Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.
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PMID:Iron and oxidative stress in pregnancy. 1273 Apr 87

The Philadelphia chromosome-negative chronic myeloproliferative disorders (CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and chronic idiopathic myelofibrosis (IMF), have overlapping clinical features but exhibit different natural histories and different therapeutic requirements. Phenotypic mimicry amongst these disorders and between them and nonclonal hematopoietic disorders, lack of clonal diagnostic markers, lack of understanding of their molecular basis and paucity of controlled, prospective therapeutic trials have made the diagnosis and management of PV, ET and IMF difficult. In Section I, Dr. Jerry Spivak introduces current clinical controversies involving the CMPD, in particular the diagnostic challenges. Two new molecular assays may prove useful in the diagnosis and classification of CMPD. In 2000, the overexpression in PV granulocytes of the mRNA for the neutrophil antigen NBI/CD177, a member of the uPAR/Ly6/CD59 family of plasma membrane proteins, was documented. Overexpression of PRV-1 mRNA appeared to be specific for PV since it was not observed in secondary erythrocytosis. At this time, it appears that overexpression of granulocyte PRV-1 in the presence of an elevated red cell mass supports a diagnosis of PV; absence of PRV-1 expression, however, should not be grounds for excluding PV as a diagnostic possibility. Impaired expression of Mpl, the receptor for thrombopoietin, in platelets and megakaryocytes has been first described in PV, but it has also been observed in some patients with ET and IMF. The biologic basis appears to be either alternative splicing of Mpl mRNA or a single nucleotide polymorphism, both of which involve Mpl exon 2 and both of which lead to impaired posttranslational glycosylation and a dominant negative effect on normal Mpl expression. To date, no Mpl DNA structural abnormality or mutation has been identified in PV, ET or IMF. In Section II, Dr. Tiziano Barbui reviews the best clinical evidence for treatment strategy design in PV and ET. Current recommendations for cytoreductive therapy in PV are still largely similar to those at the end of the PVSG era. Phlebotomy to reduce the red cell mass and keep it at a safe level (hematocrit < 45%) remains the cornerstone of treatment. Venesection is an effective and safe therapy and previous concerns about potential side effects, including severe iron deficiency and an increased tendency to thrombosis or myelofibrosis, were erroneous. Many patients require no other therapy for many years. For others, however, poor compliance to phlebotomy or progressive myeloproliferation, as indicated by increasing splenomegaly or very high leukocyte or platelet counts, may call for the introduction of cytoreductive drugs. In ET, the therapeutic trade-off between reducing thrombotic events and increasing the risk of leukemia with the use of cytoreductive drugs should be approached by patient risk stratification. Thrombotic deaths seem very rare in low-risk ET subjects and there are no data indicating that fatalities can be prevented by starting cytoreductive drugs early. Therefore, withholding chemotherapy might be justifiable in young, asymptomatic ET patients with a platelet count below 1500000/mm(3) and with no additional risk factors for thrombosis. If cardiovascular risk factors together with ET are identified (smoking, obesity, hypertension, hyperlipidemia) it is wise to consider platelet-lowering agents on an individual basis. In Section III, Dr. Gianni Tognoni discusses the role of aspirin therapy in PV based on the recently completed European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study, a multi-country, multicenter project aimed at describing the natural history of PV as well as the efficacy of low-dose aspirin. Aspirin treatment lowered the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (relative risk 0.41 [95% CI 0.15-1.15], P =.0912). Total and cardiovascular mortality were also reduced by 46% and 59%, respectively. Major bleedings were slightly increased nonsignificnsignificantly by aspirin (relative risk 1.62, 95% CI 0.27-9.71). In Section IV, Dr. Giovanni Barosi reviews our current understanding of the pathophysiology of IMF and, in particular, the contributions of anomalous megakaryocyte proliferation, neoangiogenesis and abnormal CD34(+) stem cell trafficking to disease pathogenesis. The role of newer therapies, such as low-conditioning stem cell transplantation and thalidomide, is discussed in the context of a general treatment strategy for IMF. The results of a Phase II trial of low-dose thalidomide as a single agent in 63 patients with myelofibrosis with meloid metaplasia (MMM) using a dose-escalation design and an overall low dose of the drug (The European Collaboration on MMM) will be presented. Considering only patients who completed 4 weeks of treatment, 31% had a response: this was mostly due to a beneficial effect of thalidomide on patients with transfusion dependent anemia, 39% of whom abolished transfusions, patients with moderate to severe thrombocytopenia, 28% of whom increased their platelet count by more than 50 x 10(9)/L, and patients with the largest splenomegalies, 42% of whom reduced spleen size of more than 2 cm.
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PMID:Chronic myeloproliferative disorders. 1463 83

