Source of dietary protein influences kinetics of plasma gut regulatory peptide concentration in response to feeding in preruminant calves

Anaemia in pregnancy in developing countries continues to be a public health problem of significant proportion. At least 50% of the anaemia has been blamed on iron deficiency. In populations where chronic inflammation and iron deficiency anaemia coexist, the criteria to accurately define iron status are not always clear. Similarly, in pregnancy, with marked physiological changes, cut-off points for biochemical parameters need to be re-examined. In this study we examined the diagnostic accuracy of iron parameters including mean cellular volume (MCV), serum iron, transferrin, total iron binding capacity (TIBC) and its saturation, zinc protoporphyrin (ZPP), ferritin and serum transferrin receptor (TfR) for the assessment of iron status in a population of anaemic pregnant women in Malawi. Stained bone marrow aspirates were used as the standard for comparison. Results show that for the purpose of screening, serum ferritin is the best single indicator of storage iron provided a cut-off point of 30 microg/l is used. A number of other commonly used parameters of iron status were shown to have limited diagnostic accuracy. Logistic regression was used to obtain mathematical models for the prediction of bone marrow iron status using a combination of available parameters.     

Microcytosis, anisocytosis and the red cell indices in iron deficiency

Red cell volume distribution curves have been used to measure microcytosis and anisocytosis in normal subjects, blood donors and patients with iron deficiency anaemia. These measurements were more sensitive than the conventional red cell indices for detecting blood donors with a low transferrin saturation. Three stages are suggested as iron deficiency progressively interferes with haemopoietic function. Anisocytosis and an increased percentage of microcytic cells are the first haematological abnormalities to occur and at this stage haemoglobin concentration is usually normal and trasferrin saturation less than 32%. At the second stage the MCV and MCH decline, haemoglobin concentration is generally sub-normal, though not below 9 g/dl, and transferrin saturation is usually below 16%. The final stage of iron deficiency is associated with a low MCHC, a haemoglobin concentration below 9 g/dl and a transferrin saturation of less than 16%.     

Zinc protoporphyrin (ZPP) in diagnosis of anemia

In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms ZPP/g Hb). The ZPP level and comparison with the other normally used tests in iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML, plasmocytoma was investigated. The ZPP level was determined by hematofluorometry in samples from 96 patients. Thirty five patients with iron depletion showed decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median 9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin (median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD was determined. Measurement of ZPP level in the combination with ferritin and peripheral blood morphology allows to classify the degree of iron deficiency. The ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group of anaemic patients.     

Familial idiopathic atrial fibrillation with bradyarrhythmia

OBJECTIVE: To determine whether the maternal haemoglobin and iron stores of non-anaemic mothers (haemoglobin > or = 10 g/dl) who developed postpartum anaemia were lower compared to mothers who did not develop postpartum anaemia. STUDY DESIGN: A prospective study was conducted in a teaching hospital on 467 low-risk mothers recruited from the antenatal clinic over a 3-month period, who were given only low dose iron supplement and delivered in the same hospital. Blood was drawn at 28-30 weeks for the measurement of haemoglobin, mean cell volume, serum ferritin, serum iron and total iron binding capacity. These results were compared between mothers with a postpartum day 3 haemoglobin of > or = 10 g/dl and those < 10 g/dl. Statistical analysis was performed with parametric and non-parametric methods as appropriate. RESULTS: Mothers with postpartum anaemia had a higher incidence of postpartum haemorrhage (19.6% vs. 3.9%, P < 0.001) as well as heavier mean intrapartum blood loss (444 ml vs. 304 ml, P < 0.001), but there was no difference in the haemoglobin, mean cell volume, serum ferritin, serum iron and total iron binding capacity. CONCLUSIONS: In mothers without antenatal anaemia, the development of postpartum anaemia is not related to the maternal iron status in the third trimester.     

