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A comparative trial of two oral cholecystographic contrast media—iocetamic acid (Cholebrin) and iopanoic acid (Telepaque)
Olin-Racliol. (1979) 30, 45-48
A Comparative Trial of Two Oral Cholecystographic Contrast Media Iocetamic Acid (Cholebrin) and Iopanoic Acid (Telepaque) J. A. FIELDING and G. H. WHITEHOUSE
Department of Radiodiagnosis, University o f Liverpool A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measured in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media.
INTRODUCTION Whereas iopanoic acid (Telepaque)is a long-established and frequently used cholecystographic agent, iocetamic acid (Cholebrin) was introduced in Europe only 10 years ago and more recently in the United Kingdom. Previous evaluations in Europe and the United States have suggested that Cholebrin is an effective and safe cholecystographic contrast agent (Golberg, 1976; Hekster, 1968; Janbroers et al., 1969; Parks, 19"]4; Stanley et al., 1974; Wishart and Dotter, 1973). The aim of the present study is to assess and compare the side-effects, radiological efficiency and certain biochemical parameters of Cholebrin and Telepaque.
contrast medium with a further prone obliqueradiograph 20 min after a standard fatty meal. The patients answered a questionnaire under the supervision of a radiologist. The occurrence of various symptoms was elicited (Table 1) and patients were asked if they had any other symptoms which were not specifically listed on the questionnaire, and whether or not they were currently taking medication. The serum levels of creatinine, bilirubin, alkaline phosphatase and alanine aminotransferase were estimated in a random sample of 20 patients from Table 1 - Symptoms recorded after ingestion of Cholecystographic medium
Symptom METHOD
The trial involved 100 sequential patients on whom cholecystography had been requested by clinicians. Fifty patients were given 3g Cholebrin and 50 were given 3g Telepaque by a random and blind allocation. Each patient was allotted a number in the sequence from 1 to 100, and was given the corresponding unlabeUed packet of one or other cholecystographic medium. All patients were instructed to follow the same procedure. The evening meal before the radiological examination was fat free, and only water was allowed between this meal and the completion of the examination. A supine radiograph of the abdomen and erect and prone oblique radiographs of the right Upper quadrant were taken 14 h after ingestion of the
No. of patients Cholebrin
Telepaque
Vomiting Nausea Unusual taste in mouth Diarrhoea Abdominal pain Flatulence Dyspepsia Dysuria
2 13 5 8 10 10 4 0
2 9 3 26 16 15 3 0
Pruritus Skin rash Sensation of heat Dyspnoea Palpitations Chest pain Headache Dizziness
1 1 3 1 1 2 14 2
2 1 1 0 1 4 8 2
46
CLINICAL RADIOLOGY
each of the two groups at the time o f booking the cholecystogram, and were repeated at the time of the investigation which was usually in the next two days. Assessment o f radiographs was performed b y two radiologists in conjunction, without any knowledge of the patients or their allotted contrast medium. Gallstones and other biliary abnormalities were looked for on the preliminary radiograph which was taken at the time o f booking. Visualisation of the gallbladder and also its contraction after a fatty meal were qualitatively described on a four point system: absent, faint or slight, moderate and good. Subsequent delineation o f the common bile duct was categorised as absent, partial or total. A record was made of any abnormality depicted within the biliary system. Contrast medium within the bowel was regarded as being either slight, moderate or marked in amount, and as either granular or homogeneous in nature. RESULTS
Patients. Both the Cholebrin and Telepaque groups showed a predominance of women, and there was no statistical difference (X 2 test) in sex distribution between the groups (Table 2).
