Schilling Test Research Articles

Histological Features of Neovaginal Epithelium after Vaginoplasty in Mayer-Rokitansky-Küster-Hauser Syndrome

To analyze the features of the epithelia coating neovaginas after vaginoplasty in women affected by Mayer-Rokitansky-Küster-Hauser syndrome STUDY DESIGN: We conducted a retrospective analysis of prospectively collected data. Women affected by Rokitansky syndrome who underwent neovaginal biopsy after vaginoplasty (McIndoe surgery, intestinal vaginoplasty, Vecchietti surgery, and Davydov surgery) were included. Macroscopic mucosal features were assessed through clinical examination and the Schilling test. Each biopsy specimen was prepared for examination by light microscopy and in some cases by scanning electron microscopy (SEM). Thirty-six patients (4 McIndoe, 2 intestinal vaginoplasty, 14 Vecchietti, and 16 Davydov) were included. All biopsies were performed without complications. In McIndoe's neovaginas, the mucosal microscopic features were similar to normal skin, with large areas of preserved epithelium, heterogeneous presence of dermal papillae, and superficial keratinization. The characteristics of the intestinal neovagina's surface were similar to those of a sigmoid colon, with well-shaped glands, cylindrical cells, and a secreting mucosa. In Vecchietti neovaginas, the surface the epithelium was flat and multilayered, highly similar to that of a normal vagina, with the presence of glycogen and superficial desquamation. On medium SEM magnification evaluation, the epithelium presented flattened polygonal cells. Finally, in Davydov neovaginas, none of the specimens had persistent mesothelial elements. The squamous neo-epithelium had regular aspects of differentiation with the presence of glycogen. At greater SEM magnification, microridges were evident, with a regular distribution. Each different technique of vaginoplasty leads to unique histological and structural features of the neovagina's mucosa. Knowledge of these elements must be the basis for the choice of the most appropriate intervention.

Role of LDH levels in differentiating anemias

Background: There is a need to differentiate megaloblastic anemia from mixed deficiency anemia as both require different management protocols. With the acquisition of more information about them, tests such as serum vitamin estimation and Schilling test, were found to have their limitations. Hence there is a need to search newer diagnostic candidates to differentiate between megaloblastic anemia and mixed deficiency anemia.
 Aims and Objective: The current study was undertaken to find usefulness of serum Lactate Dehydrogenase (LDH) in differentiating megaloblastic anemia from mixed deficiency anemia.
 Materials and Methods: 100 patients were included in the study. Blood smears were stained and analysed. Complete blood counts were performed. Bone marrow examination was done, where needed. Biochemical tests were performed for estimation of vitamin B12, Folate and for LDH.
 Results: Out of the 100 cases 51 were diagnosed as megaloblastic anemia and 49 were diagnosed as mixed deficiency anemia. The LDH levels were significantly higher in cases of megaloblastic anemia as compared to mixed deficiency anemia.
 Conclusion: Serum LDH levels can be used in differentiating megaloblastic anemia from mixed deficiency anemia.

Methods to assess vitamin B12 bioavailability and technologies to enhance its absorption.

Vitamin B12 (B-12) deficiency is still relatively common in low-, medium-, and high-income countries, mainly because of dietary inadequacy and, to a lesser extent, malabsorption. This narrative review is based on a systematic search of evidence on methods to assess B-12 bioavailability and technologies to enhance its absorption. A total of 2523 scientific articles identified in PubMed and 1572 patents identified in Orbit Intelligence were prescreened. Among the reviewed methods, Schilling's test and/or its food-based version (using cobalamin-labeled egg yolk) were used for decades but have been discontinued, largely because they required radioactive cobalt. The qualitative CobaSorb test, based on changes in circulating holo-transcobalamin before and after B-12 administration, and the 14C-labeled B-12 test for quantitative measurement of absorption of a low-dose radioactive tracer are currently the best available methods. Various forms of B-12 co-formulated with chemical enhancers (ie, salcaprozate sodium, 8-amino caprylate) or supplied via biotechnological methods (ie, microbiological techniques, plant cells expressing cobalamin binding proteins), encapsulation techniques (ie, emulsions, use of chitosan particles), and alternative routes of administration (ie, intranasal, transdermal administration) were identified as potential technologies to enhance B-12 absorption in humans. However, in most cases the evidence of absorption enhancement is limited.

