Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Absorption of oleic and palmitic acids from emulsions and micellar solutions.

A lipid mixture (monoolein, oleic acid-1-(14)C, and palmitic acid-9,10-(3)H) was infused intraduodenally at a steady rate for 8 hr in fasted, unanesthetized rats. The same dose of lipid was given together with pure conjugated bile salts either as an emulsion, 2.5 mM bile salts, or as a micellar solution, 10 mM bile salts. The emulsion contained very little or no micellar lipid. Thoracic duct lymph was collected and in some experiments bile and pancreatic juice were drained to the exterior. After 4-5 hr infusion the same steady lymphatic output of radioactive fatty acids was obtained with emulsion as with micellar solution. It was concluded that absorption of fatty acid could proceed efficiently in the virtual absence of micellar solubilization. In rats with biliary plus pancreatic fistulae, labeled triglyceride was absorbed poorly relative to free fatty acids in the same emulsified particles. This suggested that fatty acids were transferred to the absorptive cells in monomolecular solution and not as emulsion particles. Substitution of a synthetic nonionic detergent for bile salts in lipid mixtures given to rats with biliary and pancreatic fistulae did not affect the lymphatic output of radioactive fatty acids. This indicated that mucosal esterification of labeled free fatty acids was normal in the absence of bile salts. The physical state of the lipid did not affect the pathway of absorption. Finally, comparison of the increased output of esterified fat in the lymph with the output of labeled fat suggested that fat absorption did not greatly affect the turnover of endogenous, unlabeled fat. Results were consistent with the view that most of the endogenous lymph fat comes from reabsorbed biliary lipid.

Usefulness of chromic oxide as an internal standard for balance studies in formula-fed patients and for assessment of colonic function.

In 35 patients maintained solely on liquid formula diets, chromic oxide has been evaluated as an internal standard for balance studies that require stool collections. In 28 patients the excretion of chromic oxide was ideal: steady states were attained in which mean daily output was 90% (or more) of mean daily intake. In these patients corrections for fecal flow could validly be applied.In patients who excreted the marker ideally, the availability of chromic oxide balance data made possible the calculation of pool sizes and turnover rates of unexcreted intestinal content. These indexes bore little relationship to the usual clinical descriptions of bowel habits. In some patient who had daily bowel movements, pool sizes were very large and daily turnover was small, i.e., a large proportion of the colonic contents was not excreted for surprisingly long periods. It is critically important for investigators to recognize this possibility when carrying out balance studies for fecal constituents that may be altered by bacterial action within the gut lumen: for instance, in 6 patients a significant inverse correlation was found between daily fecal turnover and degradative losses of large amounts of dietary beta-sitosterol.7 of 35 patients failed to attain the ideal steady state of chromic oxide excretion. These patients would not have been singled out if an internal standard had not been used. In such patients balance studies that require analysis of fecal constituents must be interpreted with great caution, since the constituents in question may be handled in the same nonideal fashion as the internal standard.

Absorption of cholesterol from a micellar solution: intestinal perfusion studies in man.

The absorption of cholesterol has been studied in man by perfusing the upper jejunum with a micellar solution of bile salt, 1-monoglyceride, and cholesterol-(14)C, with a triple lumen tube with collection sites 50 cm apart. The absorption of micellar components between the collection sites was calculated from their concentration changes relative to those of the watersoluble marker, polyethylene glycol. Control experiments were performed with cholesterol-free perfusions of saline or bile salt-monoglyceride solutions. Steady state conditions were obtained.Each of the components of the micelle was absorbed to a different extent during passage through the test segment of jejunum. Bile salt was not absorbed (mean, -3%), but micellar monoglyceride was rapidly hydrolyzed and absorbed almost completely (mean, 98%). Cholesterol radioactivity was absorbed to an intermediate extent (mean, 73%), and the absorption of chemically determined cholesterol (mean, 46%) indicated that much of the disappearance of radioactivity represented true absorption and not simple exchange. The specific activity of the perfused cholesterol fell during passage through the loop. This fall was interpreted as signifying the continuous addition of nonradioactive endogenous cholesterol by the test segment. However, the decrease in specific activity may also be considered to signify exchange, in that nonradioactive molecules entered the lumen as radioactive molecules were absorbed. Plant sterols appeared in the intestinal contents during the perfusion and must have been contributed by the perfused segment. The perfusate and samples taken from the upper and lower collection sites were examined by ultracentrifugation to define the physical state of cholesterol. It was found that cholesterol in the perfusate or upper collection site samples did not sediment, but that 23% of the cholesterol in the lower collection site samples was sedimentable (mean of three experiments); bile salt, as control, was not sedimentable. Solubility experiments in model systems showed that cholesterol possessed low solubility in bile salt solution; its solubility increased markedly and in linear proportion to the amount of fatty acid or monoglyceride or both that was added to the bile salt solution. These findings suggest that polar lipid such as fatty acid or monoglyceride as well as bile salt is essential for normal micellar solubilization of cholesterol in intestinal content. They suggest the necessity of considering an insoluble sedimentable phase of particulate sterol in intestinal content as well as an oil and micellar phase for a complete description of sterol absorption. The marked difference in the rates of absorption of individual micellar components suggests that micellar lipid is not absorbed as an intact aggregate and is consistent with the view that polar lipid such as fatty acid is absorbed in molecular form by diffusion from a micellar solution. The experiments confirm previous findings demonstrating that fat absorption without bile salt absorption occurs in the upper small intestine in man.

