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International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.

The most spectacular cases of malabsorption in Africa are those often presenting with gross malnutrition and are due to chronic calcific pancreatitis, ileo-caecal tuberculosis, and small-intestinal trauma or resection. Subchnical malabsorption of carbohydrate is numerically a much greater problem. That is usually associated with systemic infection and is not directly related to marginal malnutrition, or an abnormal jejunal mucosa (tropical enteropathy). The evidence that malnutrition produces significant malabsorption is limited to severe cases of kwashiorkor in children. Megaloblastic anaemia due to dietary folate depletion is often associated with an abnormal D-xylose absorption test and the degree of impairment has been shown to correlate with the severity of the anaemia. Intestinal parasites— Strongyloides stercoralis and Giardia lamblia —are occasional causes of malabsorption. Adult hypolactasia is extremely common in African subjects. Although that does not seem to be responsible for significant ill-health in adults, a low lactase concentration is probably important in the pathogenesis of marasmus in infants. Secondary disaccharidase deficiency is an uncommon finding. The evidence for the existence of tropical sprue in Africa has been reviewed. It is rare in Europeans, compared with the high frequency in Asia. There is now some evidence for the existence of chronic tropical sprue in indigenous Africans but that also seems to be less common and is not as florid as it is in Asian people in Asia. The reasons for those differences in incidence rates have been discussed. All causes of malabsorption common to non-tropical areas must be excluded in the individual patient. Of the overt clinical causes in Africa, ileo-caecal tuberculosis is the most difficult to diagnose.

1. Perman JA, Barr RG, Watkins JB: Sucrose malabsorption in children: Noninvasive diagnosis by interval breath hydrogen determination. J PEDIATR 93:17, 1978. 2. Robb TA, Davidson GP: Advances in breath hydrogen quantitation in paediatrics: Sample collection and normalization to constant oxygen and nitrogen levels. Clin Chim Acta 111:281, 1981. 3. Barr RG, Watkins JB, Perman JA: Mucosal function and breath hydrogen excretion: Comparative studies in the cliniCal evaluation of children with non-specific abdominal complaints. Pediatrics 68:526, 1981. 4. Gray GM, lngelfinger F J: Intestinal absorption of sucrose in man: Interrelation of hydrolysis and monosaccharide product absorption. J Clin Invest 45:388, 1966. 5. Schultz SG, Strecker CK: Fructose influx across the brush border of rabbit ileum. Biochim Biophys Acta 211:586, 1970. 6. Gracey M, Burke V, Oshin A: Intestinal transport of fructose. Lancet 2:827, 1970. 7. Guy M J, Deren J J: Selective permeability of the small intestine for fructose. Am J Physiol 221:1051, 1971. 8. Macrea AR, Neudoerffer TS: Support for the existence of an active transport mechanism of fructose in the rat. Biochim Biophys Acta 288:137, 1972. 9. Chen M, Whistler RL: Metabolism of D-fructose. Adv Carbohydr Chem Biochem 34:265, 1977. 10. Holdsworth CD, Dawson AM: Glucose and fructose absorption in idiopathic steatorrhea. Gut 6:387, 1965. 11. Hardinge MG, Swarner JB, Crooks H: Carbohydrates in foods. J Am Diet Assoc 46:197, 1965. 12. Ravich W J, Bayless TM, Thomas M: Fructose: Incomplete intestinal absorption in humans. Gastroenterology 84:26, 1983.

Exercise-induced gastrointestinal syndrome (EIGS) is a common characteristic of exercise. The causes appear to be multifactorial in origin, but stem primarily from splanchnic hypoperfusion and increased sympathetic drive. These primary causes can lead to secondary outcomes that include increased intestinal epithelial injury and gastrointestinal hyperpermeability, systemic endotoxemia, and responsive cytokinemia, and impaired gastrointestinal function (i.e. transit, digestion, and absorption). Impaired gastrointestinal integrity and functional responses may predispose individuals, engaged in strenuous exercise, to gastrointestinal symptoms (GIS), and health complications of clinical significance, both of which may have exercise performance implications. There is a growing body of evidence indicating heat exposure during exercise (i.e. exertional-heat stress) can substantially exacerbate these gastrointestinal perturbations, proportionally to the magnitude of exertional-heat stress, which is of major concern for athletes preparing for and competing in the upcoming 2020 Tokyo Olympic Games. To date, various hydration and nutritional strategies have been explored to prevent or ameliorate exertional-heat stress associated gastrointestinal perturbations. The aims of the current review are to comprehensively explore the impact of exertional-heat stress on markers of EIGS, examine the evidence for the prevention and (or) management of EIGS in relation to exertional-heat stress, and establish best-practice nutritional recommendations for counteracting EIGS and associated GIS in athletes preparing for and competing in Tokyo 2020.

