Bivariate mixture modeling of transferrin saturation and serum ferritin concentration in Asians, African Americans, Hispanics, and whites in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Bivariate mixture modeling was used to analyze joint population distributions of transferrin saturation (TS) and serum ferritin concentration (SF) measured in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Four components (C1, C2, C3, and C4) with successively age-adjusted increasing means for TS and SF were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 whites. The largest component, C2, had normal mean TS (21% to 26% for women, 29% to 30% for men) and SF (43-82 microg/L for women, 165-242 microg/L for men), which consisted of component proportions greater than 0.59 for women and greater than 0.68 for men. C3 and C4 had progressively greater mean values for TS and SF with progressively lesser component proportions. C1 had mean TS values less than 16% for women (<20% for men) and SF values less than 28 microg/L for women (<47 microg/L for men). Compared with C2, adjusted odds of iron deficiency were significantly greater in C1 (14.9-47.5 for women, 60.6-3530 for men), adjusted odds of liver disease were significantly greater in C3 and C4 for African-American women and all men, and adjusted odds of any HFE mutation were increased in C3 (1.4-1.8 for women, 1.2-1.9 for men) and in C4 for Hispanic and white women (1.5 and 5.2, respectively) and men (2.8 and 4.7, respectively). Joint mixture modeling identifies a component with lesser SF and TS at risk for iron deficiency and 2 components with greater SF and TS at risk for liver disease or HFE mutations. This approach can identify populations in which hereditary or acquired factors influence metabolism measurement.     

Iron overload in urban Africans in the 1990s

BACKGROUND: In a previously described model, heterozygotes for an African iron loading locus develop iron overload only when dietary iron is high, but homozygotes may do so with normal dietary iron. If an iron loading gene is common, then homozygotes with iron overload will be found even in an urban population where traditional beer, the source of iron, is uncommon. AIMS: To determine whether iron overload and the C282Y mutation characteristic of hereditary haemochromatosis are readily identifiable in an urban African population. METHODS: Histological assessment, hepatocellular iron grading, and dry weight non-haem iron concentration were determined in post mortem tissue from liver, spleen, heart, lungs, and skin. DNA of subjects with elevated hepatic iron indexes was analysed for the C282Y mutation. Iron concentrations in other tissues were compared. RESULTS: A moderate increase (>30 micromol/g) in hepatic iron concentrations was found in 31 subjects (23%; 95% confidence interval 15.9 to 30.1%), and they were considerably elevated (>180 micromol/g) in seven subjects (5.2%; 95% confidence interval 1.5 to 8.9%). Appreciably elevated hepatic iron concentrations were associated with heavy iron deposition in both hepatocytes and macrophages, and either portal fibrosis or cirrhosis. All were negative for the C282Y mutation. Very high concentrations were uncommon in subjects dying in hospital. Concentrations of iron in spleen, heart, lung, and skin were significantly higher in subjects with elevated hepatic iron. CONCLUSIONS: Iron overload is readily identified among urban Africans and is associated with hepatic damage and iron loading of several tissues. The condition is unrelated to the genetic mutation found in hereditary haemochromatosis.     

Presence of the red cell alloantibody anti-E in an 11-week-old infant

The development of red cell (RBC) alloantibodies in infants less than 4 months of age is believed to be rare. Though there are no well-documented published accounts, the formation of alloanti-E in a multiply transfused 11-week-old infant is reported here. The infant, blood group B, D +, developed necrotizing enterocolitis and renal failure requiring 31 transfusions of washed and unwashed RBCs (group B and group O), as well as fresh-frozen plasma and platelets. Six weeks after the first blood transfusion, alloanti-E was detected. The anti-E weakly agglutinated R2R2 screening RBCs at 37 degrees C and sensitized these RBCs to react with anti-IgG. The infant's RBCs were typed as E-. Passive transfer of alloanti-E was ruled out by the negative antibody screening tests of each donor unit and the absence of any RBC alloantibodies in the mother's serum. Stored samples of the infant's sera were tested, and anti-E was shown to be present approximately 11 days after exposure to a known E+ RBC unit. The appearance of alloanti-E in this time frame is consistent with a secondary immune response. Primary immunization most likely took place in the first 4 weeks of transfusion therapy.     

External resorption presenting as an intracoronal radiolucent lesion in a pre-eruptive tooth

A large intracoronal radiolucent lesion in an unerupted permanent molar was found during the routine assessment of a young male Caucasian prior to orthodontic treatment. The tooth was extracted. Histological examination indicated the lesion was caused by external resorption. The defect extended widely into the enamel and dentine, and was repaired in part by bone. The pulp chamber was not involved. The aetiology of these lesions is often obscure but in this case it appeared to have originated in the floor of two developmental pits on the occlusal surface of the tooth.     

