Influence of Musa sapientum L. on pharmacokinetic of metformin in diabetic gastroparesis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Musa sapientum L. (MS) bark juice in diabetic gastroparesis and its effect on pharmacokinetic of metformin (MET).</p><p><b>METHODS</b>Diabetes was induced in rats by administering alloxan (120 mg/kg) saline solution and maintained for 8 week. All the 18 Sprague-Dawley rats were divided into three groups (n =6 in each group): normal control, diabetic control and MS bark juice. Assessment of diabetes was done by glucose oxidase-peroxidase method on the 3rd day of alloxan administration. The effects of MS bark juice (100 mL/kg) on gastric emptying time, intestinal transit time, contractility of fundus and pylorus as well as gastric acid secretion in chronic diabetic rats were observed after 8 weeks of alloxan administration. The effect of MS bark juice on the pharmacokinetic of orally administered single dose of MET (350 mg/kg) was evaluated on the 57th day of protocol. Any drugs that may reduce the blood glucose level or influence the fibrinolytic system were not used in this study.</p><p><b>RESULTS</b>The MS bark juice significantly reduced the blood glucose level in the diabetic rats (P<0.01). There was significant decrease in the pylorus motility and increase in the gastric emptying time, intestinal transit time, contractility of fundus, gastric acid secretion in the MS bark juice treated group (P<0.01). There was significant decrease in the time at which drug at a maximum concentration, half life of drug and increase in the maximum concentration of drug in the plasma of MET in MS bark juice treated group as compared to diabetic control group (P<0.01).</p><p><b>CONCLUSION</b>MS bark juice effectively manages diabetic gastroparesis and thereby improves the bioavailabilty of MET when administered with MS bark juice.</p>

Comparison of the Results in Gastric Carcinoma Patients undergoing Billroth I and Billroth II Gastrectomiesy

PURPOSE: The proper reconstruction technique to use after a distal subtotal gastrectomy for a gastric carcinoma, there has been a subject for debated what is the proper reconstruction technique. The aim of this study was to compare the gastric- emptying time and the quality of life following both B-I and B-II reconstructions after a distal gastrectomy for a gastric adenocarcinoma. MATERIALS AND METHODS: We studied 122 patients who had undergone a distal gastrectomy for a gastric adenocarcinoma between June 1999 and July 2002 at our hospital. 51 patients underwent B-I group, and 71 patients underwent B-II group. To evaluate the gastric-emptying time, we analyzed the T1/2 time by means of radionuclide scintigraphy using a gamma camera after ingestion of an (99m)Tc-tin-colloid steamed egg. The nutritional status was measured by the weight change. Postgastrectomy syndrome was evaluated using an abdominal symptoms survey. Dumping syndrome was measured using the Sigstad dumping score. RESULTS: The gastric-emptying time was somewhat delayed in the B-I group after a 6 month period, but there was no difference after 12 months between the two groups. There was less weight loss in the B-I group than in the B-II group (P=0.023). Fewer abdominal symptoms were occurred in the B-I group than in the B-II group. Dumping syndrome occurred less frequently in the B-I group than in the B-II group (P=0.013). CONCLUSION: In our study, the Billroth I reconstruction led to less weight loss, a better nutritional status, and a better quality of life than the Billroth II reconstruction. We concluded that after a distal subtotal gastrectomy, the Billroth I reconstruction would be considered when the procedure is oncologically suitable.

Gastric Emptying Time in Patients with Liver Cirrhosis / 대한소화관운동학회지

BACKGROUND/AIMS: Changes in gastric motility in patients with liver cirrhosis is not yet established in South Korea. In this study changes in gastric emptying time with attention to factors that effect this change in patients with liver cirrhosis were investigated. METHODS: Fifteen patients with liver cirrhosis (11 males and 4 females) and 15 healthy controls (11 males and 4 females) were enrolled in this study. Gastric emptying time was measured by gastric scintigraphy using a dual-head gamma camera after ingestion of the mixture of 99mTc-labeled egg and fried rice (754Kcal). Data acquisition was performed for 120 minutes with 15 minutes interval and geometric mean and decay correction were calculated for gastric emptying time. RESULTS: There were no differences in age and sex between the two groups. The half time of soild gastric emptying was 78.0+/-87.0 minutes and 70.2+/-2.8 minutes for liver cirrhosis and healthy control group, respectively (p>0.05). The level of serum cholesterol was statistically correlated with gastric emptying time (B=-0.165, p<0.01). CONCLUSIONS: There was no significant difference in gastric emptying time between liver cirrhosis and healthy control group.

