gastrins and Malabsorption-Syndromes

Proton pump inhibitors (PPI) are one of the most widely used groups of drugs and their potential toxicity is periodically reviewed, emphasizing aspects originally considered secondary. The present review analyzes the physiological and pharmacological bases and the scarce clinical evidence for a potential association between the continued administration of PPI and the development of osteoporosis and bone fractures. Both disorders are clearly related to calcium homeostasis and are highly important in elderly patients due to their poor general prognosis and disabling consequences.

Topics: Achlorhydria; Aging; Calcium; Calcium, Dietary; Comorbidity; Disease Susceptibility; Fractures, Spontaneous; Gastric Acid; Gastrins; Homeostasis; Humans; Hyperparathyroidism, Secondary; Intestinal Absorption; Malabsorption Syndromes; Models, Biological; Osteoporosis; Proton Pump Inhibitors; Risk

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.

Topics: Animals; Carcinoid Tumor; Cell Transformation, Neoplastic; Drug Tolerance; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrinoma; Gastrins; Gastritis; Gastroesophageal Reflux; Gastrointestinal Agents; Helicobacter pylori; Humans; Malabsorption Syndromes; Peptic Ulcer; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors; Zollinger-Ellison Syndrome

Topics: Anemia; Anti-Bacterial Agents; Anti-Ulcer Agents; Comorbidity; Disease Susceptibility; Drug Therapy, Combination; Duodenal Diseases; Duodenal Ulcer; Enzyme Inhibitors; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Kidney Failure, Chronic; Malabsorption Syndromes; Prevalence; Proton Pump Inhibitors; Renal Dialysis; Stomach Diseases; Stomach Ulcer; Urea

Topics: Gastric Acid; Gastrins; Histamine H2 Antagonists; Humans; Infections; Malabsorption Syndromes; Peptic Ulcer; Risk Factors

Topics: Burimamide; Chemical Phenomena; Chemistry; Cimetidine; Duodenal Ulcer; Esophagitis, Peptic; Gastric Acid; Gastrins; Gastrointestinal Hemorrhage; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hypersensitivity; Intrinsic Factor; Kinetics; Malabsorption Syndromes; Metiamide; Pancreas; Pepsin A; Ranitidine; Receptors, Histamine H2; Stomach Ulcer; Stress, Psychological; Zollinger-Ellison Syndrome

Topics: Animals; Dogs; Gastrins; Gastrointestinal Hormones; Humans; Intestine, Small; Kidney Failure, Chronic; Liver Cirrhosis; Malabsorption Syndromes; Peptic Ulcer; Postoperative Complications; Short Bowel Syndrome

Topics: Angiography; Biological Assay; Diarrhea; Duodenum; Endocrine System Diseases; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Neoplasms; Islets of Langerhans; Malabsorption Syndromes; Pancreatic Neoplasms; Peptic Ulcer; Prognosis; Radioimmunoassay; Stomach; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Angiography; Antacids; Celiac Disease; Diarrhea; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pancreatic Neoplasms; Physical Examination; Radioimmunoassay; Radionuclide Imaging; Zollinger-Ellison Syndrome

Topics: Afferent Loop Syndrome; Deglutition Disorders; Diet Therapy; Dumping Syndrome; Gastric Acidity Determination; Gastrins; Gastroenterostomy; Gastroscopy; Humans; Hyperparathyroidism; Malabsorption Syndromes; Pentagastrin; Peptic Ulcer; Postgastrectomy Syndromes; Postoperative Complications; Stomach; Stomach Ulcer; Sutures; Zollinger-Ellison Syndrome

Topics: Animals; Depression, Chemical; Dietary Fats; Digestion; Digestive System; Gastrins; Gastrointestinal Diseases; Humans; Intestinal Absorption; Intestinal Mucosa; Malabsorption Syndromes; Stimulation, Chemical; Vitamin B 12; Zollinger-Ellison Syndrome

Topics: Colitis, Ulcerative; Gastrins; Gastrointestinal Diseases; Gastroscopy; Humans; Lactose Intolerance; Malabsorption Syndromes; Peptic Ulcer; Stomach Neoplasms

