Supportive care including growth factors in myelodysplastic syndromes

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.     

Interaction of antioxidants and their implication in genetic anemia

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.     

自身免疫性溶血性贫血(AIHA)患者的不同输血方法与效果

目的:探讨不同输血方法治疗自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)的效果。方法:2017年1月-2018年12月选择在本院血液科诊治的64例自身免疫性溶血性贫血患儿,根据输血方法的不同分为观察组与对照组,各32例。观察组给予洗涤红细胞输注治疗,对照组给予非洗涤红细胞(悬浮红细胞)输注治疗,记录两组输血效果。结果:治疗后4 w观察组的总有效率显著高于对照组(100.0%vs.87.5%,P0.05)。两组治疗后4 w的红细胞计数与血红蛋白都显著高于治疗前,且观察组显著高于对照组(P0.05)。观察组的吸氧、机械通气、住院时间都显著少于对照组(P0.05)。观察组治疗过程的过敏反应、发热反应、紫癜等不良反应发生率显著低于对照组(3.1%vs. 21.9%,P0.05)。结论:洗涤红细胞输注治疗自身免疫性溶血性贫血患儿能促进机体红细胞计数与血红蛋白恢复正常,减少不良反应的发生,提高治疗效果与促进患儿康复。     

Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: part III: placental malaria, maternal health, and public health

Plasmodium falciparum infections of the placenta remain a major medical challenge among pregnant women in sub-Saharan Africa. A number of factors influence the prevalence of placental malaria in pregnant women, including maternal age, gravidity, use of prophylaxis, nutrition, host genetics, and level of anti-parasite immunity, as well as parasite genetics and transmission rates [1]. Maternal anemia has been shown to be one of the major complications of placental malaria in sub-Saharan Africa. The mechanisms by which malaria causes anemia are fairly well understood. The pathophysiology of malaria-associated anemia is multifactorial. The most likely mechanisms include (i) hemolysis or the direct destruction of parasitized red blood cells that occurs both intravascularly and by sequestration in the microcirculation, mainly in the spleen; (ii) specific/nonspecific immune responses, whereby red cell survival is shortened; (iii) nonspecific, defective, red cell production, which depresses erythropoiesis, inhibits reticulocyte release, and prematurely destructs red cells during maturation in the bone marrow; and (iv) hypersplenism associated with a reduction in all three blood cell series, that is, causing not only anemia but also thrombocytopenia and leucopenia [2,3]. The relationship between maternal anemia with obstetric factors, however, is not fully understood, and, thus, evaluating the link between malaria, obstetric disorders, and maternal death has been recommended [4]. There have been efforts to quantify the contribution of malaria to maternal morbidity and mortality with the expectation that this would provide the evidence necessary to improve the effectiveness of advocacy to incorporate malaria prevention strategies in Safe Motherhood Programs [5,6]. The effects of placental malaria on maternal health can better be understood when considered in relation with various maternal parameters, including maternal age, parity, peripheral malaria infection, anemia, and HIV infection.     

Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways

Fanconi anemia (FA) and ataxia telangiectasia (AT) are clinically distinct autosomal recessive disorders characterized by spontaneous chromosome breakage and hematological cancers. FA cells are hypersensitive to mitomycin C (MMC), while AT cells are hypersensitive to ionizing radiation (IR). Here, we identify the Fanconi anemia protein, FANCD2, as a link between the FA and ATM damage response pathways. ATM phosphorylates FANCD2 on serine 222 in vitro. This site is also phosphorylated in vivo in an ATM-dependent manner following IR. Phosphorylation of FANCD2 is required for activation of an S phase checkpoint. The ATM-dependent phosphorylation of FANCD2 on S222 and the FA pathway-dependent monoubiquitination of FANCD2 on K561 are independent posttranslational modifications regulating discrete cellular signaling pathways. Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity.     

