Schilling Test Research Articles

Prevalence of Undiagnosed Pernicious Anemia in the Elderly

Existing information about the prevalence of pernicious anemia is largely based on older surveys that favored florid manifestations, tended to be retrospective analyses of previously diagnosed disease, and usually studied homogeneous European populations. The lack of current data in the United States has, among other things, hampered discussions of the proposal to increase folate intake by the general population. To estimate the prevalence of undiagnosed and untreated pernicious anemia among the elderly. A prospective survey of cobalamin levels and anti-intrinsic factor antibody was done in the elderly. Blood testing was done in 729 people aged 60 years or older and follow-up assessment with the Schilling test and other tests was offered when results were abnormal. Seventeen subjects were found to have pernicious anemia, usually with only minimal clinical manifestations of cobalamin deficiency. Although cobalamin deficiency had been suspected by the physicians of three subjects, they had been treated inadequately and still had evidence of deficiency. Excluding these three partially treated subjects from the analysis, 1.9% of the survey population had unrecognized and untreated pernicious anemia. The prevalence was 2.7% in women and 1.4% in men; 4.3% of the black women and 4.0% of the white women had pernicious anemia. Undiagnosed pernicious anemia is a common finding in the elderly, especially among black and white women. If these findings can be extrapolated, almost 800000 elderly people in the United States have undiagnosed and untreated pernicious anemia, and, thus, would be at possible risk for masked cobalamin deficiency if exposed to large amounts of folate. This number does not include those elderly with cobalamin deficiency caused by other disorders or the still unknown number of younger people with unrecognized pernicious anemia and other causes of deficiency.

Plasma Lathosterol as a Screening Test for Bile Acid Malabsorption Due to Ileal Resection: Correlation with 75SeHCAT Test and Faecal Bile Acid Excretion

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

Influence of Continental Ileal Urinary Diversion on Vitamin B12 Absorption

Purpose Because vitamin B12 is mainly absorbed in the terminal ileum, we evaluated potential absorption deficiencies in continent ileal reservoirs. Materials and Methods Eight to 25 months (mean 13) after surgery we evaluated 25 patients with a Kock pouch and 29 with an ileal neobladder. A Schilling test and red blood count were done, and serum levels of vitamin B12 and folic acid were determined. Results Absorptive capacity was decreased in 20 of the 25 Kock pouch patients but none of the 29 ileal neobladder patients. Four patients in each group had low vitamin B12 levels. No patient had megaloblastic anemia. Folic acid levels were normal in all patients. Conclusions A loss of 50 cm. of terminal ileum seems to be the critical margin for sufficient vitamin B12 absorption.

Multivariate Homogeneity Testing Using an Extended Concept of Nearest Neighbors

AbstractGiven independent multivariate random samples {Xij: j = 1, …, ni} from Fi, for i = 1,2, a test is desired for H0: F1 = F2 against general alternatives. Consider the k · (n1 + n2) possible ways of choosing one observation from the combined samples and then one of its k nearest neighbors, and let Sk be the proportion of these choices in which the point and neighbor are in the same sample. Schilling (1986) proposed Sk as a test statistic, but did not indicate how to determine k. We suggest as test statistic W = N Σ kSk, which we show is equivalent to a sum of N Wilcoxon rank sums, and also to a sum of two two‐sample U‐statistics of degrees (1, 2) and (2, 1). Simulation with multivariate normal data suggests that our test is generally more powerful than Schilling's test using k = 1, 2, or 3. We illustrate its use with Fisher's iris data.

Cobalamin.

