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.     

Iron deficiency anemia. Every case is instructive

Awareness of subtle symptoms of mild iron deficiency is increasing, but unsuspected iron deficiency is a persistent problem, especially among certain groups, such as menstruating women and milk-fed infants. The diagnosis must be clearly established through appropriate testing, and an underlying cause should always be sought. Useful tests include determination of serum ferritin and iron levels and of iron-binding capacity. A nomogram is available that correlates the serum ferritin value with the degree of inflammation present, but in some patients, bone marrow aspiration and iron staining is still required. When oral iron therapy is undertaken, an appropriate non-enteric-coated, non-sustained-release preparation should be chosen. Gradually increasing the amount of iron supplementation and taking the tablets with meals help limit side effects and ensure patient compliance. Iron therapy should be continued for 6 months after the hemoglobin level returns to normal so that total iron stores are replaced. Follow-up to ensure that iron deficiency anemia has not recurred and that the diagnosis was correct is required.     

Surgical clips: a cause of late recurrent gallstones

BACKGROUND: Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form. AIM: To test whether ferric trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous sulphate. METHODS: Twenty-three patients were recruited from gastroenterology clinics, of whom 1 5 had inflammatory bowel disease, a group often difficult to treat with oral iron. Patients with iron deficiency anaemia and documented intolerance to ferrous sulphate were given 3 months of treatment with ferric trimaltol. RESULTS: Nineteen of 23 patients completed the treatment and anaemia was fully corrected in 14 of these, mean haemoglobin increased from 106 +/- 15 to 126 +/- 16 g/L, and there was a particularly low incidence of side-effects. Of 11 patients with inflammatory bowel disease who completed the study, nine fully corrected their anaemia. CONCLUSION: The results demonstrate that in patients intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and has a low incidence of side-effects.     

Management of rHuEPO resistance in CRF patients: a clinical protocol at Winthrop-University Hospital

An inadequate response to recombinant human erythropoietin (rHuEPO) therapy may be attributable to many underlying causes, with the major cause being iron deficiency. Since improved rHuEPO response can improve quality of life in end-stage renal disease (ESRD) patients, rHuEPO resistance should be investigated and corrected whenever possible. This article will discuss the Winthrop-University Hospital's continuous quality improvement (CQI) initiative that was developed to improve recognition and treatment of rHuEPO resistance.     

Calcium binding induces interaction between the N- and C-terminal domains of yeast calmodulin and modulates its overall conformation

The newly identified hemochromatosis gene, HFE, and a candidate iron transporter gene, Nramp2, have been proposed as key factors responsible for the regulation of intestinal iron absorption. Although the exact functions of these proteins in intestinal iron absorption are unknown, HFE may be required for the down-regulation of iron absorption that occurs with increasing iron status, and Nramp2 may up-regulate iron absorption when iron status is low. Thus, we examined whether the expression of the HFE and Nramp2 genes are regulated by iron status in the human intestinal cell line Caco-2. HFE mRNA and HFE protein were increased and Nramp2 mRNA was decreased by increasing cellular iron status in Caco-2 cells. This iron-mediated modulation of mRNA levels was specific to iron. Moreover, super-induction of HFE mRNA in the presence of cycloheximide suggests that HFE gene expression may be controlled by a short-lived repressor protein. HFE and Nramp2 mRNA levels also changed in opposite directions during cellular differentiation. This reciprocal modification of the HFE and Nramp2 gene expression during both iron treatment and cell differentiation in Caco-2 cells is consistent with an opposing role for these proteins in homeostatic regulation of human intestinal iron absorption.     

Functional iron deficiency in adults with cystic fibrosis

Functional iron deficiency (transferrin saturation < 16%) was found in 44 (62%) of 71 adult cystic fibrosis (CF) patients. Haemoglobin concentration and mean cell volume were lower in iron-deficient patients, in whom there was a non-significant trend for lower serum ferritin. Ten iron-deficient patients and two patients with transferrin saturation > = 16% (normal iron) were anaemic. There were no significant differences between iron-deficient and normal-iron patients in intake of calories, protein, iron and vitamin C as determined by 4-day records of dietary intake. Dietary iron deficiency is not an important factor in functional iron deficiency in adult CF patients. Impairment of absorption by exogenous pancreatic enzyme supplements is unlikely to be significant as enzyme intake was the same in the two groups. Iron-deficient patients had lower Shwachman-Kulczycki scores and lower percent predicted forced expiratory volume in 1 s (FEV1% predicted) and forced vital capacity (FVC% predicted). There was a non-significant trend for higher values of white cell count and plasma viscosity in the iron-deficient group. Chronic inflammation is likely to be the primary cause of functional iron deficiency in adult CF patients. Fifteen patients completed 3-month courses of oral iron replacement with no deterioration in pulmonary function, but with no effect on haemoglobin concentration.     