Carbonyl iron for short-term supplementation in female blood donors

A randomized, double-blind trial of iron replacement after repeated blood donation was conducted in 75 menstruating women; 51 completed the study. Volunteers were assigned randomly to one of three treatment groups: 1) carbonyl iron (nontoxic elemental iron powder), 600 mg; 2) ferrous sulfate, 300 mg (60 mg Fe++); or 3) placebo, each given three times daily for 1 week immediately after blood donation. Blood samples obtained initially and 56 days later were tested for hemoglobin, mean corpuscular volume (MCV), free erythrocyte protoporphyrin, serum ferritin, serum iron, total iron binding capacity (TIBC), and percent saturation of TIBC. The prevalence of gastrointestinal side effects was similar in both groups taking iron. At the end of the study there was no laboratory evidence of change in iron status in women who received carbonyl iron (n = 15). In those treated with ferrous sulfate (n = 17) the mean TIBC increased (p less than 0.001), and in the placebo group (n = 19) there were decreases in mean MCV (p less than 0.01), serum ferritin (p less than 0.001), and percent saturation (p = 0.027) with an increase in mean TIBC (p = 0.004). Carbonyl iron seems to be effective for short-term iron replacement in repeat blood donors and may have the advantage of decreased or absent risk of poisoning if accidentally ingested by children.     

Dietary iron overload in southern African rural blacks

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of long-term renal transplant survivors

Despite the high rates of rejection, allograft failure, and patient death in the early years of renal transplantation, some patients have done remarkably well. Forty-three (17 living related donor and 26 cadaver donor recipients) such patients with an allograft that functioned for 19 years or more (range, 19 to 29 years) were followed up at this center. The patients included 24 men and 19 women, with a mean age at transplantation of 29 years, of whom 39 were white and four were black. At most recent follow-up, the mean daily dose of azathioprine was 104 mg (range, 50 to 175 mg) and that of prednisone was 10 mg (range, 5 to 20 mg). Mean serum creatinine level was 1.6 mg/dL (range, 0.7 to 5.4 mg/dL). Acute rejection occurred in 14 (33%) patients. Nine patients had one episode and five patients had two episodes of acute rejection. Long-term risks to the recipients appeared in the form of coronary artery disease in 10 (23%) patients; malignancy in 13 (30%) patients, which included nine patients with skin malignancy; and chronic hepatitis C virus (HCV) infection in four patients, two of whom died of complications of liver failure. Other complications included avascular bone necrosis in five patients, which required total hip replacement in two patients; hyperlipidemia requiring treatment in 16 (37%) patients; posttransplantation diabetes mellitus in 10 (23%) patients after a median of 17.5 years (range, 1 to 23 years); and hypertension in 23 (53%) patients. There were seven deaths (three of coronary artery disease, two of liver failure, one each of sepsis and malignancy) and eight graft losses (five to death with function, two to chronic rejection, and one to focal and segmental glomerulosclerosis). Although long-term allograft success results in patients receiving minimal amounts of immunosuppression and having good renal function, long-term renal transplant survivors are at risk for significant morbidity even in the third decade posttransplantation.     

Second fingerstick: a simple method to increase the blood supply

Before blood donors are deferred because of a low hemoglobin determination by the copper sulfate procedure, they are routinely retested with a microhematocrit. The copper sulfate test and the microhematocrit usually are performed on blood samples taken from the same finger (or earlobe) puncture. We studied 201 male and female volunteer blood donors who failed the copper sulfate test to determine if more donors would be accepted for donation if blood from a second fingerpuncture, instead of the original fingerstick, was used for the microhematocrit determination. Venous blood samples were obtained to evaluate complete blood count and measures of iron status. The results indicated that the deferral rate was reduced by 46% using a fresh fingerpuncture for the microhematocrit determination. The iron status of the additional donors accepted on the basis of the second puncture was not significantly different from that of the donors accepted by the original fingerstick. We conclude that using a second fresh fingerpuncture for the microhematocrit determination after failing the copper sulfate test decreases the number of hematocrit deferrals and does not compromise the iron status of the additional donors.     

High-dose carbonyl iron for iron deficiency anemia: a randomized double-blind trial

To determine if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia, high-dose Fe 600 mg three times per day (given as nontoxic carbonyl Fe) was compared with standard ferrous sulfate 60 mg Fe++ three times per day in a randomized, double-blind, 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia. In animal studies, both forms of Fe have similar bioavailability when administered in equal amounts. High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with standard FeSO4 therapy. The 10-fold larger amount of Fe resulted in a mean 1.5-fold increase in estimated Fe absorption. Both regimens corrected anemia but neither replenished storage Fe. These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given.