US3862301A - Glucagon as a diagnostic aid in gastrointestinal radiology - Google Patents
Glucagon as a diagnostic aid in gastrointestinal radiology Download PDFInfo
- Publication number
- US3862301A US3862301A US371105A US37110573A US3862301A US 3862301 A US3862301 A US 3862301A US 371105 A US371105 A US 371105A US 37110573 A US37110573 A US 37110573A US 3862301 A US3862301 A US 3862301A
- Authority
- US
- United States
- Prior art keywords
- glucagon
- barium
- duodenum
- gastrointestinal
- diagnostic aid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102000051325 Glucagon Human genes 0.000 title abstract description 20
- 108060003199 Glucagon Proteins 0.000 title abstract description 20
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 title abstract description 20
- 229960004666 glucagon Drugs 0.000 title abstract description 20
- 230000002496 gastric effect Effects 0.000 title description 3
- 229910052788 barium Inorganic materials 0.000 abstract description 14
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 abstract description 14
- 210000000056 organ Anatomy 0.000 abstract description 7
- 235000012054 meals Nutrition 0.000 abstract description 5
- 230000000968 intestinal effect Effects 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 210000001198 duodenum Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000012800 visualization Methods 0.000 description 10
- 210000002784 stomach Anatomy 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000002183 duodenal effect Effects 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- DHUZAAUGHUHIDS-ONEGZZNKSA-N Isomyristicin Chemical compound COC1=CC(\C=C\C)=CC2=C1OCO2 DHUZAAUGHUHIDS-ONEGZZNKSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229960005439 propantheline bromide Drugs 0.000 description 4
- 238000002601 radiography Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 229960002028 atropine sulfate Drugs 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 210000000990 duodenal loop Anatomy 0.000 description 2
- 238000002594 fluoroscopy Methods 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 1
- 101100264195 Caenorhabditis elegans app-1 gene Proteins 0.000 description 1
- 206010011953 Decreased activity Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010046542 Urinary hesitation Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0404—X-ray contrast preparations containing barium sulfate
Definitions
- the duodenum is intubated under fluoroscopic control' allowing for the direct introduction first of barium (as part of a barium meal) and then air into the duodenum.
- barium air contrast study of the duodenum can be thus obtained.
- An anticholinergic drug is customarily administered parenterally to the patient being examined to induce duodenal hypoactivity for the better visualization of this organ.
- Anticholinegic drugs which have been used include atropine, propantheline bromide. and other similar drugs. Unfortunately, because of the large doses that need to be used to produce the desired effect, the anticholinergic drugs are accompanied by the classical side effects common to these agents.
- Glucagon is a hormone which has been stated to in hibit gastrointestinal motility in human subjects according to Foa and Galansino, Chemistry and function in Health and Disease, (Charles C. Thomas, Springfield, Ill. 1962) and to Lawrence: Medical Clinics of North America 54:l83l9(), 1970. Its relaxing effect on the gallbladder during X-ray radiography has been described by Chernish, et al: Gastroenterology 62:1218, June 1972, and its effect in hypotonic duodenography was published in (iastroenterulogy 63:392, September 1972.
- This invention provides aprocess for improving the visualization of the intestinal tract by the use of X-ray radiography and fiuoroscopy which comprises administering to the patient glucagon in addition to an X-ray visualization medium prior to radiographic examination.
- the intestinal organs which can be better visualized by the concummitant use of glucagon andan X-ray visualization medium according to the process of this invention include the stomach, duodenal cap, duodenal loop. small bowel, and the colon.
- the X-ray visualization medium is a barium meal.
- a barium enema is given.
- glucagon nor saline had any effect on the barium coating of the duodenal mucosa. Slight side effects were reported in four of the 12 patients. The results indicate that glucagon administration under these conditions could induce sufficient hypotonicity and hypomotility of the duodenum to provide a reliable demonstration of duodenal anatomy with minimal side effects.
