[Pancytopenia and hemolysis--diagnosis, differential diagnosis and therapy of pernicious anemia]

Pernicious anemia and Vitamin B12 deficiency have a wide range of symptoms and are a common finding in the elderly. A 73 year old female is admitted to the hospital because of dyspnea, fatigue and loss of appetite and weight. While previous medical history and physical examination are inconspicuous, laboratory findings show severe pancytopenia with macrocytosis, low reticulocyte count and marked signs of hemolysis. A very low serum level of vitamin B12 and chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum lead to the diagnosis of pernicious anemia. Complete restitution is achieved by parenteral vitamin B12 substitution. Nowadays, severe pernicious anemia is only rarely seen. The differential diagnosis of pancytopenia (with macrocytic anemia) combined with hemolysis and the essential hints to the diagnosis of pernicious anemia are discussed, and thereby practical aspects including therapy actualized.

Pullulation bactérienne de l'intestin grêle [Small intestine bacterial overgrowth]

Small intestine bacterial overgrowth (SIBO) is a condition characterised by nutrient malabsorption and excessive bacteria in the small intestine. It typically presents with diarrhea, flatulence and a syndrome of malabsorption (steatorrhea, macrocytic anemia). However, it may be asymptomatic in the eldery. A high index of suspicion is necessary in order to differentiate SIBO from other similar presenting disorders such as coeliac disease, lactose intolerance or the irritable bowel syndrome. A search for predisposing factor is thus necessary. These factors may be anatomical (stenosis, blind loop), or functional (intestinal hypomotility, achlorydria). The hydrogen breath test is the most frequently used diagnostic test although it lacks standardisation. The treatment of SIBO consists of eliminating predisposing factors and broad-spectrum antibiotic therapy.

Impacto do tratamento antirretroviral na ocorrência de macrocitose em pacientes com HIV/AIDS do município de Maringá, Estado do Paraná

INTRODUÇÃO: AIDS é uma doença causada pelo HIV que compromete o sistema imune do organismo. O advento da terapia antirretroviral (TARV) altamente eficaz promoveu melhora substancial do prognóstico da doença e da qualidade de vida dos pacientes com HIV/AIDS. Durante seu tratamento prolongado, notam-se algumas alterações hematológicas, dentre elas, anemia e macrocitose, bem como carências de micronutrientes, tais como, de vitamina B12 e ácido fólico. O objetivo do presente trabalho é relacionar a macrocitose e anemia ao uso de TARV, ou à deficiência de vitamina B12 ou de ácido fólico. MÉTODOS: Foram avaliados 110 pacientes HIV positivos, comparando-se aqueles em uso de TARV com zidovudina (AZT) (grupo 1), TARV sem AZT (grupo 2) ou sem uso de TARV (grupo 3). RESULTADOS: Os pacientes dos três grupos não apresentaram diferenças estatísticas significativas quanto aos níveis de hemoglobina (p = 0,584) e de ácido fólico (p = 0,956). Os pacientes do grupo 1 (G1) apresentaram volume corpuscular médio (VCM) aumentado quando comparado ao grupo 3 (G3) (p < 0,05), bem como do grupo 2 (G2) em relação ao G3 (p < 0,001). As dosagens de vitamina B12 do G1 e G3 foram menores do que as encontradas pelo G2 (p = 0,008). CONCLUSÕES: Conclui-se que os indivíduos em uso de TARV apresentaram macrocitose, embora não pudesse ser relacionada ao tipo de TARV ou a deficiência de vitamina B12. Entretanto, a deficiência de ácido fólico não esteve relacionada ao uso de TARV e nem à macrocitose.

