Plasma citrulline as a quantitative biomarker of HIV-associated villous atrophy in a tropical enteropathy population.

BACKGROUND & AIMS: Studies have shown that the circulating citrulline concentration is decreased in patients with proximal small bowel villous atrophy from coeliac disease and more so in patients with extensive damage to the intestinal mucosa, but there have been few data on HIV enteritis and tropical enteropathy (TE). Our primary aim was to correlate serum citrulline with the degree of reduction of the enterocyte mass in HIV-infected patients with TE. METHODS: Postabsorptive fasting serum citrulline was measured in 150 TE pts, 44 of whom had HIV infection, using reverse phase, high performance liquid chromatography. Absorptive capacity and permeability were measured after intrajejunal instillation of 4 sugars (5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O methyl D glucose) with assay by thin-layer chromatography. Morphometric analysis was carried out on jejunal biopsies. RESULTS: In HIV positive patients, the median serum citrulline was significantly lower (median 19, interquartile range (IQR) 17-24 µmol/L) than in HIV negative patients (median 27, IQR 23-33 µmol/L; p < 0.001). There were statistically significant correlations (p < 0.005) between citrulline and: crypt depth; villous height/crypt depth ratio; Shenk-Klipstein score; and xylose absoption, only in the HIV positive. CONCLUSIONS: Serum citrulline concentration appears to be a quantitative biomarker of small bowel mass integrity in HIV positive enteropathy and deserves assessment as a surrogate for monitoring anti-retroviral therapy.

[Tropical sprue: diagnostic difficulties. Apropos of 2 cases in Guadeloupe]. / Sprue tropicale: difficultés diagnostiques. A propos de deux cas en Guadeloupe.

The authors report two cases of tropical sprue occurring in Guadeloupe, in the French Lesser Antilles, a region in which this disease had previously been reported only once. One of the patients was treated with quinolone (ofloxacin).

The relationship between hypoalbuminaemia and the radiological appearances of the jejunum in tropical sprue.

Hypoalbuminaemia has been implicated as a possible cause of the radiological abnormalities of the small intestine in tropical sprue. Barium follow-through examination was performed in 35 southern Indian patients with documented tropical sprue, and jejunal width and fold pattern abnormalities were compared with those of a local age-matched control group. Although hypoalbuminaemia was present in 66% of patients with tropical sprue, in only one case was an increase in jejunal calibre associated with a serum albumin concentration below 27 g/l, the threshold below which jejunal dilatation occurs in hypoalbuminaemia alone. These findings suggest that other factors, such as the extent of the mucosal injury, are likely to be more important than hypoalbuminaemia in producing jejunal dilatation in this condition. Abnormalities of fold pattern occurred more frequently than increase in jejunal calibre and appear to be a more sensitive indicator of disease.

Plasma lipids in tropical sprue.

Previous studies indicated that many patients with tropical sprue in southern India have triglyceride accumulation within the cells of the intestinal mucosa. This could be due to essential fatty acid deficiency as a result of steatorrhea in subjects on a diet normally low in linoleic acid. Plasma lipids have, therefore, been studied in patients with tropical sprue and the results compared to values observed in healthy controls. The low intake of linoleic acid was found to be adequate to maintain normal levels of arachidonic acid and to repress the formation of 5,8,11-eicosatrienoic acid in rural controls. Patients with tropical sprue had decreased levels of plasma linoleic acid, raised monoenoic fatty acids and the appearance of 5,8,11-eicosatrienoic acid in the lecithin fraction. All of these observations indicate essential fatty acid depletion although unequivocal evidence of essential fatty acid deficiency was not present in any of the patients. The degree of essential fatty acid depletion observed is unlikely to be the cause of the mucosal accumulation of triglyceride in tropical sprue.

Gut hormones in tropical malabsorption.

Concentrations of various gut hormones were measured after a test breakfast in eight patients with severe tropical malabsorption and 12 controls. The patients with tropical malabsorption had greatly raised basal plasma motilin and enteroglucagon concentrations, but their postprandial release of both gastric inhibitory polypeptide and insulin was significantly reduced. The pattern of gut hormone release differed from that found in coeliac disease. The measurement of gut hormones, each of which has a specific site and function, thus throws new light on the pathophysiology of tropical malabsorption and may suggest approaches of treatment.

Advantages of the plasma uptake method for measuring vitamin B12 absorption.

The plasma uptake method for determining vitamin B12 absorption is reassessed. The results of this study demonstrate the ease with which normal controls can be separated from patients with intestinal malabsorption of vitamin B12 and from those with pernicious anaemia. This method is also shown to be a sensitive index of improved vitamin B12 absorption after treatment of small-intestinal disease and with the addition of intrinsic factor in pernicious anaemia. The advantages, particularly for developing countries, over the more commonly used Schilling test are discussed. It is emphasized that, because of the lack of a universally accepted normal value, healthy controls should be studied to define the normal range for the community under investigation.