Human metabolism of phytanic acid and pristanic acid

Phytanic acid is a methyl-branched fatty acid present in the human diet. Due to its structure, degradation by β-oxidation is impossible. Instead, phytanic acid is oxidized by -oxidation, yielding pristanic acid. Despite many efforts to elucidate the -oxidation pathway, it remained unknown for more than 30 years. In recent years, the mechanism of -oxidation as well as the enzymes involved in the process have been elucidated. The process was found to involve activation, followed by hydroxylase, lyase and dehydrogenase reactions. Part, if not all of the reactions were found to take place in peroxisomes. The final product of phytanic acid -oxidation is pristanic acid. This fatty acid is degraded by peroxisomal β-oxidation. After 3 steps of β-oxidation in the peroxisome, the product is esterified to carnitine and shuttled to the mitochondrion for further oxidation. Several inborn errors with one or more deficiencies in the phytanic acid and pristanic degradation have been described. The clinical expressions of these disorders are heterogeneus, and vary between severe neonatal and often fatal symptoms and milder syndromes with late onset. Biochemically, these disorders are characterized by accumulation of phytanic and/or pristanic acid in tissues and body fluids. Several of the inborn errors involoving phytanic acid and/or pristanic acid metabolism have been characterized on the molecular level.     

Molecular mechanisms of oxidative stress-related neonatal jaundice

Oxidative stress is a pathological condition characterized by an overload of oxidant products, named free radicals, which are not well counteracted by antioxidant systems. Free radicals induce oxidative damage to many body organs and systems. In neonatal red blood cells, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets and at the same time generators of free radicals through the Fenton and Haber-Weiss reactions. Enhanced eryptosis in case of oxidative stress damage may cause anemia if the increased loss of erythrocytes is not enough compensated by enhanced new erythrocytes synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. High levels of bilirubin are recognized to be dangerous for the central nervous system in newborns, however, many studies have highlighted the antioxidant function of bilirubin. Recently, it has been suggested that physiologic concentration of bilirubin correlates with higher antioxidant status while high pathological bilirubin levels are associated with pro-oxidants effects. The aim of this educational review is to provide an updated understanding of the molecular mechanisms underlying erythrocyte oxidant injury and its reversal in neonatal idiopathic hyperbilirubinemia.     

炎症性贫血的病因、诊断与治疗研究进展

感染、自身免疫紊乱、慢性疾病和年龄等很多原因都会导致炎症发生并发展为贫血。炎症性贫血(anemia of inflammation AI)通常为正细胞正色素性贫血,临床表现温和。系统性的铁利用、红细胞生成、红细胞生存期特征的变化导致了炎症性贫血。最佳治疗是纠正病因,然而当病因不清或难以诊断时,治疗炎症性贫血的办法就非常有限了。铁调素(Hepcidin)是近年研究铁利用调节的中心。由于铁调素定量分析技术的发展,人们逐渐认识到其在各种疾病中的作用。最近研究集中在铁调素表达调节通路,并发现了药物治疗的靶点。由于治疗上的巨大进步,分析正常血红蛋白对疾病预后的影响,就可以明确炎性疾病发生和死亡过程中贫血是否具有可逆性。     

EMOTIONAL PROBLEMS IN CHILDREN—The Uses of Drugs in Therapeutic Management

Emotional disturbances in children may be due to an anxiety state, to obsessive-compulsive neurosis, to schizophrenia or to a brain injury causing a behavior disorder. Children in an anxiety state have difficulty in school because anxiety interferes with concentration, impairs memory and makes decisions difficult. Consequently, these children often fear school and express their anxiety by behavior disturbances which alienate them from parents and teachers.There are a number of chemotherapeutic agents physicians can use as a part of the treatment of emotionally disturbed children. Phenobarbital is valuable for short-term therapy for the anxious child. Meprobamate also may be prescribed for anxiety reactions. It is of limited value for the hyperkinetic and obsessive-compulsive child and of no value in the schizophrenic child. Atarax (hydroxyzine dihydrochloride) is beneficial for the neurotic and hyperkinetic brain-injured child. Children with severe anxiety reactions and schizophrenic disorders respond best to chlorpromazine or reserpine.It must be emphasized that drug therapy is a part of the total therapeutic attack on the emotional problems of children.     