Primary bile acid malabsorption. Histologic and immunologic study in three patients.

Three patients are presented with a history of chronic watery diarrhea due to bile acid malabsorption, proved by the tauro-23[75Se]selena-25 homocholic acid test and an unequivocal response to cholestyramine therapy. Fecal fat tests, Schilling tests, and barium studies of the small intestine and colon were all normal. Jejunal biopsies were normal but multiple biopsies of the terminal ileum, performed by retrograde ileoscopy, showed uniform crypt hyperplastic villous atrophy and features of colonic metaplasia with increased mononuclear infiltration of the lamina propria. All 3 patients demonstrated evidence of abnormal immune function, including the presence of serum autoantibodies, circulating immune complexes, and hypocomplementemia. One patient had Sjögren's syndrome. This disorder, which might be immunologically mediated, should be called primary bile acid malabsorption and should be distinguished from other ileal disorders.

“Barriers" to Child Development and Human Potential: The Case for Including the “Neglected Enteric Protozoa" (NEP) and Other Enteropathy-Associated Pathogens in the NTDs

The World Health Organization (WHO) has set forth ambitious efforts to control, and where possible, eliminate the neglected tropical diseases (NTDs) that contribute to poverty and “impair the ability of those infected to achieve their full potential, both developmentally and socio-economically [1], [2]. This neglected disease initiative's (NDI) purpose has been to close the existing poverty gap between individuals living in low/middle-income and high-income countries, and thus facilitate the achievement of the 2000 Millennium Developmental Goals [3]. The gap is still large. Yet, some marked achievements of the NDI, including coordinated administration of preventive chemotherapy to nearly 670 million children globally and the imminent elimination of dracunculiasis, give hope that the WHO's NTD paradigm, a “five-pronged approach of 1) preventive chemotherapy, 2) intensified case-management, 3) vector control, 4) provision of safe water, sanitation, and hygiene, and 5) veterinary public health, are proving beneficial [1]. Malnutrition and unfulfilled human potential are widely prevalent among the 1.4 billion people also afflicted by the principal NTDs. Over the last decade, we have become increasingly aware that alterations in intestinal function not only associate with malnutrition, but are likely one of its driving forces. It was recognized half a century ago that children in developing countries had intestinal mucosa that showed morphological flattening [4] and malabsorption [5] that were reversible upon exposure to a cleaner environment. Similarly, Lindenbaum also showed in the 1960s that Peace Corps volunteers with diarrhea and malnutrition had biochemical markers of malabsorption: 40% had decreased d-xylose levels, and 52% had low Schilling tests. Moreover, 88% of intestinal biopsies from these volunteers showed mild to moderate jejunitis with decreased villus∶crypt ratios [6]. Villus blunting along with chronic inflammation associates with impaired intestinal barrier function with resultant increased intestinal permeability [7]. This combination of altered villus architecture and barrier function, so uniquely dependent upon one's environment, has been termed “environmental (EE) [8]. These characteristic EE changes have been epidemiologically linked with growth faltering and are one hypothesis for why intensive nutritional supplementation interventions done under even ideal clinical trial conditions have significant but limited success in improving weight, linear growth, and cognitive function [9]–[11]. Syndemic with environmental enteropathy are high rates of childhood diarrhea. Although children may display “catch-up growth following isolated and short-lived (3 days) diarrheal episodes [12], prolonged and persistent diarrheal (>14 days) episodes strongly associate with stunting [13]–[16]. Testament to the effectiveness of WHO campaigns, the combination of oral rehydration solution (ORS) in the 1980s and its subsequent refinements, and the introduction of rotavirus vaccines in some populations [17], have led to significant reductions in diarrhea-related mortality from 4.5 million/year over a decade ago to 1.5 million/year in 2010 [18], [19]. Currently, however, there are still >700,000 deaths per year globally related to diarrheal diseases [20], and conversely, the frequency of diarrheal episodes has not declined but remains unacceptably high [21]. Among the myriad pathogens causing diarrhea in low/middle-income countries, the Giardia lamblia (synonymous with G. intestinalis/G. duodenalis) and Cryptosporidium spp. are among the most commonly isolated [22]. Although present in PLOS NTDs' expanded NTD list [23], and added to the WHO's NDI in 2004 [2], [24], these organisms are not mentioned in the 2010 WHO NTD report [1]. Despite the call for increased surveillance [2], the true global prevalence of these infections remains poorly defined [25]. In the past few years, we have learned important lessons that make imperative an emphasis on these “neglected enteric protozoa (NEP) and other enteropathy-associated pathogens within the NDI: The enteric should be classified with the soil-transmitted helminths (STHs) as pathogens associated with stunting. We need to restructure our theoretical framework to broaden our concept of “diarrheal disease to include “asymptomatic enteric infections. We must recognize that environmental enteropathy is likely both a common and complex disease, and that infections related to the development or exacerbation of environmental enteropathy deserve prioritization in disease control strategies. Therapeutic strategies against enteropathy-associated pathogens can and should be evaluated for efficacy within the existing NDI programs.