incidence of side effects was diarrhoea, which was substantially more common in the Telepaque group than in the Cholebrin group (P < 0.001). Radiologieal Assessment
Gallbladder Opacification (Table 3). When opacifi, cation of the gallbladder was estimated on a four, point scale, 66% o f Cholebrin cases and 70% of Telepaque cases were classified as 'good'. A ×2 test showed the difference in gaUbladder opacification to reach only a low level of significance (0.1 > P > 0 05) The incidence of failure to opacify was higher with Telepaque (20%) than with Cholebrin (8%). Gallbladder Contraction (Table 4). There was no statistically significant difference in degree of gall. bladder contraction between Cholebrin and Telepaque. Delineation o f the C o m m o n Bile D u c t (Table 5). Total delineation of the common bile occurred in 29% o f Telepaque cases and 17% o f Cholebrin cases. This difference is not statistically significant (P > 0.3). Contrast Medium in Intestine (Tables 6, 7). Only three patients (two with Cholebrin and one with Telepaque) had no visible contrast medium in the bowel. Only 8% of all patients showed 'marked'
Table 2 - Sex distribution
No. of cases
Cholebrin Telepaque Total
Male
Female
50 50
15 10
35 40
100
25
75
Table 3 - Visualisation of gallbladder
No. of eases Absent Faint
Cholebrin Telepaque Total
There was no significant difference between the two groups in the incidence of demonstrated biliary tract disease. The incidence of cholelithiasis detected by each cholecystography was the same in the two groups, namely 10%. S i d e - e f f e c t s ( T a b l e 1)
Gastrointestinal symptoms were frequent in b o t h groups. The patient was often referred for cholecystography because of a history of dyspepsia, flatulence, abdominal pain, nausea and vomiting. However, only appreciable worsening of these symptoms or their occurrence de novo was recorded in the assessment. Headache was another common symptom in b o t h groups. The two cases of skin rash comprised a transient urticaria_ Chest pain, complained of by six patients, did not symptomatically suggest ischaemic cardiac disease, but rather 'heartburn' in all cases. The only significant difference found in the
Moderate Good
50 50
4 10
2 2
11 3
33 35
100
14
4
14
68
X2 = 7.20; 0.1 >P>0,05, Table 4 - Contraction of gallbladder
No. of eases None
Slight
Moderate Good
Cholebrin 45 Telepaque 3 8
3 6
8 3
7 9
27 20
Total
9
11
16
47
83
x 2 = 5,16; 0.2 > P > 0 . 1 . Table 5 - Delineation of common bile duct
No. of cases None
Cholebrin Telepaque Total
Slight
Moderate Good
50 50
2 1
28 21
18 26
2 2
100
3
49
44
4
x 2 = 2.24; 0.5 >P>0.3,
COMPARATIVE
TRIAL
OF IOCETAMIC
Table 6 - Amount of contrast medium in bowel No. o f cases None Cholebrin Telepaque Total
Slight
Moderate
Marked
50 50
2 1
28 21
18 26
2 2
100
3
49
44
4
Table 7 - Appearance of contrast medium in bowel No. o f cases
Granular
Homogeneous
Mixed
Cholebrin Telepaque
48 49
5 15
39 22
4 2
Total
97
20
61
6
X2 = 10.81; 0.01 > P > O . 0 0 1 .
amounts, and there was no significant difference between the two groups regarding the quantity of contrast medium within the bowel. However, intestinal contrast medium had a predominantly homogeneous appearance in the Cholebrin group (0.017 > P > 0.001) compared to Telepaque.
Biochemical Tests In some cases there were Changes between the initial and final values of all the biochemical paranaeters, but there was never a large difference. In only one case was there a slight rise in serum creatinine above the normal level and this followed Cholebrin ingestion. The serum bilirubin level became slightly elevated after Cholebrin in two cases, and in two other instances the serum alkaline phosphatase rose a little above normal with the same contrast medium. The serum alanine aminotransferase was slightly elevated after Cholebrin in a further case. Two patients had a slight rise to above the normal level of alkaline phosphatase after Telepaque. Statistically significant correlations were not found between the degree of opacification of the gallbladder and of the common bile duct in patients with normal or initially raised serum creatinine, bilirubin, alkaline phosphatase and alanine aminotransferase. There were three patients who had raised alkaline phosphatase and poor gallbladder 0pacification, although this did not reach a level of significance because of the small number.