Subclinical epileptic seizures; impairment of motor performance and derivative difficulties

Modern clinical observations have greatly expanded the conception of the characteristics of the various kinds of epilepsy. By simultaneously recording electroencephalograms and the performance of simple motor tasks, it has been possible to demonstrate the effects of epileptic seizures not detectable by unaided observation and not noted by the patient. The effects of these subclinical seizures have been manifested variously-by a lengthening of the time between stimulus and reaction, by inaccuracies of response to stimuli, or by total cessation of performance. From this study it is suggested that subclinical seizures probably play a role in producing some of the psychiatric conditions associated with the convulsive disorders, as well as primary behavior disturbances and undifferentiated mental deficiency. It is also suggested that such subclinical seizures may possibly contribute to the characteristics of some cases of criminality and antisocial reactions and schizophrenic reactions.     

Low red cell production may protect against severe anemia during a malaria infection—Insights from modeling

The malaria parasite causes lysis of red blood cells, resulting in anemia, a major cause of mortality and morbidity. Intuitively, one would expect the production of red blood cells to increase in order to compensate for this loss. However, it has been observed that this response is weaker than would be expected. Furthermore, iron supplementation for iron deficient children in malaria endemic regions can paradoxically adversely affect the clinical outcome of malaria infection. A possible explanation may lie in the preference that some malaria parasites show for infecting immature red blood cells (reticulocytes). In the presence of a parasite preference for immature red cells, a rise in red cell production can ‘fuel the fire’ of infection by increasing the availability of the parasite's preferred target cell.We present a mathematical model of red blood cell production and infection in order to explore this hypothesis. We assess the effect of varying the reticulocyte replacement rate and preference of the parasite for reticulocytes on four key outcome measures assessing anemia and parasitemia.For a given level of parasite preference for reticulocytes we uncover an optimal erythropoietic response which minimizes disease severity. Increasing red blood cell production much above this optimum confers no benefit to the patient, and in fact can increase the degree of anemia and parasitemia. These conclusions are consistent with epidemiological studies demonstrating that both iron deficiency and anemia are protective against severe malaria, whilst iron supplementation in malaria endemic regions is with an increased number of malaria related adverse effects. Thus, suppression of red blood cell production, rather than being an unfortunate side effect of inflammation, may be a host protective effect against severe malarial anemia.     

Reactions after pertussis vaccine: a manufacturer's experiences and difficulties since 1964

Pertussis vaccines vary in quality, safety, and efficacy according to the production strains of Bordetella pertussis, the method of manufacture, and quality control procedures. It is therefore not justifiable to combine information on the incidence, nature, and severity of reactions after all manufacturers'' pertussis vaccines as if they were a single product. Attempts were made to collect information on all suspected cases of severe reactions that occurred after administration of about 15 million doses of Wellcome pertussis vaccines in the United Kingdom and Northern Ireland from 1964 to mid-1977. Altogether six deaths, six neurological reactions with sequelae, and 17 convulsions without sequelae were reported, but some were clearly not attributable to the vaccine, while, in other cases, the available information was inadequate for assessing the role of vaccination. Neurological disorders, similar to those reported in a few children after pertussis vaccination, occur unexpectedly in apparently healthy infants at the recommended age for immunisation, so chance association between vaccination and these events can be expected in some children. The Joint Committee on Vaccination and Immunisation has made several recommendations aimed at reducing severe reactions after pertussis vaccination. These include replacing plain vaccine with aluminium-adsorbed vaccine, but there is no clear evidence that the aluminium-adsorbed vaccine produces fewer reactions than the plain.There are difficulties enough in deciding the cause of events that occur after vaccination, since these reactions often occur naturally in children of vaccination age. The task is made even harder by the assumption that various manufacturers'' vaccines are the same and the lack of information available to manufacturers about cases in which their vaccine has been implicated. Information on vaccines administered is entered on immunisation records cards; it should be used and referred to if reactions occur.     