Enteroendocrine cells secrete over a dozen different hormones responsible for coordinating digestion, absorption, metabolism, and gut motility. Loss of enteroendocrine cells is a known cause of severe congenital diarrhea. Furthermore, enteroendocrine cells regulate glucose metabolism, with the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) playing critical roles in stimulating insulin release by pancreatic β-cells. Islet1 (Isl1) is a LIM-homeodomain transcription factor expressed specifically in an array of intestinal endocrine cells, including incretin-expressing cells. To examine the impact of intestinal Isl1 on glycemic control, we set out to explore the role of intestinal Isl1 in hormone cell specification and organismal physiology. Mice with intestinal epithelial-specific ablation of Isl1 were obtained by crossing Villin-Cre transgenic animals with mice harboring a Isl1(loxP) allele (Isl1(int) model). Gene ablation of Isl1 in the intestine results in loss of GLP-1, GIP, cholecystokinin (CCK), and somatostatin-expressing cells and an increase in 5-HT (serotonin)-producing cells, while the chromogranin A population was unchanged. This dramatic change in hormonal milieu results in animals with lipid malabsorption and females smaller than their littermate controls. Interestingly, when challenged with oral, not intraperitoneal glucose, the Isl-1 intestinal-deficient animals (Isl1(int)) display impaired glucose tolerance, indicating loss of the incretin effect. Thus the Isl1(int) model confirms that intestinal biology is essential for organism physiology in glycemic control and susceptibility to diabetes.

Topics: Age Factors; Animals; Animals, Newborn; Biomarkers; Blood Glucose; Cholecystokinin; Chromogranin A; Diarrhea; Dietary Fats; Enteroendocrine Cells; Female; Gastric Inhibitory Polypeptide; Gastrins; Genotype; Ghrelin; Glucagon-Like Peptide 1; Glucose Metabolism Disorders; Glucose Tolerance Test; Integrases; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; LIM-Homeodomain Proteins; Malabsorption Syndromes; Male; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Phenotype; Serotonin; Somatostatin; Transcription Factors; Weight Gain

To study the association between Helicobacter pylori (H. pylori) infection and autoimmune type atrophic gastritis.. Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology, immunoblot-based serology, and histology to reveal a past or a present H. pylori infection. In addition, serum markers for gastric atrophy (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.. Of the 14 patients with severe gastric atrophy, as demonstrated by histology and serum markers, and no evidence for an ongoing H. pylori infection, eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with severe corpus atrophy, PCA and IF antibodies were detected in four. Among the patients with low to moderate grade atrophic gastritis (all except one with an ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity were seldom detected. However, one H. pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis.. Signs of H. pylori infection in autoimmune gastritis, and positive autoimmune serum markers in H. pylori gastritis suggest an etiological role for H. pylori in autoimmune gastritis.

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biomarkers; Female; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Pepsinogen C; Risk Factors; Severity of Illness Index; Vitamin B 12 Deficiency

Autoimmune polyglandular syndrome type I (APS I) is characterized by multiple endocrine gland failures, with other manifestations such as gastrointestinal (GI) symptoms.. The objective of the study was to study the histopathological and immunological findings in the GI mucosa of a patient with typical features of APS I, malabsorption, and pernicious anemia.. Biopsies from the GI tract of a patient with APS I were immunostained with chromogranin for GI endocrine cells (GIECs). Blinded slides were graded for numbers of endocrine cells. Normal gastric mucosa was exposed to the patient's serum to test for circulating anti-GIEC and antiparietal cell antibodies using indirect immunofluorescence.. The study was conducted at the Departments of Pediatrics and Medical Gastroenterology in an academic medical center.. The patient's GI mucosa demonstrated absence of GIECs throughout, including gastric gastrin-secreting cells, and her laboratory tests for serum gastrin levels were low normal. Both GIECs and parietal cells were absent in her gastric corpus. The patient's serum contained anti-GIEC antibody but no antiparietal cell antibody.. These observations suggest that GIECs in APS I are subject to an autoimmune destruction that can cause widespread GIEC loss. This could explain the GI dysfunctions that are often noted in the syndrome including malabsorption and atrophic gastric changes with pernicious anemia. We also hypothesize that absence of gastric parietal cells may result mainly from hypogastrinemia that is mainly the loss of gastrin-secreting cells rather than from immune-mediated destruction of parietal cells like that seen in the atrophic gastritis associated with adult-onset pernicious anemia.

Topics: Anemia, Pernicious; Autoantibodies; Biopsy; Child; Enteroendocrine Cells; Female; Fluorescent Antibody Technique, Indirect; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Malabsorption Syndromes; Polyendocrinopathies, Autoimmune

The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria.. To conduct a systematic comparative examination of gastric histology and function.. Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status.. All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection.. The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics.. Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.

Topics: Achlorhydria; Adult; Aged; Aged, 80 and over; Biopsy; Case-Control Studies; Female; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Gastroscopy; Helicobacter pylori; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Parietal Cells, Gastric; Prospective Studies; Schilling Test; Vitamin B 12 Deficiency

Two entities of considerable recent interest, Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody to H. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT < 1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0-1.99%) and 42% of 59 subjects with normal absorption (EYCAT > or = 2.0%) (chi 2 = 9.52, P < 0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03 +/- 1.83% vs 3.11 +/- 2.13%, t = 2.913, P = 0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence of H. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced by H. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.