Levamisol e dexametasona na inflamação crônica por corpo estranho em Pacu (Piaractus mesopotamicus)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hematologia como ferramenta no monitoramento do "status" da cadeia produtiva de oito espécies de Acaris ornamentais (Loricariidae) do médio Rio Guamá, estado do Pará

O presente trabalho monitorou a saúde de oito espécies de acaris ornamentais capturados e comercializados no Médio Rio Guamá - Pará, através do estabelecimento do quadro hematológico basal, avaliação de estresse de transporte e de infecção por Trypanosoma spp. São elas: ancistrus (Ancistrus sp. - L338), loricaia (Rineloricaia lanceolata - L10), picoto (Hypostomus sp. - L28), bola (Peckoltia oligospila - L06), pleco (Cochilodon sp. - L145), canoa (Lasiancistrus saetiger - L323), assacu (Pseudacanthicus spinosus - L160) e pinima (Leporacanthicus galaxias - L07). As coletas sanguíneas para a determinação do quadro hematológico basal (Capítulos I e II) foram realizadas ainda no local da captura dos peixes, sob o mínimo de estresse possível. Separarou-se as amostras sanguíneas não infectadas para possibilitar comparações com as do após-estresse de transporte (Capítulos III e IV) e também com as infectados por Trypanosoma spp. (Capítulo V). O estresse de transporte estabelecido durou 3h, com densidade de 1,5 peixe/L, simulando o processo de comercialização dos peixes na região e foi avaliado após 0, 6, 24, 48, 72 e 96h. Nos Capítulos I e II, observou-se que o hemograma basal apresentou diferença significativa (p>0,05) entre os as sete espécies de acaris, apesar de estas pertencerem a mesma família e compartilharem nichos ecológicos semelhantes. O estresse de transporte por 3h (Capítulos III e IV) não comprometeu a saúde dos acaris, pois a maioria dos parâmetros hematológicos retornou aos níveis basais em 24h em bola, em 48h em pleco e em 72h em picoto, sendo estes, respectivamente, os períodos mínimos indicados para a aclimatação destes peixes antes de uma nova comercialização. Todas as oito espécies de acaris estudadas estavam infectadas por Tryopanosoma spp. (Capítulo V). Encontrou-se anemia normocítica-hipocrômica em ancistrus e canoa, e anemia macrocítica-hipocrômica em loricaia. Pinimas infectados apresentaram quadro de estresse com linfocitopenia, neutrofilia e monocitose. Assim, os resultados deste ensaio proporcionaram a avaliação da higidez destas espécies de acaris ornamentais através de exames hematológicos, podendo assim subsidiar o desenvolvimento ou a adequação do manejo menos estressante para estes peixes, de forma a auxiliar a sustentabilidade da cadeia extrativista das espécies ornamentais.

Thyroid dysfunction and anemia in a large population-based study.

OBJECTIVE AND BACKGROUND Anemia and thyroid dysfunction are common and often co-occur. Current guidelines recommend the assessment of thyroid function in the work-up of anemia, although evidence on this association is scarce. PATIENTS AND METHODS In the "European Prospective Investigation of Cancer" (EPIC)-Norfolk population-based cohort, we aimed to examine the prevalence and type of anemia (defined as hemoglobin <13 g/dl for men and <12 g/dl for women) according to different thyroid function groups. RESULTS The mean age of the 8791 participants was 59.4 (SD 9.1) years and 55.2% were women. Thyroid dysfunction was present in 437 (5.0%) and anemia in 517 (5.9%) participants. After excluding 121 participants with three most common causes of anemia (chronic kidney disease, inflammation, iron deficiency), anemia was found in 4.7% of euthyroid participants. Compared with the euthyroid group, the prevalence of anemia was significantly higher in overt hyperthyroidism (14.6%, P < .01), higher with borderline significance in overt hypothyroidism (7.7%, P = .05) and not increased in subclinical thyroid dysfunction (5.0% in subclinical hypothyroidism, 3.3% in subclinical hyperthyroidism). Anemia associated with thyroid dysfunction was mainly normocytic (94.0%), and rarely macrocytic (6.0%). CONCLUSION The prevalence of anemia was higher in overt hyperthyroidism, but not increased in subclinical thyroid dysfunction. Systematic measurement of thyroid-stimulating hormone in anemic patients is likely to be useful only after excluding common causes of anemia.