Understanding the features of the various hereditary vascular pathologies allows consideration and confirmation of the diagnosis, and a search for treatable hidden disorders, avoiding harmful investigations, initiating follow up, performing family investigations and providing genetic counselling. Pseudoxanthoma elasticum must be considered in the presence of calcified distal arteriopathy of the lower limbs in a young subject without any other aetiological aspects. Cutaneous or mucosal lesions confirmed on histological examination, angioid streaks at the back of the eye and a family history support the diagnosis, which is confirmed by showing pathogenic mutations of the ABCC6 gene. It is then important to search for a peripheral disorder in other arterial territory, a low grade coronaropathy, hypertension and an endocardial disorder. Prescription of antithrombotics must be made carefully because of the risk of gastro-intestinal haemorrhage. Vascular Ehlers-Danlos syndrome is suspected in a subject less than 30 years old with diffuse aneurysmal disease, spontaneous arterial rupture or dissection, a carotido-cavernous fistula or early onset varices. Demonstrating an ecchymotic tendency or an acrogeric morphology, especially in a familial context, warrants cutaneous biopsy for anatomopathological examination and fibroblast culture for a study of the C0L3A1 gene. When the diagnosis is suggested, it is advisable to prohibit any arterial puncture, cold surgery or gastro-intestinal endoscopy. The search for aneurysmal lesions must be performed by non-invasive imaging. The therapeutic management requires specialised teams. The combination of repeated epistaxis, muco-cutaneous telangectasia and similar characteristics in a family suggests the diagnosis of Osler-Weber-Rendu disease. The search for iron deficiency, gastro-intestinal bleeds and pulmonary, hepatic or cerebral arterio-venous malformations is then necessary. Besides skilled endovascular management when indicated, it is important to advise every patient with a pulmonary arterio-venous malformation to take antibiotic prophylaxis against cerebral abscess in situations at risk of bacteraemia.
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PMID:[Mendelian arterial diseases. Pseudoxanthoma elasticum, Ehlers-Danlos vascular syndrome, Rendu-Osler disease]. 1469 86

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.
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PMID:[Psychiatric manifestations of vitamin B12 deficiency: a case report]. 1502 91

A balanced diet that provides an adequate supply of vitamins and minerals is essential for normal fetal development. Maternal morbidity is also lower, since such complications of pregnancy as preeclampsia and premature birth occur less frequently. Consideration should be given to folate deficiency--in particular during the periconceptive period--and iron deficiency during pregnancy. For the structural development of the fetus, long-chain polyunsaturated fatty acids also appear to have a major role to play. Daily iodine supplementation should be used to avoid goiter in mother and child. Calcium appears to have a protective effect against preeclampsia and hypertension, as also do vitamins E and C. The tocolytic action of magnesium can help reduce the incidence of premature birth. Such noxae as alcohol and nicotine should be avoided completely during the entire pregnancy.
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PMID:[Nutrition during pregnancy--current aspects]. 1515 64

