ClinicalRadiology (1990) 41, 250-252
Effects of Buscopan on Gastro-oesophageal Reflux and Hiatus Hernia R. R A N J I T RAJAH
Department of Radiology, University College Hospital, Gower Street, London WC1E 6A U
This prospective study was undertaken to establish whether Buscopan (hyosine butyl bromide) interferes with the detection of a hiatus hernia or induces gastro-oesophageal reflux. One hundred and four consecutive patients were included in the study who came for barium meal and swallow examinations over a period of 3 months. Ten patients were excluded from the study. The examinations were performed by the author. The manoeuvres to detect gastro-oesophageal reflux and hiatus hernia were performed before and after intravenous Buscopan. It was found that Buscopan does not induce gastro-oesophageal reflux in the majority of patients, or interfere with detection of a hiatus hernia. The conclusion of this study is that Buscopan can be given early on in the barium meal examination without a significant effect on hiatal function.
Since Buscopan reduces the intrinsic pressure of the lower gastro-oesophageal sphincter it may in theory lead to gastro-oesophageal reflux and it could be argued that it should only be given after checking for reflux and the presence of hiatus hernia. This timing, however, is not necessarily optimal for obtaining detailed views of the body of the stomach and duodenal cap. It was decided to examine the evidence for this view and none was found; hence a prospective study to test this hypothesis was set up.
PATIENTS This prospective study was carried out personally by the author over a period of 3 months. One hundred and four consecutive patients, both in patients and outpatients, referred for barium swallow and meal examinations were studied. There were 49 males and 45 females, with an age range of 16 years to 81 years. The weight was in the range of 35.5 - 90 kg. At the onset it was decided to exclude four categories of patients from the study. These consisted of patients with glaucoma, those with nasogastric tubes within 3 days prior to examination, patients who had undergone surgical procedures involving the gastro-oesophageal junction and patients who were on drug medication which might alter the normal physiology of the gastro-intestinal tract (Castell, 1978). The reasons for exclusion of these groups were as follows: Buscopan may aggravate glaucoma and it is conventional practice to use glucagon as an antispasmodic in such Patients. It has been reported that patients who have had a nasogastric tube in position for 3 days prior to a barium study may reflux during that period (Nagler and Spiro, 1963). It is obvious that any Correspondence to: R. Ranjit Rajah, Department of Radiology, University CollegeHospital, Gower Street, London WC1E 6AU.
surgical procedure involving the gastro-oesophageal junction may interfere with the normal anti-reflux mechanism particularly truncal vagotomy where extensive dissection takes place around the gastro:oesophageal region (Edwards, 1982). In this series of 104 patients, 10 were excluded from the study for the following reasons: one was using eye drops for an unspecified complaint and it was felt appropriate to substitute glucagon for Buscopan in this case; five patients had previous vagotomy and pyloroplasty; one patient had a Celestine tube at the lower end of the oesophagus for a carcinoma, and another had a narrow stricture at the lower end of the oesophagus with a confirmed diagnosis of achalasia. In this series there were no patients who had been intubated with nasogastric tubes within the previous three days and none who required exclusion because of medication.
