Gastrointestinal Protein Loss Research Articles

The long-term clinical course of protein-losing enteropathy combined with iron deficiency anemia in Korean toddlers: Possible association with cow's milk protein.

Protein-losing enteropathy (PLE), a rare condition with excessive gastrointestinal protein loss, presents with hypoalbuminemia, edema, or ascites. Several cases of PLE combined with severe iron deficiency anemia (IDA) have been reported in infants and toddlers that were considered to result from excessive cow's milk consumption, although the mechanism has not been clearly established. We retrospectively reviewed the clinical, laboratory, endoscopic, and radiologic characteristics of patients diagnosed and treated for PLE with IDA between 2015 and 2021. Long-term outcomes were analyzed according to dietary intervention during the follow-up period. A total of 10 patients aged 7.0-26.7 months were enrolled in the study and the median follow-up duration of them was 9.4 months (range, 1.3-18.0). Six of them were fed powdered formula, while two were fed whole cow's milk, and their median daily intake was 700mL (range, 300-900). The times to normalization of hemoglobin, albumin, and eosinophil count were shorter in patients with dietary elimination of cow's milk protein immediately after diagnosis compared to those with reduced intake or no dietary change. Early complete elimination of cow's milk protein should be considered, especially if the laboratory parameters are not normalized with adequate iron supplementation even though the clinical symptoms show improvement. We would like to draw attention to the possibility of the cow's milk protein in the pathogenesis of the condition through the non-IgE-mediated immune reactions.

Dysregulation of gastrointestinal RAGE (receptor for advanced glycation end products) expression in dogs with chronic inflammatory enteropathy

The pathogenesis of chronic inflammatory enteropathies (CIE) in dogs involves dysregulated innate immune responses. The receptor for advanced glycation end products (RAGE), a pattern recognition receptor, plays a role in chronic inflammation. Abrogation of proinflammatory RAGE signaling by ligand binding (e.g., S100/calgranulins) to soluble RAGE (sRAGE) might also be a novel therapeutic avenue. Serum sRAGE levels are decreased in canine CIE, but gastrointestinal tissue RAGE expression has not been investigated in dogs. Thus, the study aimed to evaluate the gastrointestinal mucosal RAGE expression in dogs with CIE. Further, the potential binding of RAGE to canine S100/calgranulin ligands was investigated.Epithelial RAGE expression was quantified in gastrointestinal (gastric, duodenal, ileal, and colonic) biopsies from 12 dogs with CIE and 9 healthy control dogs using confocal laser scanning microscopy. RAGE expression was compared between both groups of dogs and was tested for an association with patient characteristics, clinical variables, histologic lesion severity, and biomarkers of extra-gastrointestinal disease, systemic or gastrointestinal inflammation, function, or protein loss. Statistical significance was set at p < 0.05. RAGE:S100/calgranulin binding was assessed by immunoassay and electrophoretic techniques.RAGE expression was detected in all 59 biopsies from diseased and healthy control dogs evaluated. Epithelial RAGE expression in the duodenum and colon was significantly higher in dogs with CIE than in healthy controls (p < 0.04). Compared to healthy controls, RAGE expression in dogs with CIE also tended to be higher in the ileum but lower in the stomach. A slight (statistically not significant) shift towards more basal intestinal epithelial RAGE expression was detected in CIE dogs. Serum sRAGE was proportional to epithelial RAGE expression in the duodenum (p < 0.04), and RAGE expression in the colon inversely correlated with biomarkers of protein loss in serum (both p < 0.04). Several histologic morphologic and inflammatory lesion criteria and markers of inflammation (serum C-reactive protein and fecal calprotectin concentration) were related to epithelial RAGE expression in the duodenum, ileum, and/or colon. in vitro canine RAGE:S100A12 binding appeared more pronounced than RAGE:S100A8/A9 binding.This study showed a dysregulation of epithelial RAGE expression along the gastrointestinal tract in dogs with CIE. Compensatory regulations in the sRAGE/RAGE axis are an alternative explanation for these findings. The results suggest that RAGE signaling plays a role in dogs with CIE, but higher anti-inflammatory decoy receptor sRAGE levels paralleled RAGE overexpression. Canine S100/calgranulins were demonstrated to be ligands for RAGE.

