intrinsic-factor and Malabsorption-Syndromes

Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC) and their respective membrane receptors. Vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive diseases. This review explores the physiology of vitamin B12 absorption and the mechanisms and diseases that produce malabsorption. In the stomach, B12 is released from food carrier proteins and binds to HC. The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to IF in the duodenum. Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum. Part of liver B12 is excreted in bile, and undergoes an enterohepatic circulation. The main causes of B12 malabsorption include inherited disorders (Intrinsic factor deficiency, Imerslund-Gräsbeck disease, Addison's pernicious anemia, obesity, bariatric surgery and gastrectomies. Other causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, chronic radiation enteritis of the distal ileum and short bowel. The assessment of B12 deficit is recommended in the follow-up of subjects with bariatric surgery. The genetic causes of B12 malabsorption are probably underestimated in adult cases with B12 deficit. Despite its high prevalence in the general population and in the elderly, B12 malabsorption cannot be anymore assessed by the Schilling test, pointing out the urgent need for an equivalent reliable test.

Topics: Adult; Aged; Anemia, Megaloblastic; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12; Vitamin B 12 Deficiency

In our pioneering work in 1956, two binders of vitamin B12 (B12) alias cobalamin (Cbl) were identified in gastric juice, S with slow electrophoretic mobility, a 70 kD protein with intrinsic factor (IF) activity and another rapid (R), not IF active but probable digestion product. Numerous sources contained a protein immunologically identical to R (haptocorrin, Hc). Another IF-active component (I) was found. Isoelectric focusing showed that S, I and R were assemblies of "isoproteins" with different pI's due to varying glycosidation. Isolation of S, I and R in microquantities was achieved in 1962 using a series of ion exchange chromatographies and gel filtration. Ponderable products were obtained in 1965-1966. The B12-IF complex was a dimer, contained 13% carbohydrate and showed a different absorption spectrum than B12. Using the Schilling test, B12 absorption was shown to require Ca(++), bound in vitro to the ileal receptor and IF, but most of Ca(++) could be removed with sialidase. The receptor-substrate complex contained Ca(++) and carbohydrate. The purified receptor was shown to contain two main subunits. The Imerslund-Gräsbeck syndrome was discovered 1958-1960; it is caused by mutations in either of two genes, cubilin or amnionless, which form the multiligand receptor cubam. Testicular biopsies during and after B12-treated deficiency showed remarkable improvement after therapy. Studies of the turnover of radioactive B12 revealed biliary and fecal excretion, enterohepatic circulation and allowed calculation of biological half-life and daily need. The B12 coenzymes largely behaved like B12. To study whether radiocobalt in B12 was representative of the rest of the B12 molecule, (32)P and (57)Co labeled hydroxocobalamins were biosynthesized and shown to behave identically when given simultaneously to rats. The complex metabolism of B12 explains the pathogenesis of B12 deficiencies. Some of its mechanisms are not restricted to B12, e.g. the endocytosis of B12-IF also applies to other macromolecules.

Topics: Anemia, Megaloblastic; Animals; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment.. PubMed was systematically searched for English and French articles published from January 1990 to January 2007.. Prospective randomized studies (n = 3), a systematic review by the Cochrane group (n = 1) and prospective studies in well-determined population (n = 5) provide evidence that oral cyanocobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature may not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment.. This present review confirms the previously reported efficacy of oral cyanocobalamin treatment in elderly patients.

Topics: Administration, Oral; Aged; Diet; Dietary Supplements; Humans; Intrinsic Factor; Malabsorption Syndromes; Prospective Studies; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency

The disease is characterised by cobalamin (Cbl) deficiency in children 0-5 years old, causing failure to thrive, infections, megaloblastic anaemia, neuropathy, and mild general malabsorption; slight proteinuria is common. Cbl injections produce remission, but Cbl malabsorption and proteinuria persist. About 250 cases have been reported. Dogs also have it. The heredity is autosomal and recessive. The physiological and pathological absorption mechanisms are described: Cbl liberated from food by digestion is first bound to haptocorrin, but in the intestine it is transferred to intrinsic factor. In the ileum the complex attaches to a receptor on the enterocytes; this requires neutral pH and Ca2+. The receptor is a membrane-bound glycoprotein consisting of multiple subunits. The receptor-ligand complex is endocytosed and degraded in lysosomes, and the vitamin is transferred to transcobalamin which carries it to tissues. The same receptor is strongly expressed in the kidneys, but urine also contains its activity which can be assayed for diagnosis. The basic lesion is an error in the ileal receptor. In the affected dogs the synthesised receptor is retained intracellularly. Urine and ileal biopsies from human cases contained little receptor but it had conserved affinity for the ligand. Recently examined Arab patients did not excrete reduced amounts of the receptor. Apparently, the disease has subsets, such as different structural errors in the receptor and possibly faulty transport inside the enterocyte. The cause of the proteinuria is unknown but kidney damage due to severe Cbl deficiency and an error in a multiligand renal receptor are among the possibilities.

Topics: Animals; Child, Preschool; Dogs; Genes, Recessive; Humans; Infant; Infant, Newborn; Intrinsic Factor; Malabsorption Syndromes; Proteinuria; Receptors, Cell Surface; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Deficiency Diseases; Gastrectomy; Humans; Ileal Diseases; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Nutrition Disorders; Vitamin B 12; Vitamin B 12 Deficiency

This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.

Topics: Absorption; Adult; Alcoholism; Anemia, Pernicious; Ascorbic Acid; Autoantibodies; Biguanides; Biological Transport; Chemical Phenomena; Chemistry; Chlorpromazine; Contraceptives, Oral; Diet; Female; Gastrectomy; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Middle Aged; Neoplasms; Nervous System Diseases; Nitrous Oxide; Nutritional Requirements; Pancreatic Diseases; Parasitic Diseases; Pregnancy; Pregnancy Complications; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

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

This review focusses on research performed by the author and coworkers. The absorption, turnover and excretion of cobalamin and the pathogenesis of cobalamin deficiency states are described and the laboratory tests used to diagnose these states are discussed. Topics dealt with in detail include: overall turnover, daily need, enterohepatic circulation and excretion of cobalamin and other corrins . The soluble proteins mediating cobalamin transport and their cellular receptors are described and their nomenclature, isolation, structure and mode of action, the role of calcium in the membrane transport, the evolution of these systems and the analogies with transport systems for other substrates are discussed together with deficiency states, especially fish tapeworm anemia and familial selective vitamin B12 malabsorption with proteinuria. Folate deficiency is a relatively rare cause of megaloblastic anemia in Scandinavia but common in North America and explanations for this difference are suggested. The methods of assaying cobalamin in serum and plasma and the performance of radiovitamin B12 absorption tests are critically evaluated. The measurement of intrinsic factor in gastric juice, serum, amniotic fluid and urine is described.

Topics: Anemia, Megaloblastic; Anemia, Pernicious; Biological Transport; Corrinoids; Diet; Diphyllobothriasis; Endocytosis; Erythrocyte Indices; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Membrane Transport Proteins; Metabolic Clearance Rate; Receptors, Cell Surface; Receptors, Peptide; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Absorption; Gastric Mucosa; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Pernicious; Humans; Ileal Diseases; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Pancreatitis; Postgastrectomy Syndromes; Protein Binding; Transcobalamins; Vitamin B 12; Vitamin B Deficiency

Topics: Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Deficiency; Humans; Hydrolysis; Intestinal Absorption; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Pancreas; Pteroylpolyglutamic Acids; Sprue, Tropical; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Calcium; Chronic Disease; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pancreatectomy; Pancreatic Diseases; Pancreatic Juice; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Absorption; Aged; Anemia; Anemia, Pernicious; Chemical Phenomena; Chemistry; Food Analysis; Gastrointestinal Diseases; Humans; Intrinsic Factor; Malabsorption Syndromes; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Anemia, Hemolytic; Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Biological Transport; Bone Marrow; Bone Marrow Cells; Child; Child, Preschool; Female; Folic Acid; Folic Acid Deficiency; Homocystinuria; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Metabolism, Inborn Errors; Methionine; Methionine Adenosyltransferase; Orotic Acid; Phenylketonurias; Tetrahydrofolate Dehydrogenase; Transcobalamins; Vitamin B 12

Topics: Absorption; Aged; Anemia, Pernicious; Animals; Biological Transport; Chemical Phenomena; Chemistry; Child; Diphyllobothriasis; Food Analysis; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Nutritional Requirements; Stomach; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; Zollinger-Ellison Syndrome

Topics: Animals; Ascorbic Acid; Biological Transport; Biotin; Diet; Folic Acid; Gastrectomy; Humans; Ileum; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Niacinamide; Nicotinic Acids; Pantothenic Acid; Pyridoxine; Riboflavin; Species Specificity; Stomach; Thiamine; Vitamin B 12; Vitamins

Topics: Animals; Bicarbonates; Binding Sites; Cations, Divalent; Dogs; Drug Synergism; Humans; Hydrogen-Ion Concentration; Ileum; Intestinal Mucosa; Intrinsic Factor; Iron; Malabsorption Syndromes; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Juice; Pancreatin; Rats; Receptors, Drug; Vitamin B 12

Topics: Alcoholism; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Pernicious; Diagnosis, Differential; Folic Acid; Folic Acid Antagonists; Folic Acid Deficiency; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pyrimidine Nucleotides; Thymine Nucleotides; Uracil Nucleotides; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Age Factors; Diet; Female; Folic Acid; Folic Acid Deficiency; Gastrointestinal Diseases; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Metabolic Diseases; Metabolism, Inborn Errors; Nutrition Disorders; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Pernicious; Animals; Child; Child Nutritional Physiological Phenomena; Female; Humans; Ileum; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Anemia, Pernicious; Animals; Binding Sites; Biological Transport; Blind Loop Syndrome; Cestode Infections; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Liver; Malabsorption Syndromes; Pancreas; Postgastrectomy Syndromes; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Cobalt Isotopes; Disease Models, Animal; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pancreas; Pancreatectomy; Pancreatic Diseases; Rats; Tissue Extracts; Vitamin B 12

Topics: Administration, Oral; Anemia, Pernicious; Cobalt Isotopes; Gastric Juice; Half-Life; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Liver; Malabsorption Syndromes; Pancreas; Schilling Test; Stomach; Vitamin B 12; Vitamin B 12 Deficiency; Whole-Body Counting

Topics: Anemia, Pernicious; Diagnosis, Differential; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Gastric Mucosa; Humans; Intestinal Absorption; Intestines; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Child; Child, Preschool; Diphyllobothriasis; Female; Folic Acid Deficiency; Humans; Infant; Infant Nutrition Disorders; Infant, Newborn; Intrinsic Factor; Kwashiorkor; Malabsorption Syndromes; Male; Proteinuria; Thiamine; Transferases; Vitamin B 12 Deficiency

Topics: Animals; Carbohydrate Metabolism; Celiac Disease; Deficiency Diseases; Folic Acid; Histocytochemistry; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Lipid Metabolism; Malabsorption Syndromes; Nutrition Disorders; Postgastrectomy Syndromes; Proteins; Sprue, Tropical; Vitamin B 12; Water-Electrolyte Balance