The Study of Manometry and Gastric Emptying Time in Patients after Esophagectomy / 대한소화관운동학회지

BACKGROUND/AIMS: Resection of the esophagus for malignant disease or a benign stenosis, has a choice not only of palliative surgery, but also of replacement of the esophagus with a transposed stomach, jejunum, or colon. The first-line method is replacement with a tubulized stomach. The purpose of this study was to investigate the association of esophageal motor dysfunction and gastric emptying time with symptoms after esophagectomy. METHODS: We performed the esophageal manometry and gastric emptying time after esophagectomy for esophageal cancer in 12 patients and for benign esophageal disease in 2 patients. RESULTS: In manometric studies, a zone of high pressure in the esophago-gastric anastomosis distal to the upper esophageal sphincter was associated with symptoms after esophagectomy. The gastric emptying rate was slowed in 7 out of 14 patients, but not associated with symptoms after esophagectomy. CONCLUSIONS: Our data suggest that a high-pressure zone distal to the upper esophageal sphincter was associated with symptoms after esophagectomy in manometric study. The gastric emptying rate was not associated with postoperative symptoms.

Gastric-Emptying Patterns after Gastroduodenal Reconstruction Preservation of the truncal vagus nerve

PURPOSE: Gastric emptying after a gastric resection has been studied in early gastric cancer. Most reports are retrospective and show that gastric emptying after gastroduodenal reconstruction is faster than normal. This study was designed to evaluate the gastric-emptying pattern after a gastroduodenal reconstruction with preservation of the truncal vagus nerve had been performed on a patient whose preoperative gastric-emptying time had been normal. METHODS: From July 1996 to February 1998, we performed a distal gastrectomy with gastroduodenal reconstruction with preservation of the truncal vagus nerve in 11 patients (9 patients with early gastric cancer, 1 patient with advanced gastric cancer, and 1 patient with high-grade dysplasia) whose preoperative gastric-emptying times was normal. To evaluate the gastric emptying after the gastrectomy and gastroduodenal reconstruction, we analyzed the lag time (when 10% of food is delivered to the duodenum), T1/2 (when 50% of food is delivered to the duodenum), and the residual food in the stomach after 100 minutes (%) by means of radionuclide scintigraphy using a single-head gamma camera after ingestion of an 99mTc-tin-colloid steamed egg. We defined the delayed gastric emptying as T1/2 longer than the mean of the preoperative value by 2 standard deviation. RESULTS: Among the 11 patients with gastroduodenal reconstruction, gastric emptying was normal in 4 patients and delayed in 7 patients; only one of the delayed cases has GI symptoms such as early satiety. There were no rapid gastric emptying cases. CONCLUSION: Rapid gastric emptying after gastroduodenal recon struction with preservation of the truncal vagus nerve was rare.

Ultrasonic Assessment of Gastric Emptying According to Feeding Types and Postprandial Postures / 대한소아소화기영양학회지

PURPOSE: Regurgitation, vomiting and feeding intolerance are frequent in the neonates. Esophageal function and gastric peristalsis are not fully developed in the neonates, so we should give attention to reduce the incidence of regurgitation and vomiting after feeding. It is necessary to shorten the gastric emptying by change of feeding types and postprandial postures. Gastric emptying time was measured by ultrasound in the neonates to evaluate the effect of feeding types and postprandial postures. METHOD: We measured gastric antral cross sectional area along the abdominal aorta at the level of the superior mesenteric artery in longitudinal section at NPO state (4 hours after feeding), 0 and every 30 min. after feeding until the value goes below or back to the NPO state. Fifteen neonates were examined in each breast-fed and formula-fed group in supine position. Eighteen and 15 neonates were examined in supine and prone posture after formula feeding, respectively. We used 5 MHz convex prove with Aloka Echo Camera SSD-650. RESULT: 1) Gastric emptying time of breast-fed infants was 76.0+/-20.02 min. which was significantly shorter than 96.0+/-20.28 min. of formula-fed infants. 2) Gastric emptying time on postprandial prone posture was 85.0+/-22.43 min. which was not significantly different from 96.0+/-20.28 min. on postprandial supine posture. CONCLUSION: Breast feeding is strongly recommended to the neonates to shorten gastric emptying time. So we can expect to reduce the incidence of regurgitation, vomiting and feeding intolerance. The postprandial posture depends on the traditional trend which is safe and comfortable to the mothers.

