Comprehensive assessment of nutritional and functional status of patients with ulcerative colitis and their impact on quality of life.

INTRODUCTION: Patients with ulcerative colitis (UC) are likely to have poor nutritional intake and increased gut losses. This study was designed to study the prevalence and predictors of nutritional deficiencies in patients with UC and their impact on the quality of life (QOL). METHODS: A prospective study was conducted among consenting patients with UC (cases) and healthy relatives of the cases (controls) visiting a university teaching hospital. They were assessed for clinical, demographic, endoscopic (Mayo score) and histological profile (Robart's score). They were assessed for the presence of macronutrient and micronutrient deficiency, anthropometry, functional status (muscle strength by dynamometer and sit-to-stand test) and the quality of life (short inflammatory bowel disease questionnaire [SIBDQ]). A SIBDQ score of ≤ 50 was considered poor QOL. RESULTS: We studied 126 cases and 57 healthy controls (age [mean ± SD] 37.7 ± 13.2 years vs. 34.40 ± 11.05 years; [p = 0.10] females [38.1% vs. 38.7%]; p = 0.94). Cases more often were underweight (28% vs. 3.5%; p < 0.001), had low mid arm circumference (45% vs. 12%; p < 0.0001), lower functional status in the form of weaker hand grip strength (67% vs. 45.6%; p = 0.007) and weaker lower limb strength (80% vs. 42%; p < 0.0001). Cases more often had the evidence of macronutrient deficiencies: total serum protein deficiency (31% vs. 3.5%; p < 0.0001), serum albumin deficiency (25.4% vs. 0.00%; p < 0.0001) and cholesterol deficiency (63% vs. 28%; p < 0.0001). Micronutrient deficiencies were highly prevalent among cases: calcium (44%), phosphate (21%), magnesium (11%), zinc (76%), iron (87%), folate (16%), vitamin B12 (10%) and vitamin D (81%). Most cases had a poor quality of life (85/126; 67.5%). Factors associated with poor QOL were low hemoglobin, serum albumin, zinc and vitamin D levels and histologically active disease. On multi-variate analysis, low vitamin D levels (odds ratio [OR] = 6.1; 95% confidence interval [CI]: 1.9-19.7) and histologically active disease (OR = 4.0; 95% CI: 1.6-9.9) were identified as independent predictors of poor QOL. CONCLUSIONS: Macronutrient deficiency, micronutrient deficiency, lower functional status and poorer QOL are highly prevalent among patients with UC. The independent predictors of poor QOL were histologically active disease and low serum vitamin D levels. Identifying and correcting the deficiencies may help in improving the QOL of patients with UC.

Clinical spectrum & changing presentation of celiac disease in Indian children.

Background & objectives: Celiac disease (CD) is a genetic immune mediated disorder characterised by gluten intolerance. This single centre study, from north India was aimed to assess the clinical, serological and histological profile of CD in a large cohort of children and the changing trends in its presentation. Methods: A review of clinical details of CD children diagnosed between 2000 and 2019 and currently on follow up was performed. Information on demography, symptoms, associated conditions, serology, biopsy findings and gluten-free diet were analyzed. Results: The mean age (±standard deviation) of 891 children included in the study, at onset and at diagnosis was 4.0±2.7 and 6.2±3.1 yr, respectively. Growth faltering, abdominal pain, abdominal distension and diarrhoea were presenting symptoms in 70, 64.2, 61.2 and 58.2 per cent, respectively. A positive family history of CD was present in 14 per cent and autoimmune conditions in 12.3 per cent of children. Thyroid disorders were seen in 8.5 per cent of children and Type 1 diabetes mellitus (T1DM) in 5.7 per cent. The duration of breastfeeding had a weak positive correlation with age at onset and diagnosis of CD (P<0.001). Non-classical CD was significantly more common in children aged >10 yr and in those presenting after 2010 (P<0.01). T1DM and hypothyroidism occurred more frequently in non-compliant children. Interpretation & conclusions: This was the largest single centre study, pertaining to the presentation and follow up of CD in children. Infants and young children were more likely to present with classical symptoms of diarrhoea, abdominal distension and growth failure while older children presented with non-classical CD. There was a trend towards non-classical forms of CD in recent years.

Role of Serology, Dietary Assessment, and Fecal Gluten Immunogenic Peptides for Predicting Histologic Recovery in Children with Celiac Disease.