Hooked to vitamin B12 since 1955: A historical perspective

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 invitro 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.

Vitamin B12 Deficiency Associated With Concomitant Metformin and Proton Pump Inhibitor Use

Metformin and proton pump inhibitors have been implicated in decreasing levels of vitamin B12 independently. The purpose of this study was to evaluate the effect of concomitant use of metformin and proton pump inhibitors on the incidence of vitamin B12 deficiency. A retrospective chart review was done using the computerized patient record system at the Memphis VA Medical Center for 614 patients with type 2 diabetes and previously collected vitamin B12 levels. Patients were excluded if they were over the age of 60 years; on a vegetarian diet; had been diagnosed with pernicious anemia, documented by a positive Schilling test or anti-intrinsic factor antibody, or pancreatic exocrine insufficiency; had undergone a gastrectomy or bowel resection; or had been treated with supplemental calcium, H2 blocker, or B12 within 3 months of data collection. The vitamin B12 levels were assessed …

79-Year-Old Woman With Forgetfulness

79-Year-Old Woman With Forgetfulness

Levels of holo-transcobalamin are more closely associated with pernicious anaemia than total B12 levels

<h3>Aims</h3> Vitamin B12 deficiency is usually due to dietary factors, however clinicians always consider the possibility of autoimmune pernicious anaemia. The Schillings test is no longer routinely available and therefore diagnosis often includes the specific intrinsic factor auto-antibodies (IFAb) +/– parietal cell auto-antibodies (PCAb). Holo-transcobalamin (HoloTC), also known as active B12, has proved to be a more reliable indicator of B12 deficiency than measuring total B12 (TB12). We therefore reviewed our experience with this test to see if HoloTC was more closely associated with pernicious anaemia testing. <h3>Methods</h3> We reviewed 1359 patients where HoloTC +/– TB12 was measured as well as one or more of IFAb and PCAb. We used each patient's first B12 result(s) for the analysis. HoloTC was measured by Abbott AxSym and total B12 was measured by Abbott Architect. PCAb antibodies are detected by immunofluor-escence whereas IFAb are measured by Alegria automated ELISA. <h3>Results</h3> When HoloTC was very low (<10pmol/L), 21% of patients had positive IFAb and 42% had positive PCAb. When HoloTC was mildly low (10–22pmol/L), 8% had positive IFAb and 18% had positive PCAb. For very low TB12 (<100pmol/L), 8% had positive IFAb and 24% had positive PCAb. When TB12 was mildly low (100–149pmol/L), 4% had positive IFAb and 11% had positive PCAb. <h3>Conclusions</h3> PCAb were more likely to be positive at any B12 level consistent with its known poor specificity. The more specific IFAb positivity is more likely to be associated with low HoloTC levels than low TB12 levels.

Vitamin B-12.

Vitamin B-12.

Diagnosis and Management of Pernicious Anemia

Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is the result of intrinsic factor deficiency. Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. Serological markers suggesting the presence of oxyntic mucosa damage are increased levels of fasting gastrin and decreased levels of Pepsinogen I. Without the now obsolete Schilling's test, intrinsic factor deficiency may not be proven, and gastric intrinsic factor output after pentagastric stimulation has been proposed. Intrinsic factor autoantibodies are useful surrogate markers of pernicious anemia. The management of patients with pernicious anemia should focus on the life-long replacement treatment with cobalamin and the monitoring to early diagnose an eventual onset of iron deficiency. Moreover, these patients should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.