Lessons learned from implementation of a demonstration program to reduce the burden of anemia and hookworm in women in Yen Bai Province, Viet Nam

Background Iron deficiency, anemia and hookworm disease are important public health problems for women of reproductive age living in developing countries and affect the health of newborns and infants. Iron supplementation and deworming treatment are effective in addressing these problems in both pregnant and non-pregnant women. Daily iron supplementation and deworming after the first trimester is recommended for pregnant women although these programs usually do not operate efficiently or effectively. Weekly iron-folic acid supplementation and regular deworming for non-pregnant women may be a viable approach for improving iron status and preventing anemia during the reproductive years. Addressing these diseases at a population level before women become pregnant could significantly improve women's health before and during pregnancy, as well as their infants' growth and development. Methods and Results This paper describes the major processes undertaken in a demonstration intervention of preventive weekly iron-folic acid supplementation with regular deworming for all 52,000 women aged 15–45 years in two districts of Yen Bai province, in northern Viet Nam. The intervention strategy included extensive consultation with community leaders and village, commune, district and provincial health staff, and training for village health workers. Distribution of the drugs was integrated with the existing health service infrastructure and the village health workers were the direct point of contact with women. Iron-folic acid tablets and deworming treatment were provided free of charge from May 2006. An independent Vietnamese NGO was commissioned to evaluate compliance and identify potential problems. The program resulted in effective distribution of iron-folic acid tablets and deworming treatment to all villages in the target districts, with full or partial compliance of 85%. Conclusion Training for health staff, the strong commitment of all partners and the use of appropriate educational materials led to broad support for weekly iron-folic acid supplementation and high participation in the regular deworming days. In March 2008 the program was expanded to all districts in the province, a target population of approximately 250,000 WRA, and management was handed over to provincial authorities.

RAD51C: a novel cancer susceptibility gene is linked to Fanconi anemia and breast cancer

Germline mutations in many of the genes that are involved in homologous recombination (HR)-mediated DNA double-strand break repair (DSBR) are associated with various human genetic disorders and cancer. RAD51 and RAD51 paralogs are important for HR and in the maintenance of genome stability. Despite the identification of five RAD51 paralogs over a decade ago, the molecular mechanism(s) by which RAD51 paralogs regulate HR and genome maintenance remains obscure. In addition to the known roles of RAD51C in early and late stages of HR, it also contributes to activation of the checkpoint kinase CHK2. One recent study identifies biallelic mutation in RAD51C leading to Fanconi anemia-like disorder. Whereas a second study reports monoallelic mutation in RAD51C associated with increased risk of breast and ovarian cancer. These reports show RAD51C is a cancer susceptibility gene. In this review, we focus on describing the functions of RAD51C in HR, DNA damage signaling and as a tumor suppressor with an emphasis on the new roles of RAD51C unveiled by these reports.

Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only similar to 50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects.

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair Implications for Fanconi Anemia and Breast Cancer Susceptibility

RAD51C, a RAD51 paralog, has been implicated in homologous recombination (HR), and germ line mutations in RAD51C are known to cause Fanconi anemia (FA)-like disorder and breast and ovarian cancers. The role of RAD51C in the FA pathway of DNA interstrand cross-link (ICL) repair and as a tumor suppressor is obscure. Here, we report that RAD51C deficiency leads to ICL sensitivity, chromatid-type errors, and G(2)/M accumulation, which are hallmarks of the FA phenotype. We find that RAD51C is dispensable for ICL unhooking and FANCD2 monoubiquitination but is essential for HR, confirming the downstream role of RAD51C in ICL repair. Furthermore, we demonstrate that RAD51C plays a vital role in the HR-mediated repair of DNA lesions associated with replication. Finally, we show that RAD51C participates in ICL and double strand break-induced DNA damage signaling and controls intra-S-phase checkpoint through CHK2 activation. Our analyses with pathological mutants of RAD51C that were identified in FA and breast and ovarian cancers reveal that RAD51C regulates HR and DNA damage signaling distinctly. Together, these results unravel the critical role of RAD51C in the FA pathway of ICL repair and as a tumor suppressor.