- glucagon (2 mg.) was compared to atropine sulfate (1 mg.) and to placebo in 12 asymptomatic subjects.
- glucagon (2 mg.) was compared to propantheline bromide (30 mg.) and to placebo in another group of 12 asymptomatic volunteers.
- the medications were given doubleblind and all subjects in each study received all drugs intramuscularly. Each subject was then given 1 cup of barium and the gastrointestinal tract observed fluoroscopically. After appropriate control films were obtained, medication was given. After medication administration, the stomach, duodenum, and small bowel were observed, both at and minutes. At 10 minutes the subject was given barium and solutions of b icarbonate and citric acid to produce gas in the stomach.
- Indicated films were obtained when sufficient gas and barium were present in the stomach and small bowel. At 30 minutes, the stomach and duodenal loop were observed and at minutes a final film was obtained. A judgment of tonicity was made by -a radiologist on the basis of the caliber and distensibility of the small bowel. The radiologist also determined whether examination of the upper gastrointestinal tract was enhanced by the medication and what effect, if any, the
- glucagon significantly (p 0.00l) decreased the tonicity and motility of the stomach, duodenum, and small bowel.
- glucagon was also significantly (p 0.05) more effective than either atropine sulfate or propantheline bromide.
- the duration of action of the drug was sufficient to allow the radiologist to complete his studies, yet the drug effects had dissipated by the time the subject left the X-ray department. Side effects of glucagon were minimal and were less than those reported following the use of propantheline bromide We claim:
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- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract
Glucagon is administered at the same time as a barium meal in order to facilitate X-ray examination of various intestinal organs.
Description
Unite States atent n91 Chernish et a1.
[ GLUCAGON AS A DIAGNOSTIC AID IN GASTROINTESTINAL RADIOLOGY v [76] Inventors: Stanley M. Chernish, 4403 Radnor Rd., Indianapolis, Ind. 46217; Roscoe E. Miller, 7400 W. 88th St., Indianapolis, Ind. 46278 [22] Filed: June 18, 1973 [21] App1.No.:371,105
[52] US. Cl 424/4, 128/2 R, 424/5,
. 424/177 [51] Int. Cl A6lk 27/08 [58] Field of Search 424/4, 177, 5; 128/2 R R [56] References Cited UNITED STATES PATENTS 3,592,185 7/1971 -Frei et a1. 424/4 X Jan. 21, 1975 Primary Examiner.lerome D. Goldberg 'Assistant Examiner-Vera C. Clarke Attorney, Agent, or Firm-James L. Rowe; Everet F. Smith [57] ABSTRACT Glucagon is administered at the same time as a barium meal in order to facilitate X-ray examination of various intestinal organs.
1 Claim, N0 Drawings GLUCAGON AS A DIAGNOSTIC AID IN GASTROINTESTINAL RADIOLOGY BACKG ROU N D OF INVENTION better visualization or delineation of pathologic condi-.
tions. For example, in hypotonic duodenography, the duodenum is intubated under fluoroscopic control' allowing for the direct introduction first of barium (as part of a barium meal) and then air into the duodenum. A barium air contrast study of the duodenum can be thus obtained. An anticholinergic drug is customarily administered parenterally to the patient being examined to induce duodenal hypoactivity for the better visualization of this organ. Anticholinegic drugs which have been used include atropine, propantheline bromide. and other similar drugs. Unfortunately, because of the large doses that need to be used to produce the desired effect, the anticholinergic drugs are accompanied by the classical side effects common to these agents. These side effects include urinary hesitancy and retention. dryness of the mouth and throat, nasal pharyngeal irritation, blurring of near vision, tachycardia, headache. and general malaise. With X-ray radiography of other organs such as the stomach, small bowel, and colon. it has also been customary to use an agent which would relax the organ during the procedure.