blSCUSSION This trial indicates that Cholebrin and Telepaque have very similar cholecystographic properties, which
ACID AND
IOPANOIC
ACID
47
is in agreement with other assessments (Hekster, 1968; Parks, 1974; Stanley et aL, 1974; Wishart and Dotter, 1973). Parks (1974) considered Cholebrin in a dose of 3g produced cholecystographic qualities equal to 4.5 g of the same agent, and was associated with a lower incidence of abdominal cramps, although Stanley et aL, (1974) considered the larger dose to be superior to the lesser amount. Unlike Telepaque, Michal et al. (1976) found that fractionated administration was less effective than a single dose of Cholebrin. Nausea, abdominal pain, flatulence, unusual taste and headache were common symptoms after both Cholebrin and Telepaque. One case of transient urticaria occurred with each contrast medium. Recently Janower and Hannon (1976) reported a 0.81% incidence of skin reactions associated with Cholebrin. There was a significantly lower incidence of diarrhoea with Cholebrin compared to Telepaque, an observation also made by Parks, Stanley, Hekster. Janbroers et al. (1969) have shown that 62% of a 3 g dose of Cholebrin and 21% of the same amount of Telepaque is eliminated in the urine in the first 48 h after ingestion. The remainder of both media is excreted via the intestinal tract. It has been postulated that this relatively increased renal excretion of Cholebrin accounts for the lower incidence of diarrhoea compared to Telepaque (Hekster, 1968). Although no difference in the amount of contrast medium in the bowel has been found in the present series and in previous studies (Hekster, 1968; Stanley et aL, 1974), it was noted in the present investigation that the enteric contrast medium was usually in a homogeneous form rather than a granular form. Natham and Newman (1973) in the case of Telepaque, have suggested that the homogeneous opacification indicates that conjugation has occurred and that the contrast medium has passed through the liver and bile ducts, the granular, particulate appearances being associated with unconjugated unabsorbed contrast medium. If this holds true for Cholebrin, the implication is that absorption of Cholebrin is better than Telepaque. It is also theoretically possible that conjugated oral cholecystographic media are less likely to provoke diarrhoea than unconjugated forms. Although small changes were seen between the initial and final values of liver function tests in the 40 patients randomly selected for investigation, none of the differences were of clinical or statistical significance. Janbroers et al. (1969) showed that the total serum bilirubin increased within 14h after the ingestion of Cholebrin. This was a transient fnding which had also been seen with other cholecystographic agents and was ascribed to enzyme
48
CLINICAL R A D I O L O G Y
c o m p e t i t i o n probably at the stage of conjugation. There was no significant change in serum creatinine levels, despite the high urinary excretion o f Cholebrin in a g r e e m e n t with the findings o f Janbroers et al. It is c o n c l u d e d that Cholebrin and T e l e p a q u e are c o m p a r a b l e contrast media in terms of radiographic efficiency, and in the incidence of side effects, e x c e p t for a lower incidence o f diarrhoea with Cholebrin. Acknowledgements. - We wish to thank Napp Laboratories for providing the contrast medium, and especially to Mr Q. R. Watts for his help. REFERENCES
Golberg, B. (1976). A comparison of iocetamic acid and sodium ipodate in cholecystography. Radiologia clinica, 46, 4 2 - 4 9 . Hekster, R. E. M. (1968), Results obtained in comparative radiographic, clinical and clinical-chemical studies in iocetamic acid (DRC 120) and iopanoic acid. Radiologia clinica et biologica, 37, 338-352.
Janbroers, J. M., Sanders, J. C., Til, H. P., Feron, V. J. & de Greet, A. P. (1969). Toxicologic and pharmacologic properties of iocetamic acid, a new oral cholecystographic agent. Toxicology and Applied Pharmacology, 14, 232~ 241. Janower, M. L. &Hannon, M. A_ (1976). Skin reactions with iocetamic acid. Radiology, 118,301. Michal, J. A-, Nelson, J. A. & Koehlet, P. R. (1976). The effect of fractionated administration of iocetamic acid (Cholebrin) on gallbladder visualisation. Radiology, 119, 537-538. Nathan, M. H. & Newman, A. (1973). Conjugated iopanoic acid (Telepaque) in the small bowel. Radiology, 109, 545-548. Parks, R. E. (1974). Double blind study of four oral cholecysto~xaphic preparations. Radiology, 112, 525 528. Stanley, R. J., Melson, G. L., Cubillo, E. & Hesker, A. E. (1974). A comparison of three cholecystographic agents. Radiology, 112, 513-517. Wishart, D. L. & Dotter, C. T. (1973). Comparison of the opacifying characteristics and pharmacological responses of iocetarnic acid (Cholebrin) a new oral cholecystographic agent, with sodium tyropanoate (Bilopaque). American Journal o f Roentgenology, 119,429-432.