Cobalamin (vitamin B12) is an essential nutrient derived exclusively from bacterial sources. It is an essential cofactor for three known enzymatic reactions. Untreated deficiency, caused by either the autoimmune disease pernicious anemia or nutritional lack, results in a macrocytic anemia and/or subacute combined degeneration of the spinal cord and is eventually fatal. Cobalamin in serum is bound to two proteins, transcobalamin and haptocorrin. The former is responsible for the essential delivery of cobalamin to most tissues. Inadequate tissue availability of cobalamin results in increased concentration of methylmalonic acid and homocyst(e)ine due to inhibition of methylmalonyl-CoA mutase and methionine synthase, respectively. Strict vegetarians have long been known to be at risk of cobalamin deficiency, which develops insidiously over many years. It is now clear that a significant number of the elderly and HIV-positive individuals are also at increased risk of deficiency. Any individual with reduced ability to split cobalamin from food-protein may also become deficient even though intrinsic factor is present. Diagnosis of cobalamin deficiency has frequently relied on total serum cobalamin and the Schilling test. Newer approaches such as analysis of methylmalonic acid, homocyst(e)ine, holotranscobalamin, anti-intrinsic factor antibodies, and serum gastrin may provide more cost-effective testing, as well as identify those with a covert deficiency.

Vitamin B-12 deficiency after gastric surgery for obesity

Low serum vitamin B-12 concentrations after gastric bypass (GB) surgery for obesity were observed in 11 of 28 patients without detectable impairment of crystalline vitamin B-12 absorption. This was observed in 2 of 19 patients with vertical banded gastroplasty (VBG). In contrast, protein-bound vitamin B-12 absorption was markedly impaired, as demonstrated in eight of these patients after GB (n = 7) and VBG (n = 1). Correction of this impaired absorption occurred when protein-bound vitamin B-12 was incubated with an enzyme mixture before consumption. Simultaneous ingestion of the enzyme mixture with protein-bound vitamin B-12 did not improve absorption of the vitamin. In a separate experiment, 10 patients with a normal result from the Schilling test failed to correct low serum vitamin B-12 concentrations with a quantity of oral crystalline vitamin B-12 equal to the recommended dietary allowance of 2 micrograms, taken twice daily for 3 mo. Serum total homocysteine values declined during this interval. An oral daily dose of 350 micrograms crystalline vitamin B-12 raised the average serum vitamin B-12 concentration to an amount greater than the lower reference limit. A dose > 350 micrograms/d was required to raise all patients' vitamin B-12 concentrations above this concentration rather than just above the population mean. We conclude that because concentrations of oral crystalline vitamin B-12 were required to normalize serum vitamin B-12 concentrations, that a mechanism other than formation of a vitamin B-12 intrinsic factor complex is responsible for crystalline vitamin B-12 absorption after GB for obesity.

10 Malabsorption of food cobalamin

Food-cobalamin malabsorption is marked by the inability to release cobalamin from food, which therefore cannot be taken up by intrinsic factor for absorption. The defect is not detectable by classical clinical tests like the Schilling test which are all based on the absorption of free, crystalline cobalamin. Tests of food-cobalamin absorption have been devised, the most popular ones using cobalamin bound to eggs or to chicken serum. The disparity between the abnormal results of these tests and the normal results with the Schilling test defines the disorder of food-cobalamin malabsorption. Release of cobalamin from food requires acid and pepsin, and most food-cobalamin malabsorptive states can be traced to gastric defects. However, other mechanisms may also play a role. The malabsorption is limited to food cobalamin and any free cobalamin, presumably including recycled biliary cobalamin, will be absorbed normally, which may explain its frequently insidious nature. The effect on cobalamin status covers a broad spectrum. At one extreme, some individuals, perhaps in the earliest stages, have normal cobalamin status, while at the other extreme may be found deficiency every bit as severe as in the most florid case of pernicious anaemia. Most often, however, the deficiency is mild, frequently marked by only a low serum cobalamin level, mild evidence of metabolic insufficiency and, sometimes, minimal clinical sequelae. Moreover, in some cases the gastric defect progresses and intrinsic factor secretion is affected, thus transforming into classical pernicious anaemia; this is not inevitable, however, and probably occurs in only a minority of patients. The course of food-cobalamin malabsorption is therefore a varied one. Nevertheless, it may be the most common cause of subtle or mild cobalamin deficiency and it is also sometimes associated with severe deficiency. Its identification and treatment need to be considered more widely in the clinical setting.