METHODS All of the 94 patients remaining in the study were examined for the presence of gastro-oesophageal reflux and hiatus hernia before and after 20 mg of Buscopan was given intravenously. A hiatus hernia was defined as (Sutton, 1987): 1 A pouch with gastric folds within it extending more than 2 cm above the hiatus. 2 More than three gastric folds within the lower end of the oesophagus. 3 Areae gastricae extending into the lower end of the oesophagus for over 2 cm. 4 A wide hiatus measuring more than 3 cm. 5 A gastric fundal fold crossing the cardia and ending in a polypoid protruberance. All patients were given effervescent granules initially and were then examined swallowing barium in the prone oblique position with the left side raised about 30 ° . In this position the gastro-oesophageal junction was observed on fluoroscopy for the presence of a hiatus hernia. Under fluoroscopic control patients were then turned into a supine position to elicit gastro-oesophageal reflux, firstly in the LAO 30 ° position (table horizontal) and secondly lying in the above position with the table in the Trendelenburg position (10 ° head down). If reflux was observed in either of these positions, this was recorded as free reflux. In every case gastro-oesophageal reflux was also checked by means of the following additional manoeuvres. 1 Deep expiration. 2 With gentle manual pressure over the epigastric region. 3 While the patient was drinking 10 cc of water. These tests were performed whilst the patient was in the same two positions as previously. If any of these
EFFECTS OF BUSCOPAN ON REFLUX AND HIATUS HERNIA manoeuvres produced reflux then this was recorded as
induced reflux. RESULTS The purpose of this study was to assess the effects of Buscopan on the hiatus hernia/reflux complex and was carried out as previously described. Reflux was not detected in 59 patients (63% of the total) either before or after Buscopan, and 53 (90%) of these did not have a hiatus hernia. Five patients without reflux did have a hiatus hernia, and in one of these the hernia was not demonstrated after Buscopan (Table 1). In 21 patients (22% of the total) reflux was demonstrated both before and after Buscopan and in this group, 16 patients were shown to have reflux and a hernia on both occasions. In two patients free gastro-oesophageal reflux was seen without a hiatus hernia both before and after Buscopan. In two patients induced gastro-oesophageal reflux was noted on both occasions, one with and one without an associated hernia. One patient had induced reflux on both occasions and a hiatus hernia shown before Buscopan but not after. One of these had free reflux, with a hiatus hernia and the other had induced reflux, without a hiatus hernia (Table 2). Reflux was demonstrated after Buscopan and not before in 12 patients (13%). Five of these showed an associated hiatus hernia on both occasions and seven showed no hernia (Table 3). In two patients (2%) we were unable to demonstrate a hiatus hernia after Buscopan, which had been visible before its administration (Table 4). DISCUSSION Buscopan has been used in clinical practice for over 35 years. It is a spasmolytic or smooth muscle relaxant drug with neurotrophic or anti-cholinergic activity (Kreel, Table 1 - Patients without reflux
No reflux (F & I) before or after i.v. Buscopan No hiatus hernia Hiatus hernia present Hiatushernia not demonstrated after i.v. Buscopan
59 53 5 1
Table 2 - Patients with reflux
Refluxdemonstrated before and after i.v. Buscopan Free reflux and hiatus hernia Free reflux but no hiatus hernia Induced reflux but no hiatus hernia Induced reflux and hiatus hernia Inducedrefluxbut no hiatus hernia after i.v. Buscopan
21 16 2 i 1 1
Table 3 - Patients with reflux only after Buscopan -.....
Refluxnoted after but not beforei.v. Buscopan Hiatus hernia on both occasions No hiatus hernia on both occasions
12 5 7
-......
Table 4 - Patients with reflux before Buscopan
Refluxnoted before but not after i.v. Buscopan Free reflux before and hiatus hernia on both occasions Inducedrefluxbefore and hiatus hernia on both occasions
2 1 1
251
1975). Its anti-cholinergic activity lasts for a period of approximately 15-20 minutes, and infusion experiments suggest that it is rapidly inactivated or excreted. It also has a sympathetic ganglion blocking action but this effect is unimportant in man at the conventional dose of 20 mg commonly used in radiology (Hexheimer and Haefeli, 1966). The actions of Buscopan in the gastro-intestinal tract are well recognised. It inhibits motility in the stomach and colon and it also reduces gastric secretion and slows transit through the small bowel (Kreel, 1975). It also causes transient pylorospasm. Some studies have shown that oesophageal peristalsis is abolished by Buscopan (Liu, 1974; Novak, 1975) and that it relaxes the lower oesophageal sphincter (Cooper et al., 1977). This study was devised to determine whether the administration of intravenous Buscopan significantly affects the occurrence of gastro-oesophageal reflux and the detection of a hiatus hernia in view of its known effect on relaxing the lower oesophageal sphincter, bearing in mind that the