A Comparative Trial of Two Oral Cholecystographic Contrast Media Iocetamic Acid (Cholebrin) and Iopanoic Acid (Telepaque) J. A. FIELDING and G. H. WHITEHOUSE
Department of Radiodiagnosis, University o f Liverpool A comparative trial was made between two oral cholecystographic agents, iocetamic acid (Cholebrin) and iopanoic acid (Telepaque), Fifty patients were given Cholebrin and another 50 were given Telepaque by random allocation. The cholecystographic qualities of the two contrast media showed no significant difference. It was noted that contrast medium within the bowel at the time of the investigation tended to be homogeneous rather than granular with Cholebrin, and the significance of this is discussed. Gastrointestinal side-effects were common with both contrast media, but there was a significantly lower incidence of diarrhoea with Cholebrin than with Telepaque. Various biochemical parameters of hepatic and renal function were measured in 40 random patients and showed no clinically significant alteration following ingestion of the contrast media.
INTRODUCTION Whereas iopanoic acid (Telepaque)is a long-established and frequently used cholecystographic agent, iocetamic acid (Cholebrin) was introduced in Europe only 10 years ago and more recently in the United Kingdom. Previous evaluations in Europe and the United States have suggested that Cholebrin is an effective and safe cholecystographic contrast agent (Golberg, 1976; Hekster, 1968; Janbroers et al., 1969; Parks, 19"]4; Stanley et al., 1974; Wishart and Dotter, 1973). The aim of the present study is to assess and compare the side-effects, radiological efficiency and certain biochemical parameters of Cholebrin and Telepaque.
contrast medium with a further prone obliqueradiograph 20 min after a standard fatty meal. The patients answered a questionnaire under the supervision of a radiologist. The occurrence of various symptoms was elicited (Table 1) and patients were asked if they had any other symptoms which were not specifically listed on the questionnaire, and whether or not they were currently taking medication. The serum levels of creatinine, bilirubin, alkaline phosphatase and alanine aminotransferase were estimated in a random sample of 20 patients from Table 1 - Symptoms recorded after ingestion of Cholecystographic medium
Symptom METHOD
The trial involved 100 sequential patients on whom cholecystography had been requested by clinicians. Fifty patients were given 3g Cholebrin and 50 were given 3g Telepaque by a random and blind allocation. Each patient was allotted a number in the sequence from 1 to 100, and was given the corresponding unlabeUed packet of one or other cholecystographic medium. All patients were instructed to follow the same procedure. The evening meal before the radiological examination was fat free, and only water was allowed between this meal and the completion of the examination. A supine radiograph of the abdomen and erect and prone oblique radiographs of the right Upper quadrant were taken 14 h after ingestion of the
No. of patients Cholebrin
Telepaque
Vomiting Nausea Unusual taste in mouth Diarrhoea Abdominal pain Flatulence Dyspepsia Dysuria
2 13 5 8 10 10 4 0
2 9 3 26 16 15 3 0
Pruritus Skin rash Sensation of heat Dyspnoea Palpitations Chest pain Headache Dizziness
1 1 3 1 1 2 14 2
2 1 1 0 1 4 8 2
46
CLINICAL RADIOLOGY
each of the two groups at the time o f booking the cholecystogram, and were repeated at the time of the investigation which was usually in the next two days. Assessment o f radiographs was performed b y two radiologists in conjunction, without any knowledge of the patients or their allotted contrast medium. Gallstones and other biliary abnormalities were looked for on the preliminary radiograph which was taken at the time o f booking. Visualisation of the gallbladder and also its contraction after a fatty meal were qualitatively described on a four point system: absent, faint or slight, moderate and good. Subsequent delineation o f the common bile duct was categorised as absent, partial or total. A record was made of any abnormality depicted within the biliary system. Contrast medium within the bowel was regarded as being either slight, moderate or marked in amount, and as either granular or homogeneous in nature. RESULTS
Patients. Both the Cholebrin and Telepaque groups showed a predominance of women, and there was no statistical difference (X 2 test) in sex distribution between the groups (Table 2).