Nuclease modification in Chinese hamster cells hypersensitive to DNA cross-linking agents--a model for Fanconi anemia.

Fanconi anemia is a human inherited disease that is characterized by cellular hypersensitivity to DNA cross-linking agents. A number of potential experimental models for that disorder have been developed by selecting mutants that are hypersensitive to bifunctional mutagens. The six mutants of that class in Drosophila, all of which map to the mus308 locus, express an alteration in a mitochondrial nuclease. A recent extension of that observation to cell lines from complementation group A of Fanconi anemia has established a new cellular phenotype for that disorder. In the current study an analogous enzyme has been analyzed in eight recently isolated Chinese hamster cell lines that are hypersensitive to cross-linking agents. Among these lines. V-H4 and V-B7 are shown to exhibit an enzyme modification analogous to that observed in the mutant Drosophila and human cells. These results validate the nuclease assay as an indicator of the Fanconi defect and further establish the V-H4 cell line as a valuable cellular model for analysis of the Fanconi A defect.     

Evaluating treatment of hepatitis C for hemolytic anemia management

The combination therapy of antiviral peg-interferon and ribavirin has evolved as one of the better treatments for hepatitis C. In spite of its success in controlling hepatitis C infection, it has also been associated with treatment-related adverse side effects. The most common and life threatening among them is hemolytic anemia, necessitating dose reduction or therapy cessation. The presence of this side effect leads to a trade-off between continuing the treatment and exacerbating the side effects versus decreasing dosage to relieve severe side effects while allowing the disease to progress. The drug epoietin (epoetin) is often administered to stimulate the production of red blood cells (RBC) in the bone marrow, in order to allow treatment without anemia. This paper uses mathematical models to study the effect of combination therapy in light of anemia. In order to achieve this we introduce RBC concentration and amount of drug in the body as state variables in the usual immunological virus infection model. Analysis of this model provides a quantification of the amount of drug a body can tolerate without succumbing to hemolytic anemia. Indirect estimation of parameters allow us to calculate the necessary increment in RBC production to be ?2.3 times the patient’s original RBC production rate to sustain the entire course of treatment without encountering anemia in a sensitive patient.     

SUBCLINICAL EPILEPTIC SEIZURES—Impairment of Motor Performance and Derivative Difficulties

Modern clinical observations have greatly expanded the conception of the characteristics of the various kinds of epilepsy. By simultaneously recording electroencephalograms and the performance of simple motor tasks, it has been possible to demonstrate the effects of epileptic seizures not detectable by unaided observation and not noted by the patient. The effects of these subclinical seizures have been manifested variously—by a lengthening of the time between stimulus and reaction, by inaccuracies of response to stimuli, or by total cessation of performance.From this study it is suggested that subclinical seizures probably play a role in producing some of the psychiatric conditions associated with the convulsive disorders, as well as primary behavior disturbances and undifferentiated mental deficiency. It is also suggested that such subclinical seizures may possibly contribute to the characteristics of some cases of criminality and antisocial reactions and schizophrenic reactions.     

Depression, antidepressants, and peripheral blood components

The biological attributes of affective disorders and factors which are able to predict a response to treatment with antidepressants have not been identified sufficiently. A number of biochemical variables in peripheral blood constituents have been tested for this purpose, as a consequence of the lack of availability of human brain tissue. At first, the biological attributes of mental disorders were sought at the level of concentrations of neurotransmitters and their metabolites or precursors. Later on, attention shifted to receptor systems. Since the 1990s, intracellular processes influenced by an illness or its treatment with psychopharmaceuticals have been at the forefront of interest. Interest in biological predictors of treatment with antidepressants has reappeared in recent years, thanks to new laboratory techniques which make it possible to monitor cellular processes associated with the transmission of nerve signals in the brain. These processes can also be studied in plasma and blood elements, especially lymphocytes and platelets. The selection of the qualities to which attention is paid can be derived from today's most widely discussed biochemical hypotheses of affective disorders, especially the monoamine hypothesis and the molecular and cellular theory of depression. Mitochondrial enzymes can also play an important role in the pathophysiology of depression and the effects of antidepressants. In this paper, we sum up the cellular, neurochemical, neuroendocrine, genetic, and neuroimmunological qualities which can be measured in peripheral blood and which appear to be indicators of affective disorders, or parameters which make it possible to predict therapeutic responses to antidepressant administration.     