11 Neurological complications of acquired cobalamin deficiency: clinical aspects

Neuropsychiatric syndromes occur in about 40% of Cbl-deficient patients and are characterized by progressive and variable damage to the spinal cord, peripheral nerves and cerebrum. The first abnormality is usually sensory impairment, most often presenting as distal and symmetrical paraesthesiae of the lower limbs and frequently associated with ataxia. Almost all patients demonstrate loss of vibratory sensation, often in association with diminished proprioception and cutaneous sensation and a Romberg sign. Corticospinal tract involvement is common in more advanced cases, with abnormal reflexes, motor impairment and, ultimately, spastic paraparesis. A minority of patients exhibit mental or psychiatric disturbances or autonomic signs, but these rarely if ever occur in the absence of other neurological changes. Because N2O inactivates Cbl, abuse of the gas may lead to typical Cbl neuropathy. Haematological changes are minimal and serum Cbl levels and Schilling tests normal in most patients. The severity of neurological abnormalities prior to treatment correlates with the duration of symptoms and the haemoglobin level. Initial severity, symptom duration and initial haemoglobin also correlate with residual neurological damage after Cbl therapy. The inverse correlation between severity of anaemia and neurological damage is not understood. Diagnosis of Cbl neuropathy can usually be made in the presence of the typical neuropsychiatric abnormalities, a low serum Cbl level and evidence of megaloblastic haemopoiesis. In some patients serum MMA and HCYS determinations or a therapeutic trial may be required. A neurological response usually occurs within the first 3 months, although further improvement may occur with time. Patients with advanced disease may be left with major residual disability. Therefore early diagnosis is critical. Pharmacological doses of folic acid reverse the haematological abnormalities of Cbl deficiency. This may allow neuropathy to develop or progress and make recognition of deficiency more difficult. There is no clear evidence that folic acid therapy precipitates or exacerbates Cbl neuropathy. Haematological improvement may occur in a fraction of patients receiving small doses of folate, but the data are inadequate to predict the danger of low levels of folate supplementation in the general population.

Clinical correlates of subnormal vitamin B12 levels in patients infected with the human immunodeficiency virus.

To determine the prevalence and describe the clinical correlates of subnormal cobalamin levels in subjects infected with the human immunodeficiency virus (HIV), and to assess its relationship to virus-mediated immunosuppression and/or anti-viral therapy. Outpatient referral clinic in tertiary care hospital. 200 HIV infected individuals. Descriptive cross sectional survey, with prospective follow-up in a subgroup of patients before and after initiation of zidovudine therapy. Routine complete blood count, serum B12 assay, CD4 counts. Serum homocysteine levels, and Schilling tests were performed on subgroups of study subjects. Subnormal serum B12 levels were found in 61 subjects (30.5%). B12 deficient subjects were more likely to be taking zidovudine. (P = .007). Serum homocysteine levels were significantly higher in patients with subnormal cobalamin levels but were unrelated to CD4 counts or zidovudine use, and were rarely outside of the normal range. Malabsorption of vitamin B12 as evidenced by abnormal Schilling tests was more likely among patients with more advanced HIV disease, or gastrointestinal symptoms but was not necessarily associated with low B12 levels. Decreased cobalamin levels are found frequently in HIV disease, especially among those treated with zidovudine. Evidence of B12 malabsorption is found among those with more advanced disease and gastrointestinal symptoms.

Sensorimotor neuropathy and abnormal vitamin B12 metabolism in early HIV infection.