Prophylactic iron supplementation after Roux-en-Y gastric bypass: a prospective, double-blind, randomized study

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Roux-en-Y gastric bypass. DESIGN: Prospective, double-blind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after Roux-en-Y gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6-month intervals postoperatively in 56 menstruating women who had Roux-en-Y gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebo-treated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebo-treated than iron-treated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after Roux-en-Y gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have Roux-en-Y gastric bypass.     

Strategies for the prevention of iron deficiency through foods in the household

Iron deficiency can be caused not only by diets deficient in iron but by poor absorption of available dietary iron. Extrinsically tagging foods with radioiron allows the exact measurement of iron absorbed from heme and nonheme iron foods. It has furthered the study of the effect of enhancers and inhibitors of iron absorption. As a result, we have a greater understanding of why iron deficiency and iron deficiency anemia are prevalent in populations of low socioeconomic status and of which food vehicles and iron compounds are most suitable for iron fortification.     

Iron balance in hemodialysis patients

Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.     

Pernicious anaemia patients should be screened for iron deficiency during follow up

AIMS: To investigate if patients with pernicious anaemia (PA) are prone to develop iron deficiency and if there is a difference for this manifestation between younger and older age groups. METHODS: Ninety-five patients with pernicious anaemia were evaluated for body iron status at the time of diagnosis and during follow up. Patients were also divided into two groups; younger than 60 (53 patients) and older than 60 (42 patients) years of age. Groups were compared for iron deficiency both at the time of diagnosis and at the end of follow up period. RESULTS: Iron deficiency was a common finding in patients with pernicious anaemia. This deficiency state was more common in the elderly. During B12 therapy, iron deficiency increased in all groups, but the increased rate of iron deficiency was more prominent in the elderly patients. CONCLUSION: Pernicious anaemia is an atrophic gastropathy in which gastric parietal cells no longer produce hydrochloric acid. These patients with achlorhydria demonstrate impaired absorption of iron. On the other hand, with ageing, gastric acidity is already diminished. Iron deficiency commonly accompanies patients with pernicious anaemia and this is more pronounced in the elderly group. We suggest that all patients with pernicious anaemia, especially the elderly, should be screened for iron deficiency both at the beginning and during the follow up.     

Sperm characteristics and zona pellucida binding in relation to field fertility of frozen-thawed semen from dairy AI bulls

There is still debate in the literature on whether or not endurance athletes tend to have low iron stores. In this article, we propose that endurance athletes really are at risk of becoming iron deficient due to an imbalance between absorption of dietary iron and exercise-induced iron loss. The purpose of this article is to present a critical review of the literature on iron supplementation in sport. The effect of iron deficiency on performance, its diagnosis and suggestions for treatment are also discussed. Studies of the nutritional status of athletes in various disciplines have shown that male, but not female, athletes clearly achieve the recommended dietary intake of iron (10 to 15 mg/day). This reflects the situation in the general population, with menstruating women being the main risk group for mild iron deficiency, even in developed countries. Whereas the benefit of iron supplementation in athletes with iron deficiency anaemia is well established, this is apparently not true for non-anaemic athletes who have exhausted iron stores alone (prelatent iron deficiency); most of the studies in the literature show no significant changes due to supplementation in the physical capacity of athletes with prelatent iron deficiency. However, the treatment protocols used in some of these studies do not meet the general recommendations for the optimal clinical management of iron deficiency, that is, with respect to adequate daily dosage, mode of administration and treatment period. For future studies, we recommend a prolonged treatment period (> or = 3 months) with standardised conditions of administration (use of a pharmaceutical iron preparation with known high bioavailability and a dosage of ferrous (Fe++) iron 100 mg/day, taken on an empty stomach). Currently, decisions regarding iron supplementation are best made on the basis of taking care of individual athletes. We believe that there are sufficient arguments to support controlled iron supplementation in all athletes with low serum ferritin levels. Firstly, the development of iron deficiency is prevented. Secondly, the nonspecific upregulation of intestinal metal ion absorption is reverted to normal, thus limiting the hyperabsorption of potentially toxic lead and cadmium even in individuals with mild iron deficiency.     