incidence of side effects was diarrhoea, which was substantially more common in the Telepaque group than in the Cholebrin group (P < 0.001). Radiologieal Assessment
Gallbladder Opacification (Table 3). When opacifi, cation of the gallbladder was estimated on a four, point scale, 66% o f Cholebrin cases and 70% of Telepaque cases were classified as 'good'. A ×2 test showed the difference in gaUbladder opacification to reach only a low level of significance (0.1 > P > 0 05) The incidence of failure to opacify was higher with Telepaque (20%) than with Cholebrin (8%). Gallbladder Contraction (Table 4). There was no statistically significant difference in degree of gall. bladder contraction between Cholebrin and Telepaque. Delineation o f the C o m m o n Bile D u c t (Table 5). Total delineation of the common bile occurred in 29% o f Telepaque cases and 17% o f Cholebrin cases. This difference is not statistically significant (P > 0.3). Contrast Medium in Intestine (Tables 6, 7). Only three patients (two with Cholebrin and one with Telepaque) had no visible contrast medium in the bowel. Only 8% of all patients showed 'marked'
Table 2 - Sex distribution
No. of cases
Cholebrin Telepaque Total
Male
Female
50 50
15 10
35 40
100
25
75
Table 3 - Visualisation of gallbladder
No. of eases Absent Faint
Cholebrin Telepaque Total
There was no significant difference between the two groups in the incidence of demonstrated biliary tract disease. The incidence of cholelithiasis detected by each cholecystography was the same in the two groups, namely 10%. S i d e - e f f e c t s ( T a b l e 1)
Gastrointestinal symptoms were frequent in b o t h groups. The patient was often referred for cholecystography because of a history of dyspepsia, flatulence, abdominal pain, nausea and vomiting. However, only appreciable worsening of these symptoms or their occurrence de novo was recorded in the assessment. Headache was another common symptom in b o t h groups. The two cases of skin rash comprised a transient urticaria_ Chest pain, complained of by six patients, did not symptomatically suggest ischaemic cardiac disease, but rather 'heartburn' in all cases. The only significant difference found in the
Moderate Good
50 50
4 10
2 2
11 3
33 35
100
14
4
14
68
X2 = 7.20; 0.1 >P>0,05, Table 4 - Contraction of gallbladder
No. of eases None
Slight
Moderate Good
Cholebrin 45 Telepaque 3 8
3 6
8 3
7 9
27 20
Total
9
11
16
47
83
x 2 = 5,16; 0.2 > P > 0 . 1 . Table 5 - Delineation of common bile duct
No. of cases None
Cholebrin Telepaque Total
Slight
Moderate Good
50 50
2 1
28 21
18 26
2 2
100
3
49
44
4
x 2 = 2.24; 0.5 >P>0.3,
COMPARATIVE
TRIAL
OF IOCETAMIC
Table 6 - Amount of contrast medium in bowel No. o f cases None Cholebrin Telepaque Total
Slight
Moderate
Marked
50 50
2 1
28 21
18 26
2 2
100
3
49
44
4
Table 7 - Appearance of contrast medium in bowel No. o f cases
Granular
Homogeneous
Mixed
Cholebrin Telepaque
48 49
5 15
39 22
4 2
Total
97
20
61
6
X2 = 10.81; 0.01 > P > O . 0 0 1 .
amounts, and there was no significant difference between the two groups regarding the quantity of contrast medium within the bowel. However, intestinal contrast medium had a predominantly homogeneous appearance in the Cholebrin group (0.017 > P > 0.001) compared to Telepaque.
Biochemical Tests In some cases there were Changes between the initial and final values of all the biochemical paranaeters, but there was never a large difference. In only one case was there a slight rise in serum creatinine above the normal level and this followed Cholebrin ingestion. The serum bilirubin level became slightly elevated after Cholebrin in two cases, and in two other instances the serum alkaline phosphatase rose a little above normal with the same contrast medium. The serum alanine aminotransferase was slightly elevated after Cholebrin in a further case. Two patients had a slight rise to above the normal level of alkaline phosphatase after Telepaque. Statistically significant correlations were not found between the degree of opacification of the gallbladder and of the common bile duct in patients with normal or initially raised serum creatinine, bilirubin, alkaline phosphatase and alanine aminotransferase. There were three patients who had raised alkaline phosphatase and poor gallbladder 0pacification, although this did not reach a level of significance because of the small number.