DYSREGULATION OF GASTROINTESTINAL RAGE (RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS) EXPRESSION IN A SPONTANEOUS ANIMAL MODEL OF INFLAMMATORY BOWEL DISEASE

Abstract The receptor for advanced glycation end products (RAGE), a pattern recognition receptor, plays a role in chronic inflammation. Abrogation of proinflammatory RAGE signaling by ligand binding (e.g., S100/calgranulins) to soluble RAGE decoy (sRAGE) is a promising novel therapeutic avenue for chronic inflammatory diseases, such as inflammatory bowel disease (IBD). However, the opportunities for studying S100/calgranulin-RAGE pathways in conventional animal models are limited due to species differences in the expression and function of S100/calgranulins (e.g., lack of the S100A12 protein in rodents). The pathogenesis of IBD in dogs involves dysregulated innate immune responses, and serum sRAGE levels are decreased in canine IBD and normalize only with clinical remission. Thus, canine IBD may serve as a spontaneous model of IBD for such studies. This study evaluated gastrointestinal mucosal RAGE expression in dogs with IBD and the binding of RAGE to canine S100/calgranulin ligands. Epithelial RAGE expression was quantified in endoscopic gastrointestinal (i.e., gastric, duodenal, ileal, and colonic) biopsies from 12 dogs with IBD and 9 healthy control dogs by laser scanning microscopy. RAGE expression was compared between both groups of dogs and was tested for an association with patient characteristics, clinical variables, histologic lesion severity, and biomarkers of extra-gastrointestinal disease, systemic or gastrointestinal inflammation, function, or protein loss. Statistical significance (non-parametric tests) was set at p&amp;lt;0.05. RAGE:S100/calgranulin binding was investigated by immunoassay and electrophoretic techniques. RAGE expression was detected in all biopsies evaluated. Epithelial RAGE expression in the duodenum and colon was significantly higher in dogs with IBD than in healthy controls (p&amp;lt;0.04), with a trend for overexpression in the ileum, underexpression in the stomach, and a general shift towards more basal than apical epithelial RAGE expression. Serum sRAGE was correlated with duodenal RAGE expression. Several histologic (structural and inflammatory) lesion criteria and markers of gastrointestinal inflammation or protein loss were related to segmental RAGE expression (all p&amp;lt;0.04). In vitro, canine RAGE:S100A12 binding appeared more pronounced than RAGE:S100A8/A9 binding. Alterations in the epithelial expression of RAGE along the gastrointestinal tract provide evidence for a dysregulated sRAGE/RAGE axis as a characteristic of canine IBD. S100/calgranulin (S100A8/A9 and S100A12) proteins are ligands for RAGE in dogs. The role of RAGE signaling in IBD pathogenesis and its potential for developing novel targeted therapeutics warrants further exploration. Furthermore, canine IBD is a suitable spontaneous model for human IBD that may benefit further research into pathway-specific IBD treatment options that target the sRAGE/RAGE axis.

Gastrointestinal protein loss in children with portal hypertension.

Portal hypertension increases pressure in lymphatic ducts, which may lead to gastrointestinal(GI) protein loss. Reports have shown that adults with portal hypertension had resolution of protein-losing enteropathy after transplantation; but studies in children are very limited. We therefore aimed to evaluate GI protein loss in children with portal hypertension and defined changes after liver transplantation. Children aged 3months to 18years with portal hypertension and the age-matched healthy controls were enrolled during August 2018 to September 2019. Random fecal alpha-1 antitrypsin measurements were obtained at the initial visit, 3months later, 1week before, and 3months after liver transplantation (if applicable). One or more positive test (> 0.795mg/dL) was interpreted as a positive result. We enrolled 76 children (n = 38 in each group) with a median age of 15.5months (interquartile range [IQR], 11.2-41.7), female 51%, and 92% with biliary atresia in the portal hypertension group. We noted GI protein loss in 4/38 children (10.5%) with portal hypertension, while none in the controls (p = 0.11). We found no significant differences on the markers of severity of liver disease and serum albumin between patients with vs. the ones without GI protein loss (p > 0.05). After liver transplantation, 2/4 patients with GI protein loss had undetectable loss. We found that, in a small group of children, 10.5% with portal hypertension had notable GI protein loss without significant relationships with the severity of liver disease.