Iron deficiency and anaemia in a longitudinal study of New Zealanders at ages 11 and 21 years

AIMS: To determine iron status in a longitudinal study of New Zealanders, the Dunedin Multidisciplinary Health and Development Study (DMHDS), at ages 11 (1983-4) and 21 (1993-4). METHODS: Red cell variables were measured in 553 (298 males, 255 females) and 784 (413 males, 371 females) members of the DMHDS at ages 11 and 21, respectively. A total of 456 (259 males, 197 females) members were tested at both ages. Serum ferritin was measured at age 21 only. RESULTS: The prevalence of anaemia in females (haemoglobin < 120 g/L) increased from 3.1% at age 11 to 5.8% at age 21 (pregnant women excluded). There was a significant association between low haemoglobin at age 11 and low haemoglobin at age 21. In males, prevalence of anaemia decreased from 2.3% at age 11 to 0.97% (haemoglobin < 130 g/L) at age 21. The prevalence of iron deficiency (ferritin < 12 ng/mL) at age 21 was 0.24% in men and 6.7% in women. The prevalence of iron deficiency with anaemia at age 21 was zero in men and 2.2% in women. CONCLUSIONS: The prevalences of anaemia and iron deficiency in the DMHDS appear to be low by comparison with similar populations in other countries. Anaemia appears to be a stable trait in young women and screening may be useful for its early detection.     

Opposite effects of bezafibrate and gemfibrozil in both normal and hypertriglyceridemic rats

The diagnostic value of zinc protoporphyrin (ZPP) as an indicator of iron-deficient anemia (IDA) in hospitalized patients is assessed in this study. ZPP was measured using an AVIV hematofluorometer with a coefficient of variation (CV) less than 5% and a recovery of greater than 97%. A reference range of 53-70 mu mol/mol heme was determined for ZPP in non-anemic patients in a hospital population. Hospitalized patients (221) with low hemoglobin (< 120 g/l) were evaluated for their iron status. ZPP and other anemia tests were performed. Macrocytic patients with mean corpuscular volume (MCV) greater than 98 fl) were excluded from the study. Seventy-four microcytic patients (MCV < 80 fl) were determined as having IDA according to a diagnostic algorithm. A distribution study of these microcytic patients showed that there was a significant overlap of values between the IDA and non-IDA patients for all serum anemia tests. A receiver-operator curve analysis revealed that ZPP has a relatively high degree of diagnostic efficiency better than iron and ferritin for this patient population. At a cutoff value > 170 mu mol/mol heme, ZPP has a sensitivity of 93% and a specificity of 90%. In addition, ZPP is also elevated in normocytic patients (MCV = 80-98 fl) with low ferritin values, who may have iron depletion. From these data, it is proposed that ZPP may be used as a screening tool for IDA in hospitalized patients.     

A study on the boundary value of hemoglobin concentration for screening iron deficiency anemia in pregnant women

To evaluate whether a pregnant woman is in anemia or there exist the needs to replenish iron is usually based on the measurement of hemoglobin (HB) concentration, because the evaluation of iron nutritional status has not yet been used widely in our country. Blood specimens were collected from 258 pregnant women, and concentrations of Hb, serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were determined to find out a reasonably boundary value of Hb concentration from the two different ones set by our country and WHO, respectively, and the one averaged the former two, i.e, 100g/L, 110g/L and 105g/L. False positivity and false negativity in diagnosis of iron deficiency anemia (IDA) for pregnant women were evaluated based on the measurement of SF and FEP concentrations as gold standards. Results showed that the optimal Hb concentration for preliminary diagnosis of IDA was 105g/L with maximizing Yorden index.     

Nursing informatics--what on earth?