Topics: Adult; Aged; Antibodies, Bacterial; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Malabsorption Syndromes; Male; Middle Aged; Serologic Tests; Vitamin B 12 Deficiency

Surgical approach to short bowel syndrome has been dealing with two major problems: lack in absorptive surface and dysfunction of the peristalsis of the widely distended loop above the anastomosis. In those children having a very short intestine, one is reluctant to either resect or reduce the diameter of this loop. Bianchi, followed by Boeckman and Traylor, described a procedure of loop lengthening by dividing it longitudinally. Their procedure has the advantage of restoring normal peristalsis without losing any absorptive surface. A modification of the original procedure of Bianchi is described. We report on its application in a child born with laparoschisis and intestinal atresia; she had in fact 25 centimetres of duodenum and proximal jejunum anastomosed with left colonic angle. This child was referred to us with functional occlusion related to distension above an intact and unobstructed anastomosis. She was operated on at six weeks of age. Postoperatively oral feeding could be started after one month. Broviak's catheter for parenteral nutrition was removed at six months. In conclusion we believe that this technique offers a chance of better and faster adaptation to children born with short bowel syndrome.

Topics: Dietary Fats; Enteral Nutrition; Feces; Female; Gastrins; Gastroesophageal Reflux; Humans; Infant; Infant, Newborn; Intestinal Absorption; Intestine, Small; Malabsorption Syndromes; Nitrogen; Parenteral Nutrition; Pneumoperitoneum; Postoperative Complications; Short Bowel Syndrome

Excess gastric acid secretion and gastrin production may occur in patients with the short bowel syndrome but the two measurements have never been made simultaneously in man in response to a food stimulus. Using the technique of intragastric titration, this was carried out in eight patients after extensive small bowel resection resulting mainly from vascular occlusion and in eight matched normal control subjects. Basal acid output and peak acid output in response to pentagastrin was also measured separately. Although peak and integrated serum gastrin concentrations were significantly greater in patients (450 +/- SE 109 pg/ml; 113 +/- 2.9X10(-3) pg/ml/min) compared with control subjects (174 +/- 98 pg/ml; 6.1 +/- 2.0X10(-3) pg/ml/min p less than 0.05), no concomitant increase in acid secretion was shown either during intragastric titration or in response to pentagastrin. These findings indicate that there is no rationale for treating these patients with long term anti-ulcer therapy.

Topics: Female; Gastric Acid; Gastrins; Humans; Malabsorption Syndromes; Male; Middle Aged; Pentagastrin; Short Bowel Syndrome

Extensive small bowel resection produces pancreatic hyperplasia and increases plasma gastrin levels in the rat. Because gastrin is known as a trophic factor for the exocrine pancreas, we studied the effect of endogenous variations of gastrin induced by different gastric operations on the rat pancreas in both resected and transected animals. Vagotomy increased plasma gastrin level while antrectomy decreased it; pyloroplasty was without any effect. These gastric operations enhanced slightly but not significantly the pancreatic weight, its protein and DNA content. A 90% jejunoileal resection alone increased markedly these parameters while mitotic figures appeared in acinar cells. Pyloroplasty, vagotomy and antrectomy did not modify the changes induced by intestinal resection itself except the level of protein. These findings suggest that hypergastrinemia produced by intestinal resection is not responsible for pancreatic hyperplasia.

Topics: Animals; Body Weight; DNA; Gastrectomy; Gastrins; Hyperplasia; Intestine, Small; Malabsorption Syndromes; Male; Organ Size; Pancreas; Proteins; Pylorus; Rats; Rats, Inbred Strains; Short Bowel Syndrome; Vagotomy, Proximal Gastric

Eleven adult Basenji dogs with immunoproliferative small intestinal disease (IPSID) were studied. Two items of history related to the digestive tract were characteristic: (i) chronic intractable diarrhea in most dogs, and (ii) progressive emaciation. Anorexia was intermittent in only a few dogs. In addition, skin lesions of various degrees of severity were observed, including alopecia of pinnae and ventrum, hyperpigmentation and hyperkeratosis of pinnae, and necrosis and ulcerations of margins of pinnae. The cause of the skin lesions was not determined; however, hypothyroidism did not appear to contribute to the skin changes. Standard hematologic and serum chemical values were not consistently abnormal. However, a poorly regenerative anemia, mild neutrophilia, and increased aspartate aminotransferase and alanine aminotransferase activities were generally observed in severely affected dogs. The Pelger-Huet anomaly was identified in dog 3. Maldigestion and malabsorption as determined by the N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test was documented to varying degrees in dogs with IPSID. Maldigestion was correlated with functional pancreatic exocrine insufficiency. Severe malabsorption was documented in only 3 dogs. Serum gastrin values were evaluated in these dogs because of a prior observation of parietal cell hyperplasia and gastric ulceration. Hypergastrinemia was documented in 3 dogs. Additional studies will be necessary to determine whether an acid hypersecretory state contributes to the pathogenesis of IPSID in Basenjis.