Enhanced serum immunoglobulin G clearance in myotonic dystrophy-associated hypogammaglobulinemia: a case series and review of the literature

BackgroundMyotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear.Case presentationHere we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels.ConclusionsOngoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.

M\xe9n\xe9trier\u2019s disease presenting as recurrent unprovoked venous thrombosis: a case report

BackgroundAcquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier’s disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier’s disease are exceedingly scarce.Case presentationWe report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier’s disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier’s disease.ConclusionsThis case describes an acquired thrombophilic state in a patient with Ménétrier’s disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient’s thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient’s recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology.

Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS).

Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS. For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α1 -proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3. These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation.

Serum and fecal canine α1-proteinase inhibitor concentrations reflect the severity of intestinal crypt abscesses and/or lacteal dilation in dogs

Gastrointestinal (GI) protein loss, due to lymphangiectasia or chronic inflammation, can be challenging to diagnose. This study evaluated the diagnostic accuracy of serum and fecal canine α1-proteinase inhibitor (cα1PI) concentrations to detect crypt abscesses and/or lacteal dilation in dogs. Serum and fecal cα1PI concentrations were measured in 120 dogs undergoing GI tissue biopsies, and were compared between dogs with and without crypt abscesses/lacteal dilation. Sensitivity and specificity were calculated for dichotomous outcomes. Serial serum cα1PI concentrations were also evaluated in 12 healthy corticosteroid-treated dogs.Serum cα1PI and albumin concentrations were significantly lower in dogs with crypt abscesses and/or lacteal dilation than in those without (both P < 0.001), and more severe lesions were associated with lower serum cα1PI concentrations, higher 3 days-mean fecal cα1PI concentrations, and lower serum/fecal cα1PI ratios. Serum and fecal cα1PI, and their ratios, distinguished dogs with moderate or severe GI crypt abscesses/lacteal dilation from dogs with only mild or none such lesions with moderate sensitivity (56–92%) and specificity (67–81%). Serum cα1PI concentrations increased during corticosteroid administration. We conclude that serum and fecal α1PI concentrations reflect the severity of intestinal crypt abscesses/lacteal dilation in dogs. Due to its specificity for the GI tract, measurement of fecal cα1PI appears to be superior to serum cα1PI for diagnosing GI protein loss in dogs. In addition, the serum/fecal cα1PI ratio has an improved accuracy in hypoalbuminemic dogs, but serum cα1PI concentrations should be carefully interpreted in corticosteroid-treated dogs.

Gastro-entéropathies exsudatives

Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation.

Review of Commonly Used Clinical Pathology Parameters for General Gastrointestinal Disease with Emphasis on Small Animals

A wide variety of markers are available to assess the function and pathology of the gastrointestinal (GI) tract. This review describes some of these markers with special emphasis given to markers used in dogs and cats. Small intestinal disease can be confirmed and localized by the measurement of serum concentrations of folate and cobalamin. Fecal α1-proteinase inhibitor concentration can increase in individuals with excessive GI protein loss. A wide variety of inflammatory markers are available for a variety of species that can be used to assess the inflammatory activity of various types of inflammatory cells in the GI tract, although most of these markers assess neutrophilic inflammation, such as neutrophil elastase, calprotectin, or S100A12. N-methylhistamine can serve as a marker of mast cell infiltration. Markers for lymphocytic or eosinophilic inflammation are currently under investigation. Exocrine pancreatic function can be assessed by measurement of serum concentrations of pancreatic lipase immunoreactivity (PLI) and trypsin-like immunoreactivity (TLI). Serum PLI concentration is increased in individuals with pancreatitis and has been shown to be highly specific for exocrine pancreatic function and sensitive for pancreatitis. Serum TLI concentration is severely decreased in individuals with exocrine pancreatic insufficiency.