Clinical significance of the tests used in the diagnosis of pancreatic diseases

Different methods available for investigating patients for pancreatic disease are discussed. They first include measurement of pancreatic enzymes in biological fluids. Basal amylase and/or lipase in blood are truly diagnostic in acute pancreatitis but their utility is low in chronic pancreatic diseases. Evocative tests have been performed to increase the sensitivity of blood enzyme measurement. The procedure is based on enzyme determination following administration of pancreozymin and secretin, and offers a valuable aid in diagnosis of chronic pancreatitis and cancer of the pancreas. They are capable of discerning pancreatic lesions but are not really discriminatory because similar changes are observed in both diseases. The measurement of urinary enzyme levels in patients with acute pancreatitis is a sensitive indicator of disease. The urinary amylase excretion rises to abnormal levels and persists at significant values for a longer period of time than the serum amylase in acute pancreatitis. The fractional urinary amylase escretion seems to be more sensitive than daily urinary measurement. The pancreatic exocrin function can be assessed by examining the duodenal contents after intravenous administration of pancreozymin and secretin. Different abnormal secretory patterns can be determinated. Total secretory deficiency is observed in patients with obstruction of excretory ducts by tumors of the head of the pancreas and in the end stage of chronic pancreatitis. Low volume with normal bicarbonate and enzyme concentration is another typical pattern seen in neoplastic obstruction of escretory ducts. In chronic pancreatitis the chief defect is the inability of the gland to secrete a juice with a high bicarbonate concentration; but in the advanced stage diminution of enzyme and volume is also evident. Diagnostic procedures for pancreatic diseases include digestion and absorption tests. The microscopic examination and chemical estimation of the fats in stool specimens in different conditions of intake are still important screening tests. Isotopic estimates of steatorrhea and distinction between labeled triolein and oleic acid absorption do not provide greater diagnostic discrimination than traditional procedures. 131I labeled proteins permit a good evaluation of a negative nitrogen balance. Sophisticated procedures to estimate exocrine pancreatic insufficiency are based on the study of endoluminal digestive processes at several times and different level of the small intestine. They permite esclusion of extrapancreatic factors interfering in digestion and absorption functions. The endocrin pancreatic function is evaluated by mean of oral tolerance test an radioimmunoassay of blood insulin. It is generally agreed that "diabetes" caused by insulin deficiency and digestion and absorption defects are the result of diffuse pancreatic destruction. Many methods are now available investigating patients with pancreatic disease but the single use of one of them is never satisfactory...     

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.     

Antidiarrheal agents for the management of treatment-related diarrhea in cancer patients

The efficacy and use of antidiarrheal agents in patients who diarrhea associated with cancer treatments are reviewed. Diarrhea is common in cancer patients and may interfere with cancer treatment. Diarrhea may be induced by chemotherapy, radiation therapy, surgery, graft-versus-hot disease (GVHD) or infection after bone marrow transplantation, and other causes. The general goal of antidiarrheal therapy is to reduce fluid loss in the stool by inhibiting intestinal secretion, promoting absorption, and decreasing intestinal motility. Antidiarrheal agents may be classified as intestinal transit inhibitors, intraluminal agents, proabsorptive agents, and antisecretory drugs. Opiate agonists are the most commonly used intestinal transit inhibitors; they can be effective in treating cancer treatment-related diarrheas but must be used cautiously. Intraluminal agents include clays, activated charcoal, and cholestyramine; these adsorbents and other binding resins can interfere with the absorption of orally administered antidiarrheals and other drugs and are unlikely candidates for use in most cases of diarrhea in cancer patients. Clonidine, a proabsorptive agent, should be used only in patients with secretory diarrhea refractory to opiate agonist treatment. Octreotide is an antisecretory drug that has shown considerable efficacy in clinical trails as a treatment for diarrhea caused by chemotherapy of GVHD; its use for radiation therapy-induced diarrhea, although not studied clinically, is nevertheless an option. In general, opiate agonists and octreotide appears to offer the most efficacy and flexibility. Opiate agonists and octreotide are effective agents for cancer treatment-related diarrhea.     

The short bowel syndrome: what's new and old?

Conditions which resulted in colonic preservation such as strangulated hernia, intestinal volvulus, and mesenteric infarction were once the main reasons for a major intestinal resection leading to the short bowel syndrome. Now Crohn's disease is the most common underlying diagnosis; such patients often have a jejunostomy. A measurement of the residual jejunal length from the duodenojejunal flexure makes possible predictions of patient outcome. Patients with a jejunostomy and less than 100 cm jejunum usually need long-term parenteral support, whereas 50 cm or more of jejunum usually suffices for adequate oral nutrition if the colon is preserved. While patients with and without a colon have problems with nutrient absorption, those with a jejunostomy also have problems of water, sodium and magnesium losses. Stomal losses may exceed oral intake and all such patients ('secretors') need parenteral supplements. Fluid and sodium losses can be reduced by octreotide, omeprazole or H2 blockers but not sufficiently to avoid the need for intravenous supplements. Colonic preservation increases the incidence of calcium oxalate renal stones (20%). Patients with and without a colon have a high prevalence of gallstones (40%). Clinically important intestinal adaptation occurs in those with a colon but not in those with a jejunostomy. Many surgical techniques, including small bowel transplantation, have been suggested to improve absorption, but as the quality of life of most patients with a short bowel is good with current treatments, they are not at present recommended.     