Distal sensory peripheral neuropathy (DSPN) has been reported in 5 to 75% of patients with human immunodeficiency virus (HIV) infection, particularly in advanced stages of the disease. Twenty HIV seropositive patients were studied prospectively to determine the frequency of DSPN in clinical stage II and III of the HIV infection, and to investigate the role of vitamin B12 deficiency on the frequency of DSPN in HIV patients. All patients had complete blood count, serum vitamin B12 level, anti-intrinsic factor antibody, Schilling test, and electrodiagnostic studies including nerve conduction studies and concentric needle examination in the lower extremities, and sympathetic skin responses. Only 1 patient (5%) had clinical and electrophysiological evidence of possible DSPN. Of the 6 patients with abnormal Schilling test, only one had DSPN based on distal sensory symptoms, abnormal neurological examination and electrodiagnostic studies. Evidence for possible DSPN was present in 5% of patients with early HIV infection and did not appear to be more frequent in patients with concurrent vitamin B12 deficiency.

Familial selective vitamin B12 malabsorption (Imerslund-Gräsbeck syndrome) in a pool of Turkish patients.

Thirty-six patients with Imerslund-Gräsbeck syndrome are presented. The mean ages at presentation and diagnosis were 4.7 +/- 3.7 years and 7.2 +/- 4.2 years, respectively. The mean hemoglobin level was 5.8 +/- 2.2 g/dL, the mean cell volume was 104.9 +/- 11.6 fL, the white blood cell count was 4479 +/- 2022/mm3, and the serum vitamin B12 level was 96.9 +/- 73 pg/mL. At diagnosis, 5 of the 36 patients, aged 5 to 16 years, had neurologic symptoms. All the patients had severe megaloblastic changes in bone marrow precursor cells. Proteinuria was detected in 78% of them. Patients with proteinuria had a younger age of onset (P < 0.0001) and diagnosis (P < 0.001) compared with those without proteinuria. In all patients, vitamin B12 excretion unbound to intrinsic factor after a flushing dose of vitamin B12 was lower than normal, and there was no appreciable correction in urinary vitamin B12 excretion after binding of intrinsic factor. The impairment of vitamin B12 absorption studies in Schilling tests; however, showed great variation among patients. Serum haptoglobin values were close to zero in all patients, indicating the presence of that intravascular hemolysis in Imerslund-Gräsbeck syndrome. Variations among patients in the age of presentation, degree of impairment of vitamin B12 absorption, and presence or absence of proteinuria suggest a heterogeneity in etiology of Imerslund-Gräsbeck syndrome at the molecular level.

Detection of Protein Bound Vitamin B12 Malabsorption

The Schilling test is used to identify the cause of vitamin B12 malabsorption in patients with low serum vitamin B12 levels. The initial step required for vitamin B12 absorption is a process of separation from the protein complexes of food. The crystalline Co-57 vitamin B12 used in the Schilling test does not reproduce this physiologic process. Thus, a crystalline stage I Schilling test may be normal even in the face of cobalamin malabsorption. An adjunctive stage I Schilling test using Co-57 vitamin B12 bound to protein has been developed. The authors describe a patient with protein-bound vitamin B12 malabsorption whose crystalline Co-57 vitamin B12 stage I Schilling test was normal. A subsequent stage I Schilling test using Co-57 vitamin B12 bound to chicken serum revealed significant cobalamin malabsorption. A review of the history and literature of this diagnostic test using protein bound vitamin B12 is also presented.

Follow-up results of hematology data before and after restorative proctocolectomy. Clinical outcome.