BACKGROUND: A strict lifelong gluten-free diet (GFD) remains the only treatment of celiac disease (CD). Adherence to gluten-free diet is best reflected by mucosal healing. Noninvasive tools capable of predicting mucosal recovery in CD patients need to be identified. AIMS: To compare the ability of various modalities used to assess compliance to GFD, for predicting persistent mucosal damage in children with CD. METHODS: A prospective, single-center, observational study on children with CD on a GFD was conducted between January 2020 and April 2021. Children with CD on GFD were consecutively enrolled and various modalities used to assess adherence to GFD were compared. RESULTS: One hundred and fifty children (Mean age 12.2 ± 3.6 years, 58% Boys) on GFD (Mean duration 6 ± 3.1 years) were enrolled in the study. Persistent mucosal damage was seen in 88% of the enrolled. Fecal gluten immunogenic peptide (GIP) was positive in 87.8% (129/147). Antibodies to tissue transglutaminase (TGA-IgA) and/or deamidated gliadin peptide (DGP) were positive in 32% (48/150) whereas antibody to synthetic neoepitopes of TGA-IgA was positive in 24.8% (37/149). Non-compliance as assessed by local questionnaire, Biagi score, and dietitian detailed interview were 62.7%, 60%, and 75.3%, respectively. Serology had the highest specificity (83%) and fecal GIP had the highest sensitivity (89%). On logistic regression analysis, only non-compliance by Biagi score predicted poor mucosal recovery. CONCLUSION: Fecal GIP may be sensitive to detect only "one-point dietary transgression." None of the existing modalities used to assess compliance to GFD accurately predict persistent mucosal damage. A subset of patients may develop gluten tolerance.

Association of serotonin transporter promoter polymorphism (5-HTTLPR) with orocecal transit time in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a multifactorial disorder with altered intestinal motility, secretion, and sensation. Serotonin (5-HT) stimulates gut motility and alters serotonin signaling that may lead to both intestinal and extraintestinal symptoms in IBS. AIM: The aim of this study was to examine the association of serotonin transporter gene promoter polymorphism (5-HTTLPR) in IBS with orocecal transit time (OCTT) measured by lactulose hydrogen breath test. METHOD: This prospective case-control study included 151 IBS patients (mean±SD 37.4±11.6 years, median 36, range 19-68). Ninety-two patients were diarrhea-predominant IBS (D-IBS), 44 constipation-predominant IBS (C-IBS), 15 alternating diarrhea and constipation IBS (M-IBS), and 100 healthy controls (mean±SD 37.2±11.4 years, median 36, range 20-64 years). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based method. 5-HT levels were measured by enzyme-linked immunosorbent assay (ELISA). Orocecal transit time (OCTT) was measured by a non-invasive lactulose hydrogen breath test. OCTT was also compared with respect to 5-HTTLPR genotypes in different IBS phenotypes. RESULTS: Serum serotonin levels were significantly higher in overall IBS patients (152±77 ng/mL, p<0.001), D-IBS (184±76 ng/mL, p<0.001), compared to healthy controls (129±56 ng/mL). There was no difference in 5-HT levels between C-IBS (124±53 ng/mL) and controls. In the case of M-IBS, 5-HT levels were (88±49 ng/mL p<0.05) significantly lower than that of controls. OCTT was significantly shorter in D-IBS patients (95±36 min) as compared to controls (112±41 min). In contrast, C-IBS showed significantly prolonged OCTT (136±54 min). There was a significant difference in OCTT between D-IBS and C-IBS patients (p<0.001). There was no significant association found between OCTT and 5-HTTLPR. CONCLUSIONS: Serum serotonin concentrations were increased in D-IBS compared to controls and C-IBS. OCTT was shorter in D-IBS and delayed in C-IBS patients. There was no association of 5-HTLPR polymorphism with OCTT.

Safety and efficacy of non-fluoroscopic endoscopic dilatation of gastrointestinal tuberculosis related strictures.