Topics: Bacteroides; Bile Acids and Salts; Biliary Tract Diseases; Blind Loop Syndrome; Celiac Disease; Cholestyramine Resin; Diagnosis, Differential; Digestion; Escherichia coli; Fatty Acids; Humans; Ileum; Intestinal Diseases; Intestinal Obstruction; Intrinsic Factor; Lipid Metabolism; Liver Circulation; Malabsorption Syndromes; Metabolic Diseases; Triglycerides; Vitamin B 12

Topics: Adolescent; Anemia, Pernicious; Autoantibodies; Child; Chronic Disease; Female; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Ileum; Infant; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Male; Pancreatic Diseases; Pregnancy; Vitamin B 12 Deficiency

Topics: Anemia, Macrocytic; Anemia, Pernicious; Child, Preschool; Gastric Mucosa; Humans; Ileum; Infant; Infant, Newborn; Intestinal Mucosa; Intrinsic Factor; Kidney; Malabsorption Syndromes; Proteinuria; Urogenital Abnormalities; Vitamin B 12

Topics: Anemia, Hypochromic; Anemia, Macrocytic; Carbohydrate Metabolism; Dumping Syndrome; Gastroenterostomy; Hematopoiesis; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Malabsorption Syndromes; Methods; Postgastrectomy Syndromes; Protein-Losing Enteropathies; Vitamin B 12

Topics: Anemia, Pernicious; Clinical Trials as Topic; Humans; Intrinsic Factor; Malabsorption Syndromes; Postgastrectomy Syndromes; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Anemia, Pernicious; Clinical Trials as Topic; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; Radioisotopes; Schilling Test; Spectrometry, Gamma; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult.. We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12  years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients.. Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved.. Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of Cbl malabsorption. Early diagnosis improves the lifelong care required by these patients and prevents potential neurological long-term complications. This study provides the first comprehensive overview of the genetics that underlies the inherited Cbl malabsorption phenotype.

Topics: Anemia, Megaloblastic; Ethnicity; Female; Founder Effect; Genetic Association Studies; Genetic Heterogeneity; Genetic Testing; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Membrane Proteins; Mutation; Proteins; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

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

Current tests for evaluation of vitamin B(12) absorption are problematic because they involve the use of radioactively labeled vitamin B(12). We describe a vitamin B(12) absorption test that circumvents this problem.. We measured cobalamin or transcobalamin saturated with cobalamin (holo-TC) 24 h after three 9-microg doses of vitamin B(12) given orally at 6-h intervals. We studied 17 patients with inherited malabsorption of vitamin B(12) attributable to Imerslund-Grasbeck syndrome (n = 13) or intrinsic factor deficiency (n = 4), their obligate heterozygous biological parents (n = 19), and healthy controls (n = 44).. In the patients, the median (range) change of holo-TC after the B(12) load was not significant [1 (-42 to 5) pmol/L], nor was the change of cobalamin [-3 (-32 to 22) pmol/L], consistent with a lack of measurable active or passive absorption. In controls, however, the median (range) increases of holo-TC and cobalamin were 26 (-6 to 63) pmol/L and 41 (-37 to 109) pmol/L, respectively. Similarly, the parents showed increases of 23 (-2 to 47) pmol/L and 27 (-15 to 94) pmol/L. The mean areas under the ROC curves (95% confidence intervals) were 0.97 (0.93-1.0) for holo-TC and 0.87 (0.79-0.94) for cobalamin, distinguishing patients from controls. At a cutoff of 6 pmol/L for holo-TC, the diagnostic sensitivity (95% confidence interval) was 100 (81-100)%, and the diagnostic specificity was 92 (82-97)%.. Measurement of holo-TC after administration of vitamin B(12) is a promising approach for evaluating vitamin B(12) absorption.

Topics: Absorption; Adolescent; Adult; Child; Female; Heterozygote; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Reference Values; Transcobalamins; Vitamin B 12

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

Topics: Adolescent; Adult; Anemia, Megaloblastic; Child; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Receptors, Cell Surface; Reference Values; Vitamin B 12

Although it is recognized that glossitis is a classical sign of pernicious anemia, occurring in the evolution of this disease, it is unfrequent for this sign to reveal this affection. We report two cases where diagnosis was evacuated on the presence of glossitis and macrocytosis despite absence of anemia. Confirmation was done by low serum cobalamin level, gastritis atrophy and presence of intrinsic factor antibody. We emphasize that increased clinical suspicion may lead to early diagnosis even if anemia is lacking.

Topics: Aged; Anemia, Pernicious; Autoimmune Diseases; Erythrocyte Indices; Female; Glossitis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12 Deficiency

Topics: Diagnosis, Differential; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Transcobalamins; Vitamin B 12

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and an in vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best with in vivo egg yolk-cobalamin absorption test results in the 14 patients (r = 0.731, P < 0.005). Transfer also correlated inversely with gastric juice pH (r = -0.619, P < 0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0-1.3. Pepsin levels did not correlate with in vitro transfer or with absorption in vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poor in vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Gastric Juice; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Intrinsic Factor; Malabsorption Syndromes; Pentagastrin; Pepsin A; Schilling Test; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Gastric Acid; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Parietal Cells, Gastric; Prospective Studies; Vitamin B 12

Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Gräsbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.