Background Environmental enteropathy is an example of a poorly-understood intestinal disorder affecting millions of children worldwide, characterized by malabsorption and stunting. Although there is increasing interest in non-invasive means of assessing intestinal structure and function, the potential value of intestinal biopsy for histology, immunostaining, RNA sequencing and epigenetic work means that endoscopic biopsy remains extremely valuable. We here report our experience in the BEECH (Biomarkers of Environmental Enteropathy in CHildren) study of stunting in Zambia, in the belief that it may help address the knowledge gap regarding the safety of endoscopic biopsy in vulnerable young children. Methods We report our experience of safety in 119 children undergoing endoscopic biopsy in the BEECH study in Lusaka Children’s Hospital, Lusaka, and discuss ethical considerations in this light. Results Upper gastrointestinal endoscopy was performed on children with stunting (length-for-age z score -2 or less) not responsive to nutritional interventions. Conscious sedation was provided by anaesthetists. Of 119 children, 5 (4%) developed transient desaturation, but no serious adverse events were experienced; no clinical, demographic or anaesthetic characteristics were identified as predictive of desaturation. Two children derived clinically useful information from the endoscopy, one life-saving. Of 105 lactase tests, 59 (54%) showed hypolactasia. Discussion Children with stunting underwent endoscopy safely, and some derived clinical benefit. Safety and the possibility of clinical benefit are usually felt to be preconditions for the ethical justification for endoscopy for research in children, and we believe that these conditions were met in this study.

Alcohol use disorder (AUD) results in increased intestinal permeability, nutrient malabsorption, and increased risk of colorectal cancer (CRC). Our understanding of the mechanisms underlying these morbidities remains limited because studies to date have relied almost exclusively on short-term heavy/binge drinking rodent models and colonic biopsies/fecal samples collected from AUD subjects with alcoholic liver disease (ALD). Consequently, the dose- and site-dependent impact of chronic alcohol consumption in the absence of overt liver disease remains poorly understood. In this study, we addressed this knowledge gap using a nonhuman primate model of voluntary ethanol self-administration where rhesus macaques consume varying amounts of 4% ethanol in water for 12 months. Specifically, we performed RNA-Seq and 16S rRNA gene sequencing on duodenum, jejunum, ileum, and colon biopsies collected from 4 controls and 8 ethanol-consuming male macaques. Our analysis revealed that chronic ethanol consumption leads to changes in the expression of genes involved in protein trafficking, metabolism, inflammation, and CRC development. Additionally, we observed differences in the relative abundance of putatively beneficial bacteria as well as those associated with inflammation and CRC. Given that the animals studied in this manuscript did not exhibit signs of ALD or CRC, our data suggest that alterations in gene expression and bacterial communities precede clinical disease and could serve as biomarkers as well as facilitate future studies aimed at developing interventions to restore gut homeostasis.

Background Lactose malabsorption is a common condition that affects a broad segment of the population. Clinical diagnosis based on symptom recall can be unreliable and conventional testing can be inconvenient, requiring expensive laboratory-based equipment and conduction of the testing in a clinical setting. Objective The aim of this study is to assess the performance of a digital handheld hydrogen breath monitor (GIMate) in diagnosing lactose malabsorption compared to a US Food and Drug Administration (FDA)–cleared device (H2 Check) for the same indication. Methods An interventional crossover study was performed in adult participants with a prior confirmed diagnosis of lactose malabsorption or a suspected history of lactose intolerance. Results A total of 31 participants (mean age 33.9 years) were enrolled in the study. There was 100% positive percent agreement and 100% negative percent agreement between the GIMate monitor and the H2 Check. Correlation between gastrointestinal symptoms and hydrogen values was positive at 0.82 (P Conclusions The digital handheld GIMate breath monitor achieved equivalent diagnostic performance to that of an FDA-cleared device in the diagnosis of lactose malabsorption. Trial Registration ClinicalTrials.gov NCT04754724; https://clinicaltrials.gov/ct2/show/NCT04754724