AIM AND BACKGROUND: Two forms of hypochromic microcytic anaemia i.e. iron deficiency and beta-thalassaemia trait are common in our society. This study reports the prevalence of iron deficiency anaemia and beta-thalassaemia trait and predictive value of MCV/RBC count ratio to discriminate between two. METHODS: Venous blood was taken from 299 students of Karachi Medical & Dental College and Ziauddin Medical University in Na2 EDTA and analyzed by semi-automated Sysmex K-1000 haematology analyzer. MCV/RBC count ratio was used to discriminate between iron deficiency and beta-thalassaemia trait and > 14% was marked as iron deficiency. Hb electrophoresis was used as gold standard test for confirmation. Serum iron and TIBC was performed to confirm iron deficiency anaemia. RESULTS: Iron deficiency was found in 9% while beta-thalassaemia was seen in 3% students. MCV/RBC count ratio showed a positive predictive value of 91%. CONCLUSIONS: In areas where iron deficiency anaemia and beta-thalassaemia trait are common, MCV/RBC count ratio can be used to screen out beta-thalassaemia trait.     

Iron supplementation in haemodialysis--practical clinical guidelines

BACKGROUND: The aim of this prospective study was to test a new protocol for iron supplementation in haemodialysis patients, as well as to assess the utility of different iron metabolism markers in common use and their 'target' values for the correction of iron deficiency. METHODS: Thirty-three of 56 chronic haemodialysis patients were selected for long-term (6 months) i.v. iron therapy at 20 mg three times per week post-dialysis based on the presence of at least one of the following iron metabolism markers: percentage of transferrin saturation (%TSAT) <20%; percentage of hypochromic erythrocytes (%HypoE) > 10% and serum ferritin (SF) <400 microg/l. Reasons for patient exclusion were active inflammatory or infectious diseases, haematological diseases, psychosis, probable iron overload (SF > or =400 microg/l) and/or acute need of blood transfusion mostly due to haemorrhage and change in renal replacement treatment. RESULTS: More than half (51.8%) of the patients of our dialysis centre proved to have some degree of iron deficiency in spite of their regular oral iron supplementation. At the start of the study the mean haemoglobin was 10.8 g/dl and increased after the 6 months of iron treatment to 12.8 g/dl (P<0.0001). The use of erythropoietin decreased from 118 units/kg/week to 84 units/kg/week. The criterion for iron supplementation with the best sensitivity/specificity relationship (100/87.9%) was ferritin <400 microg/l. Patients with ferritin < 100 [microg/l and those with ferritin between 100 microg/l and 400 microg/l had the same increase in haemoglobin but other parameters of iron metabolism were different between the two groups. CONCLUSIONS: Routine supplementation of iron in haemodialysis patients should be performed intravenously. Target ferritin values should be considered individually and the best mean haemoglobin values were achieved at 6 months with a mean ferritin of 456 microg/l (variation from to 919 microg/l). The percentage of transferrin saturation, percentage of hypochromic erythrocytes and ferritin <100 microg/l, were not considered useful parameters to monitor routine iron supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed.     

Iron requirements and iron balance during pregnancy. Is iron supplementation needed for pregnant women?

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that iron-treated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebo-treated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 60-70 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.     

Nonreentrant supraventricular tachycardia due to double ventricular response via dual atrioventricular nodal pathways

In twenty eight patients with iron deficiency the efficacy of iron-acetil-transferrin treatment (2-3 mg/kg/die) has been evaluated from the changes of the following variables: RBC and reticulocyte count, Hb concentration, MCV, MCH, serum ferritin, serum iron, TIBC, and ZnPP. These variables were assessed before and after three months of treatment in all patients, and after three months from the end of the treatment in thirteen patients. At the end of the treatment there was a significant increase of RBC count, Hb concentration, MCV, MCH, serum ferritin, serum iron, and TIBC, a significant decrease of ZnPP, while reticulocyte count remained essentially unchanged. After three months from the end of the treatment only serum ferritin and ZnPP underwent an additional significant increase and decrease, respectively. In twenty-six patients serum ferritin values returned to normal. The changes of RBC and reticulocyte count, Hb concentration, MCV, serum iron, and TIBC were larger the lower the initial values, suggesting that the efficacy of the treatment is greater the more serious the iron deficiency.     

