Showing papers on "Monocytosis published in 2013"

Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes

Abstract: We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical (inflammatory/Gr1(hi) ) or non-classical (resident/Gr1(lo) ) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient (Apoe(-/-) ) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient Apoe(-/-) mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or CX3 CR1 in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.

Virological and clinical characterizations of respiratory infections in hospitalized children

Abstract: The purpose of this study was to determine the incidence and seasonal distribution of viral etiological agents and to compare their clinical manifestations and disease severity, including single and co infections. Multiplex reverse-transcription PCR was performed for the detection of viruses in nasopharyngeal aspirat. Disease severity was grouped using a categorization index as very mild/mild, and moderate/severe. Clinical and laboratory characteristics of hospitalized children with viral respiratory tract infection were analyzed. Viral pathogens were detected in 103/155 (66.5%) of patients. In order of frequency, identified pathogens were respiratory syncytial virus (32.0%), adenovirus (26.2%), parainfluenza viruses type 1–4 (19.4%), rhinovirus (18.4%), influenza A and B (12.6%), human metapneumovirus (12.6%), coronavirus (2.9%), and bocavirus (0.9%). Coinfections were present in 21 samples. Most of the children had very mild (38.8%) and mild disease (37.9%). Severity of illness was not worse with coinfections. The most common discharge diagnoses were "URTI" with or without LRTI/asthma (n=58). Most viruses exhibited strong seasonal patterns. Leukocytosis (22.2%) and neutrophilia (36.6%) were most commonly detected in patients with adenovirus and rhinovirus (p<0.05). Monocytosis was the most remarkable finding in the patients (n=48, 53.3%), especially in patients with adenovirus (p<0.05). RSV and RhV were associated with higher severity of illness in hospitalized children. RSV found to account for half of LRTI hospitalizations. In AdV and FluA and B infections, fever lasted longer than in other viruses. Coinfections were detected in 21 of the patients. The presence of coinfections was not associated with increased disease severity.

Hypercholesterolemia links hematopoiesis with atherosclerosis

Abstract: Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease.

Absolute monocytosis at diagnosis correlates with survival in diffuse large B-cell lymphoma-possible link with monocytic myeloid-derived suppressor cells.

Abstract: Some patients with lymphoma have monocytosis at diagnosis, but its significance is unclear. The recently recognized subpopulation, monocytic myeloid-derived suppressor cells (M-MDSCs), has immunoregulatory function, suppresses host anti-tumour immunity and plays a role in cancer tolerance. Data from 91 untreated patients with diffuse large B-cell lymphoma (DLBCL) were evaluated for monocytosis >1000/mm(3) at diagnosis and its significance compared with a number of well-established prognostic factors for DLBCL including age, stage, gender, B symptoms, extranodal sites, LDH and CRP levels, bone marrow involvement and International Prognostic Index (IPI) score. In 23 of these patients with DLBCL and 15 healthy controls, the proportion of M-MDSCs in the peripheral blood was determined by flow cytometry. Monocytosis was found in 17.6% of the patient cohort examined. In the multivariate analysis, bone marrow involvement, IPI score and monocytosis were the only independent prognostic factors seen to be associated with decreased progression free and overall survival. Patients with DLBCL had on average increased M-MDSCs counts at diagnosis compared with controls, which returned to normal after achieving remission. In conclusion, monocytosis was identified as an independent prognostic factor in DLBCL and correlated with worse overall survival. The significant increases in the M-MDSCs pool observed in some of the cases examined may possibly help to explain why monocytosis is associated with poor outcome in these patients.

Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis

Abstract: Background—The number of circulating blood monocytes impacts atherosclerotic lesion size, and in mouse models, elevated levels of high-density lipoprotein cholesterol suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced high-density lipoprotein levels, high blood monocyte counts, and accelerated atherosclerosis. Methods and Results—To test whether mild renal dysfunction is associated with an increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmo Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (P=0.02). Cystatin C levels were positively and plasma high-density lipoprotein cholesterol levels negatively ...

Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia

Abstract: Background Wiskott–Aldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by defects of the WAS protein (WASP) gene. Patients with WAS typically demonstrate micro-thrombocytopenia. Procedures The report describes seven male infants with WAS that initially presented with leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood (PB) and dysplasia in the bone marrow (BM), which was initially indistinguishable from juvenile myelomonocytic leukaemia (JMML). Results The median age of affected patients was 1 month (range, 1–4 months). Splenomegaly was absent in four of these patients, which was unusual for JMML. A mutation analysis of genes in the RAS-signalling pathway did not support a diagnosis of JMML. Non-haematological features, such as eczema (n = 7) and bloody stools (n = 6), ultimately led to the diagnosis of WAS at a median age of 4 months (range, 3–8 months), which was confirmed by absent (n = 6) or reduced (n = 1) WASP expression in lymphocytes by flow cytometry (FCM) and a WASP gene mutation. Interestingly, mean platelet volume (MPV) was normal in three of five patients and six of seven patients demonstrated occasional giant platelets, which was not compatible with WAS. Conclusions These data suggest that WAS should be considered in male infants presenting with JMML-like features if no molecular markers of JMML can be detected. Pediatr Blood Cancer 2013; 60: 836–841. © 2012 Wiley Periodicals, Inc.

Possible impact of microglial cells and the monocyte-macrophage system on suicidal behavior.

Abstract: Immune dysfunction, including monocytosis, increased blood levels of interleukin-1 (IL-1), interleukin-6 (IL- 6) and tumor necrosis factor-alpha (TNF-alpha), as well as an increased microglial density in certain brain areas, have been described in schizophrenia and depression. Interestingly, similar immune alterations have been observed in suicide patients regardless of their underlying psychiatric diagnosis. This review summarizes relevant data from previous studies that have examined peripheral blood, cerebrospinal fluid and human brains (using postmortem histology and in vivo positron emission tomography) to investigate immune mechanisms in suicidal patients. We discuss whether the observed findings indicate that microgliosis and monocyte-macrophage system activation may be a useful marker of disease acuity/severity or whether they instead indicate a distinct neurobiology of suicide. Notably, pathophysiological mechanisms could change during the long-term course of psychiatric diseases. Therefore, different patterns of immune activation may be observed when comparing newly diseased patients with those who are chronically ill.

Chronic myelomonocytic leukemia: 2013 update on diagnosis, risk stratification, and management

Abstract: Disease overview Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is classified as a myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization classification of hematopoietic tumors. It is characterized by absolute monocytosis (>1 × 109/L) in the peripheral blood that persists for at least 3 months. Diagnosis The diagnosis of CMML rests on a combination of morphologic, histopathologic and chromosomal abnormalities in the bone marrow. It is important to exclude other myeloproliferative neoplasms and infectious/autoimmune conditions that can cause monocytosis. Risk stratification Several CMML-specific prognostic models incorporating novel mutations have been recently reported. The Mayo prognostic model classified CMML patients into three risk groups based on: increased absolute monocyte count, presence of circulating blasts, hemoglobin 65 years, WBC >15 × 109/L, anemia, platelets <100 × 109/L, and ASXL1 mutation status. After a median follow-up of 2.5 years, survival ranged from not reached in the low-risk group to 14.4 months in the high-risk group. Risk-adapted therapy The Food and Drug Administration has approved azacitidine and decitabine for the treatment of patients with CMML. An allogeneic stem cell transplant can potentially offer a curative option to a subset of CMML patients. It is hoped that with the discovery of several novel mutations, targeted therapies will become available in the near future. Am. J. Heamtol. 88:968–974, 2013. © 2013 Wiley Periodicals, Inc.

Hematologic and bone marrow changes in dogs experimentally infected with Rangelia vitalii