INTRODUCTION: Stricturing gastrointestinal tuberculosis (GITB) may result in persistent symptoms even after antitubercular therapy (ATT) and may require surgical intervention. Data on efficacy and safety of endoscopic dilatation for management GITB related strictures is scarce. METHODS: A retrospective analysis of database of patients who underwent endoscopic balloon dilatation for suspected or proven gastrointestinal tuberculosis was performed. The analysis included the site of involvement, technical success, clinical success (response), relapse and requirement of surgery in these patients. RESULTS: Out of 34 patients (47.1% males, mean age 31.9 ± 12.9 years), eventually four patients were diagnosed to have Crohn's disease while the rest had GITB. Initial technical success was achieved in 30 (88.2%) patients. Initial clinical success was achieved in 28 (82.3%) patients. Median number of dilatation sessions required to obtain symptomatic relief were 2.5 (1-5) per patient. Two patients with initial clinical success had recurrence of symptoms over follow up of 1 year, out of which one patient was managed with repeat endoscopic balloon dilatation successfully. Of 30 patients with technical success, 16 (53.4%) were on ATT when they underwent dilatation while two were in intestinal obstruction. Eventually 7 patients required surgical intervention for various reasons. CONCLUSION: Non-fluoroscopic endoscopic balloon dilatation is an acceptable and fairly safe modality for symptomatic tuberculous strictures of gastrointestinal tract.

Oral Nano Vitamin D Supplementation Reduces Disease Activity in Ulcerative Colitis: A Double-Blind Randomized Parallel Group Placebo-controlled Trial.

INTRODUCTION: Vitamin D possesses anti-inflammatory properties and could be beneficial in ulcerative colitis (UC). METHODS: We studied the effect of oral nano vitamin D3 supplementation on disease activity in active UC [ulcerative colitis disease activity index (UCDAI)≥3]. Patients with active UC and vitamin D <40 ng/mL were randomized to receive either oral nano vitamin D (60,000 IU/d×8 d) or placebo. They were evaluated for disease activity (UCDAI scores, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin) at baseline and reassessed at 4 weeks. The response was defined as a 3-point reduction in UCDAI score at 4 weeks and reduction in inflammatory markers. RESULTS: The median vitamin D levels increased from 15.4 to 40.83 mg/dL in vitamin D group (P≤0.001) and marginally from 13.45 to 18.85 mg/dL (P=0.027) in controls. The 3-point reduction in UCDAI was seen more often in vitamin D group as compared with the control (53% vs. 13%; P=0.001). Increase in vitamin D levels correlated with reduction in UCDAI score (P≤0.001; ρ=-0.713), C-reactive protein (P≤0.001; ρ=-0.603), and calprotectin (P=0.004; ρ=-0.368). Patients who achieved target vitamin D of >40 ng/mL (n=17) more often had a 3-point reduction in UCDAI (80% vs. 20%; P≤0.001) and reduction in grade of severity from 60% to 35% (P=0.038). Vitamin D administration (odds ratio, 9.17; 95% confidence interval, 2.02-41.67) and baseline histologic activity (odds ratio, 1.92; 95% confidence intervals, 1.2-3.08) independently predicted response. CONCLUSIONS: Oral nano vitamin D supplementation in active UC is associated with a reduction in disease activity and severity grade and is seen more often in those who achieved a target vitamin D level of 40 ng/mL.

Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients.

Background: Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by nonsteroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC. Methods: Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein. Results: The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings. Conclusion: Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.

Anemia in celiac disease is multifactorial in etiology: A prospective study from India.

BACKGROUND AND AIMS: Anemia is one of the most common extraintestinal manifestations of celiac disease (CD), with iron deficiency anemia (IDA) being the predominant cause. However, anemia in CD can have varied etiologies, including mixed nutritional deficiency. We aimed to study the prevalence and etiology of anemia in CD in a north Indian population. METHODS: In this prospective observational study, consecutive patients with documented CD between January 2012 and December 2013 were included, and all patients underwent detailed clinical assessment; hematological investigations including iron profile, serum folate, and vitamin B12 levels; and esophageoduodenoscopy with duodenal biopsies for histopathological examination. Prevalence of anemia and different deficiencies were calculated, and a correlation between hematological parameters and histological findings was found. RESULTS: Of the 103 patients studied, anemia was detected in 96 patients, giving a prevalence of 93.2% with a baseline hemoglobin of 8.94 ± 2.54 g/dL. Overall, iron deficiency was seen in 84 (81.5%) patients, followed by vitamin B12 deficiency in 14 (13.6%) and folate deficiency in 11 (10.7%) patients; 17 (16.5%) patients had anemia due to mixed nutritional deficiencies, and 4 (3.9%) patients had anemia of chronic disease. The mean hemoglobin and median ferritin levels were significantly lower in patients with severe villous atrophy compared to those with mild atrophy. CONCLUSION: Anemia in patients with CD is multifactorial. Even though iron deficiency is the most common cause, other nutrient deficiencies should always be explored.