Evaluation of hemoglobin and hematocrit in pregnant women receiving folate and iron supplements

BACKGROUND AND AIMS: From week 8 there is a reduction in hemoglobin and hematocrit (owing to the increased plasma volume which exceeds the increased erythrocytic content) that continues to fall steadily until week 16-22, flattening out at a level of 10-11 g/100 ml for hemoglobin and 32-34% for hematocrit. Bone marrow produces red blood cells and hemoglobin in proportion to the increase in plasma volume, provided that there is an adequate iron supply (higher in pregnancy compared to the usual dietary intake). For this reason, the authors examined the systematic supplementation of pregnant women with ferrous gluconate and folic acid, another important element for numerous metabolic reactions which is also lacking in pregnancy owing to increased requirements. METHODS: The study showed that pregnant patients receiving folic acid and iron supplements from week 5 to 40 presented hematocrit readings and hemoglobin levels from week 12 that were constantly higher compared to the population not receiving supplements, with statistically significant and highly significant differences respectively. The few collateral effects observed in a limited group of patients allow the authors to define the tolerability of the proposed treatment as "excellent". They emphasise, however, the importance of constant supplementation with folic acid and iron throughout pregnancy to avoid sideropenic anemia, with considerable benefits in terms of the physical conditions of the pregnant woman, the supply of O2 to the villi, fetal wellbeing and the need to resort to possible blood transfusions in the event of major blood losses at birth.     

Biotin deficiency in chicks fed a wheat-based diet

A wheat-based diet produced severe biotin deficiency symptoms appearing at the age of ten to fourteen days and becoming very severe in the third and fourth week (group 1). Biotin supplementation with 50 mug/kg (group 2) reduced the symptoms almost completely, but did not restore completely growth compared to chicks receiving the diet supplemented with 300 mug biotin/kg compared to chicks receiving the diet supplemented with 300 mug biotin/kg (group 3). The plasma level of biotin was about, or lower than, 100 ng/100 ml plasma in groups 1 and 2, indicating biotin deficiency. In group 3, plasma biotin was above 200 ng/100 ml. Liver biotin, after two weeks, was low in group 1 (less than 600 ng/g), medium in group 2 (1000 to 1500 ng/g) and in group 3 above 2000 ng/g. Plasma and liver biotin levels are found to be suitable parameters for diagnosis of subclinical biotin deficiency in chicks.     

Thiamine, riboflavin, folate, and vitamin B12 status of infants with low birth Weights receiving enteral nutrition

The purpose of the present study was to monitor the vitamin status of 14 low-birth-weight (LBW) infants (< 1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 micrograms/100 kcal thiamine, 617 micrograms/100 kcal riboflavin, 37 micrograms/100 kcal folate, and 0.55 micrograms/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 +/- 259 g, and mean gestational age was 29 +/- 2 weeks. Weekly blood, 24-h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 micrograms/100 kcal thiamine and 370 micrograms/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 +/- 11 ng/ml at 2 weeks and 18 +/- 5 ng/ml at 3 weeks. RBC folate levels were 455 +/- 280 ng/ml at 2 weeks and 391 +/- 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 +/- 394 pg/ml at 2 weeks and 768 +/- 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive.     

The role of iron in the regulation of hepatic transferrin synthesis

The role of iron supply in the regulation of hepatic transferrin synthesis by the isolated perfused rat liver was studied using nutritional iron deficiency as the experimental model. The increased transferrin release encountered in iron deficiency could be equated with enhanced de novo synthesis as evidenced by the inhibitory effects of cycloheximide and measurements of intrahepatic protein pools before and after perfusion. Refeeding with iron, sufficient to restore plasma iron and hepatic ferritin iron but before correction of anaemia, promoted a reduction towards normal in the transferrin synthetic rate. This effect was not produced by transfusional correction of the anaemia, suggesting a specific response to iron supply. Phenobarbitone treatment, which produced a marked fall in hepatic ferritin iron concentration but no change in haemoglobin or plasma iron concentrations, promoted a specific enhancement of transferrin synthesis in both control and iron deficient livers. The concentration of liver iron stores appears to be a major regulatory factor in the control of hepatic transferrin synthesis.     

