OBJECTIVETo confirm prevalent iron deficiency among Yupik Eskimos living in Alaska and to explore the frequency of and potential lesions accounting for occult gastrointestinal bleeding.DESIGNDescriptive survey.SETTINGRural Arctic community.SUBJECTSA total of 140 adult volunteers from 3 villages in the Yukon-Kuskokwim Delta region of western Alaska.MAIN OUTCOME MEASURESDaily iron intake, hematologic and biochemical indexes of iron status, fecal hemoglobin levels, stool parasites, and endoscopic findings.RESULTSWhile dietary iron intake by Yupiks was similar to that of a reference population, iron deficiency prevalence was increased 13-fold in Yupik men and 4-fold in Yupik women. Fecal hemoglobin levels were elevated in 90% of subjects contrasted with only 4% of a reference group; median levels were 5.9 and 0.5 mg of hemoglobin per gram of stool, respectively. Among 70 Yupik subjects with elevated fecal hemoglobin levels who had endoscopy performed, 68 (97%) had an abnormal gastric appearance consisting of erythema, mucosal thickening, diffuse mucosal hemorrhages, erosions, or ulcerations. Gastric biopsies revealed chronic active gastritis with associated Helicobacter pylori in 68 (99%) of 69. No other hemorrhagic gastrointestinal disease was detected.CONCLUSIONSBased on this study sample, occult gastrointestinal bleeding appears to be pervasive in the Yupik population and likely underlies the prevalent iron deficiency. An atypical hemorrhagic gastritis associated with H pylori infection is present almost universally and may represent the bleeding source.

Aging decreases rat liver regeneration. We (1) compared the expression of ornithine decarboxylase (ODC), a critical enzyme for liver regeneration, and polyamine levels in regenerating liver of 6-week-old and 1-year-old rats and (2) evaluated the effect of exogenous putrescine supplementation on liver regeneration in 1-year-old rats. ODC messenger ribonucleic acid (mRNA) transcript sizes were the same in rats of both ages. ODC mRNA content and enzyme activity were higher in the younger rats; however, magnitudes of increase after partial hepatectomy were greater in the older rats. From peak levels, the rate of decline of the mRNA was slower in the older rats, but enzyme activity declined at the same rate in both ages. ODC apoenzyme content was significantly less in normal liver tissue from 1-year-old rats, but there was little change after partial hepatectomy in rats of either age. No change in ODC transcriptional activity was found. Hepatic putrescine levels were lower in 48 hours regenerating liver tissue from 1-year-old rats. To determine whether supplemental putrescine would increase liver regeneration in 1-year-old rats, putrescine (600 mumol/kg IP every 4 hours) was administered beginning 4 days before or at the time of partial hepatectomy. This raised polyamine levels and decreased ODC activity significantly, but there was no change in regenerating liver weight, total DNA and RNA content, and tritiated thymidine incorporation at 48 hours. These results indicate that ODC expression is different and polyamine levels are lower in 1-year-old rats than in 6-week-old rats. However, putrescine supplementation that is sufficient to decrease ODC activity has no apparent effect on regeneration.

Carbon monoxide is stoichiometrically released when heme is converted to bilirubin. This report describes and validates a novel technique that permits the estimation of heme turnover and red blood cell survival from the carbon monoxide concentration of end-expiratory breath samples. The end-alveolar Pco of a subject was corrected for environmental carbon monoxide exposure with a simple device that equilibrates with atmospheric carbon monoxide at the same rate as does the subject. The resultant value (endogenous Pco) was tested for its ability to predict heme turnover and red blood cell survival. Red cell survival times of 32 healthy subjects, as calculated from the endogenous Pco, averaged 101 +/- 19 days, a value close to the expected 110-day survival time; 13 patients with clinical evidence of shortened red blood cell survival times had measured erythrocyte life spans ranging from 10 to 59 days. The endogenous Pco of each of seven patients increased after red blood cell transfusion, demonstrating that this technique detected the known rapid turnover of a small fraction of transfused cells. A good correlation (r = 0.91) was observed between heme turnover calculated from endogenous Pco and total fecal biliary pigment output. Carbon monoxide measurements reflect red blood cell destruction in both the marrow and the circulation, therefore yielding shorter life spans than did chromium 51 survival studies. This breath test appears to yield a rapid, semiquantitative assessment of heme turnover and red blood cell survival that is not provided by any other presently available technique. This simple, noninvasive carbon monoxide breath test may find widespread use in the evaluation of anemia and jaundice.