Abstract: Background Rangelia vitalii is a tick-transmitted piroplasm that causes both hemolytic and hemorrhagic disease in dogs in Brazil. Objective The aim of this study was to evaluate the response of the bone marrow in dogs experimentally infected with R vitalii during the acute stage of the disease. Methods For this study, 2 groups of a total of 12 young dogs were used. Group A was composed of healthy dogs (n = 5), and group B consisted of animals infected with R vitalii (n = 7). Blood samples were collected on days 0, 10, 20, and 30 post-inoculation and stored in EDTA tubes for a full hematology profile, including a reticulocyte count. On days 10 and 20, bone marrow samples were collected, stained, and examined. Results In infected dogs anemia was identified on days 10 and 20 post-inoculation (P < .01), and on day 20 reticulocytosis was present. Infected dogs had leukopenia due to neutropenia and eosinopenia, along with lymphocytosis and monocytosis, when compared with control animals. In bone marrow, the myeloid:erythroid ratio was significantly decreased (P < .05) in infected dogs due to increased erythroid precursors. Conclusions Dogs experimentally infected with R vitalii develop regenerative extravascular hemolytic anemia accompanied by erythroid hyperplasia in the bone marrow. During the acute phase of the disease, leukopenia due to neutropenia and eosinopenia suggests intense tissue recruitment of these cells in response to the endothelial damage caused by this parasite.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antituberculosis drugs and associated with human herpes virus-7 (HHV-7)

Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious reaction to drugs with a clinical presentation of rash, fever, lymph node enlargement and internal organ involvement. Reports have described the reactivation of human herpes virus 6 (HHV-6) and other HHVs in association with this syndrome. We report a 41-year-old woman who developed a rash, fever, liver dysfunction, eosinophilia and atypical monocytosis 21 days after initiation of the quadruple therapy for tuberculous cervical lymphadnitis. HHV-7 DNA was detected in blood by PCR suggesting infection with or more likely reactivation of HHV-7 as a contributing factor or consequence of this serious adverse drug reaction.

Screening diagnostics to identify triggers in 21 cases of steroid-responsive meningitis-arteritis.

Abstract: Objectives To evaluate whether screening tests used to identify infectious and neoplastic triggers for immune-mediated haemolytic anaemia, in particular a complete blood count and differential, serum biochemistry profile, urine analysis (including culture), abdominal ultrasound and thoracic radiographs, can identify triggers for steroid-responsive meningitis-arteritis. Methods Retrospective descriptive review. Results Twenty-one steroid-responsive meningitis-arteritis cases were identified in which all screening tests had been performed. All cases had changes in complete blood count (including neutrophilia, monocytosis, lymphocytosis, eosinopenia or anaemia); 19 had changes in biochemistry (including hypoalbuminaemia, hyperglobulinaemia, increased alkaline phosphatase activity, hyperphosphataemia, increased total calcium concentration, hypercholesterolaemia, hyperkalaemia, increased urea concentration and increased alanine aminotransferase activity); two cases had an elevated urine protein to creatinine ratio but none had positive urine culture results; no cases had abnormalities on orthogonal radiographs of the thorax; four cases had abnormalities identified on abdominal ultrasound, which following cytological examination suggested inflammation in the absence of pathological organisms. Clinical Significance Screening tests used to identify infectious and neoplastic triggers in immune-mediated haemolytic anaemia did not isolate triggers for steroid-responsive meningitis-arteritis in the population of dogs under investigation.

Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

Abstract: Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in comparison with the controls (median, 8.6%; range, 0–27.7% vs. median, 17.6%; range, 2.8–49.6%), suggesting an increased CD34+ cell survival. The functional evaluation of circulating hematopoietic progenitors showed specific patterns in NS and NS/MPD. These tests are a reliable integrative tool that, together with clinical data and other hematological parameters, could help detect NS patients with a high risk for a myeloproliferative evolution.

Effects of tetra-arsenic tetra-sulfide on BXSB lupus-prone mice: a pilot study:

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Arsenic trioxide (ATO) has been used in lupus-prone mice with a regulatory effect on immune abnormality. Tetra-arsenic tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects than ATO. In this study, a pilot study was performed to investigate the effects and the mechanism of As4S4 on the lupus-prone BXSB mice. Improvement of monocytosis (p < 0.05) in spleen and decreased serum interleukin-6 (IL-6) (p = 0.0277) were observed with As4S4 treatment. As4S4-treated mice exhibited amelioration of skin, liver and renal disease with mild side effects. Histological analysis revealed that As4S4 suppressed immune complex deposition, mesangial proliferation and inflammatory cell infiltration in kidney and liver. Our study support that As4S4 selectively suppresses cutaneous lupus and nephritis in BXSB mice and might be a potential ...

Atypical chronic myeloid leukemia harboring NUP98-HOXA9.