Topics: Animals; Dog Diseases; Dogs; Female; Genes, Recessive; Ileum; Intrinsic Factor; Malabsorption Syndromes; Male; Methylmalonic Acid; Pedigree; Receptors, Cell Surface; Vitamin B 12; Vitamin B 12 Deficiency

Ligand binding activity of intrinsic factor-cobalamin receptor (IFCR) was determined in homogenates and isolated brush-border membranes (BBM) of ileum and kidney from dogs exhibiting simple autosomal recessive inheritance of selective cobalamin malabsorption (Fyfe, J. C., Giger, U., Hall, C. A., Jezyk, P. F., Klumpp, S. A., Levine, J. S., and Patterson, D. F. (1991) Pediatr. Res. 29, 24-31). IFCR activity of affected dog ileal homogenates was 3-4-fold higher than normal whereas IFCR activity in affected dog kidney homogenates was one-tenth of normal. The recovery of IFCR activity in the BBM of ileum and renal cortex of affected dogs was 30- and 20-fold less than normal, respectively. The dissociation constant (Kd) for intrinsic factor-cobalamin was similar in BBM of both tissues and was the same in affected and normal dogs. In the affected dog ileal BBM, activities of alkaline phosphatase and sucrase-isomaltase and vesicular transport of glucose and Na(+)-taurocholate were normal. Immunoblots showed no IFCR cross-reactive material in the ileal or renal BBM of affected dogs. IFCR purified by affinity chromatography from kidney of both normal and affected dogs had an Mr = 230,000. However, amino acid analysis revealed that the affected dog IFCR had more lysine than the normal, and protease cleavage of the purified IFCRs revealed different peptide maps. Asparagine-linked oligosaccharides of both proteins were sensitive to peptide N-glycosidase F cleavage, but only the affected dog IFCR was endoglycosidase H sensitive. These results suggest that cobalamin malabsorption in this canine family is caused by inefficient BBM expression of IFCR due to a mutation of IFCR and its retention in an early biosynthetic compartment.

Topics: Alkaline Phosphatase; Amino Acids; Animals; Blotting, Western; Cell Compartmentation; Dog Diseases; Dogs; Glucose; Ileum; Intestinal Mucosa; Intrinsic Factor; Kidney; Malabsorption Syndromes; Microvilli; Peptide Mapping; Sodium; Sucrase; Taurocholic Acid

A case of pernicious anemia in a 30 years old men is described. This disease was typical for the hematologic, immunologic and medullary patterns, for his evolution, but the Schilling test, a dual tracer method, did not confirm the diagnosis. The contradictory of this result can be explained wether by the bias of the test itself, or by the intestinal malabsorption due to the vitamin B12 deficiency, or by other factors like bacterial overgrowth state (associated in the pernicious anemia) and a high level of antibodies to intrinsic factor.

Topics: Adult; Anemia, Pernicious; False Negative Reactions; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Follow-Up Studies; Humans; Intestinal Absorption; Intrinsic Factor; Lymphangiectasis, Intestinal; Malabsorption Syndromes; Male; Protein-Losing Enteropathies; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The intraluminal transport of cobalamin (Cbl) remains controversial in chronic pancreatitis. We have determined the ability of intestinal juice to degrade the digestive holohaptocorrin (R binder) and the binding of endogenous Cbl in basal intestinal juice from 22 chronic pancreatitis patients and 22 controls. The intestinal juice from patients and controls degraded 34.7 +/- 32.3% and 95.2 +/- 7.2% of holohaptocorrin, respectively. This percentage was correlated with the trypsin output but not with the Schilling test. The unsaturated Cbl-binding capacity was similar in both groups. Respectively, 62.5 +/- 26.6% and 19.6 +/- 11.7% of endogenous Cbl was bound to haptocorrin in intestinal juice from patients and controls. These percentages were correlated with the Schilling test and with the ability of intestinal juice to degrade haptocorrin. We concluded that 1) the sequestration of Cbl to haptocorrin is one of the factors responsible for the malabsorption of crystalline Cbl in patients with chronic pancreatitis and 2) enterohepatic circulation of Cbl can be interrupted in some cases of chronic pancreatitis.

Topics: Adult; Aged; Chronic Disease; Chymotrypsin; Corrinoids; Humans; Intestinal Secretions; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; Pancreatitis; Schilling Test; Trypsin; Vitamin B 12

One of the diverse group of disorders that cause pernicious anemia in childhood, juvenile pernicious anemia, has been characterized by normal acid secretion, normal gastric mucosal histology, adequate intestinal absorption of cobalamin in the presence of exogenous gastric intrinsic factor (IF), but the inadequate "production" of IF from birth. Inadequate production has been inferred from the absence of measured IF in stimulated gastric secretions. To assess whether immunogenic IF was commonly present within the parietal cells of subjects with juvenile pernicious anemia, we studied paraffin-embedded biopsy material from the largest reported series of childhood pernicious anemia, using a well-characterized indirect immunoperoxidase method. Preliminary studies were able to identify IF in fundic mucosal biopsy specimens that had been stored for as long as 27 yr. In a blinded evaluation, six of the nine fundic biopsy specimens from children with juvenile pernicious anemia demonstrated immunogenic IF. Two sets of siblings were concordant for the presence or absence of intracellular IF, and six gastric biopsy specimens from patients with Imerslund's syndrome were all positive for IF. These findings indicate that juvenile pernicious anemia is a heterogeneous group of disorders whose similar clinical expression might be caused by (a) inadequate synthesis of IF, (b) a block in IF secretion, (c) the secretion of an abnormal IF that does not bind to cobalamin, or (d) the secretion of other abnormal IFs that could contain a number of other functional defects.

Topics: Anemia, Pernicious; Child, Preschool; Gastric Fundus; Histocytochemistry; Humans; Immunoenzyme Techniques; Intrinsic Factor; Malabsorption Syndromes; Parietal Cells, Gastric; Retrospective Studies; Vitamin B 12 Deficiency

Topics: Child, Preschool; Female; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12

Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Vitamin B 12 Deficiency

In a survey of 46 randomly selected diabetic patients on biguanide therapy, 30% had malabsorption of vitamin B12. Withdrawal of the drug resulted in normal absorption in only half of those with malabsorption. In most patients with persistent malabsorption, the results of absorption tests with exogenous intrinsic factor suggested the diagnosis of coincidental intrinsic factor deficiency. Further considerations, however, led to the concept that biguanides can induce malabsorption by two different mechanisms. One of these is temporary and unrelated to intrinsic factor secretion and the other is permanent and mediated by depression of intrinsic factor secretion.

