION IN A TWO-YEAR-OLD
SIR,-Pulmonary oedema associated with salicylate intoxication has occasionally been reported in adults9-12 and older children, but not, to our knowledge, in young children. We have seen a fatal case of accidental salicylate ingestion in a 26-month-old girl. 1. Gebhardt C, Stolte M. Die ausschaltung des exokrinen pankreasparenchyms durch intraductale injektion einer schnell härtenden aminosäurelösung.
Chirurg 1978; 49:428. 2. Gebhardt C, Stolte M. Pankreasgang-okklusion durch injektion einer schnell härtenden animosäurelösung. Langenbecks Arch Chir 1978; 346: 149. 3. Rösch W, Phillip J, Gebhardt C. Endoscopic duct obstruction in chronic pancreatitis. Endoscopy 1979; 10:43. 4. Gall FP, Gebhardt C. Ein neues konzept in der chirurgie der chronischen pankreatitis: Rezidivverhütung durch gangokklusion und erhaltung des magens. Dtsch Med Wschr 1979; 104: 1003. 5. Dubernard JM, Traeger J, Neyra P, Touraine G-L, Devonec M, BlancBrunat N, Ruitton A. Une nouvelle méthode de préparation du greffon pancréatique en vue de la transplantation. Chirurgie 1978; 104: 242. 6. Traeger J, Dubernard JM, Touraine J-L, Neyra P, Malik MC, Pelissard C, Ruitton A. Pancreatic transplantation in man: A new method of pancreas preparation and results on diabetes correction. Transp Proc 1979; 11: 331. 7. Gebhardt C, Stolte M. Pankreasgang-okklusion durch injektion einer schnellhärtenden aminosäurelösung. Langenbecks Arch Chir 1978; 149: 149. 8. Gebhardt C, Stolte M. Die ausschaltung des exkretorischen pankreasparenchyms durch intraductale injektion einer schnell härtenden aminosäurelösung. Chirurg 1978; 49: 428. 9. Davis PR, Burch RE. Pulmonary edema and salicylate intoxication. Ann Intern Med 1974; 80: 553-54. 10. Hrnicek G, Skelton J, Miller WC. Pulmonary edema and salicylate intoxication. JAMA 1974; 230: 866-67. 11. Tashima CK, Rose M. Pulmonary edema and salicylates. Ann Intern Med.
1974; 81: 274. PG, Hague JR. Observations on phenothiazine ing agents. Am J Psychiat 1964; 120: 1000-02.
6. Lever
concentrates
and dilut-
12. Sørensen SC. Adult
respiratory-distress syndrome
Lancet 1979; i: 1025.
in
salicylate intoxication.