Juvenile Selective Vitamin B12 Malabsorption: 50 Years After Its Description—10 Years of Genetic Testing

Fifty years have passed since the description of juvenile selective malabsorption of cobalamin (Cbl). Quality of life improvements have dramatically reduced the incidence of parasite-induced or nutritional Cbl deficiency. Consequently, inherited defects have become a leading cause of Cbl deficiency in children, which is not always expressed as anemia. Unfortunately, the gold standard for clinical diagnosis, the Schilling test, has increasingly become unavailable, and replacement tests are only in their infancy. Genetic testing is complicated by genetic heterogeneity and differential diagnosis. This review documents the history, research, and advances in genetics that have elucidated the causes of juvenile Cbl malabsorption. Genetic research has unearthed many cases in the past decade, mostly in Europe and North America, often among immigrants from the Middle East or North Africa. Lack of suitable clinical testing potentially leaves many patients inadequately diagnosed. The consequences of suboptimal Cbl levels for neurological development are well documented. By raising awareness, we wish to push for fast track development of better clinical tools and suitable genetic testing. Clinical awareness must include attention to ethnicity, a sensitive topic but effective for fast diagnosis. The treatment with monthly parenteral Cbl for life offers a simple and cost-effective solution once proper diagnosis is made.

Pernicious anemia: What are the actual diagnosis criteria?

A gastric intrinsic factor output under 200 U/h after pentagastrin stimulation (N > 2000 U/h) is specific for pernicious anemia. The other findings are either variable or non specific. Serum intrinsic factor antibodies, considered as specific in general practice, are present only in half of the patients with pernicious anemia. In their absence, since the disappearance of the Schilling tests, the gastric tubage currently used for the study of gastric acid secretion, is obligatory for the simultaneous study of intrinsic factor output. This study is important to eliminate another disease much more frequent than pernicious anemia, the protein bound to cobalamin malabsorption was observed in achlorhydric simple atrophic gastritis in the presence of intrinsic factor secretion.

Poster Abstracts from the AAAP 20th Annual Meeting and Symposium

Poster Abstracts from the AAAP 20th Annual Meeting and Symposium

Vitamin B12 deficiency in a 15-year old boy due to mutations in the intrinsic factor gene, GIF

The discoveries of new genes involved in cobalamin assimilation and metabolism has increased our understanding of the rare inborn errors of cobalamin metabolism (Quadros 2009). The following case documents a compound heterozygote mutation in the gastric intrinsic factor (GIF) gene, with a previously described mutation (c.79+1G>A) and a novel mutation (c.290T>C; M97T) leading to a megaloblastic anaemia in an adolescent.

Oral B12 in Crohnʼs Disease: Is B12 by injection obsolete?

It has been known for several years that there is an alternate pathway for vitamin B12 absorption that requires neither Intrinsic Factor nor the terminal ileum. It was established many years ago that resection of more than 60 cm of ileum almost always results in B12 malabsorption. To replace monthly B12 injections with daily high dose oral B12 in patients with Crohn's disease. Patients with more than 60 cm of ileal resection and/or disease were assumed to have B12 malabsorption. For patients with less than 60 cm ileal resection and/or disease, a Schilling test was performed. A trough serum B12 was obtained for each patient just prior to the due date of the next B12 injection. Oral B12 therapy was then started, with one tablet of 1200 mcg, once daily. Serum B12 levels were measured at 3 and 6 months. Six patients declined to switch to oral therapy; their reasons were recorded. Of 30 patients, all but one attained or maintained normal serum B12 levels. In many patients, the levels increased from baseline values, including 4 patients with short bowel syndrome. However, compliance with follow-up testing was fair, meaning that some patients had to be contacted and reminded to get their levels checked. For the one patient whose 3-month level was below normal, his dose was increased to 2 tablets daily, with a small improvement. High-dose oral B12 tablets should be the first choice for Crohn's patients with ileal resection and/or disease sufficient to produce vitamin B12 malabsorption. B12 injections should be reserved for those people who fail oral therapy, or who are reimbursed for injection therapy and cannot afford the cost of oral therapy.

Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review.