Topics: Adult; Aged; Biguanides; Diabetes Mellitus; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Metformin; Middle Aged; Phenformin; Vitamin B 12

Classic pernicious anemia with abnormal Schilling test results developed in a previously described vegan patient who had coexisting subtle cobalamin malabsorption (demonstrable by abnormal ovalbumin-cobalamin absorption test results but normal Schilling test results). This suggests that the ovalbumin-cobalamin absorption test or a modified version may serve as a prodromal phenomenon to identify patients at risk for developing pernicious anemia. The patient's transformation was also accompanied by the appearance of serum anti-intrinsic factor antibody. A modified assay retrospectively detected this antibody a year earlier than did the standard assay, indicating that such modification enhances the sensitivity of this useful test.

Topics: Anemia, Pernicious; Antibodies; Diet, Vegetarian; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12

It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

Topics: 4-Aminobenzoic Acid; Amylases; Carbon Radioisotopes; Exocrine Pancreatic Insufficiency; Fats; Feces; Humans; Intrinsic Factor; Lipase; Malabsorption Syndromes; Pancreas; Pancreatic Function Tests; Pancreatin; Secretin; Triolein; Vitamin B 12

Topics: Anemia, Pernicious; Humans; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12; Vitamin B 12 Deficiency

The megaloblastic anaemia observed in patients with chronic atrophic gastritis is usually due to malabsorption of vitamin B12. In some cases, the absence of intrinsic factor supports the diagnosis of pernicious anaemia but other factors, the importance of which varies from case to case, are also involved. They include proliferation of bacteria in the lumen of the gut, intestinal cell abnormalities resulting from lack of vitamin B12 and low hydrochloric acid output with subsequent reduction in the release of vitamin B12 from foodstuffs. With regard to treatment, it would seem justified to combine oral broad-spectrum antibiotics with parenteral administration of vitamin B12.

Topics: Achlorhydria; Aged; Anemia, Megaloblastic; Female; Gastritis; Gastritis, Atrophic; Humans; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12 Deficiency

The clinical and laboratory data from 75 patients with altered vitamin B 12 absorption were reviewed. In 36 cases the diagnosis of pernicious anaemia had been established. Of these, 14 patients showed malabsorption of radiolabelled vitamin B 12, but the absorption of vitamin B 12 bound to the intrinsic factor (IF) was normal (Group A). The other 22 patients with pernicious anaemia showed altered free and IF-bound vitamin B 12 absorption (Group B). Laboratory and clinical data and the absorption tests (xylose and fat excretion) were more abnormal in group B than in group A. Finally, 39 patients (Group C) with general malabsorption showed alternation of the absorption of free and IF-bound vitamin B 12 (Group C). The clinical nd biological data were different in these patients from that found in groups A and B. It is possible that in patients with pernicious anaemia who are untreated an alteration of the intestinal mucosa may produce a malabsorption of vitamin B 12 even in the presence of intrinsic factor.

Topics: Anemia, Pernicious; Cobalt Radioisotopes; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Protein Binding; Vitamin B 12

Topics: Alcoholism; Celiac Disease; Exocrine Pancreatic Insufficiency; Folic Acid; Folic Acid Deficiency; Gastric Mucosa; Glutamates; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Protein Binding; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

Protein- (chicken serum) bound [57Co]cyanocobalamin absorption was evaluated in five hypochlorhydric patients who had developed B12 deficiency despite having normal absorption of unbound crystalline vitamin B12. All five patients had decreased urinary excretion of protein-bound B12 (0.06--0.34%) as compared to twelve normal controls (0.61--5.6%), P less than .001. Improvement in protein-bound B12 absorption in four of the five patients occurred with the exogenous administration of hydrochloric acid, pepsin, gastric intrinsic factor, or a combination thereof. Vitamin B12 deficiency developing in the setting of hypochlorhydria may result from deficiency of acid-peptic digestion of B12 bound to protein and/or a relative deficiency of intrinsic factor. This digestive defect is not detected with tests which measure the absorption of unbound crystalline B12 but is detected by a simple test which employs B12 bound to chicken serum as the form of protein-bound B12.

Topics: Aged; Female; Gastrectomy; Humans; Hydrochloric Acid; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Pepsin A; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Human bile incubated with vitamin B12 bound to intrinsic factor in human gastric juice will effectively dissociate this complex, and the vitamin will transfer to non-intrinsic factor unsaturated binding protein(s) contained in bile. Preincubation of the bile with pancreatic enzymes, particularly trypsin, and pepsin, decreases this effect of bile on the intrinsic factor--vitamin B12 complex by digesting the unsaturated binder(s) in the bile. These studies help explain why there is malabsorption of tracer amounts of vitamin B12 in some patients with pancreatic insufficiency, and why this abnormality is correctable by the administration of pancreatic extract.

Topics: Bile; Humans; Intrinsic Factor; Malabsorption Syndromes; Pancreatic Diseases; Pepsin A; Trypsin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Aged; Anemia, Pernicious; Atrophy; Chronic Disease; Female; Gastritis; Humans; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Pepsin A

Topics: Adult; Child, Preschool; Cystic Fibrosis; Diabetes Complications; Dysgammaglobulinemia; Female; Humans; Immunoglobulin A; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin Light Chains; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male

A patient with otherwise typical addisonian pernicious anaemia and serum anti-intrinsic-factor antibody failed to respond to oral intrinsic factor on repeated testing during three years of therapy with parenteral vitamin B 12. There was no evidence of generalised malaborption. To test the hypothesis that binding of intrinsic factor to gut secretory antibody was responsible, an "augmented" Schilling test was devised using eight times the usual dose of intrinsic factor. This increased dose of intrinsic factor resulted in normal absorption of the test dose of vitamin B 12 confirming the diagnosis. It is suggested that the augmented Schilling test may be useful in the diagnosis of the occasional patient with features of pernicious anaemia who fails to respond to conventional doses of intrinsic factor in the Schilling test.