Abstract: A previously healthy 67-year-old Japanese male visited our hospital to undergo a work up for leukocytosis. Laboratory tests showed a hemoglobin level of 11.9 g/dL, platelets 225 9 10/L, and leukocytes 23.0 9 10/L. The neutrophil alkaline phosphatase (NAP) score was 107 (control, 238). A peripheral blood smear showed neutrophilia (77.0 %) with a hypersegmented nucleus (Fig. 1a). Neither monocytosis (5.5 %), basophilia (0.0 %), nor eosinophilia (0.5 %) was seen. Bone marrow aspiration revealed marked myeloid proliferation without any differentiation block. Dysgranulopoiesis and dysmegakaryopoiesis were observed, including pseudo-Pelger-Huet anomaly, hypogranulation and bizarrely segmented nuclei in the neutrophils, and small megakaryocytes with hypolobulated nuclei (Fig. 1b, c). The erythroid lineage cells did not have apparent dysplasia. Karyotypic and molecular analysis of the bone marrow cells showed only one abnormality t(7;11)(p15;p15), and the resultant NUP98-HOXA9 expression. Neither BCR-ABL1 nor JAK2V617F was detected. The patient was diagnosed with atypical chronic myeloid leukemia (atypical CML) harboring t(7;11)(p15;p15)/NUP98-HOXA9. t(7;11)(p15;p15)/NUP98-HOXA9 is known to be a poor prognostic factor in acute myeloid leukemia, as well as an additional genetic event in CML progressing to blastic crisis [1]. Several reports have described Ph-negative CML or chronic myelomonocytic leukemia to harbor only t(7;11)(p15;p15)/NUP98-HOXA9 [2, 3]. These cases were accompanied by dysgranulopoiesis and/or monocytosis, which are not usually seen in CML. A low NAP score cannot discriminate such patients from CML cases. To date, no treatment strategy or prognostic methods have yet been established for such cases. Our patient was followed up without any particular treatment, and his complete blood count and differentials have remained unchanged for more than 6 months.

Интегральные гематологические индексы и иммунологические показатели при острых отравлениях у детей

Abstract: Objective: to study the immune status in a group of children with acute chemical injury and to define the role of integral hematological parameters in the rapid evaluation of the functional state of the immune system. Subjects and methods. Ten patients aged 1 to 3 years with acute chemical poisoning were examined. They underwent immune status examination and clinical blood analysis with calculation of integral hematological parameters, by using the conventional formulas. Results. Within the first 24 hours of the disease, the children were found to have higher neutrophils, lower lymphocytes, and moderate monocytosis. Immunological studies revealed a reduction in total lymphocyte counts due to a decreased T-cell ratios. The level of B lymphocytes did not differ from the normal values, but at the same time there was impaired B-lymphocyte production of immunoglobulins. The absorbing capacity of neutrophils remained unchanged and oxygen-dependent cellular metabolism was enhanced. Conclusion. Immunological findings and integral hematological indices point to immune system functional changes forming in children via a systemic response to acute chemical poisoning. Key words: children, acute chemical injury, hematological indices, immune status.

Chronic myelomonocytic leukemia presenting as relapsing thrombotic thrombocytopenic purpura

Abstract: A 67-year-old woman presented with fever, purpura, and confusion. A preliminary diagnosis of thrombotic thrombocytopenic purpura (TTP) was made on the basis of clinical presentation and lab findings, such as reduced platelet count, increased bilirubin, and so on. She was treated with therapeutic plasma exchange (TPE) and methylprednisolone. During the treatment, peripheral blood monocytosis (monocyte 4 × 109/L) was noticed. The monocytes were CD56 positive. A putative diagnosis of chronic myelomonocytic leukemia (CMML) was proposed. Three months later, the diagnosis of CMML was established on the basis of persistent monocytosis. All other potential causes were considered (e.g., quinine exposure, diarrhea) and excluded. This case highlights the needs to consider hematological malignancy such as CMML in patients with TTP.

Evolution of chronic myelomonocytic leukemia from refractory anemia: the unusual course of a myelodysplastic syndrome.