Background Corpus atrophic gastritis (CAG) may lead to intrinsic factor (IF) deficiency and vitamin B12 malabsorption. Intrinsic factor autoantibodies (IFA) are considered markers of pernicious anemia, but their clinical utility in CAG has not been evaluated. This study aimed to assess IFA in CAG patients and controls using a luciferase immunoprecipitation system (LIPS). Methods Recombinant nanoluciferase-tagged IF secreted from transfected Expi293F cells was used as antigen in an IFA-LIPS assay. IFA IgG were measured in sera from subjects undergoing gastroscopy and biopsy (updated Sydney system) mainly for anemia (57%) or dyspepsia (34%). This cohort comprised 105 patients with histologically-proven-CAG (cases: median age 64 years, 68% females) and 110 subjects with suspected CAG that were histologically negative (controls: median age 67 years, 54% females). Cut-off values were selected by Q-Q-plot analysis (negative, Highlights • A novel diagnostic autoantibody test for intrinsic factor autoantibodies using a LIPS in histologically-proven CAG patients and controls. • This assay discriminated between patients and controls with a good specificity and a relatively low sensitivity that reflects the likely low prevalence of intrinsic factor antibodies in CAG. • Positivity occurred independently from anemia and vitamin B12 deficiency. • Intrinsic factor antibodies should be assessed in patients at high clinical suspicion of CAG.