Evaluation of fecal α1-proteinase inhibitor concentrations in cats with idiopathic inflammatory bowel disease and cats with gastrointestinal neoplasia

Idiopathic inflammatory bowel disease (IBD) and gastrointestinal lymphoma are common disorders in cats. The aim of this study was to evaluate fecal α1-PI concentrations, a marker of gastrointestinal protein loss, in cats with histopathological evidence of gastrointestinal inflammation or gastrointestinal neoplasia.Fecal and serum samples were obtained from 20 cats with chronic gastrointestinal disease in which endoscopic biopsies were performed. Two groups of cats were assembled based on histopathology: Group A (n=8), mild to moderate IBD; Group B (n=12), severe IBD or gastrointestinal neoplasia. Fecal α1-PI concentrations and serum concentrations of total protein, albumin, globulin, cobalamin, folate, pancreatic lipase immunoreactivity, and trypsin-like immunoreactivity were determined.Nineteen of the 20 diseased cats had elevated fecal α1-PI concentrations, ranging from 1.9 to 233.6μg/g compared to 20 healthy control cats (normal range: ⩽1.6μg/g). Fecal α1-PI concentrations were statistically significantly different between healthy cats and cats of Group A (median: 3.9μg/g, range: 1.3–9.2μg/g, P<0.001) or cats of Group B (median: 20.6μg/g, 4.3–233.6μg/g; P<0.001), and between cats of Groups A and B (P<0.01). Hypoalbuminemia, hypoproteinemia, and hypocobalaminemia were detected in 88%, 83%, and 56% of the diseased cats, respectively.This study suggests that increased fecal α1-PI concentrations in association with low serum albumin and total protein concentrations may be a common finding in cats with IBD or gastrointestinal neoplasia. Furthermore, fecal α1-PI concentrations appear to be higher in cats with severe IBD or confirmed gastrointestinal neoplasia when compared to cats with mild to moderate IBD.

Successful treatment of protein-losing enteropathy due to AA amyloidosis with octreotide in a patient with rheumatoid arthritis

Protein-losing enteropathy (PLE) is a rare syndrome of gastrointestinal protein loss that may complicate a variety of diseases. This excessive protein loss across the gut epithelium can be explained by several mechanisms, such as augmentation of the intestinal mucosal capillary permeability, mucosal disruption, intestinal or mesenteric vasculitis, and lymphangiectasia. However, these pathophysiologic alterations of the gut are closely linked to the underlying cause, and primary treatment for PLE should be directed at the underlying condition. Here, we report a female patient with rheumatoid arthritis who developed severe PLE due to AA amyloidosis and was successfully treated with octreotide. She had been suffered from rheumatoid arthritis for 18 years, and her arthritic symptoms at the time of presentation were not definite but manifested as severe diarrhea and general edema with hypoalbuminemia. PLE due to gastrointestinal amyloidosis was confirmed by increased fecal α1-antitrypsin clearance and a colonoscopic biopsy that was positive for amyloid deposits. The diarrhea dissipated with conventional treatment, but the general edema resolved only after introducing a long-acting somatostatin analog (octreotide), along with a gradual recovery of the serum albumin level. This case teaches us that in the case of PLE due to AA amyloidosis that is refractory to conventional treatment, the administration of octreotide should be considered.