Changes of the Gastric Motility after Pylorus Preserving Pancreaticoduodenectomy

BACKGROUND: To evaluate delayed gastric emptying after a pylorus-preserving pancreaticoduodenectomy, we studied gastric motility in 11 normal volunteers and 11 patients who had undergone a pylorus-preserving pancreaticoduodenectomy. Additionally, the 24 hour esophageal Ph recordings were examined to evaluate gastroesophageal reflux after a pylorus-preserving pancreaticoduodenectomy. METHODS: Gastric motility was evaluated by using the gastric-emptying time and electrogastrograms. The gastric-emptying time was measured using a solid meal containing 99mTc-tin colloid. The half gastric-emptying time (GET1/2) was defined as the half time (T1/2) of the fall of gastric isotopic activity from the peak. Electrogastrogram (EGG) signals were detected from the surface electrodes on the skin overlying the gastric antrum. The 24-hour esophageal Ph was monitored by using a nasoesophageal probe placed in the distal esophagus 5 cm above the lower esophageal sphincter. RESULTS: In our study, the normal volunteers showed a 99+/-35 minute half gastric-emptying time. The patients were divided into two groups by a time of 2 months after the operation, early and late postoperative groups. Delayed gastric emptying after a pylorus-preserving pancreaticoduodenectomy in the early postoperative period (272+/-176 minutes) was normalized in the late period (106+/-37 minutes), p=0.020. Abnormal early EGG patterns also normalized in the late postoperative period. There was no significant difference of total Ph<4-time % between patients in the early (0.1+/-0.1%) and the late postoperative periods (0.4+/-0.4%), p=0.064. CONCLUSIONS: It is supposed that anatomical and functional preservation of the stomach and the proximal part of the duodenum after a pylorus-preserving pancreaticoduodenectomy enabled gastric motor activity to be normal in the late postoperative period.

Relationship of Recurrent Abdominal Pain Syndrome and Gastric Emptying Time

PURPOSE: Recurrent abdominal pain syndrome (RAPS) is not uncommon in school-aged children, but the etiology and pathogenesis are not understood well. But recent studies suggest that motility disorder makes up a majority of the pathogenesis. The aim of this study was to investigate gastric emptying time (GET) which is a method to evaluate gastrointestinal motility in patients with recurrent abdominal pain syndrome. METHODS: Radionuclide GET was investigated in 34 patients who visited the Department of Pediatrics, Pusan National University Hospital due to recurrent abdominal pain from January 1996 to June 1997. After 8 hours of fasting, the patient received two pieces of toast and a fried egg tagged with 2 mci of 99mTc albumin colloid and sequential counting was accomplished. We calculated the geometric mean of two counts measured from AP-PA scans and investigated 60 minutes of intragastric radionuclide retention rate. RESULTS: A total of 34 patients (12 boys, 22 girls, M : F=1 : 1.8) participated in this study. The age ranged from 5 to 12 years and the mean age was 8.8 years. Associated symptoms were headache (7 patients), nausea (7 patients), constipation (2 patients), vomiting (1 patient), and diarrhea (1 patient). Anti-Helicobacter pylori IgG Ab was positive in 4 cases. Endoscopic gastritis was found in 6 cases. The mean of 60 minutes of intragastric radionuclide retention rate was 72 +/- 17% and 27 cases (79%) were delayed significantly. CONCLUSION: The results of our study suggest that delayed gastric emptying time is a cause of abdominal pain in patients with recurrent abdominal pain syndrome.