The first clear description of ‘fibrocystic disease of the pancreas’ or Cystic Fibrosis (CF) came in the late 1930s1 and evidence of vitamin A deficiency was reported in 10 of 49 patients as early as 1939.2 Indeed, this paper recommended ‘generous dosages’ of vitamin A for these patients. Biochemical evidence of fat-soluble vitamin deficiency occurs early in infants diagnosed with CF by newborn screening.3–6 Sokol et al. reported the fat-soluble vitamin status of 36 infants diagnosed by newborn screening between 1984 and 1987 with the initial evaluation being undertaken at around seven weeks of age. There was an inverse correlation between three-day faecal fat excretion and serum α-tocopherol levels (vitamin E). Twenty-one percent of patients had low vitamin A levels, 35% low vitamin D, 38% low vitamin E and vitamin E:lipid ratio though none had an elevated PIVKA-II (protein induced by vitamin K absence or antagonism) – one indicator of vitamin K deficiency. Introduction of pancreatic enzyme replacement therapy, and standard fat-soluble vitamin supplementation corrected vitamin A and D status at 6 and 12 months of age. However, 10% of patients remained vitamin E deficient.3 Feranchak et al. reported that 44 of 96 (45.8%) infants diagnosed by newborn screening between 1984 and 1997 had a deficiency of one or more of the fat-soluble vitamins by 4–8 weeks of age. Vitamin A deficiency occurred in 29% of patients, vitamin D deficiency in 22.5% and vitamin E deficiency in 22.8%.4 Bines et al. reported low serum retinol in 20 out of 39 (51%) infants and low α-tocopherol in nine of 38 (24%) infants diagnosed by newborn screening between 1991 and 1994.5 These studies are supported by more contemporaneous data. Neville and Ranganathan reported 58 infants diagnosed by newborn screening between 2001 and 2006. Median age of diagnosis was 1 month (range 0–3 months). Vitamin D deficiency was described in 11 of 30 infants (37%), vitamin E deficiency in seven of 45 (16%) and vitamin A deficiency 27 of 45 (60%). Vitamin A and E levels were significantly lower in pancreatic insufficient patients. Vitamin A and E status was significantly correlated with pancreatic status though there was no significant correlation with pancreatic status and vitamin D deficiency.6 Why bother to take vitamins? Firstly, because at the time of diagnosis of CF there is clear biochemical evidence of vitamin A deficiency in up to 60% of infants6 and vitamin D and E deficiency in up to 37%6 and 38%,3 respectively. Untreated, the incidence of biochemical and later clinical vitamin deficiencies will increase. Most people with CF are at risk of fat-soluble vitamin deficiencies due to fat malabsorption and maldigestion as a consequence of pancreatic insufficiency and bile salt deficiency. Patients treated with pancreatic enzyme replacement therapy may still experience refractory steatorrhoea due to enzyme inactivation as a consequence of high intestinal pH, small bowel bacterial overgrowth,7 the presence of a mucus barrier lining the intestine, short gut syndrome due to previous bowel resection and CF-related liver disease. Adherence rates are difficult to assess8 but non-adherence to pancreatic enzyme replacement is commonly reported9,10 and contributes to malabsorption. We know that some patients do not bother to take their prescribed vitamins as adherence rates in people with CF of 47% of the recommended vitamin prescription have been reported.9,11 Modi et al. compared different methods of assessing adherence to vitamin therapy. Adherence was variable and ranged from 22% when recorded in a diet diary to 94% for self-report by children.10 Non-adherence to therapy, poor dietary intake either due to anorexia or poor dietary sources of vitamins can also contribute to fat-soluble vitamin deficiency in CF. All of these factors put people with CF at high risk of vitamin deficiencies and in addition there are vitamin-specific risk factors detailed below. Advances in the clinical and medical management of people with CF have led to improved life expectancy and new and emerging co-morbidities. The introduction of newborn screening allowing for earlier and more aggressive intervention together with improved pancreatic enzyme replacement therapy, the early introduction of appropriate fat soluble vitamin supplementation and an overall improvement in nutritional status together with advances in our understanding of fat-soluble vitamin metabolism12 mean we need to consider fat-soluble vitamin status in the context of modern disease. The emphasis of how vitamin status is defined has shifted. Traditionally vitamin status was discussed in terms of overt deficiency resulting in the classically recognized deficiency symptoms such as night blindness and xeropthalmia in vitamin A deficiency. Now vitamin status is also considered in terms of subclinical deficiencies which are defined as low serum, tissue or airway surface liquid vitamin levels with no visible signs or symptoms of deficiency. It is increasingly recognized that subclinical deficiencies in CF may play a significant role. Vitamin status may now be considered in the context of health outcomes rather than overt deficiency12 with levels being described as deficient, insufficient, adequate, optimal and toxic.

Bile acids (BAs) are important endogenous signaling molecules that play vital roles in the pathological development of various diseases including colitis-associated cancer (CAC). BAs were previously found dysregulated under conditions of CAC; however, the exact patterns and underlying molecular mechanisms remain largely elusive. Based on the development of a method for comprehensive analysis of BAs, this study aims to elucidate the dysregulation patterns and involved mechanisms in a typical CAC model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). CAC mice showed decreased BAs transformation in gut and glucuronidation in colon, leading to accumulation of primary BAs but reduction of secondary BAs in colon. CAC mice were characterized by an accumulation of BAs in various compartments except ileum, which is in line with repressed ileal FXR-FGF15 feedback signaling and the increased expression of hepatic CYP7A1. The compromised ileal FXR-FGF15 signaling was caused in part by the reduced absorption of FXR ligands including free and tauro-conjungated BAs due to the downregulation of various transporters of BAs in the ileum of CAC mice.

Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon.Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery.Female (4-week old) piglets (5-6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry.SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.

With the rapid development of the knowledge and techniques in bariatric surgery, as well as extensive expansion of indications for metabolic operations, surgeons have started to realize that the procedures they choose are not always suited to the needs and behavior of patients. Second and very frequently third revisional procedures are thus necessary in order to achieve desired outcomes and fulfill patients’ expectations. Restoration of restriction is commonly the first procedure, but not all may benefit from it. We hence want to illustrate the decision-making process by presenting a patient with the background of initial Rouxen-Y gastric bypass (RYGB) and redo-RYGB, who then underwent a further revision by a 2-stage approach due to weight regain. The first stage involved shortening of the common channel and the second one reconstruction of his gastric pouch with duodenal switch (DS). Consequently we wish to focus here on a discussion about operative techniques and strategies to improve outcomes in such patients.