Molecular Diagnosis of Analbuminemia: A New Case Caused by a Nonsense Mutation in the Albumin Gene

Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin (ALB). We report here a new case diagnosed in a 45 years old man of Southwestern Asian origin, living in Switzerland, on the basis of his low ALB concentration (0.9 g/L) in the absence of renal or gastrointestinal protein loss, or liver dysfunction. The clinical diagnosis was confirmed by a mutational analysis of the albumin (ALB) gene, carried out by single-strand conformational polymorphism (SSCP), heteroduplex analysis (HA), and DNA sequencing. This screening of the ALB gene revealed that the proband is homozygous for two mutations: the insertion of a T in a stretch of eight Ts spanning positions c.1289 + 23–c.1289 + 30 of intron 10 and a c.802 G > T transversion in exon 7. Whereas the presence of an additional T in the poly-T tract has no direct deleterious effect, the latter nonsense mutation changes the codon GAA for Glu244 to the stop codon TAA, resulting in a premature termination of the polypeptide chain. The putative protein product would have a length of only 243 amino acid residues instead of the normal 585 found in the mature serum albumin, but no evidence for the presence in serum of such a truncated polypeptide chain could be obtained by two dimensional electrophoresis and western blotting analysis.

Decreased Serum Albumin as a Biomarker for Severe Acute Graft-versus-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Biomarkers capable of predicting the onset and severity of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) would enable preemptive and risk-stratified therapy. Severe aGVHD leads to gastrointestinal protein loss, resulting in hypoalbuminemia. We hypothesized that decreases in serum albumin at onset of aGVHD would predict the risk of progression to severe aGVHD. We identified 401 patients who developed aGVHD grades II-IV after reduced-intensity allogeneic HCT and reviewed all available serum albumin values from 30 days before HCT to 45 days after initiation of treatment for aGVHD. A ≥0.5 g/dL decrease in serum albumin concentration from pretransplantation baseline to the onset of treatment for aGVHD predicted the subsequent development of grade III/IV aGVHD (versus grade II aGVHD) with a sensitivity of 69% and a specificity of 73%. Overall mortality at 6 months after initiation of aGVHD treatment was 36% versus 17% for patients with and without ≥0.5 g/dL decreases in serum albumin, respectively (P = .0009). We conclude that change in serum albumin concentration from baseline to initiationof aGVHD treatment is an inexpensive, readily available, and predictive biomarker of GVHD severity and mortality after reduced-intensity allogeneic HCT.

Development and analytical validation of a radioimmunoassay for the measurement of alpha1-proteinase inhibitor concentrations in feces from healthy puppies and adult dogs

Canine α(1)-proteinase inhibitor (cα(1)-PI), a proteolysis-resistant protein with a molecular weight similar to albumin, has been shown to be clinically useful as a marker for gastrointestinal protein loss in dogs. A competitive, liquid-phase radioimmunoassay was developed and analytically validated. Fecal samples were collected from 101 healthy pet dogs of various breeds and ages, and fecal cα(1)-PI (Fcα(1)-PI) concentrations were compared between dogs of different age groups. A reference interval for Fcα(1)-PI concentration was calculated using the central 95th percentile. Analytical sensitivity of the assay was 2.2 µg Fcα(1)-PI/g feces. Observed-to-expected ratios for the serial dilution and spiking recovery of 9 and 6 fecal extracts ranged from 90.4 to 152.0% and from 71.3 to 112.3%, respectively. Coefficients of variation for intra- and interassay variability for 6 fecal extracts were ≤10.8% and ≤12.5%, respectively. The reference intervals for the mean and maximum Fcα(1)-PI from fecal samples collected on 3 consecutive days were 2.2-13.9 µg/g and 2.2-21.0 µg/g, respectively. Fcα(1)-PI was significantly higher in dogs <1 year of age (P < 0.0001 for both mean and maximum Fcα(1)-PI for the 3 samples). The radioimmunoassay described is sensitive, linear, precise, reproducible, and accurate for clinical use, thus allowing reliable quantification of Fcα(1)-PI in clinical patients. Using this assay, a mean or a maximum Fcα(1)-PI for 3 sampling days of >13.9 µg/g or >21.0 µg/g, respectively, should be considered abnormal in dogs >1 year of age. Fecal cα(1)-PI concentrations in dogs <1 year of age were significantly higher and should be carefully interpreted in this age group.