The importance of the lysophosphatidylcholine and choline moiety of bile phosphatidylcholine in lymphatic transport of fat.

A luminal supply of biliary phosphatidylcholine is important in the translocation of absorbed fat into lymph and in the amount and composition of phosphatidylcholine concurrently synthesized. This study was undertaken to determine whether the effect was due to absorbed lysophosphatidylcholine, to a specific (1-palmitoyl) biliary lysophosphatidylcholine or to extra choline supplied by lysophosphatidylcholine. Rats with bile fistulae and thoracic duct lymph fistulae were given test meals of oleic acid and monoolein (molar ratio 2 : 1) infused duodenally for 8 h. Addition of choline chloride to the test meal increased lymphatic output of triglyceride and phospholipid but not to values found previously in rats with supplements of bile phosphatidylcholine or with bile ducts intact. Addition of dioleoyl phosphatidylcholine increased triglyceride and phospholipid output to values found in rats with intact bile ducts. Since dioleoyl phosphatidylcholine was as efficient as biliary phosphatidylcholine it was concluded that a luminal supply of 1-palmitoyl lysophosphatidylcholine was not essential. It seemed likely from the smaller effect of supplemented choline and from the fatty acid composition of lymph phosphatidylcholine that the essential requirement was a supply of absorbed lysophosphatidylcholine for rapid reacylation to phosphatidylcholine.

The effect of monostearoylglycerol on the metabolism of chylomicron-like lipid emulsions injected intravenously in rats.

In rats, remnant particles derived from chylomicron-like emulsions containing 1,3-dioleoyl-2-stearoylglycerol (OSO) are removed from plasma more slowly than remnants derived from triolein emulsions. The effect associated with a saturated acyl chain at the glycerol 2-position could be reproduced by incorporating 2-stearoylglycerol (MS) in a triolein emulsion. When MS solubilized with rat albumin or in plasma was injected before the injection of a triolein emulsion, clearance of the triolein emulsion was unchanged. The metabolic fate of MS, monitored with 14C-labelled MS, was similar whether incorporated in triacylglycerol emulsion or injected independently. More than 95% of MS had disappeared from the circulation by 5 min after the injection and the radioactivity was found in liver, spleen, muscle and adipose tissue. Some MS label appeared in plasma triacylglycerol. Remnants made in vitro by incubating triolein or OSO emulsions with post-heparin plasma showed no differences in their disappearance from plasma. With OSO emulsion, the in vitro remnants were found to contain more MS than remnants made in vivo in hepatectomized rats. Simultaneous injections of mixtures containing OSO and triolein emulsions, or triolein emulsions with and without MS, each labelled with either [3H]cholesteryl oleate or [14C]cholesteryl oleate showed consistently slower remnant removal and decreased liver uptake of the emulsions containing OSO or MS. Affinity columns and immunodiffusion all indicated that there was no difference in the amounts of apolipoprotein E associated with OSO or triolein particles. The protein spectra of in vivo remnants derived from OSO and triolein emulsion were also similar when examined by SDS-PAGE and isoelectric focusing gels. Our results show that the effects due to OSO or MS are mediated by the presence of MS in the emulsion particle surface, while indirect effects expressed in plasma or liver are excluded. The precise mechanism of the effect remains to be established, but it does not correlate with measurable changes in the spectra of apolipoproteins associated with the emulsion remnants.

The effect of added monoacylglycerols on the removal from plasma of chylomicron-like emulsions injected intravenously in rats.