Topics: 4-Aminobenzoic Acid; Animals; Diarrhea; Dog Diseases; Dogs; Female; Gastrins; Hypergammaglobulinemia; Immunoglobulin G; Immunoglobulin M; Intestinal Absorption; Intestinal Diseases; Malabsorption Syndromes; Male; para-Aminobenzoates; Xylose

Topics: Adult; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Digestion; Duodenal Ulcer; Female; Gastrins; Growth Hormone; Humans; Insulin; Intestinal Absorption; Malabsorption Syndromes; Male; Middle Aged

The intestine's ability to adapt following extensive resection is well known, and includes augmentation in calibre and the thickness of the wall, increased villus height, changes in motility, and qualitative and quantitative alterations in the flora. Positive identification of the mechanisms through which this morphological and functional adaptation takes place still forms the subject of research. An account is given of the latest views concerning the way in which compensation of the intestine takes place after resection and by-pass surgery.

Topics: Adaptation, Physiological; Gastrins; Gastrointestinal Motility; Humans; Intestinal Mucosa; Intestines; Malabsorption Syndromes

Topics: Cimetidine; Gastric Emptying; Gastric Juice; Gastrins; Guanidines; Humans; Intestinal Absorption; Intestine, Small; Malabsorption Syndromes; Postoperative Complications; Syndrome

Extensive metabolic studies were conducted in five normal controls and in five study patients after total gastric resection with Roux-en-Y (RY) reconstruction to determine the nutritional consequences of this particular technique of restoring gastrointestinal continuity. Although malabsorption of fat (19.2 +/- 2.2%) and nitrogen (22 +/- 2.5%) demonstrated in the study patients was moderate, it was significantly greater than normal ( less than 0.01). In spite of the demonstrated malabsorption, however, positive nitrogen balances (+ 0.33 +/- 0.18 gm/day) were maintained in the RY patients throughout the investigative period. These observations suggest that malabsorption after RY is infrequently of clinical significance, even in this "worst-case" situation characterized by complete removal of gastric tissue. Malnutrition should occur in only those patients with more limited gastric resections and RY reconstruction who are unable to increase caloric intake to cover losses due to malabsorption. A significant decrease in both trypsin and lipase concentrations and a marked delay in secretion of these enzymes was noted in the RY patients in response to a test meal (p less than 0.01). Malabsorption of fat and nitrogen in RY patients improved after exogenous pancreatic enzymes, but not after administration of tetracycline. Bacterial overgrowth as a cause of postoperative malabsorption may be less important than previously thought. Malabsorption after RY is due primarily to maldigestion brought about by duodenal bypass which, in turn, results in either an absolute or a relative pancreatic enzyme insufficiency.

Topics: Bile Acids and Salts; Cholecystokinin; Dietary Fats; Female; Gastrectomy; Gastrins; Humans; Jejunum; Lipase; Malabsorption Syndromes; Male; Nitrogen; Postgastrectomy Syndromes; Secretin; Tetracycline; Trypsin

Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms.

Topics: Adult; Cell Count; Colon; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Histamine; Humans; Malabsorption Syndromes; Male; Mast Cells; Middle Aged; Stomach Ulcer; Urticaria; Urticaria Pigmentosa

Topics: Achlorhydria; Diagnosis, Differential; Duodenal Ulcer; Fasting; Gastrectomy; Gastrins; Humans; Hyperplasia; Malabsorption Syndromes; Male; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Stomach Diseases; Zollinger-Ellison Syndrome

Topics: Anti-Bacterial Agents; Bacteriuria; Diarrhea; Gastric Juice; Gastrins; Glucose; Humans; Hydrogen-Ion Concentration; Intestines; Jejunum; Malabsorption Syndromes; Sodium; Water-Electrolyte Balance; Zollinger-Ellison Syndrome

Topics: Achlorhydria; Anemia, Macrocytic; Gastrins; Histamine; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Radioimmunoassay; Stimulation, Chemical; Time Factors; Vitamin B 12