Objectives—To determine the occurrence of celiac disease in a population of ataxic patients without definite diagnosis and to characterise distinctive features which may help to diVerentiate cerebellar ataxia with and without celiac disease. Methods—Twenty four ataxic patients without definite diagnosis (group A) and 23 ataxic patients with definite diagnosis (group B) were screened for antigliadin (AGAs) and antiendomysium antibodies (EMAs). Patients with a positive AGA or EMA test underwent endoscopic biopsy of the duodenal mucosa. Results—There was an increased prevalence of celiac disease in group A (3/24) compared with group B (0/23). None of the celiac patients presented gastrointestinal symptoms or malabsorption signs. None of the ataxic patients with celiac disease had early onset ataxia. Conclusions—Celiac disease is associated with ataxic syndromes without definite diagnosis, suggesting that it plays a part in the pathogenesis of some ataxic syndromes. The absence of distinctive neurological features in ataxic patients with celiac disease suggests that a search should be made for celiac disease markers in all ataxic patients without definite diagnosis. (J Neurol Neurosurg Psychiatry 1999;66:32‐35)

A development of the double-tracer calcium absorption test, in which a function is derived for single-passage entry rate from the gut with time, has been assessed in various disorders of calcium homoeostasis. Single tests are diagnostically useful in calcium malabsorption but because of the wide spectrum of normal values a single test can only moderately enhance the accuracy of the diagnosis of hypercalcaemic states made primarily by other methods. On the other hand serial studies in the same subject can be much more informative because the test is normally highly reproducible if conditions are unchanged. Serial studies play an important part in assessing the efficacy of established methods of treatment in disorders of calcium homoeostasis and should be particularly helpful in studying the effects of new forms of therapy on the absorption process.

Essential fatty acid deficiency was found on four occasions in three adult patients with malabsorption after intestinal resection. Diagnosis was primarily based on the gas chromatographic finding of the abnormal fatty acid 5, 8, 11- (omega9) eicosatrienoic acid in plasma lecithin. None of the patients had received parenteral nutrition with a fat-free source of calories but all had been on a reduced intake of dietary fat at some stage. Treatment with intravenous Intralipid rapidly reversed the abnormal plasma fatty acid pattern and also cleared the rash in the patient wih he most severe deficiency.

of serum levels of vitamin B12 and folate has meant that megalo blastic anaemias can be more readily classified as being due to deficiency of one or occasionally both of these substances. The excretion of formiminoglutamic acid (figlu) in the urine of patients with folic-acid deficiency has further aided this differen tiation. However, unless these tests clearly indicate deficiency of one substance with normal levels of the other, differentiation is often not precise. It has been shown that in vitamin-B12 deficiency serum-folate levels can be low, normal, or raised (Hansen and Weinfeld, 1962), and in folic-acid deficiency the vitamin-B12 level may be normal or reduced (Johnson et al., 1962. Figlu excretion may also occur in patients with vitamin B12 deficiency (Chanarin et al., 1962). There would therefore seem to be a place for the use of a therapeutic trial of vitamin

Forty-five cases of pancreatic calcification are reported, and it is shown that in Western Nigeria this malady afflicts younger people than in Europe and the United States of America. Males and females seem about equally affected in Western Nigeria, whereas it predominantly affects males in France, Britain, and North America. Diabetes mellitus was the commonest complication in this series, and brought many patients to the doctor. In this series chronic relapsing pancreatitis was a rare cause; there was no history of alcoholism; and protein malnutrition was thought to be responsible for pancreatic calcification in over 90% of the patients.

Twenty-one patients with dermatitis herpetiformis initially controlled by dapsone or sulphonamides have been treated with a gluten-free diet and reassessed at intervals for up to 15 months (mean 11·9 months). According to routine histological and dissecting microscope criteria the small-bowel lesion improved in 10, but when mean epithelial cell height was used as a measure 15 patients improved. Five of the patients with diarrhoea improved after withdrawing gluten from the diet but none reverted to completely normal bowel habit. The tests for malabsorption showed little improvement in the treatment period. Twelve patients needed less dapsone to control their skin complaint, the mean dose falling from 144 mg. to a mean of 70 mg. per day; of these three stopped using this drug altogether.