Topics: Administration, Oral; Adult; Anemia, Pernicious; Autoantibodies; Binding Sites, Antibody; Diagnosis, Differential; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Vitamin B 12 Deficiency

The intraluminal fate of orally administered radioactive vitamin B12 has been studied in control subjects with normal vitamin B12 absorption and those with vitamin B12 malabsorption due to tropical sprue. In control subjects 1 to 21% of the dose was bound to sedimentable material and 37 to 75% was bound to immunoreactive intrinsic factor. In subjects with vitamin B12 malabsorption due to tropical sprue, the results were identical with the control subjects. Bacteriological studies showed a statistically significant correlation between both the number of flora in the jejunum and the number of bacteroides in both the jejunum and ileum and vitamin B12 malabsorption. In patients with tropical sprue who have normal intrinsic factor secretion, the vitamin B12 absorptive defect is not due to binding of the vitamin to bacteria or to alteration to the intrinsic factor vitamin B12 complex in the intestinal lumen. The lesion appears to be one of the mucosal cell receptors or of the cells themselves, possibly caused by bacterial toxins.

Topics: Bacteroides; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Intubation, Gastrointestinal; Jejunum; Malabsorption Syndromes; Sprue, Tropical; Tetracycline; Vitamin B 12

Topics: Adult; Alcoholism; Biological Transport, Active; Chronic Disease; Cobalt Radioisotopes; Diet Therapy; Dose-Response Relationship, Drug; Ethanol; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Lipid Metabolism; Malabsorption Syndromes; Male; Middle Aged; Nutrition Disorders; Pancreatin; Vitamin B 12; Vitamins; Xylose

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Gastrectomy; Humans; Ileum; Intrinsic Factor; Malabsorption Syndromes; Metabolism, Inborn Errors; Schilling Test; Time Factors; Vitamin B 12

Topics: Achlorhydria; Adult; Aged; Anemia, Pernicious; Atrophy; Autoantibodies; Autoimmune Diseases; Female; Follow-Up Studies; Gastritis; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Time Factors; Vitamin B 12

Topics: Adult; Female; Gastric Acidity Determination; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Multiple Sclerosis; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Cobalt Radioisotopes; Duodenum; Erythrocyte Count; Female; Hemoglobins; Humans; Intestinal Secretions; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Pancreatitis; Schilling Test; Trypsin; Vitamin B 12

Topics: Administration, Oral; Adult; Anemia; Chronic Disease; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Pancreatitis; Schilling Test; Trypsin; Vitamin B 12

Topics: Anemia, Pernicious; Cobalt Radioisotopes; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Methods; Time Factors; Vitamin B 12

Topics: Adolescent; Adult; Agammaglobulinemia; Anemia, Macrocytic; Anemia, Megaloblastic; Antibody Formation; Chronic Disease; Female; Gastric Juice; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male; Proteinuria; Syndrome; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Anemia, Pernicious; Chronic Disease; Consanguinity; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Recurrence; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Cobalt Radioisotopes; Humans; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Vitamin B 12

Topics: Anemia, Pernicious; Animals; Cobalt Radioisotopes; Gastric Acidity Determination; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Stomach; Swine; Vitamin B 12

Topics: Adolescent; Adult; Aged; Alcoholism; Anemia, Pernicious; Diagnostic Errors; Female; Folic Acid; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Achlorhydria; Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Antibodies; Erythrocyte Count; Folic Acid; Histamine; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; Pentagastrin; Reticulocytes; Schilling Test; South Africa; Stimulation, Chemical; Syndrome; Tetracycline; Vitamin B 12

Topics: Body Height; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Cobalt Isotopes; Convalescence; Creatinine; Diarrhea; Diarrhea, Infantile; Diet Therapy; Dietary Proteins; Humans; Ileum; Infant; Infant Nutrition Disorders; Infant Nutritional Physiological Phenomena; Intrinsic Factor; Malabsorption Syndromes; Nutrition Disorders; Protein-Energy Malnutrition; Schilling Test; Vitamin B 12

Topics: Adolescent; Adult; Agglutination; Anemia, Pernicious; Animals; Antibodies; Antibodies, Antinuclear; Child; Cobalt Radioisotopes; Female; Fluorescent Antibody Technique; Gastric Mucosa; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Schilling Test; Swine; Thyroid Gland; Vitamin B 12; Vitamin B 12 Deficiency

After cobalt teletherapy for carcinoma of the bladder, eight out of 14 consecutively admitted patients were shown to have malabsorption of vitamin B(12), though none had developed a megaloblastic anaemia. Despite lack of symptoms this group of patients is at risk after radiotherapy.