Role of endoscopic retrograde cholangiography in ruptured hepatic hydatid cyst.

AIM: To report endoscopic retrograde cholangiopancreatography (ERCP) findings of intrabiliary hydatid cyst rupture. MATERIAL AND METHODS: A retrospective study of cases with intrabiliary rupture of hydatid cyst was conducted. A total of 4 cases (all female with a mean age of 32 years) were included. ERCP and ultrasound data were evaluated. Assessment involved number, location, size, internal and wall characteristics of cyst; intrahepatic biliary radicle dilatation (IHBRD); common bile duct (CBD) dilatation and evidence of extrabiliary rupture on ultrasound. ERCP evaluation included IHBRD, CBD dilatation, communication between cysts and intrahepatic biliary radicles (IHBR) and filling defects within the IHBR and CBD. Treatment details were also obtained. RESULTS: A total of 5 cysts were evaluated in 4 patients. Left lobe cysts were most common (n=4). Segment II/III were the most commonly affected segments (n=3). Cyst outline was smooth and cystobiliary communication noted in all cases. Deformation of cyst wall was noted in 2 cases. Isolated (left or right) IHBRD lateralised to the side of the cyst was most common (n=4). CBD dilatation was seen in all cases with a mean calibre of 1.4 cm. Concomitant extrabiliary rupture was seen in 3 cases. Endoscopic management was done in all cases without complications. Three patients underwent surgical excision after a mean period of 8 weeks following ERCP. CONCLUSION: Isolated IHBRD lateralized to the side of hydatid cyst with CBD dilatation is the commonest ERCP finding of intrabiliary rupture of hydatid cyst.

Primary versus secondary achalasia: New signs on barium esophagogram.

AIM: To investigate new signs on barium swallow that can differentiate primary from secondary achalasia. MATERIALS AND METHODS: Records of 30 patients with primary achalasia and 17 patients with secondary achalasia were reviewed. Clinical, endoscopic, and manometric data was recorded. Barium esophagograms were evaluated for peristalsis and morphology of distal esophageal segment (length, symmetry, nodularity, shouldering, filling defects, and "tram-track sign"). RESULTS: Mean age at presentation was 39 years in primary achalasia and 49 years in secondary achalasia. The mean duration of symptoms was 3.5 years in primary achalasia and 3 months in secondary achalasia. False-negative endoscopic results were noted in the first instance in five patients. In the secondary achalasia group, five patients had distal esophageal segment morphology indistinguishable from that of primary achalasia. None of the patients with primary achalasia and 35% patients with secondary achalasia had a length of the distal segment approaching combined height of two vertebral bodies. None of the patients with secondary achalasia and 34% patients with primary achalasia had maximum caliber of esophagus approaching combined height of two vertebral bodies. Tertiary contractions were noted in 90% patients with primary achalasia and 24% patients with secondary achalasia. Tram-track sign was found in 55% patients with primary achalasia. Filling defects in the distal esophageal segment were noted in 94% patients with secondary achalasia. CONCLUSION: Length of distal esophageal segment, tertiary contractions, tram-track sign, and filling defects in distal esophageal segment are useful esophagographic features distinguishing primary from secondary achalasia.

Association of Serotonin Transporter Promoter Polymorphism (5-HTTLPR) with Microscopic Colitis and Ulcerative Colitis.