Effect of zinc deficiency and varying zinc supplements on resorption and retention in dairy cows

5 lactating cows were used in a trial to investigate the process of Zn absorption and Zn retention under conditions of Zn deficiency and variations in Zn supplementation. The apparent Zn absorption was found to be markedly increased if the animals were fed a Zn deficient semisynthetic diet containing 6 mg Zn per kg of dry matter during the depletion period. Apparent Zn absorption continued to rise with continuing Zn depletion. Over a period of 6 weeks of Zn depletion the mean rate of Zn absorption was 58% with increases from 51% to 64% between the 1st and 6th week of experiment. After 19 weeks of Zn depletion 75% of the supplemented zinc were absorbed. With a Zn supply of 22 ppm and 54 ppm the rate of apparent Zn absorption decreased to 51% and 44% while still higher Zn supplements, up to 436 ppm, produced only a slight further decline down to 40%. The absolute Zn balances were shown to be directly associated with the level of Zn supply, all the more so because a linear relationship was found to exist between the levels of alimentary zinc supplementation and absolute Zn retention. Under conditions of Zn deficiency the cows exhibited a negative Zn balance, where animals with the highest milk yields showed the most negative Zn balances and remained for the longest period in the negative phase. With increasing periods of Zn depletion a homeostatic mechanism of Zn regulation in the organism of the animals became more and more pronounced so that at advanced stages of Zn depletion Zn retention of some extent occurred.     

Primary hemochromatosis and dietary iron

Primary haemochromatosis is characterized by an unusually high degree of iron absorption resulting in the accumulation of excessive amounts of tissue iron. Excess stores of iron are removed by repeated phlebotomy. Health personnel and a number of patients with primary haemochromatosis have expressed their desire for advice on special diets to try and reduce the number of phlebotomies per year. This article gives advice on how patients with primary haemochromatosis can decrease their dietary iron intake and how they can put together meals to obtain low bioavailability, and therefore a lower iron absorption. The diet should be varied and be rich in bread and cereals, and fruit and vegetables. The amount of meat, Norwegian brown whey cheese (iron supplemented) and alcohol should be limited. Tea or coffee with meals will reduce iron absorption. Food rich in ascorbic acid (fruit and fruit juice) should be avoided with meals. Ascorbic acid supplements are not recommended.     

Metabolism of magnesium in health and disease

Magnesium (Mg) is an intracellular cation. It is an essential element which catalyses more than 300 enzymatic reactions, in particular those involving ATP. Approximately half of the total Mg in the body is present intracellularly in soft tissues, and the other half is present in bone. Serum Mg determination represents only 1% of total body's Mg concentration. Modern instruments will soon be available to determine physiologically active intracellular ionised Mg. Despite the ubiquitous nature of Mg, low serum Mg occurs either from decreased absorption or due to increased excretion. Hypomagnesaemia is surprisingly common in hospital populations and is more prevalent in acute than in chronic cases but often remains undetected or overlooked. Magnesium deficiency may result in hypokalaemia and hypocalcaemia. Myocardial Mg depletion may result in influx of Na+ and Ca+2 into the mitochondria which may lead to myocardial cell death. Hence, low Mg concentration may be a factor for a wide variety of clinical conditions.     

The use of millimeter waves in neurosurgery under electrophysiological control]

Duodenal iron absorption from food is selectively blocked to prevent iron intoxication. The prime example of pathologic increase in intestinal iron absorption is seen in patients with hemochromatosis. They suffer iron damage to the heart, liver, and other tissues resulting in premature death if the iron is not removed by vigorous phlebotomy. Examples of overcoming the intestinal barrier to iron are alcohol consumption, vitamin preparations with vitamin C, and iron consumed by individuals without anemia. Endogenous generation of excess iron by hemolysis, owing to abnormal hemoglobin or many transfusions, are not controlled by the intestinal barrier.     

Anaemia and thrombocytopenia due to haemophagocytosis in a 7-month-old boy with galactosialidosis

There is a need for revising the current practice for treatment of acute tonsillitis in France, i.e., systematic antibiotic treatment. There are three main reasons for this revision: 1) group A betahemolytic streptococcus is involved in only 20% of acute tonsillitis (80% being viral); 2) rheumatic fever has become very rare; 3) efficient rapid diagnostic tests are now available, allowing a selection of patients with streptococcal tonsillitis who must be treated.