Rats fed a high-salt diet developed indicanuria with the formation of indigotin and indirubin in the urine. Thus, they resembled children with the blue diaper syndrome. Investigation of those factors controlling pigment formation in the urine suggests that the pigmented dimers arise in consequence of a series of biochemical events initiated by intestinal malabsorption of tryptophan. Primary malabsorption of tryptophan is seen in the blue-diaper syndrome, but it is also seen in other pediatric disorders not characterized by blue diapers. An explanation for this apparent paradox is suggested by the animal experiments.

The excretion in the urine of (58)Co after an oral dose of (58)Co vitamin B(12) given together with intrinsic factor has been found to be reduced in a number of patients with psoriasis, eczema, and other less common dermatoses. There is a correlation between the abnormality and the extent of the rash. A reduced glomerular filtration rate was found in a few of the patients in whom it was measured, and this must have been responsible, at least in part, for the reduced excretion of vitamin B(12) in these patients, but abnormal vitamin B(12) excretion also occurred in the absence of impaired renal function. Our evidence is insufficient to show whether malabsorption or increased tissue utilization of vitamin B(12) was the explanation in other cases. Certainly a number of patients had steatorrhoea, and in these it is most likely that malabsorption was the major factor. In patients without steatorrhoea a lone malabsorption of vitamin B(12) cannot be excluded. A decreased serum concentration of vitamin B(12) was found in only one of the patients.

An investigation into B(12) absorption in diabetic patients on long-term phenformin therapy was undertaken and the results were compared to a similar investigation previously reported in diabetics on long-term metformin. Forty-six per cent of patients were found to have B(12) malabsorption as shown by abnormal results of Schilling tests.The mechanism of B(12) malabsorption is unknown but it is suggested that all patients on long-term phenformin therapy should, like the patients on metformin, have annual serum B(12) estimations until the results of a longer follow-up series are known.

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.

In a population study on the western coast of Greenland the incidence of sucrose malabsorption was estimated by means of sucrose tolerance tests in 190 persons. Small-intestinal disaccharidase activity was estimated in 19 patients. Sucrose malabsorption was present in 10.5% of the cases studied-a surprisingly high figure and much higher than the incidence reported elsewhere in the world. This incidence is, however, lower than that of lactose malabsorption in Greenland Eskimos (54%). In contrast to lactose malabsorption, sucrose malabsorption is present from birth; this may have important clinical implications since chronic diarrhoea and malnutrition are fairly common during infancy in Greenland.

Thirty-four cases of malabsorption are described in young adults after brief periods of overland travel to India. Symptoms included diarrhoea, abdominal distension, and weight loss. Investigation revealed fat, xylose, and vitamin B(12) malabsorption with marked morphological changes in the mucosa. Lower levels of serum folate and vitamin B(12) were observed in those with protracted diarrhoea, but no anaemia developed. Malabsorption may persist for many months after return to the U.K. Most patients responded initially to antibiotics, but some subsequently relapsed. The reasons why these patients developed tropical sprue are discussed.

A cross-over trial of pancreatic enzyme replacement therapy has been conducted on 12 children with cystic fibrosis using Pancrex V forte and Nutrizym tablets in equivalent dosage. No differences were found in the effectiveness of these products as measured by stool volume, number of bowel actions, faecal fat excretion, and urine urea excretion. Neither product eliminated the steatorrhoea. Though there was no laboratory evidence to support their choice nine patients expressed a preference for Nutrizym at the conclusion of the trial. This preference was based partly on the smaller number of tablets which are required.

A review of the literature on subclinical intestinal disease shows its probable relevance in certain nutritional deficiencies in the indigenous residents of tropical climates. A significant incidence of intestinal disease has been defined among asymptomatic fit-looking adult Nigerians. The results of subsequent investigation into the pathogenesis of this disorder strongly point to hypoalbuminaemia as the important factor capable of producing a biochemically and histologically defined malabsorptive state leading to subnormal nutritional status among members of this community.