Glucagon is a hormone which has been stated to in hibit gastrointestinal motility in human subjects according to Foa and Galansino, Chemistry and function in Health and Disease, (Charles C. Thomas, Springfield, Ill. 1962) and to Lawrence: Medical Clinics of North America 54:l83l9(), 1970. Its relaxing effect on the gallbladder during X-ray radiography has been described by Chernish, et al: Gastroenterology 62:1218, June 1972, and its effect in hypotonic duodenography was published in (iastroenterulogy 63:392, September 1972. It is an object of this invention to provide a method for conducting X-ray radiography and fluoroscopy of various intestinal organs in which a relaxant free from undesirable side effects is used in conjunction with an X-ray visualization medium in order to obtain better visualization of the gastrointestinal tract.
SUMMARY OF THIS INVENTION This invention provides aprocess for improving the visualization of the intestinal tract by the use of X-ray radiography and fiuoroscopy which comprises administering to the patient glucagon in addition to an X-ray visualization medium prior to radiographic examination. The intestinal organs which can be better visualized by the concummitant use of glucagon andan X-ray visualization medium according to the process of this invention include the stomach, duodenal cap, duodenal loop. small bowel, and the colon. For a visualization of the stomach, duodenum, and small bowel the X-ray visualization medium is a barium meal. For colon studies, a barium enema is given.
A particularly valuable use of the processof this invention is in connection with hypotonic duodenography. The use of glucagon as a relaxant of the intestinal tract in this radiographic procedure is illustrated by the following example.
In a double-blind study, 12 healthy males ranging in age from 21 to 31 years were given either 2 ml. of normal saline or 2 mg. of glucagon intravenously. Drugs were coded numerically in consecutive order so that the radiologist had no indication of the medication that was given. On the day of the test, after a light liquid breakfast, no other fluids or smoking was allowed. In the early afternoon, each subject was given /2 to 1 cup of a barium meal and the duodenum was observed fluoroscopically. Medication was then administered (either saline or glucagon) by the intravenous route and the duodenum in each subject was observed for short periods at 1-2 minute intervals for l minutes. At
this point each subject was given one teaspoonful each of sodium bicarbonate and citric acid 'to produce CO gas in the stomach. When sufficient gas and barium were present in the duodenum as indicated by fluoroscopy, X-ray films were obtained. At the completion of this study, preand post-medication films were reviewed and compared. The results of this study indicated that glucagon produced a highly significant (p 0.00l) decrease in duodenal motility and tonicity when compared with placebo. There was also a significant response and a significant enhancement of the radiologists ability to examine the duodenum'by gascontrast after administration of glucagon as compared with administration of normal saline. Neither glucagon nor saline had any effect on the barium coating of the duodenal mucosa. Slight side effects were reported in four of the 12 patients. The results indicate that glucagon administration under these conditions could induce sufficient hypotonicity and hypomotility of the duodenum to provide a reliable demonstration of duodenal anatomy with minimal side effects.
In another similar study, Study I, glucagon (2 mg.) was compared to atropine sulfate (1 mg.) and to placebo in 12 asymptomatic subjects. In Study II, glucagon (2 mg.) was compared to propantheline bromide (30 mg.) and to placebo in another group of 12 asymptomatic volunteers. The medications were given doubleblind and all subjects in each study received all drugs intramuscularly. Each subject was then given 1 cup of barium and the gastrointestinal tract observed fluoroscopically. After appropriate control films were obtained, medication was given. After medication administration, the stomach, duodenum, and small bowel were observed, both at and minutes. At 10 minutes the subject was given barium and solutions of b icarbonate and citric acid to produce gas in the stomach. Indicated films were obtained when sufficient gas and barium were present in the stomach and small bowel. At 30 minutes, the stomach and duodenal loop were observed and at minutes a final film was obtained. A judgment of tonicity was made by -a radiologist on the basis of the caliber and distensibility of the small bowel. The radiologist also determined whether examination of the upper gastrointestinal tract was enhanced by the medication and what effect, if any, the
drug had on the barium coating of the gut.