Abstract: TO THE EDITOR: Transformation from myelodysplastic syndrome (MDS) to chronic myelomonocytic leukemia (CMML) is rarely observed. However, this has been reported in cases of refractory anemia with ring sideroblasts or excess of blasts [1-4]. Moreover, MDS patients may present with monocytosis that does not meet the diagnostic criteria of CMML, which makes diagnosis and classification of these atypical mixed disorders a challenge [5, 6]. These difficulties in diagnostic classification and prognostic stratification may be concerning with regard to decision-making, particularly in this new era of effective disease-modifying therapies, such as hypomethylating agents [6, 7]. Recently, we faced such concerns during the management of a patient who developed CMML 7 years after having been diagnosed with refractory anemia (RA). The full clinical onset of CMML was preceded by progressive loss of response to ongoing treatment with an erythropoiesis-stimulating agent (ESA), worsening anemia, thrombocytopenia, leukocytosis, and increasing monocytosis. A morphological study of the peripheral blood (PB) and bone marrow (BM) revealed the coexistence of myelodysplastic and myeloproliferative syndromes. A cytogenetic alteration (45, X0,-Y), which was not present at diagnosis of RA 7 years earlier, was also detected during the CMML phase. The patient received azacitidine and showed a good response. Here, we describe this rare case and its implications in disease classification and management. On January 2005, a 74-year-old man presented with moderately macrocytic slight thrombocytopenia. Five years earlier (in 2000), he had received postoperative radiotherapy after radical prostatectomy for prostate cancer. Apart from this prostatic neoplasm, for which a regular oncological follow-up had confirmed a persistent complete remission until then, he mentioned one previously cured gastric ulcer and well-controlled hypertension. He complained of fatigue and general unease for the past few weeks. A complete blood count prescribed by his general practitioner had revealed macrocytic anemia with a low reticulocyte count, mild thrombocytopenia, and slight neutropenia. On admission, he appeared pale and fatigued. A comprehensive laboratory evaluation did not reveal any remarkable abnormalities. His coagulative profile and renal and hepatic function were normal. Suspicions of hemolytic disorders, virus infections, and iron and vitamin deficiencies were also dismissed. Morphological examination of PB smears showed isolated erythrocyte macrocytosis but did not provide any other diagnostic findings. BM aspiration and trephine biopsy were performed. BM examination revealed hypercellular BM with evident erythrodysplasia and 6% of blasts without fibrosis. Conventional karyotyping and fluorescence in situ hybridization analyses did not show abnormalities. Therefore, the patient was diagnosed with MDS, RA, according to the French-American-British classification. The patient had an International Prognostic Scoring System score of 1 (intermediate-1 risk). On admission and during the diagnostic phase, he received 4 units of red blood cell (RBC) concentrates. Thus, the patient was scheduled to receive ESA at a weekly dose of 40,000 units by subcutaneous injection (in January 2005). Since then, the patient was regularly followed-up at our clinic and continued to receive erythropoietin treatment. Normal PB values were maintained without the requirement for transfusion, clinical complications, or side effects until June 2012, when his hematologic status slowly began to deteriorate. Worsening anemia (requiring RBC transfusions), thrombocytopenia, and leukocytosis with absolute monocytosis became prominent. A comprehensive medical examination was performed. The examination of PB smears showed absolute monocitosis with 2% of circulating blasts. BM examination showed marked erythroid dysplasia and monocytosis with 15% blasts. A karyotype abnormality, such as 45, X0,-Y, which was not detected at initial diagnosis of RA 7 years earlier, was also found; however, the JAK2 V617F mutation was absent. Therefore, the patient was diagnosed with RA, coexisting with type II CMML. The patient had a MD Anderson Prognostic Score of 3 (intermediate-2 risk) [8]. After a brief course of hydroxycarbamide, administered in order to reduce leukocytosis, the patient received 6 cycles of azacitidine (75 mg/m2, schedule 5+2+2, each cycle every 4 weeks), according to approved indications [9]. After the second course, transfusion independence was achieved and the PB counts significantly improved with disappearance of monocytosis. Complete remission of CMML was achieved after 6 courses of hypomethylating therapy, without any adverse events. In conclusion, this case represents an atypical presentation of CMML secondary to MDS. In addition to its rarity and anecdotal interest, we believe that this report should be discussed with regard to several topics, such as the possible evolution of low-risk MDS in CMML, the existence of secondary CMML as a distinct disease, its absence in the current classification systems, and, finally, the efficacy of hypomethylating therapy [4, 10].