Protein-Losing Enteropathy: Case Illustrations and Clinical Review

Protein-losing enteropathy (PLE) is a rare syndrome of gastrointestinal protein loss that may complicate a variety of diseases. The primary causes can be divided into erosive gastrointestinal disorders, nonerosive gastrointestinal disorders, and disorders involving increased central venous pressure or mesenteric lymphatic obstruction. The diagnosis of PLE should be considered in patients with hypoproteinemia after other causes, such as malnutrition, proteinuria, and impaired protein synthesis due to cirrhosis, have been excluded. The diagnosis of PLE is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Treatment of PLE targets the underlying disease but also includes dietary modification, supportive care, and maintenance of nutritional status. In this article, cases illustrating a variety of clinical presentations and etiologies of PLE are presented, and its diagnostic approach and treatment are reviewed.

GASTROINTESTINAL protein loss and hypoproteinemia.

Gastrointestinal Protein Loss and Hypoproteinemia Get access Nutrition Reviews, Volume 17, Issue 9, September 1959, Pages 261–263, https://doi.org/10.1111/j.1753-4887.1959.tb03629.x Published: 01 September 1959

111Indium-transferrin for localization and quantification of gastrointestinal protein loss

Objective. To evaluate the indium-111 (111In)-transferrin method as a means of localization and quantification of gastrointestinal protein loss. Methods. Fourteen patients and 15 healthy subjects underwent an 111In-transferrin study consisting of abdominal scintigraphy, whole-body counting measurement and determination of plasma activity of 111In during the course of 5 days. Two of the patients went through a subsequent chromium-51–trichloride test with analysis of radioactivity in faeces in order to compare the results of the two methods. Results. The patients had a mean±SEM whole-body loss of 111In of 10.9±2.9% for 96 h, while the healthy controls lost 1.8±1.3% (p=0.0045). The decay in plasma activity followed biexponential kinetics. The characteristic plasma transit time was 5.0±1.0 h in patients and 12.1±1.5 h in controls (p=0.0007). Scintigraphically, patients had obvious abdominal foci of activity, while the control subjects showed diffuse activity. Anatomic localization of the leaking spot seemed more uncertain. By comparison with the 51Cr trichloride test, the loss of radio-labelled protein appeared to be in the same order of magnitude. Conclusions. Quantification of gastrointestinal protein loss can be done without collecting faeces. Normal subjects have a loss of a few per cent, making the 111In-transferrin method comparable with the former standard using 51CrCl3–trichloride. Plasma measurements of 111In are not predictive of the magnitude of the loss. Scintigraphic localization of the site of the loss needs to be optimized, for instance by serial imaging or image fusion with an anatomical modality.

Successful Surgical Treatment of Protein-Losing Enteropathy Complicating Rheumatic Tricuspid Regurgitation

Protein-losing enteropathy may uncommonly complicate cardiac disease. While well described as a complication for patients having undergone previous Fontan surgery for congenital heart disease, pericardial and valvular aetiologies are much less frequent. We report a 35-year-old female presenting with marked hypoalbuminaemia and peripheral oedema on a background of known rheumatic valvular heart disease. After extensive investigation for gastrointestinal, hepatic and renal causes of protein loss, echocardiography demonstrated severe tricuspid valve incompetence. Subsequent invasive testing confirmed severe tricuspid valve regurgitation in the absence of pericardial constriction. The patient proceeded to tricuspid valve repair with resolution of the protein-losing state and correction of hypoalbuminaemia. While cardiac causes of gastrointestinal protein loss are uncommon, they should be considered when initial diagnostic work up is negative. The importance of correction of haemodynamic precipitants of protein-losing enteropathy is also discussed.

The Effect of Training and Sustained Exercise on Gastric Ulceration and Gastrointestinal Protein Loss in Racing Sled Dogs

The Effect of Training and Sustained Exercise on Gastric Ulceration and Gastrointestinal Protein Loss in Racing Sled Dogs