In a patient with severely impaired amino acid absorption and cystic fibrosis, the urinary excretion of metabolites of phenylalanine and tyrosine was found to be highly increased. Presumably, for the greater part, these metabolites are products of bacterial degradation of the amino acids in the intestinal lumen. The main urinary metabolites were phenylacetic (con j.+ free), benzoic (conj.+ free), p-hydroxyphenylacetic and p-hydroxybenzoic (conj.+ free) acids; the first two represent a considerable percentage of phenylalanine intake and the latter two that of tyrosine intake. Minor urinary metabolites, probably typical for tyrosine malabsorption, were p-hydroxyphenylpropionic and p-hydroxyphenylacrylic acids; the latter compound, however, occurs seldom or never. In the faeces were found small amounts of p-hydroxyphenylpropionic, p-hydroxyphenylacetic, p-hydroxybenzoic and p-hydroxyphenyllactic acids, all derived from tyrosine. Also small quantities of the phenylalanine metabolites phenylacetic and benzoic acid were present. Faecal excretion of the metabolites was clearly less than their urinary elimination. The analytical data obtained from urine and faeces indicate that the tyrosine ammonia-lyase pathway and possibly also the phenylalanine ammonia-lyase pathway are important metabolic routes of intestinal bacteria. The urinary excretion of phenyl acids and p-hydroxyphenyl acids may be an important parameter for phenylalanine and tyrosine malabsorption.

Of eight patients with Paget's disease one had diarrhoea, steatorrhoea, impaired xylose absorption, and macrocytic anaemia due to folic acid deficiency, while another had diarrhoea and very low xylose absorption. In both patients jejunal biopsy was normal, and they responded to folic acid therapy with considerable increase in xylose absorption. Low xylose excretion was seen in three more patients, one of whom also had steatorrhoea. Thus malabsorption may be a systemic complication of Paget's disease of bone, possibly due either to secondary folate deficiency or to relative ischaemia of the bowel.

Tests of absorption of folic acid (pteroylglutamic acid) and of dietary folates (pteroylpolyglutamates) were performed in 10 patients with untreated adult coeliac disease, five with dermatitis herpetiformis, and three with nutritional folate deficiency. Absorption of pteroylglutamic acid was impaired in eight patients with coeliac disease and in two with dermatitis herpetiformis. Absorption of pteroylpolyglutamates was impaired in all 10 coeliac patients and in four of the five patients with dermatitis herpetiformis. Absorption of both forms of folate was normal in all three patients with nutritional folate deficiency.

Malabsorption of folate polyglutamates prepared from yeast has been shown in eight patients with untreated tropical sprue and in three out of six patients receiving therapy for sprue. The absorptive defect for folate polyglutamates among these 14 patients occurred more frequently and in all but one patient more severely than for folic acid. Folate polyglutamates, the principal dietary form of folate, probably require deconjugation by the jejunal enzyme, folate conjugase, before absorption. The mean concentration of jejunal folate conjugase of 21 patients with untreated sprue and of 13 patients with sprue receiving therapy were both significantly less than the mean concentration in a control group. Nevertheless, all but five of the 34 patients had jejunal folate concentrations within the control range. There was no correlation in the individual patients between the jejunal folate conjugase concentration measured in vitro and the ability to absorb folate polyglutamates—nine patients having normal jejunal folate conjugase levels despite showing malabsorption of folate polyglutamates.

Thirteen cases are described of temporary malabsorption in adults presenting after an episode of apparent infective enteritis. Clinical features included diarrohea, anorexia, and weight loss. Investigations indicated diffuse impairment of function in the small bowel, including the ileum, with well-preserved mucosal morphology in the upper jejunum and a tendency to rapid folate depletion. Spontaneous recovery usually occurred within weeks but two cases ran a more prolonged and severe course. The clinical features of this syndrome are those of tropical sprue, but the outcome of the illness is probably influenced by nutritional as well as environmental factors. There may be a gradation of severity of illness from megaloblastic anaemia to florid malabsorption syndrome.