lower oesophageal sphincter pressure is the major factor which prevents reflux in the normal patient. Several other mechanical anti-reflux mechanisms at the gastro-oesophageal junction have been described (Edwards, 1982). These include oblique angle of entry of the oesophagus into the stomach, a mucosal rosette, and a mucosal choke, or a flap valve of stomach mucosa at the entry of the oesophagus. All have aroused interest but are now largely discounted as significant factors in the antireflux mechanism. The flap valve concept, in which closure is caused by the difference in pressure between the abdomen and thorax acting on the flattened tube of gut as it passes through the hiatus, was once considered a major factor by some but its importance was probably overrated. The lower oesophageal sphincter pressure is probably the important factor in preventing gastro-oesophageal reflux. The sphincter lies at the cardio-oesophageal junction and measures 3 cm in length (Habibulla, 1972). This junction consists of the hiatus and the sphincter, and the lower oesophageal sphincter pressure is contributed to by both. The lower oesophageal sphincter consists entirely of smooth muscles arranged in two rows and is supplied by cholinergic and sympathetic nerve endings (Last, 1979). The intra-abdominal, hiatal, sphincteric and intra-thoracic pressures have been measured simultaneously in a normal subject in different positions. The difference in pressure between abdomen and thorax changed but hiatal and sphincteric pressure did not (Dilwari et al., 1974). This suggests that the abdominalthoracic pressure gradient changes without much change in t h e sphincteric pressure. The intra-abdominal and intra-thoracic pressure changed from slight in expiration to considerable in inspiration, but the sphincter pressure did not change (Edwards, 1982). These extensive studies have revealed the fact that the lower oesophageal sphincter pressure is the most important factor which prevents gastro-oesophageal reflux. When there is a change in the position of the sphincter or when there is a drop in the lower oesophageal pressure the occurrence of reflux is highly likely. If there is a change in the relationship between the hiatus and the sphincter the lower oesophageal sphincter pressure falls and this may lead to gastro-oesophageal reflux (Edwards, 1982). It is known that gastro-oesophageal reflux can occur without a demonstrable hiatus hernia, but several publications suggest that patients with a hiatus hernia and
252
CLINICAL RADIOLOGY
reflux t e n d to h a v e m o r e severe reflux a n d a s s o c i a t e d c o m p l i c a t i o n s t h a n those w i t h o u t ( K a u l et al., 1986). H e n c e the i m p o r t a n c e o f d e t e c t i o n o f the h i a t u s h e r n i a / reflux c o m p l e x . T h e c o n c l u s i o n o f this s t u d y is t h a t even t h o u g h B u s c o p a n is k n o w n to r e d u c e the lower o e s o p h a g e a l s p h i n c t e r pressure, it does n o t i n d u c e reflux or interfere w i t h d e t e c t i o n o f a h i a t u s h e r n i a to a n y clinically significant degree.
Acknowledgement: I thank Dr B. M. Thomas for his constructive criticism and review of the manuscript.
REFERENCES
Castell, C (1978). Medical measures that influence the gastro-oesophageal function. Southern Medical Journal supplement No. 1. pp. 26-28. Cooper, JD, Gill, SS, Nelems, JM & Pearson, FG (1977). Intraoperative and postoperative oesophageal manometric findings with Collis gastroplasty and Belsey hiatal hernia repair for gastro-eosophageal reflux. Journal of Thoracic Cardiovascular Surgery, 74, 744 751. Dilwari, JB, Edwards, DAW & Girimes, DH (1974). The probability of
symptoms or of radiographic evidence of reflux predicted by lower oesophageal sphincter pressure. In Proceedings of the Fourth International Symposium on Gastrointestinal Motility, Ed. Daniel EE. pp. 441-448. Mitchell Press, Vancouver. Edwards, DA (1982). The anti-reflux mechanisms its disorder and their consequences. Clinics in Gastroenterology, 11,479-496. Habibulla, KS (1972) The diaphragm as an anti-reflux barrier. Thorax, 27, 679 702. Hexheimer, A & Ha&eli, L (1966). Human pharmacology of hyosine butyl bromide. Lancet, 2, 418-421. Kaul, B, Petersen, H, Myrvold, HE, Grette, K & Roysland, P (1986) Hiatus hernia in gastro-oesophageal reflux disease. Scandinavian Journal of Gastroenterology, 21, 31-34. Kreel, L (1975). Pharmacoradiology in barium examination with special reference to glucagon. The British Journal of Radiology, 48, 691-703. Last, RJ (1979). Anatomy Regional and Applied, 7th Edition. pp. 240241. Churchill Livingstone, London. Liu, C (1974). Visualisation of oesophageal varices by Buscopan. American Journal of Roentgenology, 121, 232-233. Nagler, R & Spiro, HM (1963). Persistent gastro-oesophageal reflux induced during prolonged gastric intubation. New England Journal of Medicine, 269, 495-496. Novak, D (1975). Hypotonic oesophagography using propantheline bromide. Fortschritte auf dem Gebiete der R6ntgenstrahlen, 123, 409-414. Sutton, D (1987). A Text Book of Radiology and Imaging, 4th Edition, Vol 1. pp 794-795. Churchill Livingstone, London.