This study was designed to investigate the development of anemia during functional ileoanal pouch. Eighty-three patients received an ileoanal pouch between 1980 and 1987. The hematology data deviations among the preoperative period, defunctionalized stage, and after ileal pouch in function were monitored. Aspects studied included serum hemoglobin, iron, folates, vitamin B12, white blood cell, erythrocyte sedimentation rate, pt-B12, and fat absorption. Specimens were collected before colectomy, during ileostomy prior to pouch operation, before loop ileostomy closure, and at 6, 12, 18, 24, and 36 months after loop ileostomy closure. Two patients developed iron deficiency anemia after 2.5 and 5 years of pouch function: one patient, a vegetarian, had low hemoglobin, iron, and vitamin B12 postoperatively, the other patient developed low iron and hemoglobin 5 years after the operation. Significant elevations of serum hemoglobin, iron, and folates were seen preoperatively vs. postoperatively from 123.46 +/- 2.845 g/l, 10.282 +/- 0.992 mumol/l, and 9.983 +/- 1.308 mmol/l to 138.842 +/- 1.563 g/l (P < 0.0001), 17.544 +/- 1.529 mumol/l (P < 0.0003), and 16.784 +/- 1.757 mmol/l (P < 0.01) (mean +/- SE) of the defunctionalized loop ileostomy. Serum B12 decreased insignificantly. After loop ileostomy closure, at 6 and 36 months of functional ileal pouch-anal anastomosis, the elevations were still significant; serum hemoglobin was P < 0.0001 and P < 0.01, and serum iron was P < 0.001 and P < 0.01, respectively. Vitamin B12 levels decreased insignificantly at six months in controls and significantly (P < 0.01) at 36 months. There was a significant increase of serum folates (P < 0.01 and P < 0.001). Patients with low iron were 50 percent at precolectomy, 23 percent with ileostomy, 16 percent with loop ileostomy, 15 percent at six-month follow-up, and 11 percent at 12-month follow-up. Although only 3 percent and 11 percent of the patients with ileal pouch-anal anastomosis had low serum vitamin B12 values at the 12-month and 36-month follow-up, 31 percent and 36 percent had decreased Schilling tests. Thirty-three percent and 41 percent had decreased 14C-triolein breath tests. In five patients vitamin B12 deficiency began during the first six months of pouch function: in two patients after one year and in one patient after two years. Eight of 83 patients have had substitution therapy with vitamin B12. The therapy was discontinued in three patients after two to four years; these patients developed no further symptoms and had normal Schilling tests in the succeeding 30 months to 46 months. Five patients continue with substitution after 40 months to 68 months. During the functional period, serum erythrocyte sedimentation rate and white blood cells were elevated in some controls on different occasions. Folates were normal throughout the functional period. For predicting hematologic data outcome in patients with functional ileal reservoir, the results justify the necessity for control during both manipulative and functional periods until evaluations are reliable and satisfying.

Gastric Acid Secretion and Vitamin B 12 Absorption After Vertical Ronx‐en‐Y Gastric Bypass for Morbid Obesity

It is difficult to imagine that the morbidly obese patient suffers from nutritional deficiencies. Nonetheless, severe obesity can lead to hepatic steatosis and cirrhosis, which may significantly alter protein synthesis and immune response. Early surgical therapy for morbidly obese patients involved creating a short gut by performing a jejunoileal bypass. Many of these patients developed malabsorption and blind‐loop syndrome, with significant metabolic abnormalities, and some died.1 Recently, the vertical‐banded gastric bypass has been shown to be effective in morbidly obese patients, not only by reducing the volume of food eaten, but also by discouraging the consumption of concentrated sweets by causing dumping. A small upper‐gastric pouch is created that is completely excluded from the distal stomach and duodenum. A Roux‐en‐Y limb of jejunum is then anastomosed to this pouch to restore intestinal continuity.2 Although weight loss is significant, many of these patients develop pernicious anemia. It is unclear whether this is caused by a lack of intrinsic factor from the stomach itself, inasmuch as the large parietal cell mass remains intact, or by hypoacidity of the proximal pouch. Pernicious anemia is seen in other states of hypoacidity, which are recreated by these small pouches.Ten patients who had undergone vertical Roux‐en‐Y gastric bypass were compared with 15 healthy volunteers. Gastric tubes were positioned in the stomach or proximal pouch to assess acid production. The patients underwent a Schilling test using either free or food‐bound 57Co‐labeled cyanocobalamin (Vitamin B12). Twenty‐four hours later, urine was collected, and the percentage of labeled B12 that was detected represented gastrointestinal tract absorption.Acid secretion from the proximal gastric pouch was markedly less than the acid output in the total stomach of age‐matched hospital controls (0 ± 0 vs 5 ± 0.7 mEq/h; p &lt;.001). This may explain the incidental fmding of few anastomotic gastrojejunal ulcers. Crystalline Vitamin B12 absorption was normal in both groups, suggesting that intrinsic factor continued to be produced and bound with the B12 in the jejunum before its absorption. However, when food‐bound Vitamin B12 was given, uptake was significantly decreased in the bypass patients (0.8% ± 0.2% vs 3.7% ± 0.5%; p &lt;.01).