Polyamines are considered critical for cell proliferation. During liver regeneration in the rat, ornithine decarboxylase (ODC) mRNA and enzyme activity and polyamines (primarily putrescine and spermidine) are known to increase substantially. We examined the effect of inhibition of polyamine synthesis with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of the ODC enzyme, on regenerating liver weight and total DNA, RNA, and protein, [3H]thymidine and [14C]leucine incorporation, number of mitotic figures, and putrescine, spermidine, and spermine contents. Rats received DFMO beginning 4 days before or immediately after two-thirds partial hepatectomy. In control rats, ODC activity, putrescine, and spermidine increased significantly during regeneration, whereas spermine was unchanged. In rats receiving DFMO, ODC and putrescine changed minimally but spermidine increased as usual. Spermine levels were modestly higher in rats receiving DFMO beginning 4 days before partial hepatectomy. However, despite ODC inhibition and substantially lower levels of putrescine, the course of liver regeneration in rats treated with DFMO was not affected. Total liver mass, DNA, RNA, and protein increased over 5 days equally in rats receiving DFMO and control rats. In addition, there were no differences in [3H]thymidine incorporation into DNA, [14C]leucine incorporation into protein or mitotic indexes between DFMO-treated and control rats at 24 and 48 h after partial hepatectomy. These results suggest that the well-known increases in ODC activity and polyamines that occur during regeneration are not required for liver to undergo its proliferative response to partial hepatectomy.

Despite widespread fecal blood testing, the technique of gathering stool for sampling has remained uncontrolled. We sought to describe how patients have contended with this awkward step, to study artifact caused by toilet water, and to construct a collection device that prevents sampling problems. A survey of 250 patients showed that most (56%) had retrieved stools from the toilet basin, 17% used a pan or other household receptacle, 10% used newspaper or tissue paper, and 17% had been unable or unwilling. Sampling stool from the toilet basin introduces error because 4% to 75% of blood leaches from the fecal surface into surrounding water after only 4 to 12 minutes, and many toilet sanitizers cause false-positive guaiac reactions. We describe an inexpensive, disposable stool collector; outpatient compliance has been 97% using this device. To avoid biochemical artifact and facilitate stool sampling, we advocate that a collection device be incorporated into the occult blood testing process.

Feces from 27 dogs were evaluated to establish baseline fecal hemoglobin (Hb) concentrations when the dogs were fed diets containing varying amounts of Hb. Fecal Hb concentration was measured, using a quantitative fluorometric assay that was based on the conversion of nonfluorescing Hb heme to fluorescing porphyrins. Mean fecal Hb concentration was 0.31 mg/g of feces when the dogs were fed a dry diet low in Hb. This corresponded to a daily fecal blood loss of 0.043 ml/kg of body weight. The fecal Hb concentration was directly related to the dietary Hb concentration. The average recovery of orally ingested blood was 41% in 4 dogs. This fluorometric assay quantitatively detected small amounts of gastrointestinal bleeding over a wide range of fecal Hb concentrations for which feces appeared normal. Results of this study establish dietary conditions necessary for quantitative evaluation of experimental and clinical gastrointestinal bleeding.

Blood, meat, or fish, or any combination thereof, were ingested by 9 normal volunteers to permit studies of the contained hemes during total gastrointestinal transit. Quantitative analysis of ingested heme and of fecal heme and its degradation products was made possible by a new specific and extremely sensitive test, HemoQuant. The average fecal recovery of hemoglobin-heme from 10 to 36 ml of blood was 88%, as determined in 13 separate studies. All Hemoccult tests remained negative despite >20-fold increases in fecal heme. Up to 83% of the blood heme was converted in the intestinal tract to porphyrins. These porphyrins are included in the HemoQuant, but not in Hemoccult or other leukodye assays. Negligible amounts of heme were found in fish and fowl, and their ingestion led to no significant increase in fecal heme. An average of only 25% of the heme in ingested meat was subsequently recovered in feces. Control fecal values represented an average of ~0.5 ml of blood per day. The recovery data obtained show that fecal HemoQuant results reliably reflect the total amount of blood hemoglobin that enters the gastrointestinal tract.

We describe a new, specific, quantitative method for fecal blood, based on conversion of nonfluorescing heme to fluorescing porphyrins, that obviates serious deficiencies inherent in currently used tests. A two-reagent system is used to determine the two hemoglobin-related fractions that are found in feces. The hot citric acid extract includes only the variable fraction of porphyrins that have been preformed from heme in the intestinal tract; this often is the major fraction. Total hemoglobin is indirectly determined by reaction with heated oxalic acid:FeSO4 reagent, which converts the remaining heme to porphyrin without loss of the preformed porphyrins. A three-step purification procedure eliminates interfering materials. Analytical recovery of added hemoglobin is linearly related to concentration over a several-thousand-fold range. The assay is equally applicable to whole blood or to sub-microgram amounts of hemoglobin in the 8-mg (wet weight) fecal sample tested. Quality control by liquid chromatographic and fluorometric analysis documents fluorescence specificity of the heme-derived porphyrins.