Iron and/or vitamin B12 deficiency anemias, which have adverse effects on patients' quality of life, are commonly observed and often overlooked complications after restorative proctocolectomy. We performed a systematic review of publications on the prevalence of anemia as well as on the impact of anemia on a range of clinical, functional, quality of life, and economic outcomes in restorative proctocolectomy patients. This information is important to help healthcare providers through a comprehensive overview to increase awareness about a condition that could require therapy to improve patient healthcare and quality of life. We reviewed the English language publications on the incidence of anemia and its adverse effect after restorative proctocolectomy The United States National Library of Medicine database (MEDLINE), the Excerpta Medica database (EMBASE), the Cochran Library, and the Google search engine were searched for published articles on the prevalence and impact of anemia in post-restorative proctocolectomy surgical patients. The long-term complication most frequently described after RPC is pouchitis. Pouchitis is significantly associated with iron deficiency anemia caused by pouch mucosal bleeding. Other causes are insufficient and/or impaired iron absorption. It has also been observed, however, that restorative proctocolectomy patients with underlying familial adenomatous polyposis rarely develop pouchitis yet show higher rates of iron deficiency anemia compared to those patients with underlying ulcerative colitis. Other causes shown as independent risk factors for iron deficiency anemia in restorative proctocolectomy patients are malignancy, desmoid tumors, and J-pouch configuration. Vitamin B12 deficiency anemia is also common after restorative proctocolectomy. About one-third of restorative proctocolectomy patients show abnormal Schilling test and 5 percent have low referenced serum cobalamin. It has been observed that the degree resection of the terminal-ileum, malabsorption, bacterial overgrowth, and dietary factors are among the known causes of cobalamin deficiency. Folate deficiency has not been reported in restorative proctocolectomy patients. Describing restorative proctocolectomy surgery and its outcomes, in patients without anemia, the quality of life is reported excellent regardless of operative technique. Anemia is not uncommon following restorative proctocolectomy and has been shown to have negative effects on the patient's quality of life and the economy and may substantially increase healthcare costs. The treatment of anemia and its underlying causes is important to improving clinical and economic outcomes.

Pernicious anemia: New insights from a gastroenterological point of view

Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.

Classification of anemia for gastroenterologists

Most anemia is related to the digestive system by dietary deficiency, malabsorption, or chronic bleeding. We review the World Health Organization definition of anemia, its morphological classification (microcytic, macrocytic and normocytic) and pathogenic classification (regenerative and hypo regenerative), and integration of these classifications. Interpretation of laboratory tests is included, from the simplest (blood count, routine biochemistry) to the more specific (iron metabolism, vitamin B12, folic acid, reticulocytes, erythropoietin, bone marrow examination and Schilling test). In the text and various algorithms, we propose a hierarchical and logical way to reach a diagnosis as quickly as possible, by properly managing the medical interview, physical examination, appropriate laboratory tests, bone marrow examination, and other complementary tests. The prevalence is emphasized in all sections so that the gastroenterologist can direct the diagnosis to the most common diseases, although the tables also include rare diseases. Digestive diseases potentially causing anemia have been studied in preference, but other causes of anemia have been included in the text and tables. Primitive hematological diseases that cause anemia are only listed, but are not discussed in depth. The last section is dedicated to simplifying all items discussed above, using practical rules to guide diagnosis and medical care with the greatest economy of resources and time.

Pernicious anemia in a patient with Type 1 diabetes mellitus and alopecia areata universalis

A 27-year-old male, who had developed diabetes mellitus type 1 (DMT1) since the age of eighteen and alopecia areata universalis nine months later, attended the outpatient clinics complaining of general fatigue and shortness of breath. A Schilling test was indicative of pernicious anemia. Antigastric parietal cell (AGPA) and anti-intrinsic factor antibodies were positive, confirming diagnosis of pernicious anemia. Thyroid and Addison's disease were excluded. Gastroscopy revealed atrophic gastritis without any evidence of carcinoid tumors. The aim of this case, which, to our knowledge, is the first one to describe a correlation between diabetes mellitus Type 1 (DMT1), pernicious anaemia, and alopecia areata universalis, is to remind the clinician of the increased risk of pernicious anaemia and gastric carcinoids in DMT1 patients. Screening for AGPA followed by serum gastrin and vitamin B 12 levels constitute the most evidence-based diagnostic approach.