blSCUSSION This trial indicates that Cholebrin and Telepaque have very similar cholecystographic properties, which
ACID AND
IOPANOIC
ACID
47
is in agreement with other assessments (Hekster, 1968; Parks, 1974; Stanley et aL, 1974; Wishart and Dotter, 1973). Parks (1974) considered Cholebrin in a dose of 3g produced cholecystographic qualities equal to 4.5 g of the same agent, and was associated with a lower incidence of abdominal cramps, although Stanley et aL, (1974) considered the larger dose to be superior to the lesser amount. Unlike Telepaque, Michal et al. (1976) found that fractionated administration was less effective than a single dose of Cholebrin. Nausea, abdominal pain, flatulence, unusual taste and headache were common symptoms after both Cholebrin and Telepaque. One case of transient urticaria occurred with each contrast medium. Recently Janower and Hannon (1976) reported a 0.81% incidence of skin reactions associated with Cholebrin. There was a significantly lower incidence of diarrhoea with Cholebrin compared to Telepaque, an observation also made by Parks, Stanley, Hekster. Janbroers et al. (1969) have shown that 62% of a 3 g dose of Cholebrin and 21% of the same amount of Telepaque is eliminated in the urine in the first 48 h after ingestion. The remainder of both media is excreted via the intestinal tract. It has been postulated that this relatively increased renal excretion of Cholebrin accounts for the lower incidence of diarrhoea compared to Telepaque (Hekster, 1968). Although no difference in the amount of contrast medium in the bowel has been found in the present series and in previous studies (Hekster, 1968; Stanley et aL, 1974), it was noted in the present investigation that the enteric contrast medium was usually in a homogeneous form rather than a granular form. Natham and Newman (1973) in the case of Telepaque, have suggested that the homogeneous opacification indicates that conjugation has occurred and that the contrast medium has passed through the liver and bile ducts, the granular, particulate appearances being associated with unconjugated unabsorbed contrast medium. If this holds true for Cholebrin, the implication is that absorption of Cholebrin is better than Telepaque. It is also theoretically possible that conjugated oral cholecystographic media are less likely to provoke diarrhoea than unconjugated forms. Although small changes were seen between the initial and final values of liver function tests in the 40 patients randomly selected for investigation, none of the differences were of clinical or statistical significance. Janbroers et al. (1969) showed that the total serum bilirubin increased within 14h after the ingestion of Cholebrin. This was a transient fnding which had also been seen with other cholecystographic agents and was ascribed to enzyme
48
CLINICAL R A D I O L O G Y
c o m p e t i t i o n probably at the stage of conjugation. There was no significant change in serum creatinine levels, despite the high urinary excretion o f Cholebrin in a g r e e m e n t with the findings o f Janbroers et al. It is c o n c l u d e d that Cholebrin and T e l e p a q u e are c o m p a r a b l e contrast media in terms of radiographic efficiency, and in the incidence of side effects, e x c e p t for a lower incidence o f diarrhoea with Cholebrin. Acknowledgements. - We wish to thank Napp Laboratories for providing the contrast medium, and especially to Mr Q. R. Watts for his help. REFERENCES
Golberg, B. (1976). A comparison of iocetamic acid and sodium ipodate in cholecystography. Radiologia clinica, 46, 4 2 - 4 9 . Hekster, R. E. M. (1968), Results obtained in comparative radiographic, clinical and clinical-chemical studies in iocetamic acid (DRC 120) and iopanoic acid. Radiologia clinica et biologica, 37, 338-352.
Janbroers, J. M., Sanders, J. C., Til, H. P., Feron, V. J. & de Greet, A. P. (1969). Toxicologic and pharmacologic properties of iocetamic acid, a new oral cholecystographic agent. Toxicology and Applied Pharmacology, 14, 232~ 241. Janower, M. L. &Hannon, M. A_ (1976). Skin reactions with iocetamic acid. Radiology, 118,301. Michal, J. A-, Nelson, J. A. & Koehlet, P. R. (1976). The effect of fractionated administration of iocetamic acid (Cholebrin) on gallbladder visualisation. Radiology, 119, 537-538. Nathan, M. H. & Newman, A. (1973). Conjugated iopanoic acid (Telepaque) in the small bowel. Radiology, 109, 545-548. Parks, R. E. (1974). Double blind study of four oral cholecysto~xaphic preparations. Radiology, 112, 525 528. Stanley, R. J., Melson, G. L., Cubillo, E. & Hesker, A. E. (1974). A comparison of three cholecystographic agents. Radiology, 112, 513-517. Wishart, D. L. & Dotter, C. T. (1973). Comparison of the opacifying characteristics and pharmacological responses of iocetarnic acid (Cholebrin) a new oral cholecystographic agent, with sodium tyropanoate (Bilopaque). American Journal o f Roentgenology, 119,429-432.