Stroke affects up to 13 of 100,000 children, is more common in boys and African Americans, and is associated with considerable cognitive and psychiatric morbidity, as well as motor disability. Around half are hemorrhagic and half are ischemic. Underlying conditions include sickle cell disease, cardiac abnormalities, chromosomal abnormalities (eg, Down syndrome), and neurocutaneous conditions (eg, neurofibromatosis), but up to half the patients with ischemic stroke have no previously diagnosed condition. Although there is almost certainly an important genetic component to stroke risk, head trauma, infections, drugs and radiation appear to play an etiological role in some patients. The majority of the patients with infarction in an arterial distribution have associated cerebrovascular disease. Vascular pathologies include carotid or vertebrobasilar dissection, intracranial vasculopathy affecting the middle and anterior cerebral arteries, which is often transient, and moyamoya. Intermediate risk factors may include hypertension, hypoxia, and poor nutrition leading, for example, to iron deficiency and hyperhomocysteinemia. Some chronic conditions may directly influence the child's behavior and stroke recurrence risk, although large cohorts and randomized controlled trials will be needed before strategies for modification can be evidence-based.
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PMID:Risk factors for arterial ischemic stroke in childhood. 1516 88

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Professor F. Gejyo of Niigata University, now publishes an original Japanese guideline entitled 'Guidelines for Renal Anemia in Chronic Hemodialysis Patients'. It includes the re-evaluation of the usage of recombinant human erythropoietin (rHuEPO) with the medical and economical arguments regarding the prognosis and the quality of life of Japanese hemodialysis patients. This guideline consists of 7 sections. The first section comprises the general definition and the differential diagnosis of anemia. The hemoglobin (Hb) level of the Japanese population seemed to be low when compared with that of the European and American populations. The second section describes the target Hb level in hemodialysis patients. Multivariate analysis of the data that were collected from dialysis institutions throughout the country showed that an Hb level of 10-11 g/dL (Ht level 30-33%) at the first dialysis session in a week is the ideal range for chronic hemodialysis patients in terms of the 3-5 year survival rate. The supine position at blood sampling and the sampling timing at the first dialysis session in a week might affect the lower setting of target Hb hematocrit (Ht), compared to that of European and American guidelines. However, we particularly recommended that an Hb level of 11-12 g/dL (Ht level from 33 to 36%) at the first dialysis session in a week is desirable in relatively young patients. In the third section, the markers of iron deficiency are discussed. The Transferin saturation test (TSAT) and serum ferritin were emphasized as the standard markers. The routes of administration of rHuEPO and its dosages are written in the fourth section. The subcutaneous route was associated with the occurrence of secondary red cell aplasia due to anti-rHuEPO antibodies; however, secondary red cell aplasia was seldom observed in the venous injection. From this fact we recommend venous injection for chronic hemodialysis patients. We advocate an initial dosage of 1500 U three times per week. The fifth section deals with the factors refractory to treatment with rHuEPO. If the patient shows an inadequate response to the usage of 9000 U per week, this condition defines the inadequate response to rHuEPO in Japan. Blood transfusion must be avoided where possible. The reasons for this and the adverse effects are interpreted in section six. In the final section, the adverse effects of rHuEPO are listed. Among them, hypertension, thrombotic events and secondary red cell aplasia were emphasized as the major complications.
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PMID:2004 Japanese Society for Dialysis Therapy guidelines for renal anemia in chronic hemodialysis patients. 1566 44