Effects of Buscopan on Gastro-oesophageal Reflux and Hiatus Hernia R. R A N J I T RAJAH
Department of Radiology, University College Hospital, Gower Street, London WC1E 6A U
This prospective study was undertaken to establish whether Buscopan (hyosine butyl bromide) interferes with the detection of a hiatus hernia or induces gastro-oesophageal reflux. One hundred and four consecutive patients were included in the study who came for barium meal and swallow examinations over a period of 3 months. Ten patients were excluded from the study. The examinations were performed by the author. The manoeuvres to detect gastro-oesophageal reflux and hiatus hernia were performed before and after intravenous Buscopan. It was found that Buscopan does not induce gastro-oesophageal reflux in the majority of patients, or interfere with detection of a hiatus hernia. The conclusion of this study is that Buscopan can be given early on in the barium meal examination without a significant effect on hiatal function.
Since Buscopan reduces the intrinsic pressure of the lower gastro-oesophageal sphincter it may in theory lead to gastro-oesophageal reflux and it could be argued that it should only be given after checking for reflux and the presence of hiatus hernia. This timing, however, is not necessarily optimal for obtaining detailed views of the body of the stomach and duodenal cap. It was decided to examine the evidence for this view and none was found; hence a prospective study to test this hypothesis was set up.
PATIENTS This prospective study was carried out personally by the author over a period of 3 months. One hundred and four consecutive patients, both in patients and outpatients, referred for barium swallow and meal examinations were studied. There were 49 males and 45 females, with an age range of 16 years to 81 years. The weight was in the range of 35.5 - 90 kg. At the onset it was decided to exclude four categories of patients from the study. These consisted of patients with glaucoma, those with nasogastric tubes within 3 days prior to examination, patients who had undergone surgical procedures involving the gastro-oesophageal junction and patients who were on drug medication which might alter the normal physiology of the gastro-intestinal tract (Castell, 1978). The reasons for exclusion of these groups were as follows: Buscopan may aggravate glaucoma and it is conventional practice to use glucagon as an antispasmodic in such Patients. It has been reported that patients who have had a nasogastric tube in position for 3 days prior to a barium study may reflux during that period (Nagler and Spiro, 1963). It is obvious that any Correspondence to: R. Ranjit Rajah, Department of Radiology, University CollegeHospital, Gower Street, London WC1E 6AU.
surgical procedure involving the gastro-oesophageal junction may interfere with the normal anti-reflux mechanism particularly truncal vagotomy where extensive dissection takes place around the gastro:oesophageal region (Edwards, 1982). In this series of 104 patients, 10 were excluded from the study for the following reasons: one was using eye drops for an unspecified complaint and it was felt appropriate to substitute glucagon for Buscopan in this case; five patients had previous vagotomy and pyloroplasty; one patient had a Celestine tube at the lower end of the oesophagus for a carcinoma, and another had a narrow stricture at the lower end of the oesophagus with a confirmed diagnosis of achalasia. In this series there were no patients who had been intubated with nasogastric tubes within the previous three days and none who required exclusion because of medication.