Effect of lead,calcium, iron,zinc, copper and magnesium on anemia in children with BLLs ≥ 100 μg/L

ObjectiveAdverse effects of lead exposure on children's health have been demonstrated. While studies have examined the relationship between iron status and low-level lead exposure in children with blood lead levels (BLLs) < 100 μg/L, few have investigated the association between blood lead and other trace elements and anemia in children with BLLs ≥ 100 μg/L. This study aimed to assess the levels of lead, iron, copper, zinc, magnesium, and calcium in children aged 0–14 with BLLs≥ 100 μg/L between 2009 and 2021, and to examine the relationship between blood lead, trace elements and anemia.MethodsA total of 11,541 children with BLLs ≥ 100 μg/L were included in this study. Venous blood samples were collected to measure blood lead levels, hemoglobin levels, and trace element levels. According to the World Health Organization standard, outpatients with hemoglobin levels < 110 g / L were defined as having anemia.ResultsThe study results found that high BLLs and blood calcium had a negative influence on Hb with odds ratios (95% confidence interval) of 1.411(1.208, 1.649) and 1.219(1.043, 1.424). High blood iron had a positive influence on Hb with odds ratios of 0.421(0.355, 0.499).ConclusionThe results suggest that the risk of anemia rose significantly with higher BLLs, blood copper, and blood calcium levels, and decreases considerably with higher blood iron levels.     

What's new and what's true of what's new in dermatology

Within the past few years it has been noted that abnormal types of hemoglobin found in certain persons are associated with definite clinical disorders. At least four different varieties of sickle cell anemia are now recognized, three of them being heterozygous and one homozygous. When the gene for sickling is represented once, the person is asymptomatic and is said to have "sickle cell trait." However, when the sickle cell trait is present in combination with certain other hemoglobin abnormalities such as hemoglobin C or D or with thalassemia trait, symptomatic clinical disease results. The homozygous condition, in which two genes for hemoglobin C are present in the same person, has been observed in a few instances. A similar condition as regards hemoglobin D has not as yet been recognized.     

Porotic hyperostosis: a new perspective.

Porotic hyperostosis is a paleopathologic condition that has intrigued researchers for over a century and a half. It is now generally accepted that anemia, most probably an iron deficiency anemia, is the etiologic factor responsible for lesion production. Although there can be a number of factors involved in the development of iron deficiency anemia, a dietary explanation has often been invoked to explain the occurrence of porotic hyperostosis in past human skeletal populations. In fact, porotic hyperostosis has been referred to as a "nutritional" stress indicator. Traditionally those groups with a higher incidence of porotic hyperostosis have been considered to be less successful in adapting to their environment or more nutritionally disadvantaged than other groups. A new perspective is emerging that is challenging previous views of the role of iron in health and disease, thus having profound implications for the understanding of porotic hyperostosis. There is a new appreciation of the adaptability and flexibility of iron metabolism; as a result it has become apparent that diet plays a very minor role in the development of iron deficiency anemia. It is now understood that, rather than being detrimental, hypoferremia (deficiency of iron in the blood) is actually an adaptation to disease and microorganism invasion. When faced with chronic and/or heavy pathogen loads individuals become hypoferremic as part of their defense against these pathogens, thus increasing their susceptibility to iron deficiency anemia. Within the context of this new perspective porotic hyperostosis is seen not as a nutritional stress indicator, but as a indication that a population is attempting to adapt to the pathogen load in its environment.