The results indicated that, when compared to placebo, at 10 and 30 minutes, glucagon significantly (p 0.00l) decreased the tonicity and motility of the stomach, duodenum, and small bowel. At 10 minutes, glucagon was also significantly (p 0.05) more effective than either atropine sulfate or propantheline bromide. The duration of action of the drug was sufficient to allow the radiologist to complete his studies, yet the drug effects had dissipated by the time the subject left the X-ray department. Side effects of glucagon were minimal and were less than those reported following the use of propantheline bromide We claim:
1. The process of enhancing the visualization of the UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PATENT NO. 5,852,301
|NVENT0R(S) 1 Stanley M. Uierirlsh, Roscoe I"... Milli-31 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
On she Title e column one recedin item [22], insert [T5] Assignae: Eli Lilly and Company Indianapolis, Indiana- (SEAL) Attest:
C. MARSHALL DANN Commissioner of Patents RUTH C. MASON and Trademarks Attesting Officer
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US371105A US3862301A (en) | 1973-06-18 | 1973-06-18 | Glucagon as a diagnostic aid in gastrointestinal radiology |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US371105A US3862301A (en) | 1973-06-18 | 1973-06-18 | Glucagon as a diagnostic aid in gastrointestinal radiology |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3862301A true US3862301A (en) | 1975-01-21 |
Family
ID=23462495
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US371105A Expired - Lifetime US3862301A (en) | 1973-06-18 | 1973-06-18 | Glucagon as a diagnostic aid in gastrointestinal radiology |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3862301A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984004888A1 (en) * | 1983-06-09 | 1984-12-20 | Field Group Chemicals | Radiopaque medium |
| WO1998005351A1 (en) * | 1996-08-08 | 1998-02-12 | Amylin Pharmaceuticals, Inc. | Methods for regulating gastrointestinal motility |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3592185A (en) * | 1967-04-18 | 1971-07-13 | Yeda Res & Dev | Ferromagnetic contrast media and method of use |
| US3705140A (en) * | 1967-10-05 | 1972-12-05 | Luigi Bernardi | Peptides related to the c-terminal sequence of cck-pz and caerulein |
| US3773744A (en) * | 1971-04-05 | 1973-11-20 | Lilly Co Eli | Nitroglucagons and process for their preparation |
-
1973
- 1973-06-18 US US371105A patent/US3862301A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3592185A (en) * | 1967-04-18 | 1971-07-13 | Yeda Res & Dev | Ferromagnetic contrast media and method of use |
| US3705140A (en) * | 1967-10-05 | 1972-12-05 | Luigi Bernardi | Peptides related to the c-terminal sequence of cck-pz and caerulein |
| US3773744A (en) * | 1971-04-05 | 1973-11-20 | Lilly Co Eli | Nitroglucagons and process for their preparation |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984004888A1 (en) * | 1983-06-09 | 1984-12-20 | Field Group Chemicals | Radiopaque medium |
| WO1998005351A1 (en) * | 1996-08-08 | 1998-02-12 | Amylin Pharmaceuticals, Inc. | Methods for regulating gastrointestinal motility |
| US6858576B1 (en) * | 1996-08-08 | 2005-02-22 | Amylin Pharmaceuticals, Inc. | Methods for regulating gastrointestinal motility |
| US7521423B2 (en) | 1996-08-08 | 2009-04-21 | Amylin Pharmaceuticals, Inc. | Exendin pharmaceutical compositions |
| US20090163423A1 (en) * | 1996-08-08 | 2009-06-25 | Amylin Pharmaceuticals, Inc. | Exendins and Exendin Agonist Analogs to Regulate Gastrointestinal Motility |
| US8026210B2 (en) | 1996-08-08 | 2011-09-27 | Amylin Pharmaceuticals, Inc. | Exendins and exendin agonist analogs to regulate gastrointestinal motility |
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