BACKGROUND: Serotonin (5-HT) release and serotonin reuptake transporter (5-HTT) expression have been reported to be decreased in experimental colitis, in interleukin-10 knockout-associated colitis, and in patients with ulcerative colitis. Serotonin is known to play an important role in the pathogenesis of colitis, but individual genetic variants of 5-HTT gene in microscopic colitis and ulcerative colitis are not known. AIM: This study aimed to evaluate the association between the serotonin transporter gene promoter polymorphism (5-HTTLPR) and 5-HT concentration in microscopic colitis (MC) and ulcerative colitis (UC) patients. METHOD: This prospective case-control study included 41 patients with microscopic colitis (age 19-82 years, mean 35 ± 13.6), 75 patients with ulcerative colitis (age 16-65 years, mean 38.5 ± 11.6), and 100 controls (age 20-64 years, mean 38 ± 11). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based assay. 5-HT levels were measured by ELISA. RESULTS: The frequency of the 5-HTTLPR (SS) genotype was significantly lower in MC (12 %) patients compared to controls (30 %) (p < 0.05). When the L/L and L/S genotypes were combined into one group, the frequencies of the non-S genotype were significantly higher than those of S/S genotype between the MC patients and the controls (p < 0.05). 5-HT levels were significantly higher in UC and MC patients compared to healthy controls (p < 0.01). CONCLUSIONS: A significant association was observed between LL genotype of 5-HTTLPR polymorphism and microscopic colitis, suggesting that 5-HTTLPR is a potential candidate gene involved in the pathogenesis of microscopic colitis. Serotonin levels were significantly higher in microscopic colitis and ulcerative colitis patients compared to healthy controls.

Abdominal tuberculosis of the gastrointestinal tract: revisited.

Abdominal tuberculosis is an increasingly common disease that poses diagnostic challenge, as the nonspecific features of the disease which may lead to diagnostic delays and development of complications. This condition is regarded as a great mimicker of other abdominal pathology. A high index of suspicion is an important factor in early diagnosis. Abdominal involvement may occur in the gastrointestinal tract, peritoneum, lymphnodes or solid viscera. Various investigative methods have been used to aid in the diagnosis of abdominal tuberculosis. Early diagnosis and initiation of antituberculous therapy and surgical treatment are essential to prevent morbidity and mortality. Most of the patients respond very well to standard antitubercular therapy and surgery is required only in a minority of cases. Imaging plays an important role in diagnosis of abdominal tuberculosis because early recognition of this condition is important. We reviewed our experience with the findings on various imaging modalities for diagnosis of this potentially treatable disease.

Upper gastrointestinal barium evaluation of duodenal pathology: A pictorial review.

Like other parts of the gastrointestinal tract (GIT), duodenum is subject to a variety of lesions both congenital and acquired. However, unlike other parts of the GIT viz. esophagus, rest of the small intestine and large intestine, barium evaluation of duodenal lesions is technically more challenging and hence not frequently reported. With significant advances in computed tomography technology, a thorough evaluation including intraluminal, mural and extramural is feasible in a single non-invasive examination. Notwithstanding, barium evaluation still remains the initial and sometimes the only imaging study in several parts of the world. Hence, a thorough acquaintance with the morphology of various duodenal lesions on upper gastrointestinal barium examination is essential in guiding further evaluation. We reviewed our experience with various common and uncommon barium findings in duodenal abnormalities.

Pancreatic trauma: a concise review.

Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma.

Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection.

BACKGROUND & OBJECTIVES: Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. METHODS: Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. RESULTS: Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. INTERPRETATION & CONCLUSIONS: Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals.

The frequency of histologic lesion variability of the duodenal mucosa in children with celiac disease.

BACKGROUND: Celiac disease (CD) may cause changes throughout the gastrointestinal tract. Patchy distribution of duodenal mucosal lesions has been described in adults as well as in children. This study aimed to verify the concept and to evaluate the frequency of histologic lesion variability of the duodenal mucosa in Indian children with CD. METHODS: We enrolled 67 children prospectively who underwent upper gastrointestinal endoscopy because of positive tissue transglutaminase antibodies and biopsy as the final evaluation for suspected CD. Four biopsies were taken from the descending duodenum distal to the papilla, and duodenal bulb. The histologic lesions were classified according to the Oberhuber classification with modification proposed by our group. RESULTS: Forty-three CD children (64.2%) had a "mixed" type 3 lesion characterized by a different degree of villous atrophy at different biopsy sites. Eight children (11.9%) showed two different types of histologic lesions in the same patient at different biopsy sites. The overall variability of histologic lesion (variability in the grade of villous atrophy [type 3a, 3b, or 3c], and coexistence of villous atrophy and type 2 lesion) was seen in 51 (76.1%) of the CD patients. CONCLUSIONS: Children with CD show a high frequency of variability of histologic lesions. Therefore, multiple endoscopic biopsy specimens should be obtained not only from the distal duodenum but also from the bulb.