Comparison of the Differences of Gastric Emptying Time After Upper Gastrointestinal Surgeries Using the Acetaminophen Method

Gastric emptying in patients after several upper gastrointestinal surgeries was studied using the acetaminophen method. The subjects consisted of 23 gastric cancer patients, 2 duodenal ulcer patients, 5 periampullary cancer patients and 4 normal subjects. As an indicator of the gastric emptying rate, the serum acetaminophen concentration was measured by fluorescence polarization immunoassay, in units of g/ml, at 0, 30, 60, 120, and 180 minutes after ingestion of a liquid meal with 1.5 g of acetaminophen. In the normal subjects, the acetaminophen concentrations were 0, 16.35+/-5.06, 18.71+/-5.58, 16.38+/-4.82, and 11.09+/-3.62 g/ml at time 0, 30, 60, 120, and 180 min, respectively. The concentration peaked at 60 min after ingestion of the test meal in the normal subjects. We observed significant delayed gastric emptying after pancreas preserving pancreaticoduodenectomy (PPPD) and a standard Whipple's operation in the early postoperative period. In all patients with a subtotal gastrectomy, a truncal vagotomy was done. However, in patients with a pancreaticoduodenectomy, the vagus nerves were preserved. The gastric emptying pattern was different between the patients with a subtotal gastrectomy and the patients with a pancreaticoduodenectomy, despite similar reconstructions of the gastroenterostomy (Billroth I or Billroth II type reconstruction). There was more rapid gastric emptying in patients with a truncal vagotomy and pyloroplasty than in the normal subjects. Hence, we speculate that the truncal vagotomy was the main cause of the different gastric emptying between the patients with a pancreaticoduodenectomy and the patients with a subtotal gastrectomy.

The Effect of Dialysate Dwelling on Gastric Emptying Time in Patients with Continuous Ambulatory Peritoneal Dialysis (CAPD) / 대한신장학회잡지

We evaluated gastric emptying time (GET) by using Tc99m-sulfur colloid gastric emptying scintigraphy in 11 patients with CAPD (6 male, 5 female) and 14 healthy volunteers. We investigated the effect of dialysate dwelling on GET by studying twice, once without dialysate in the abdomen (drained) and once with 2 L of dialysate in the abdomen (full), and the relationship between body surface area (BSA) and delayed gastric emptying. 1) The mean of gastric emptying rate in 120 minute in patients with CAPD when drained (67.8+/-13.4%) was not different from that in healthy volunteers (65.4+/-8.6%) 2) The mean of gastric emptying rate in 120 minute when full (55.6+/-14.6%) was significantly lower than that when drained (67.8+/-13.4%) (P<0.05). In four of the 11 patients (36.4%), gastric emptying was extremely delayed from normal to abnormal range when full. 3) The BSA (1.5+/-0.11m2)of patients who had extremely delayed GET from normal to abnormal range was smaller than that (1.74+/-0.22m2) of patients who had minimal delayed or unchanged GET when full. This study showed the patient with CAPD had normal gastric emptying when drained, and that gastric emptying was delayed by dialysate dwelling, especially in the patients who has less than 1.5m2 of body surface area. Therefore, we suggest that intermittent nocturnal peritoneal dialysis or a small volume of dialysate may be considered for the patient with small body surface area based on the adequacy.

Abnormal Electrogastrography and Gastric Emptying Time in Patients with Cyclic Vomiting Syndrome during Symptom Free Interval

PURPOSE: Cyclic vomiting syndrome is characterized by repeated, unpredictable, explosive and unexplained bouts of vomiting and recur after intervals of uncertain length. In the absence of either known etiology or pathogenesis, deciphering the mystery of cyclic vomiting syndrome presents us with a daunting clinical challenge. As we seek to understand this mysterious vomiting disorder of unknown etiology and pathogenic mechanism, we perfomed electrogastrography (EGG) and measured radionuclide gastric emptying time and compared the data with that of control. METHODS: Total 13 patients with cyclic vomiting (ages from 1 yr 6 m to 13 yr 3 m : mean 7 yr 2 m ) and 9 normal controls (ages from to 1 yr 8 m to 13 y 4 m, mean; 7 y 6 m) were enrolled in this study. Among them 16 children (9 patients and 7 controls) undertook gastric emptying time and 13 children (7 patients and 5 controls) undertook EGG. EGG : after midnight NPO, total 3 triplet of electrodes (two for the recoding of gastric electricity along the antral axis, and the other one for references) were used. After 1 hour recording of EGG we analysed the dominant frequencies. Gastric emptying: gastric emptying was evaluated by a radiolabeled (1mCi [99mTc] sulfur colloid incorporated into egg albumin) solid phase meal after an overnight fast of at least 8 hr. Radioisotope counts were obtained immediately after ingestion and continued for 10-min intervals for 120 min. The half emptying time (T1/2) and percent gastric residual at 2 hr were calculated. RESULTS: EGG: the dominant frequencies were significanlty different between case and control group (p=0.005, median values; 4.1 Hz and 3.1 Hz in case group and control group respectively ). Gastric emptying time: the gastic emptying rates at 120 min were 53.1+/-16% and 66.9+/-7.0% in patients and control groups respectively, which showed the gastric emptying was significantly delayed in patient groups (p=0.042) CONCLUSIONS: With the results of our study, we felt that the patients with cyclic vomiting has a some sort of motility disorders, like as a variant of chronic idiopathic intestinal pseudoobstruction or gastroparesis. But further sophisticated designed studies are needed to confirm this.