METHODS All of the 94 patients remaining in the study were examined for the presence of gastro-oesophageal reflux and hiatus hernia before and after 20 mg of Buscopan was given intravenously. A hiatus hernia was defined as (Sutton, 1987): 1 A pouch with gastric folds within it extending more than 2 cm above the hiatus. 2 More than three gastric folds within the lower end of the oesophagus. 3 Areae gastricae extending into the lower end of the oesophagus for over 2 cm. 4 A wide hiatus measuring more than 3 cm. 5 A gastric fundal fold crossing the cardia and ending in a polypoid protruberance. All patients were given effervescent granules initially and were then examined swallowing barium in the prone oblique position with the left side raised about 30 ° . In this position the gastro-oesophageal junction was observed on fluoroscopy for the presence of a hiatus hernia. Under fluoroscopic control patients were then turned into a supine position to elicit gastro-oesophageal reflux, firstly in the LAO 30 ° position (table horizontal) and secondly lying in the above position with the table in the Trendelenburg position (10 ° head down). If reflux was observed in either of these positions, this was recorded as free reflux. In every case gastro-oesophageal reflux was also checked by means of the following additional manoeuvres. 1 Deep expiration. 2 With gentle manual pressure over the epigastric region. 3 While the patient was drinking 10 cc of water. These tests were performed whilst the patient was in the same two positions as previously. If any of these
EFFECTS OF BUSCOPAN ON REFLUX AND HIATUS HERNIA manoeuvres produced reflux then this was recorded as
induced reflux. RESULTS The purpose of this study was to assess the effects of Buscopan on the hiatus hernia/reflux complex and was carried out as previously described. Reflux was not detected in 59 patients (63% of the total) either before or after Buscopan, and 53 (90%) of these did not have a hiatus hernia. Five patients without reflux did have a hiatus hernia, and in one of these the hernia was not demonstrated after Buscopan (Table 1). In 21 patients (22% of the total) reflux was demonstrated both before and after Buscopan and in this group, 16 patients were shown to have reflux and a hernia on both occasions. In two patients free gastro-oesophageal reflux was seen without a hiatus hernia both before and after Buscopan. In two patients induced gastro-oesophageal reflux was noted on both occasions, one with and one without an associated hernia. One patient had induced reflux on both occasions and a hiatus hernia shown before Buscopan but not after. One of these had free reflux, with a hiatus hernia and the other had induced reflux, without a hiatus hernia (Table 2). Reflux was demonstrated after Buscopan and not before in 12 patients (13%). Five of these showed an associated hiatus hernia on both occasions and seven showed no hernia (Table 3). In two patients (2%) we were unable to demonstrate a hiatus hernia after Buscopan, which had been visible before its administration (Table 4). DISCUSSION Buscopan has been used in clinical practice for over 35 years. It is a spasmolytic or smooth muscle relaxant drug with neurotrophic or anti-cholinergic activity (Kreel, Table 1 - Patients without reflux
No reflux (F & I) before or after i.v. Buscopan No hiatus hernia Hiatus hernia present Hiatushernia not demonstrated after i.v. Buscopan
59 53 5 1
Table 2 - Patients with reflux
Refluxdemonstrated before and after i.v. Buscopan Free reflux and hiatus hernia Free reflux but no hiatus hernia Induced reflux but no hiatus hernia Induced reflux and hiatus hernia Inducedrefluxbut no hiatus hernia after i.v. Buscopan
21 16 2 i 1 1
Table 3 - Patients with reflux only after Buscopan -.....
Refluxnoted after but not beforei.v. Buscopan Hiatus hernia on both occasions No hiatus hernia on both occasions
12 5 7
-......
Table 4 - Patients with reflux before Buscopan
Refluxnoted before but not after i.v. Buscopan Free reflux before and hiatus hernia on both occasions Inducedrefluxbefore and hiatus hernia on both occasions
2 1 1
251
1975). Its anti-cholinergic activity lasts for a period of approximately 15-20 minutes, and infusion experiments suggest that it is rapidly inactivated or excreted. It also has a sympathetic ganglion blocking action but this effect is unimportant in man at the conventional dose of 20 mg commonly used in radiology (Hexheimer and Haefeli, 1966). The actions of Buscopan in the gastro-intestinal tract are well recognised. It inhibits motility in the stomach and colon and it also reduces gastric secretion and slows transit through the small bowel (Kreel, 1975). It also causes transient pylorospasm. Some studies have shown that oesophageal peristalsis is abolished by Buscopan (Liu, 1974; Novak, 1975) and that it relaxes the lower oesophageal sphincter (Cooper et al., 1977). This study was devised to determine whether the administration of intravenous Buscopan significantly affects the occurrence of gastro-oesophageal reflux and the detection of a hiatus hernia in view of its known effect on relaxing the lower oesophageal sphincter, bearing in mind that the