The role of serum transferrin receptor in the diagnosis of iron deficiency

BACKGROUND AND OBJECTIVE: Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. DESIGN AND METHODS: A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). RESULTS: The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). INTERPRETATION AND CONCLUSIONS: This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.     

Serum ferritin as a control parameter for oral iron therapy (author's transl)

Ferrritin can be measured in blood serum radioimmunometrically. Serum ferritin is directly correlated to body iron stores. In comparison to other parameters of storage iron (bone marrow iron, intestinal iron absorption) this quantitative diagnostic parameter is easily available. Thus it can be used to judge body iron status. In 20 patients with chronic haemorrhagic and 7 patients with posthaemorrhagic iron deficiency anaemia as well as nine blood donors with latent iron deficiency serum ferritin was used to control oral iron therapy. The continuous determination of serum ferritin during therapy gives a quantitative value of the relevant level of body iron stores. This value shows whether therapy was effective and when iron stores are replenished. The results demonstrate that oral iron therapy should be continued for at least 3 months from the time of normalisation of haemoglobin to obtain a sufficient restoration of iron depots.     

Effects of paramagnetic cations on the nonexponential spin-lattice relaxation of rare spin nuclei in solids

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.     

Developmental change in red blood cell volume: implication in screening infants and children for iron deficiency and thalassemia trait

The mean corpuscular volumen when determined by electronic counter is an accurate tool for identification of children with microcytosis due to either iron deficiency or thalassemia trait. The purpose of this report is to describe the normal developmental changes in MCV that occur in children afler 6 months of age. In 211 healthy infants and children screened to exclude those with borderline or overt iron deficiency, thalassemia trait, or hemoglobinopathy, we found that the lower limit of normal for MCV is 70 ft between 10 and 17 months of age and that there is a gradual increase of MCV with age; the lower limit is 74 between 1 1/2 and 4 years and 76 between 4 and 7 years. All of these values are well below the minimum adult level of 80 fl.     

Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria

The activity of heme synthetase, which catalyzes the chelation of ferrous iron to protoporphyrin to form heme, is deficient in sonicates of skin fibroblasts cultured from patients with protoporphyria. During culture in Eagle's medium supplemented with fetal calf serum, these cells do not accumulate protoporphyrin, however. This may be due to a minimal requirement for heme synthesis, since glycine is incorporated into heme at a low rate which is similar to that in normal fibroblasts. In addition, the activity of delta-aminolevulinic acid (ALA) synthetase, the first and rate-limiting enzyme of heme biosynthesis which catalyzes the formation of ALA from glycine, is normal in lysates of the fibroblasts. Cultured fibroblasts were therefore incubated with ALA in order to bypass the rate-limiting step of heme biosynthesis. In the presence of 25 muM iron, protoporphyrin was detected in protoporphyria cell lines when the concentration of ALA in the medium reached 50 muM, but not in normal lines. As the concentration of ALA was increased above 50 muM, all lines accumulated protoporphyrin. However, the amount was 2-3 times more in cultured fibroblasts from patients with protoporphyria, reflecting their deficiency of heme synthetase activity. When iron was not added to the medium, protoporphyrin accumulated to a similar degree in normal and protoporphyria fibroblasts; this was significantly more than that in the presence of iron. These studies indicate that excessive protoporphyrin accumulation in protoporphyria, which is due principally to deficient heme synthetase activity, may be modified by the rate of ALA formation in heme-producing tissues, and by the availability of iron.