Letters: Omeprazole and Vitamin B_12

Letters1 July 1994Letters: Omeprazole and Vitamin B12Stefan P. Marcuard, MDStefan P. Marcuard, MDEast Carolina University School of Medicine; Greenville, NC 27858-4354Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-1-199407010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Our study design to evaluate protein-bound B12 absorption before and during treatment with omeprazole is appropriate and is known as “self-pairing” [1, 2]. This method eliminates the variability between study patients and “controls.” Although we agree that a placebo group would have strengthened our results, our straightforward study design is adequate to show changes in vitamin B12 absorption during omeprazole therapy.Dr. Lavy's comments indicate a misunderstanding of vitamin B12 digestion and absorption. To correct protein-bound vitamin B12 malabsorption, hydrochloric acid (not vitamin B12) is added to the modified Schilling tests. In fact, this has been done by ...

Angina Pectoris Caused by Pernicious Anemia

Angina Pectoris Caused by Pernicious Anemia

Pernicious Anemia Revisited

We discuss the pathophysiologic mechanisms, clinical features, diagnosis, and treatment of pernicious anemia (PA). A review of the clinical applications of the diagnostic and therapeutic progress of PA is presented. A patient with PA may have a wide range of initial complaints that affect various organ systems or may be entirely asymptomatic. Hematologic variables may be normal in patients with cobalamin (Cbl) deficiency. Because of the difficulties in diagnosing Cbl deficiency, alternatives to measuring Cbl have been sought. Determining the urinary methylmalonic acid level is a less invasive, more practical, and, possibly, more sensitive method. The Schilling test is performed for assessment of the absorption of orally ingested radiolabeled crystalline cyano-Cbl; results should be interpreted cautiously. Vitamin B12 therapy should be lifelong. It is customarily administered intramuscularly. Other routes of administration have been studied. PA is one of the most treatable hematologic disorders.

Helicobacter pylori infection and food-cobalamin malabsorption.

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.

How to diagnose cobalamin deficiency.

Cobalamin deficiency must be suspected in all patients with unexplained neuropsychiatric symptoms or unexplained anemia. Special attention should be paid to patients at risk of developing cobalamin deficiency such as elderly people, vegetarians, HIV-infected patients, patients with gastrointestinal diseases and patients with autoimmunity or a family history of pernicious anemia. The assays aimed to answer the question: does this patient suffer from cobalamin deficiency, include analysis of P--cobalamins and analyses of the metabolites that accumulate upon cellular cobalamin deficiency, P--methylmalonate and P--homocysteine. P--cobalamins or especially a fraction of P--cobalamins, P--TC cobalamins are markers for latent cobalamin deficiency. An increased concentration of P--methylmalonate that decreases upon injection of cobalamin indicates overt metabolic cobalamin deficiency. The same holds for P--homocysteine but this analysis is less specific than P--methylmalonate. We suggest that either assay of P--cobalamins or P--methylmalonate is employed as screening test for cobalamin deficiency, and that further tests are performed only if the initial test in combination with the clinical picture gives an unclear answer. Once cobalamin deficiency has been diagnosed, the cause for the deficiency should be sought and the patient should be treated for life. Cobalamin absorption tests such as the Schilling test are considered of limited use. Gastric atrophy is likely to be present in patients with increased P--gastrin or decreased P--pepsinogen A. However, this condition can be diagnosed also by upper gastrointestinal endoscopy.

Cobalamin Deficiency in the Elderly

Cobalamin Deficiency in the Elderly