Topics: Cobalt Isotopes; Female; Follow-Up Studies; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Radioisotope Teletherapy; Schilling Test; Urinary Bladder Neoplasms; Vitamin B 12

Topics: Adolescent; Adult; Age Factors; Aged; Anemia, Macrocytic; Anemia, Pernicious; Autoantibodies; Black or African American; Black People; Diagnosis, Differential; Ethnicity; Folic Acid; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Middle Aged; South Africa; Syndrome; Tetracycline; Vitamin B 12

Topics: Anemia, Macrocytic; Cobalt Isotopes; Feces; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Cobalt Isotopes; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Pancreatic Diseases; Pancreatic Extracts; Schilling Test; Vitamin B 12

Topics: Anemia, Macrocytic; Female; Fetus; Glycoproteins; Humans; Ileum; Intrinsic Factor; Malabsorption Syndromes; Pregnancy; Protein Binding; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Anemia, Sideroblastic; Blind Loop Syndrome; Crohn Disease; Diverticulitis; Folic Acid Deficiency; Gastritis; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12 Deficiency; Whipple Disease

Topics: Administration, Oral; Adult; Aged; Anemia, Pernicious; Biological Assay; Cobalt Isotopes; Euglena gracilis; Female; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Diet; Female; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Nutritional Physiological Phenomena; Nutritional Requirements; Pregnancy; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Anemia, Macrocytic; Humans; Immunologic Deficiency Syndromes; Intrinsic Factor; Malabsorption Syndromes; Male; Proteinuria; Vitamin B 12; Vitamin B 12 Deficiency

The effect of partial pancreatectomy (80-90%) on vitamin B(12) absorption was studied in the rat. The absorption of 5 ng of (57)Co-labeled vitamin B(12) was significantly reduced from 70 +/-2.5% (mean +/-SE) in control and sham-operated rats to 32 +/-2.6% in partially pancreatectomized rats. Hog pancreatic extract (0.17 g/kg) improved vitamin B(12) absorption from 30.0 to 61.0% in partially pancreatectomized rats but did not alter vitamin B(12) absorption in control rats. Chloramphenicol did not enhance vitamin B(12) absorption in partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption. The partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption were sacrificed and the stomach and small bowel studied in vitro to further define the pathogenesis of the vitamin B(12) malabsorption. Rat gastric intrinsic factor stimulated vitamin B(12) uptake by intestinal sacs prepared from partially pancreatectomized rats 3.1-fold. Gastric intrinsic factor prepared from partially pancreatectomized rats was as effective in promoting vitamin B(12) uptake by rat intestinal sacs as intrinsic factor prepared from control rats. These data indicate that partially pancreatectomized rats develop an abnormality in the absorption of labeled vitamin B(12) which can be corrected by pancreatic extract. The vitamin B(12) malabsorption is due to neither an alteration in gastric intrinsic factor activity nor an impairment of the intrinsic factor-vitamin B(12) receptor in the intestine. It is suggested that in the partially pancreatectomized rats the intrinsic factor-vitamin B(12) complex exists in a form which is not available for absorption.

Topics: Animals; Body Weight; Chloramphenicol; Cobalt Isotopes; Disease Models, Animal; Gastric Mucosa; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Male; Pancreas; Pancreatectomy; Rats; Vitamin B 12

Topics: Adolescent; Anemia, Pernicious; Binding Sites; Biopsy; Child; Gastric Juice; Humans; Ileum; Intestinal Absorption; Intestinal Mucosa; Intrinsic Factor; Malabsorption Syndromes; Male; Microscopy, Electron; Proteinuria; Vitamin B 12

Topics: Animals; Bacteria; Blind Loop Syndrome; Cobalt Isotopes; Culture Media; Gastric Juice; Intestinal Absorption; Intrinsic Factor; Jejunum; Malabsorption Syndromes; Male; Methods; Neomycin; Rats; Tetracycline; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Pernicious; Antigens; Autoantibodies; Cell Migration Inhibition; Female; Gastric Juice; Humans; Hypersensitivity, Delayed; Immunoglobulins; Intrinsic Factor; Leukocytes; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12

Topics: Adolescent; Anemia, Macrocytic; Anemia, Pernicious; Antigens; Chromatography; Chromatography, Gel; Cobalt Isotopes; Gastric Juice; Humans; Intestinal Mucosa; Intrinsic Factor; Isoelectric Focusing; Malabsorption Syndromes; Male; Vitamin B 12

Topics: Administration, Oral; Anemia, Pernicious; Cobalt Isotopes; Crohn Disease; Female; Humans; Intestinal Absorption; Intrinsic Factor; Kidney Diseases; Malabsorption Syndromes; Male; Methods; Schilling Test; Time Factors; Vitamin B 12

Topics: Achlorhydria; Anemia, Pernicious; Antibodies; Biopsy; Cobalt Isotopes; Complement Fixation Tests; Deficiency Diseases; Fats; Feces; Female; Folic Acid; Gastric Juice; Gastric Mucosa; Gastritis; Humans; India; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12; Xylose

Topics: Adolescent; Anemia, Macrocytic; Bone Marrow Examination; Female; Gastric Juice; Humans; Hydrochloric Acid; Infant; Intrinsic Factor; Kidney Function Tests; Malabsorption Syndromes; Male; Proteinuria; Schilling Test; Vitamin B 12

Topics: Bile Acids and Salts; Blind Loop Syndrome; Celiac Disease; Humans; Indican; Intrinsic Factor; Jejunum; Malabsorption Syndromes; Schilling Test

Topics: Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Vitamin B 12

Topics: Administration, Oral; Antibodies; Bacteria; Calcium; Chronic Disease; Cobalt Isotopes; Feces; Hemoglobins; Humans; Hydrogen-Ion Concentration; Ileum; Intestinal Absorption; Intestinal Secretions; Intrinsic Factor; Jejunum; Lipid Metabolism; Lipids; Malabsorption Syndromes; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Vitamin B 12

Vitamin-B(12) malabsorption has been found in 21 (30%) of 71 diabetic patients taking long-term metformin therapy in addition to dietary management. The patients with evidence of B(12) malabsorption had significantly lower haemoglobin levels (and significantly higher serum folic acid levels) than those with normal B(12) absorption. Steatorrhoea was found in only one patient. Stopping metformin therapy resulted in reversion of B(12) absorption to normal in most patients examined. Four patients with B(12) malabsorption were found to have pathologically low serum B(12) levels. The causes and implications of these findings are discussed and it is concluded that all patients on long-term metformin therapy should have annual serum B(12) estimations.