The Effect of PPG on Reducing Postgastrectomy Syndrome

A Radical gastrectomy can affect the dumping syndrome, reflux gastritis, injury of the autonomic nervous system and the small capacity syndrome and can cause some problems in the quality of life for post-gastrectomy patients. To minimize these complications in the treatment of early gastric cancer (EGC), various gastric-reduced operations have been discussed by gastric surgeons. A pylorus preserving gastrectomy (PPG) is a kind of reduced-gastric operation which preserves the distal portion (1.5 cm) of the gastric antrum and reduces postoperative complications such as the dumping syndrome and reflux esophagitis. However, a limitation of this operation is that complete lymph node dissection of the suprapyloric lymph node is undesirable for preservation of the pyloric branch of the vagus nerve. Nowadays, some reports state that this operation may be applicable in EGC confined to the mucosa and located at the gastric mid-body. (Purpose) This study was designed to evaluate the gastric function after PPG by using solid foods to obtain the gastric emptying time. (Materials and Method) From June 1995 to December 1995, we performed PPGs on 7 patients (4 patients with mucosal cancer, 2 patients with gastric ulcer and 1 patient with a leiomyoma) and Billroth I reconstruction in 7 patients (5 patients with mucosal cancer, 1 patient with advanced gastric cancer and 1 patient with gastric ulcer). To compare the gastric function between these two subgroups, we analyzed the lag time, T1/2 and the residual food after 100 min using 99mTc-tin-colloid-steamed eggs to obtain the gastric emptying time for the PPG group (n=7), the Billroth I reconstruction group (n=7), and the normal control group (n=7). A statistical analysis was done by using the Kruskal-Wallis test (Chi-square approximation). (Results) There were no differences in the amount of transfusion, the hospital stay, the operation time, and the body weight loss after operation between the PPG group and the Billroth I reconstruction group. The severe dumping syndrome and reflux esophagitis were found in one of the patients after Billroth I reconstruction, but were not found in PPG group. Statistically, there was no difference in T1/2 between the Billroth I reconstruction group and the PPG group; however, both lag times were longer than that of the normal control group. We also found that the residual food 100 min after oral intake was greater in both the Billroth I reconstruction and the PPG groups than in the normal control group. (Conclusion) Though both PPG and Billroth I reconstruction showed delayed gastric emptying, we found that PPG is superior to Billroth I reconstruction in lag time and in the amount of residual food after 100 min. We conclude that PPG is superior to Billroth I reconstruction in gastric motility, and if this operation is applied in indicated gastric cancer patients, post-operative complications, such as the dumping syndrome and reflux esophagitis can be reduced and the quality of life in post-gastrectomy patients can be increased.