Sleep complaints are very common in patients with end-stage renal disease (ESRD) and contribute to their impaired quality of life. Both obstructive and central sleep apnea syndromes are reported more often in patients on dialysis than in the general population. Impaired daytime functioning, sleepiness, and fatigue, as well as cognitive problems, are well known in patients with sleep apnea. Increasing evidence supports the pathophysiological role of sleep apnea in cardiovascular disorders, which are the leading cause of death in ESRD patients. Uremic factors may be involved in the pathogenesis of sleep apnea in this patient population and optimal dialysis may reduce disease severity. Furthermore, treatment with continuous positive airway pressure may improve quality of life and may help to manage hypertension in these patients. Secondary restless legs syndrome is highly prevalent in patients on maintenance dialysis. The pathophysiology of the disorder may also involve uremia-related factors, iron deficiency, and anemia, but genetic and lifestyle factors might also play a role. The treatment of restless legs syndrome involves various pharmacologic approaches and might be challenging in severe cases. In this article we review the diagnosis and treatment of sleep apnea and restless legs syndrome, with a focus on dialysis patients. We also briefly review current data regarding sleep problems after transplantation, since these studies may indirectly shed light on the possible pathophysiological role of uremia or dialysis in the etiology of sleep disorders. Considering the importance of sleep disorders, more awareness among professionals involved in the care of patients on dialysis is necessary. Appropriate management of sleep disorders could improve the quality of life and possibly even impact upon survival of renal patients.
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PMID:Diagnosis and management of sleep apnea syndrome and restless legs syndrome in dialysis patients. 1668 72

Both iron deficiency and iron excess during the fetal and neonatal period bode poorly for developing organ systems. Maternal conditions such as iron deficiency, diabetes mellitus, hypertension and smoking, and preterm birth are the common causes of perinatal iron deficiency. Long-term neurodevelopmental impairments and predisposition to future iron deficiency that are prevalent in infants with perinatal iron deficiency require early diagnosis, optimal treatment and adequate follow-up of infants at risk for the condition. However, due to the potential for oxidant-mediated tissue injury, iron overload should be avoided in the perinatal period, especially in preterm infants.
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PMID:Iron in fetal and neonatal nutrition. 1715 88

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks. We do not recommend the use of higher than standard initial doses of erythropoietic proteins with the aim of producing higher haematological responses, due to the limited body of evidence available. There is Level I evidence that, within reasonable limits of body weight, fixed doses of erythropoietic proteins can be used to treat patients with chemotherapy-induced anaemia. This analysis confirms that there are no baseline predictive factors of response to erythropoietic proteins that can be routinely used in clinical practice if functional iron deficiency or vitamin deficiency is ruled out; a low serum erythropoietin (EPO) level (only in haematological malignancies) appears to be the only predictive factor to be verified in Level I studies. Further studies are needed to investigate the value of hepcidin, c-reactive protein, and other measures as predictive factors. In these updated guidelines, we explored a new question of whether oral or intravenous iron supplementation increases the response rate to erythropoietic proteins. We found no evidence of increased response with the addition of oral iron supplementation, but there is Level II evidence of improved response to erythropoietic proteins with the addition of intravenous iron. However, the doses and schedules for intravenous iron supplementation are not yet well defined, and further studies in this area are warranted. The two major goals of erythropoietic protein therapy are prevention or elimination of transfusions and improvement of QoL. The total body of evidence shows that red blood cell (RBC) transfusion requirements are reduced following treatment with erythropoietic proteins. This analysis also confirms that QoL is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease following erythropoietic protein therapy, with more robust evidence now available that QoL was improved in studies investigating early intervention in cases of chemotherapy- or radiotherapy-induced anaemia. There is only indirect evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase. None of the studies addressed the question in a prospective, randomised fashion, and so the Taskforce does not recommend dose escalation as a general approach in all patients who are not responding. There is still insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. Our analysis of survival endpoints in studies involving patients receiving radio(chemo)therapy found that most studies were inconclusive, with no clear link between the use of erythropoietic proteins and survival. Likewise, we found no clear link between erythropoietic therapy and other endpoints such as local tumour control, time to progression, and progression-free survival. There is no evidence that pure red cell aplasia occurs in cancer patients following treatment with erythropoietic proteins, and the fear of this condition developing should not lead to erythropoietic proteins being withheld in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Additional trials are warranted, especially to define the optimal doses and schedules of intravenous iron supplementation during erythropoietic therapy. While our review did not address cost benefit evaluations in detail, the consensus is that studies taking into account all real determinants of cost and benefit need to be performed prospectively.
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PMID:EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. 1718 41


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