Topics: Aged; Cobalt Isotopes; Diabetes Mellitus; Dietary Fats; Folic Acid; Hemoglobinometry; Humans; Ileum; Intestinal Absorption; Intrinsic Factor; Lipid Metabolism; Malabsorption Syndromes; Metformin; Middle Aged; Radiography; Vitamin B 12

Topics: Achlorhydria; Anemia, Pernicious; Cobalt Isotopes; Diagnosis, Differential; Gastric Juice; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Radiometry; Succinates; Vitamin B 12

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Child, Preschool; Diagnosis, Differential; Female; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Vitamin B 12 Deficiency

Topics: Adolescent; Adrenal Gland Diseases; Adrenal Insufficiency; Adrenalectomy; Adult; Aged; Anemia, Pernicious; Antibodies; Antigens; Cobalt Isotopes; Cortisone; Cushing Syndrome; Female; Humans; Hypopituitarism; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12

Topics: Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12 Deficiency

Topics: Adult; Aged; Anemia, Macrocytic; Anemia, Pernicious; Cobalt Isotopes; Female; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Vitamin B 12

Topics: Absorption; Achlorhydria; Anemia, Pernicious; Cobalt Isotopes; Diagnosis, Differential; Diet; Fasting; Gastrectomy; Humans; Intrinsic Factor; Malabsorption Syndromes; Methods; Radionuclide Imaging; Stomach; Vitamin B 12

Three patients are described, and they provide further evidence that deficiency of folic acid and vitamin B(12) may sometimes affect small intestinal function. Malabsorption of both xylose and vitamin B(12) returned to normal in one patient after treatment of a megaloblastic anaemia due to dietary deficiency of folic acid. Impaired absorption of vitamin B(12) was corrected by vitamin B(12) therapy in the other two patients. The initial cause of the vitamin B(12) deficiency in one patient was not apparent, but she was taking Gynovlar 21, which may have been an aetiological factor. In the third patient the small intestinal defect was secondary to pernicious anaemia, and in a group of 98 other patients with pernicious anaemia intrinsic factor did not improve vitamin B(12) absorption in six, and only partially corrected absorption in 30. The significance of these observations is discussed.

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Contraceptives, Oral; Female; Folic Acid; Folic Acid Deficiency; Humans; Intestinal Absorption; Intestine, Small; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12; Vitamin B 12 Deficiency; Xylose

Topics: Anemia, Pernicious; Cobalt Isotopes; Diagnosis, Differential; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Radionuclide Imaging; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Macrocytic; Anemia, Pernicious; Autoantibodies; Blood Cell Count; Diagnosis, Differential; Diphyllobothriasis; Female; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Antibodies; Blood Cell Count; Bone Marrow Examination; Deficiency Diseases; Diverticulum; Fats; Feces; Female; Folic Acid; Hematocrit; Hemoglobinometry; Humans; Intrinsic Factor; Malabsorption Syndromes; Neomycin; Schilling Test; Vitamin B 12

Topics: Adult; Anemia, Pernicious; Autoantibodies; Child; Gastric Juice; Humans; Intrinsic Factor; Malabsorption Syndromes; Vitamin B 12

Topics: Adult; Bicarbonates; Binding Sites; Celiac Disease; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adolescent; Adult; Aged; Child; Crohn Disease; Dietary Fats; Female; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Vitamin B 12; Xylose

Topics: Adult; Aged; Aminosalicylic Acids; Blood Cell Count; Feces; Female; Folic Acid; Humans; Intestinal Absorption; Intrinsic Factor; Iron; Jejunum; Lipid Metabolism; Malabsorption Syndromes; Male; Middle Aged; Schilling Test; Tuberculosis, Pulmonary; Vitamin B 12; Xylose

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

Topics: Anemia, Pernicious; Animals; Cobalt Isotopes; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Swine; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Antibodies; Cobalt Isotopes; Digestive System; Gastric Juice; Humans; Intestinal Absorption; Intrinsic Factor; Malabsorption Syndromes; Neutralization Tests; Schilling Test; Vitamin B 12

Topics: Anemia, Pernicious; Animals; Child, Preschool; Feces; Female; Humans; Intrinsic Factor; Kidney; Lipids; Malabsorption Syndromes; Schilling Test; Swine; Vitamin B 12 Deficiency; Xylose

Topics: Adolescent; Anemia, Macrocytic; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12 Deficiency

Topics: Aminosalicylic Acids; Animals; Dialysis; Intestines; Intrinsic Factor; Malabsorption Syndromes; Rats; Stomach; Tissue Extracts; Vitamin B 12

Topics: Achlorhydria; Anemia, Pernicious; Antibodies; Blood; Carotenoids; Humans; In Vitro Techniques; Intrinsic Factor; Malabsorption Syndromes; Schilling Test; Vitamin A; Vitamin B 12; Vitamin B 12 Deficiency; Xylose

Topics: Anemia; Anemia, Pernicious; Antibody Formation; Diagnosis; Humans; Intrinsic Factor; Malabsorption Syndromes; Metabolism; Pharmacology; Schilling Test; Vitamin B 12

Topics: Anemia, Pernicious; Animals; Blood; Humans; Intrinsic Factor; Iodine Isotopes; Liver; Malabsorption Syndromes; Swine; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Anemia, Pernicious; Celiac Disease; Deficiency Diseases; Diagnosis; Female; Folic Acid; Humans; Intrinsic Factor; Malabsorption Syndromes; Physiology; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Sprue, Tropical; Vitamin B 12

Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Blood Cell Count; Deficiency Diseases; Drug Therapy; Female; Folic Acid; Folic Acid Deficiency; Humans; Intrinsic Factor; Malabsorption Syndromes; Metabolism; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Vitamin B 12; Vitamin B 12 Deficiency