Clinical Significance of Gastroptosis / 대한내과학회지

OBJECTIVES: Gastroptosis is defined as a condition in which the gastric angel is located below the interiliac line in standing position in the UGI barium study. The present study was designed to evaluate its prevalence, relation to clinical symptoms, body weight and gastric emptying time. METHODS: Two hundred-twenty seven consecutive subjects undertaken a UGI barium study for general check-up. We analyzed age, sex distribution, body weight percentile according to ideal body weight, and clinical manifestations. Gastric emptying scan was performed with a semi-solid test meal (2mCi of labeled (99m)Tc-suifur colloid-scrambled egg) on 12 healthy, asymptomatic subjects and 17 patients with gastroptosis. RESULTS: Twenty-one (9.3%) of the 227 subjects had gastroptosis. The ratio of male to female was 1 to 4.57. In age, three (16.7%) of the patients were below the age 40, 14(8.9%) were between 40 to 49, 4(7.8%) were above 50. According to the percentile of ideal body weight, 4(8.6%) of the 14 subjects were under the 90 percentile, 15(12.6%) of the 179 subjects were between 90 to 110 percentile, and 2(0.02%) of the 94 were above 110 percentile, which significantly higher in that of under 110 percentile of ideal body weight. The symptoms, which were complained in 8 of the 21 patients, were epigastric discomfort, belching, hunger pain, constipation, and nausea. The mean gastric emptying time (T1/2) was 69.8min and 92.6min in control and gastroptosis group, respectively. T1/2 was delayed in 7(63.6%) patients with symptomatic gastroptosis and 1 control. CONCLUSION: The gastroptosis was more common in female and lower body weight group and had a tendency of delay in T1/2z. We consider that gastroptosis may be one of the possible cause of non-ulcer dyspepsia in Korea.

Study of Gastric Emptying and Orocecal Transit in Patients with Dysmotility like Functional Dyspepsia(DLFD) / 대한내과학회지

OBJECTIVES: Although DLFD is the most common subtype of functional dyspepsia in the Orient including Korea, previous studies on gastric emptying in DLFD patients are inconclusive and reports on small bowel transit in these patients are uncommon. This study is to evaluate the occurrence of delayed gastric emptying(GET) and orocecal transit time(OCTT) in DLFD patients.' METHODS: 98 DLFD patients without organic disease including diabetes (M:F=23:75, Mean Age=43.1(23-69)) and 67 normal subjects (20 for GET and 47 for OCTT, Mean Age=39.9(25-69)) without gastrointestinal problems were recruited. Solid phase gastric emptying was assessed by radionuclide scintigraphy using ADAC dual head gamma camera after ingestion of 99mTc labeled 425 calorie solid meal. OCTT was determined by the measuring exhaled hydrogen every 10 minutes for 3 hours after ingestion of 60.5 calorie potato soap with 20gm lactulose. OCTT was defined by the time interval between test meal to sustained increase in exhaled breath hydrogen by 10ppm above baseline. A delayed GET was defined as T1/2 above the mean value plus 1 SD of controls (74.6 +/- 17.6 min, M +/- SD) and a delayed OCTT as time exceeding the mean value plus 2 SD(81.9 +/- 13.3 min, MSD). RESULTS: Among the 98 DLFD patients, only 7(7.1%) patients had a delayed GET(66.04 +/- 16.1 min vs 74.6 +/- 17.6 min, p=0.14) while a delayed OCTT was found in 36(36.7%) patients(100 +/- 32.9 min vs 81.9 +/- 13.3 min, p<0.01) and 3(3.1%) had both delayed GET and OCTT. CONCLUSION: Delayed OCTT was more frequently observed than delayed GET which was not significant comparing to wide ranged controls. Small bowel transit rather than gastric emptying plays some role in pathophysiology of the patients with DLFD.

STUDY OF GASTRIC EMPTYING IN PATIENTS WITH ATROPHIC GASTRITIS AND CARCINOMA OF STOMACH / 解放军医学杂志

By using 99m Tc-resin meal method, we measured the gastric emptying time (GET) in patients with chronic atrophic gastritis (CAG) and gastric carcinoma(GCa). Change in gastric movement in CAG and GCa patients was discussed in this report. The results of present study showed that, GET 1/2 in control group (n = 36) was 37.3?16.0 min; mild CAG (n = 21) 35.0?10.5min. In moderate and severe CAG group (n = 13), GET was 68.3?35.3 min before pentagastrin treatment, and 37.1?6.5 min after pentagastrin treatment. In gastric autrum carcinoma (n = 8) it was 80.9?47.9 min, and in cardiac carcinoma (n = 3) 26.9?7.2min. Significant differentiation existed between moderate or severe CAG and gastric autrum carcinoma groups. Labelled meal v-photography was a physiological examination. Anatomic foundation of prolonged GET 1/2 in moderate and severe CAG was possibly related with atrophy of gastric muscles. Prolonged GET 1/2 could be a promoting factor of development of grastric carcinoma. In order to prevent the development of gastric carcinoma, great attention should be given to those patients with moderate to severe CAG.