lower oesophageal sphincter pressure is the major factor which prevents reflux in the normal patient. Several other mechanical anti-reflux mechanisms at the gastro-oesophageal junction have been described (Edwards, 1982). These include oblique angle of entry of the oesophagus into the stomach, a mucosal rosette, and a mucosal choke, or a flap valve of stomach mucosa at the entry of the oesophagus. All have aroused interest but are now largely discounted as significant factors in the antireflux mechanism. The flap valve concept, in which closure is caused by the difference in pressure between the abdomen and thorax acting on the flattened tube of gut as it passes through the hiatus, was once considered a major factor by some but its importance was probably overrated. The lower oesophageal sphincter pressure is probably the important factor in preventing gastro-oesophageal reflux. The sphincter lies at the cardio-oesophageal junction and measures 3 cm in length (Habibulla, 1972). This junction consists of the hiatus and the sphincter, and the lower oesophageal sphincter pressure is contributed to by both. The lower oesophageal sphincter consists entirely of smooth muscles arranged in two rows and is supplied by cholinergic and sympathetic nerve endings (Last, 1979). The intra-abdominal, hiatal, sphincteric and intra-thoracic pressures have been measured simultaneously in a normal subject in different positions. The difference in pressure between abdomen and thorax changed but hiatal and sphincteric pressure did not (Dilwari et al., 1974). This suggests that the abdominalthoracic pressure gradient changes without much change in t h e sphincteric pressure. The intra-abdominal and intra-thoracic pressure changed from slight in expiration to considerable in inspiration, but the sphincter pressure did not change (Edwards, 1982). These extensive studies have revealed the fact that the lower oesophageal sphincter pressure is the most important factor which prevents gastro-oesophageal reflux. When there is a change in the position of the sphincter or when there is a drop in the lower oesophageal pressure the occurrence of reflux is highly likely. If there is a change in the relationship between the hiatus and the sphincter the lower oesophageal sphincter pressure falls and this may lead to gastro-oesophageal reflux (Edwards, 1982). It is known that gastro-oesophageal reflux can occur without a demonstrable hiatus hernia, but several publications suggest that patients with a hiatus hernia and
252
CLINICAL RADIOLOGY
reflux t e n d to h a v e m o r e severe reflux a n d a s s o c i a t e d c o m p l i c a t i o n s t h a n those w i t h o u t ( K a u l et al., 1986). H e n c e the i m p o r t a n c e o f d e t e c t i o n o f the h i a t u s h e r n i a / reflux c o m p l e x . T h e c o n c l u s i o n o f this s t u d y is t h a t even t h o u g h B u s c o p a n is k n o w n to r e d u c e the lower o e s o p h a g e a l s p h i n c t e r pressure, it does n o t i n d u c e reflux or interfere w i t h d e t e c t i o n o f a h i a t u s h e r n i a to a n y clinically significant degree.
Acknowledgement: I thank Dr B. M. Thomas for his constructive criticism and review of the manuscript.
REFERENCES
Castell, C (1978). Medical measures that influence the gastro-oesophageal function. Southern Medical Journal supplement No. 1. pp. 26-28. Cooper, JD, Gill, SS, Nelems, JM & Pearson, FG (1977). Intraoperative and postoperative oesophageal manometric findings with Collis gastroplasty and Belsey hiatal hernia repair for gastro-eosophageal reflux. Journal of Thoracic Cardiovascular Surgery, 74, 744 751. Dilwari, JB, Edwards, DAW & Girimes, DH (1974). The probability of
symptoms or of radiographic evidence of reflux predicted by lower oesophageal sphincter pressure. In Proceedings of the Fourth International Symposium on Gastrointestinal Motility, Ed. Daniel EE. pp. 441-448. Mitchell Press, Vancouver. Edwards, DA (1982). The anti-reflux mechanisms its disorder and their consequences. Clinics in Gastroenterology, 11,479-496. Habibulla, KS (1972) The diaphragm as an anti-reflux barrier. Thorax, 27, 679 702. Hexheimer, A & Ha&eli, L (1966). Human pharmacology of hyosine butyl bromide. Lancet, 2, 418-421. Kaul, B, Petersen, H, Myrvold, HE, Grette, K & Roysland, P (1986) Hiatus hernia in gastro-oesophageal reflux disease. Scandinavian Journal of Gastroenterology, 21, 31-34. Kreel, L (1975). Pharmacoradiology in barium examination with special reference to glucagon. The British Journal of Radiology, 48, 691-703. Last, RJ (1979). Anatomy Regional and Applied, 7th Edition. pp. 240241. Churchill Livingstone, London. Liu, C (1974). Visualisation of oesophageal varices by Buscopan. American Journal of Roentgenology, 121, 232-233. Nagler, R & Spiro, HM (1963). Persistent gastro-oesophageal reflux induced during prolonged gastric intubation. New England Journal of Medicine, 269, 495-496. Novak, D (1975). Hypotonic oesophagography using propantheline bromide. Fortschritte auf dem Gebiete der R6ntgenstrahlen, 123, 409-414. Sutton, D (1987). A Text Book of Radiology and Imaging, 4th Edition, Vol 1. pp 794-795. Churchill Livingstone, London.