Cholinesterase activity in serum, whole blood and lymphocytes of dogs experimentally infected with Rangelia vitalii

Abstract: Background: The cholinergic system is involved in many biological functions in mammals and is associated with pathogenesis of infectious diseases, as has participation in transmission of nerve impulses in cholinergic synapses, haematopoiesis, regulation of inflammatory markers, production and coordination of movement, and memory. Rangelia vitalii is a parasite endemic to south of Brazil. This parasite multiplies in the blood and can be visualized in plasma in its free form and/or within leukocytes and erythrocytes, causing various pathologies. Therefore, the purpose of this study was to investigate the activity of cholinergic system enzymes in dogs experimentally infected with R. vitalii. Materials, Methods & Results: Twelve dogs were used, divided into two groups: control group (n = 5), consisting of healthy animals, and infected group with R. vitalii (n = 7). Fresh blood samples of these infected animals were inoculated in seven dogs (2 mL/dog through the jugular vein). Blood samples were collected on days 0, 10 and 20 post-infection (PI). Butyrylcholinesterase (BChE) activity was measured in serum and acetylcholinesterase (AChE) in lymphocytes and whole blood. Boold samples were diluted 1:50 (v/v) in lysis solution (0.1 mmol/L potassium/sodium phosphate buffer containing 0.03% Triton X-100) and frozen (-20 oC by 7 days) to determine AChE activity in whole blood. Lymphocytes were also obtained from whole blood with EDTA by gradient separation using Ficoll-Histopaque™ plus to AChE activity this cell. After analysis of the samples, was observed that the dogs infected with R. vitalii presented a significant (P < 0.01) increase in AChE activity in whole blood on days 10 and 20 PI. However, the infected group showed a reduced activity in AChE in lymphocytes (P < 0.01) and BChE in serum (P < 0.05) on day 20 PI. Discussion: According to the literature, infected dogs R. vitalii develop regenerative anemia evidenced by an increase in the erytroid precursors in bone marrow associated with alterations of leucogram as leukopenia, neutropenia, eosinopenia, lymphocytosis and monocytosis. Furthermore, it was observed severe thrombocytopenia, with alteration in platelet aggregation and activity of enzymes involved in the control of ATP, ADP and adenosine levels on platelets, thereby influencing hemostasis and contributing to the typical bleeding disease. AChE activity in whole blood was increased in dogs parasitized by R. vitalii observed in this study. This increase may be a compensatory effect to severe anemia caused by the parasite infection, because this enzyme is involved in the maturation of erythrocytes and in the regulation of hematopoiesis. In the present study, we found that the reduction in AChE activity in lymphocytes is associated to lymphocytosis; and it is known that ACh is produced within lymphocytes and has the ability to negatively modulate the immune response, acting directly on the inhibition of inflammatory mediators. Therefore, the decrease of AChE activity may have an anti-inflammatory action in order to have more free ACh to bind lymphocytes and inhibit inflammation. The enzyme BChE can also act as an inflammatory marker in various diseases, similar to AChE, because the enzyme can hydrolyze acetylcholine when AChE is inhibited. In conclusion, our results indicate that canine rangeliosis alters the activity of cholinesterase’s, which may be involved in the pathogenesis of the disease, as well as various pathological conditions.

Peritoneal EMH in a dog with immune-mediated hemolytic anemia.

Abstract: Extramedullary hematopoiesis (EMH) is the process by which normal blood cells are produced outside the bone marrow. In humans, EMH effusions are rare and are characterized by the presence of megakaryocytes, immature erythrocytes, immature leukocytes, or combinations of those cells. To the authors’ knowledge, this is the first report to describe a case of peritoneal EMH effusion in a dog. A 5 yr old castrated male shorthaired dachshund presented with a 2 day history of pigmenturia and inappetence. A complete blood count revealed regenerative anemia with marked agglutination, spherocytosis, and an acute inflammatory leukogram characterized by a neutrophilia, regenerative left shift, and monocytosis. Ultrasound-guided aspiration of peritoneal effusion yielded a sample of high nucleated cellularity predominantly composed of mature and immature neutrophils and erythroid precursor cells. The patient was diagnosed with primary immune-mediated hemolytic anemia with concurrent EMH peritoneal effusion. The followin...

