Inherited disorders of hemoglobin: A review of old and new diagnostic methods.

The genetic regulation of hemoglobin is complex and there are a number of genetic abnormalities that result in clinically important hemoglobin disorders. Here, we review the molecular pathophysiology of hemoglobin disorders and review both old and new methods of diagnosing these disorders. Timely diagnosis of hemoglobinopathies in infants is essential to coordinate optimal life-saving interventions, and accurate identification of carriers of deleterious mutations allows for genetic counseling and informed family planning. The initial laboratory workup of inherited disorders of hemoglobin should include a complete blood count (CBC) and peripheral blood smear, followed by carefully selected tests based on clinical suspicion and available methodology. We discuss the utility and limitations of the various methodologies to fractionate hemoglobin, including cellulose acetate and citrate agar hemoglobin electrophoresis, isoelectric focusing, high-resolution high-performance liquid chromatography, and capillary zone electrophoresis. Recognizing that most of the global burden of hemoglobin disorders exists in low- and middle-income countries, we review the increasingly available array of point-of-care-tests (POCT), which have an increasingly important role in expanding early diagnosis programs to address the global burden of sickle cell disease, including Sickle SCAN, HemoTypeSC, Gazelle Hb Variant, and Smart LifeLC. A comprehensive understanding of the molecular pathophysiology of hemoglobin and the globin genes, as well as a clear understanding of the utility and limitations of currently available diagnostic tests, is essential in reducing global disease burden.

Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque.

Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

Discrete cutaneous lesions in a critically ill patient treated only for AIDS and miliary tuberculosis: a case report of disseminated histoplasmosis.

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, with disseminated histoplasmosis (HD) being one of its clinical forms. As a consequence of the HIV-AIDS pandemic, HD has become prevalent not only in regions that are recognized as endemic but also in areas not considered endemic, such as Europe and Asia. Its clinical manifestations are varied and mimic several infectious diseases, mainly tuberculosis. In endemic areas, it is the first manifestation of AIDS in 50 to 70% of patients. The diagnosis of histoplasmosis is difficult and HD can lead to death if not diagnosed early and if proper treatment is not instituted. The present report presents a patient with a recent diagnosis of HIV-AIDS, in treatment for miliary tuberculosis, who was diagnosed with disseminated histoplasmosis because of his dermatological manifestations.

Extra ocular sebaceous adenocarcinoma in HIV-positive patient--case report.

Sebaceous adenocarcinoma is a rare adnexal tumor that can affect the skin and is divided into ocular, a more common form and extra ocular, of a rarer occurrence. We report the case of a patient diagnosed with Acquired Immune Deficiency Syndrome (AIDS) who developed an extra ocular, bulky and fast-growing sebaceous adenocarcinoma on the face. The literature has suggested that transplanted patients and HIV-positive patients have an excess risk for developing adnexal tumors, including sebaceous adenocarcinoma.

Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin.

Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.

Extra ocular sebaceous adenocarcinoma in HIV-positive patient - case report / Adenocarcinoma sebaceo extra-ocular em paciente HIV positivo - relato de caso

Sebaceous adenocarcinoma is a rare adnexal tumor that can affect the skin and is divided into ocular, a more common form and extra ocular, of a rarer occurrence. We report the case of a patient diagnosed with Acquired Immune Deficiency Syndrome (AIDS) who developed an extra ocular, bulky and fast-growing sebaceous adenocarcinoma on the face. The literature has suggested that transplanted patients and HIV-positive patients have an excess risk for developing adnexal tumors, including sebaceous adenocarcinoma.

Adenocarcinoma sebáceo é um tumor anexial raro que pode envolver a pele e é dividido em ocular, mais comum e extraocular, mais raro. Relatamos o caso de um paciente com diagnóstico de Síndrome da Imunodeficiência Adquirida que desenvolveu um adenocarcinoma sebáceo extra-ocular, na face, volumoso, de rápido crescimento. A literatura tem sugerido que pacientes transplantados e portadores do vírus da imunodeficiência humana têm um excesso de risco para o desenvolvimento de tumores anexiais, incluindo o Adenocarcinoma sebáceo.

Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin / Hanseniase boderline tuberculoide e reacao hansenica do tipo 1 em paciente com hepatite C durante tratamento com interferon e ribavirina

Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.

A hepatite C é uma doença inflamatória fígado causada por um vírus RNA de fita simples, pertencente ao gênero Hepacivirus e à família Flaviviridae, denominado de vírus da hepatite C. Após infecção inicial 70 a 85% dos pacientes infectados evoluem para hepatite C crônica, com fibrose progressiva. Além das alterações hepáticas específicas, várias manifestações extra-hepáticas têm sido relacionadas à infecção pelo vírus da hepatite C ou às medicações utilizadas no seu tratamento. Nesse trabalho, apresenta-se caso de paciente portador de hepatite C crônica, que manifestou um quadro hanseníase boderline tuberculóide e reação hansênica do tipo I, quatro meses após início do tratamento com interferon peguilado associado à ribavirina.

Rosai-Dorfman primário do sistema nervoso central simulando meningioma de tórcula: relato de caso / Rosai-Dorfman disease mimicking torculae meningioma: case report

Relatamos o caso de uma mulher de 65 anos de idade, com queixa de cefaleia, portadora de uma lesão expansiva em região posterior da tenda do cerebelo, implantado na tórcula, sugestivo de meningioma pelos exames de imagens, foi submetida ao tratamento neurocirúrgico para ressecção. Ao exame anatomopatológico, foi sugerido diagnóstico de doença de Rosai-Dorfman, confirmado pela imunohistoquímica. Trata-se de uma rara linfadenopatia proliferativa histiocítica, de comportamento benigno, com acometimento mais frequente da cadeia linfonodal cervical e outros sítios extranodais, sendo extremamente rara sua localização no sistema nervoso central, principalmente na fossa posterior, sem acometimento de outras estruturas anatômicas.

We report the case of a woman 65 years old, complaining of headache, carries a lesion in the posterior region of the tent of the cerebellum, implanted in torcula, suggestive of meningioma by imaging tests, was subjected to neurosurgical procedures for resection. When pathological examination suggested a diagnosis of Rosai-Dorfman disease, confirmed by immunohistochemistry. It is a rare proliferative histiocytic lymphadenopathy in benign behavior, with more frequent involvement of cervical lymph node and other extranodal sites, its location is extremely rare in the central nervous system, especially in the posterior fossa without involvement of other anatomical structures.