Lipid emulsions were prepared with compositions similar to the triacylglycerol-rich plasma lipoproteins, but also incorporating added small amounts of monoacylglycerols. Control emulsions without monoacylglycerol were metabolized similarly to natural chylomicrons or very-low-density lipoproteins when injected intravenously in rats. The emulsion triacylglycerols and cholesteryl esters were both removed rapidly from the bloodstream, with the removal rates of triacylglycerols faster than those of cholesteryl esters. Much of the removed cholesteryl ester was found in the liver, but only a small fraction of the triacylglycerol, consistent with hepatic uptake of the triacylglycerol-depleted remnants of the injected emulsion. Emulsions incorporating added monooleoylglycerol or stearic acid were metabolized similarly. Added 1- or 2-monostearoylglycerol had no effect on triacylglycerol removal from plasma, but the removal rate of cholesteryl esters was decreased and less cholesteryl ester was found in the liver. These effects are similar to those recently described when emulsions and chylomicrons contained triacylglycerols with a saturated acyl chain at the glycerol 2-position, suggesting that saturated monoacylglycerol produced by the action of lipoprotein lipase may cause triacylglycerol-depleted remnant particles to remain in the plasma instead of being rapidly taken up by the liver.

Glutathione and enzymes related to free radical metabolism in liver of rats fed a choline-devoid low-methionine diet.

Fischer F-344 male rats, fed a choline-devoid diet that leads to a highly reproducible sequence of biochemical and biological changes with an ultimate development of hepatocellular carcinoma, show elevated levels of glutathione in the liver at 3, 6 and 8 days. Several enzymes related to the metabolism of free radicals, including superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and DT-diaphorase show neither increased nor decreased activity as measured between 12 h and 8 days on the diet. Thus, of several known cellular components related to the possible scavenger of free radicals in the liver, only glutathione responded to the feeding of the CD diet. It is tentatively concluded that a decrease in the levels of possible scavengers for free radicals is not a major basis for the nuclear and mitochondrial lipid peroxidation seen early in rats fed a choline-devoid diet.

Kinetic analysis of the rapid intraoperative parathyroid hormone assay in patients during operation for hyperparathyroidism.

BACKGROUND: Rapid intraoperative parathyroid hormone (RI-PTH) assay is used to guide adequacy of resection during operation for hyperparathyroidism. We compared the RI-PTH assay (15 minutes) with a standard PTH assay, determined whether the PTH half-life varied between patients, and constructed a kinetic analysis of the RI-PTH data. METHODS: Forty-five patients with hyperparathyroidism had blood sampled at baseline and at times after parathyroid resection. Intact PTH was determined using RI-PTH and a standard assay. Values were fitted to an exponential decay curve using the baseline and the follow-up time points. PTH half-life and the new postexcision baseline value were calculated from the decay curve. RESULTS: The RI-PTH assay and the standard PTH assay correlated well. Average PTH half-life was 1.68 +/- 0.94 minutes (0.42 to 3.81 minutes). A kinetic analysis yielded a formula for the generation of a PTH decay curve. Using a 50% reduction in RI-PTH at 5 minutes as the criterion for adequate resection, 2 patients were incorrectly classified as not being cured. These patients were correctly classified using the kinetic analysis. CONCLUSIONS: PTH half-life can vary substantially. A kinetic analysis may be more accurate in assessing adequacy of resection. This method allows the surgeon to interpret RI-PTH data independent of the timing of samples.

Homeostasis of mucosal cholesterol in the small intestine of the rat.

This study was undertaken to investigate the capacity of the intestinal mucosa to maintain a constant cholesterol content under conditions where mucosal uptake or cholesterol transport into the lymph were manipulated. Two series of bile-diverted unanaesthetised rats were infused intraduodenally with saline, triolein emulsified with Pluronic F68, or taurocholate with or without added tomatine. Pluronic F68 is a nontoxic detergent which promotes mucosal uptake of polar lipids but not cholesterol. Tomatine is a cholesterol-binding saponin. One series of rats was used for measuring mucosal cholesterol content, DNA and protein after the test infusions. A second series of rats had the thoracic lymph duct cannulated but otherwise remained the same as the first series. The second series was used for measuring the effect of the different infusions on mass cholesterol output into lymph. Mucosal cholesterol content of rats that were not fed decreased with bile-diversion and was restored with taurocholate infusion. This suggested a contribution of luminal cholesterol to the mucosal cholesterol pool. However, evidence for a contribution from the lumen was provided by only one of two groups of rats given infusions which did not promote mucosal uptake of cholesterol. First, addition of tomatine to the taurocholate infusate prevented both the increase in lymph output of cholesterol and the increased mucosal cholesterol content shown in rats given taurocholate alone. Second, in another group of rats in which mucosal uptake of cholesterol was prevented, i.e. in rats given Pluronic F68-triolein emulsions, the increased fat absorption was accompanied by a marked increase in cholesterol output into lymph without a concomitant decrease in mucosal cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS)