- Email: [email protected]
ASPIRIN AND GASTRIC DAMAGE
861
persistence of abnormal transaminase levels and could have had chronic hepatitis. As these enzyme levels can fluctuate, serial estimations of SGPT were done in 30 cases to exclude this possibility. 5 cases with normal enzyme levels have had repeat liver biopsies and these showed normal liver histology. With these data we believe that the incidence of chronic hepatitis following nonwith the data parenteral NANB is very low and does contrast following post-transfusion NANB hepatitis.2 Medical Unit II,
Department of Medicine, Medical College, Srinagar, Kashmir, India-190010
MOHAMMED SULTAN KHUROO
ASPIRIN AND GASTRIC DAMAGE
SiR,—Dr Rees and Professor Turnberg (Aug. 23, p. 410) conclude that the case against aspirin in the pathogenesis of serious gastric disturbance may have been overstated. They cite animal studies in which damage to the gastric mucosa seen on initial exposure to aspirin disappeared during continuous administration over a period of weeks. Comparable studies in human volunteers’-5 have shown no such tendency for the lesions to abate during prolonged administration of aspirin. Also, Rees and Turnberg fail to cite all the relevant evidence from the studyin which 4500 patients who had recovered from myocardial infarction were randomly assigned to a group taking 1 g aspirin/day for 13 months or to a group taking placebo. Among patients admitted to hospital for gastrointestinal problems during the study, the following items had a significantly (p<0-01) higher frequency in those taking aspirin than in the placebo group: ulcer diagnosis (6 -5times higher), blood transfusion (2.55 times higher), and decrease’in haematocrit of 5% or more (1-88 times higher). Large prospective studies such as these are needed to detect even sizable increases in incidence of important events. Center for Ulcer Research and Education, V. A. Wadsworth Medical Center, Los Angeles, California 90073, U.S.A.
MORTON I. GROSSMAN
SOMATOSTATIN IN PEPTIC ULCER BLEEDING
SIR,-Dr Thomas and Dr Forbes (July 26, p. 200) are concerned about the conclusion drawn from our randomised controlled study7 with sequential design because of possible inaccuracy of pairing. They should note the following: (1) They claim that haemorrhage from gastric ulcer has a higher mortality rate than that from duodenal ulcer and that the source of bleeding should have been matched as well. This statement is controversial and probably based on data from retrospective studies not stratified for age and sex. Schiler et al8 found that the increased mortality of gastric ulcer was almost entirely a function of age and was due to a larger proportion of elderly patients in this group. We therefore did not consider it necessary to stratify for bleeding source, since the pairs were matched for age. This seems to have been justified; of the 3 patients who died in our study 2 had duodenal ulcers (n= 11) and only 1 a gastric lesion (n=8).
et al. Development of chronic liver disease after acute NANB posttransfusion hepatitis. Gastroenterology 1977; 72: 902-09. 3 Metzger WH, McAdamL, BluestoneR, GuthPH. Acutegastric mucosal injuryduring continuous or interrupted aspirin ingestion in humans. Am J Dig Dis 1976; 21:
(2) The criticism asks for many more data for underlying disease, site, extent, and aggressiveness of haemorrhage, and so on; at the same time, Thomas and Forbes complain about the study’s long duration. Although the stratification suggested may theoretically be ideal,it may endlessly prolong the trial and invalidate its outcome because of the time elapsed between 2 cases matched. We therefore concentrated on patients at high risk whose selection criteria were clearly stated, but whose data could not be described in detail. The duration of the study and the small number of patients included indicate the strict selection applied. (3) Thomas and Forbes’ statement that surgery was less common in duodenal ulcer patients must reflect a counting error; 3/11 patients with duodenal ulcer and 2/8 with gastric ulcer underwent surgery. (4) We are well aware of the problems related to studies using a sequential design. Nevertheless, sequential analysis was chosen so that the minimum number of patients would be needed to give a statistically significant result as soon as possible. It is clearly not permissible to analyse small subgroups out of the sequence, as Thomas and Forbes do. We feel that the criticisms raised are theoretical and, in most instances, inadequate. They do not invalidate our conclusion that somatostatin seems to be effective to control peptic ulcer hxmorrhage in many patients who are high-risk candidates for surgery.
L. KAYASSEH
K. GYR U. KELLER G. A. STALDER
Division of
Gastroenterology, Kantosspital, CH-4031 Basel, Switzerland
PREPARATION FOR ENDOSCOPY
SiR,-Dr Thompson and colleagues (Aug. 30, p. 469) conclude that patients benefit from premedication with’diazepam before endoscopy. I investigated 316 consecutive outpatient cases; all patients had been given a written explanation about the procedure several days before the endoscopy and were then randomly allocated to no preparation (98), throat analgesia by 10% lidocaine (93), or sedation with 10 mg diazepam (125). All endoscopies were done by one endoscopist, using Olympus GIF-K and GIF-D3 instruments. The groups were fully comparable for age, sex, diagnosis, and former endoscopy experience. I timed the introduction of the endoscope into the oesophagus and the duration of the endoscopy (time for biopsies excluded) and recorded patient’s tolerance scores and degree of retching and belching. The results are given in the table. RESULTS
2. Knodell R
963-68. 4. Lanza FL, Royer GL, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coatedaspirin on gastricandduodenal mucosa. N Engl
J Med 1980; 303: 136-38. 5. Chernish SM, Rosenak BD, Brunelle RL, Crabtree R. Comparison of gastrointestinal effects of aspirin and fenoprofen. Arthritis Rheum 1979; 22: 376-83. 6 AspirinMyocardial InfarctionStudyResearchGroup. Arandomizedcontrolledtrialof aspirininpersonsrecovered frommyocardial infarction. JAMA 1980; 243: 661-69. 7. Kayasseh L, Gyr K, Keller U et al. Somatostatin and cimetidine in peptic ulcer hæmorrhage: a randomised controlled trial. Lancet 1980; i: 344-46. 8. Schiller KFR, Truelove SC, Williams DG. Hæmatemesis and melæna, with special reference to factors influencing the outcome. Br Med J 1970; ii: 7-14.
*"Unpleasant" =repeat only tf strictly necessary; "intermediate"= repeat only if of benefit for medical care; "not too unpleasant" repeat also ifnecessary for scientific purposes". - [-p<001$p<005. =
&mid ot;
The longer introduction time in those given throat analgesia may be caused by a diminished deglutition reflex and the lower acceptability scores in those premedicated with diazepam may be due to 1. Nelis GF. Preparation for upper gastrointestinal endoscopy: controlled comparison of three regimens Netherl J Med (in press).
persistence of abnormal transaminase levels and could have had chronic hepatitis. As these enzyme levels can fluctuate, serial estimations of SGPT were done in 30 cases to exclude this possibility. 5 cases with normal enzyme levels have had repeat liver biopsies and these showed normal liver histology. With these data we believe that the incidence of chronic hepatitis following nonwith the data parenteral NANB is very low and does contrast following post-transfusion NANB hepatitis.2 Medical Unit II,
Department of Medicine, Medical College, Srinagar, Kashmir, India-190010
MOHAMMED SULTAN KHUROO
ASPIRIN AND GASTRIC DAMAGE
SiR,—Dr Rees and Professor Turnberg (Aug. 23, p. 410) conclude that the case against aspirin in the pathogenesis of serious gastric disturbance may have been overstated. They cite animal studies in which damage to the gastric mucosa seen on initial exposure to aspirin disappeared during continuous administration over a period of weeks. Comparable studies in human volunteers’-5 have shown no such tendency for the lesions to abate during prolonged administration of aspirin. Also, Rees and Turnberg fail to cite all the relevant evidence from the studyin which 4500 patients who had recovered from myocardial infarction were randomly assigned to a group taking 1 g aspirin/day for 13 months or to a group taking placebo. Among patients admitted to hospital for gastrointestinal problems during the study, the following items had a significantly (p<0-01) higher frequency in those taking aspirin than in the placebo group: ulcer diagnosis (6 -5times higher), blood transfusion (2.55 times higher), and decrease’in haematocrit of 5% or more (1-88 times higher). Large prospective studies such as these are needed to detect even sizable increases in incidence of important events. Center for Ulcer Research and Education, V. A. Wadsworth Medical Center, Los Angeles, California 90073, U.S.A.
MORTON I. GROSSMAN
SOMATOSTATIN IN PEPTIC ULCER BLEEDING
SIR,-Dr Thomas and Dr Forbes (July 26, p. 200) are concerned about the conclusion drawn from our randomised controlled study7 with sequential design because of possible inaccuracy of pairing. They should note the following: (1) They claim that haemorrhage from gastric ulcer has a higher mortality rate than that from duodenal ulcer and that the source of bleeding should have been matched as well. This statement is controversial and probably based on data from retrospective studies not stratified for age and sex. Schiler et al8 found that the increased mortality of gastric ulcer was almost entirely a function of age and was due to a larger proportion of elderly patients in this group. We therefore did not consider it necessary to stratify for bleeding source, since the pairs were matched for age. This seems to have been justified; of the 3 patients who died in our study 2 had duodenal ulcers (n= 11) and only 1 a gastric lesion (n=8).
et al. Development of chronic liver disease after acute NANB posttransfusion hepatitis. Gastroenterology 1977; 72: 902-09. 3 Metzger WH, McAdamL, BluestoneR, GuthPH. Acutegastric mucosal injuryduring continuous or interrupted aspirin ingestion in humans. Am J Dig Dis 1976; 21:
(2) The criticism asks for many more data for underlying disease, site, extent, and aggressiveness of haemorrhage, and so on; at the same time, Thomas and Forbes complain about the study’s long duration. Although the stratification suggested may theoretically be ideal,it may endlessly prolong the trial and invalidate its outcome because of the time elapsed between 2 cases matched. We therefore concentrated on patients at high risk whose selection criteria were clearly stated, but whose data could not be described in detail. The duration of the study and the small number of patients included indicate the strict selection applied. (3) Thomas and Forbes’ statement that surgery was less common in duodenal ulcer patients must reflect a counting error; 3/11 patients with duodenal ulcer and 2/8 with gastric ulcer underwent surgery. (4) We are well aware of the problems related to studies using a sequential design. Nevertheless, sequential analysis was chosen so that the minimum number of patients would be needed to give a statistically significant result as soon as possible. It is clearly not permissible to analyse small subgroups out of the sequence, as Thomas and Forbes do. We feel that the criticisms raised are theoretical and, in most instances, inadequate. They do not invalidate our conclusion that somatostatin seems to be effective to control peptic ulcer hxmorrhage in many patients who are high-risk candidates for surgery.
L. KAYASSEH
K. GYR U. KELLER G. A. STALDER
Division of
Gastroenterology, Kantosspital, CH-4031 Basel, Switzerland
PREPARATION FOR ENDOSCOPY
SiR,-Dr Thompson and colleagues (Aug. 30, p. 469) conclude that patients benefit from premedication with’diazepam before endoscopy. I investigated 316 consecutive outpatient cases; all patients had been given a written explanation about the procedure several days before the endoscopy and were then randomly allocated to no preparation (98), throat analgesia by 10% lidocaine (93), or sedation with 10 mg diazepam (125). All endoscopies were done by one endoscopist, using Olympus GIF-K and GIF-D3 instruments. The groups were fully comparable for age, sex, diagnosis, and former endoscopy experience. I timed the introduction of the endoscope into the oesophagus and the duration of the endoscopy (time for biopsies excluded) and recorded patient’s tolerance scores and degree of retching and belching. The results are given in the table. RESULTS
2. Knodell R
963-68. 4. Lanza FL, Royer GL, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coatedaspirin on gastricandduodenal mucosa. N Engl
J Med 1980; 303: 136-38. 5. Chernish SM, Rosenak BD, Brunelle RL, Crabtree R. Comparison of gastrointestinal effects of aspirin and fenoprofen. Arthritis Rheum 1979; 22: 376-83. 6 AspirinMyocardial InfarctionStudyResearchGroup. Arandomizedcontrolledtrialof aspirininpersonsrecovered frommyocardial infarction. JAMA 1980; 243: 661-69. 7. Kayasseh L, Gyr K, Keller U et al. Somatostatin and cimetidine in peptic ulcer hæmorrhage: a randomised controlled trial. Lancet 1980; i: 344-46. 8. Schiller KFR, Truelove SC, Williams DG. Hæmatemesis and melæna, with special reference to factors influencing the outcome. Br Med J 1970; ii: 7-14.
*"Unpleasant" =repeat only tf strictly necessary; "intermediate"= repeat only if of benefit for medical care; "not too unpleasant" repeat also ifnecessary for scientific purposes". - [-p<001$p<005. =
&mid ot;
The longer introduction time in those given throat analgesia may be caused by a diminished deglutition reflex and the lower acceptability scores in those premedicated with diazepam may be due to 1. Nelis GF. Preparation for upper gastrointestinal endoscopy: controlled comparison of three regimens Netherl J Med (in press).