Juvenile myelomonocytic leukemia.

Abstract: Juvenile myelomonocytic leukemia (JMML) is a rare fatal hematopoietic disorder of early childhood. We are presenting a case of 9-month-old female child who was admitted with abdominal distension, irritability, and hepatosplenomegaly. Peripheral blood film examination showed leukoerythroblastosis with leukocytosis, absolute monocytosis, microcytic hypo chromic anemia, and thrombocytopenia. Bone marrow examination showed myeloid hyperplasia, Hb HPLC revealed normal HbF (1.3 %) and HbA2 (2.9 %). There was absolute gamma globulinemia and DCT positivity. Cytogenetic studies revealed a normal karyotype with absence of Philadelphia (Ph) chromosome, monosomy 7 or any other chromosomal abnormality. Diagnosis of JMML was rendered according to the diagnostic criteria laid down by WHO classification 2008 with presence of peripheral blood monocytosis >1 × 109/L, blasts 10 × 109/L. The patient was then started on a regimen of chemotherapy to which she gave a promising response.

Leucemia linfoblástica aguda em um cão

Abstract: Background: Leukemias are malign neoplasias of the hematopoietic precursor cells from the bone marrow. These neoplastic cells may or may not reach the blood circulation. Leukemias are classifi ed as lymphoid or myeloid depending on the leukocyte cell lineage affected. In addition, leukemias are classifi ed as either acute or chronic based on their cellular differentiation and proliferative aggressiveness. The leukemias from lymphoid cells that affect dogs include acute lymphoblastic leukemia and chronic lymphocytic leukemia. This paper describes the clinical and laboratorial findings of a case of acute lymphoblastic leukemia in a female dog. Case: A seven-year-old female mixed-breed dog was referred to the Veterinary Hospital of the Universidade Federal Rural do Semi-Arido (UFERSA), Mossoro, State of Rio Grande do Norte, Brazil, for apathy, anorexia, weakness and weight loss. The clinical examination confirmed the apathy and weakness. The mucous membranes were pale, the body temperature was 40.5°C, the heart rate was 120 bpm, the capillary refi ll time was 2 s, and no abnormalities were found on auscultation. Diagnostic laboratory tests were completed, including a serum test for canine leishmaniasis, a serum biochemistry panel, a complete blood cell count, and a bone marrow analysis. The canine leishmaniasis serology (enzyme-linked immunosorbent assay and indirect fl uorescent-antibody test) was negative. The serum biochemistry panel revealed an increased level of aspartate aminotransferase (AST - 56.0 U/l), hypocalcemia (6.9 mg/dL), hypoalbuminemia (1.91 g/dL), hypobetaglobulinemia (0.51 g/dL), hypergammaglobulinemia (2.91 g/dL), and a decreased albumin/globulin (A/G) ratio (0.41). The observed hematological changes included a normocytic normochromic anemia (RBC = 2.55 x 106/mm3, hemoglobina = 5.8 g/dL, PCV = 18%), leukocytosis (332,800/mm3) with a left shift (3,328/mm3), eosinopenia (0), monocytosis (6,656/mm3), lymphocytosis (89,856/mm3) with a pronounced presence of lymphoblasts (226,304/mm3) and thrombocytopenia (10 x 103/mm3). The blood smear evaluation revealed anisocytosis, polychromasia, hypochromia, giant platelets, smudge cells and lymphoid cells showing predominantly cytoplasmic basophilia, coarse nuclear chromatin, atypical nucleoli, asynchrony of cell maturation and degenerative cytoplasmic vacuolization, and lymphocytes with donut-shaped nuclei. The analysis of a sternal-puncture bone marrow sample revealed that the bone marrow was diffusely occupied by neoplasic lymphoblasts. Discussion: The anemia and thrombocytopenia observed in this female dog can be attributed to the growth of neoplastic cells in the bone marrow. Another finding was the presence of smudge cells, which are broken degenerated leukocytes, and the presence of these cells in large numbers has been described in humans with chronic lymphocytic leukemia or acute lymphoblastic leukemia. The observed hypoalbuminemia, hypergammaglobulinemia and reduced A/G ratio are probably due to the infl ammatory process stimulated by the leukemia. In fact, albumin is a negative acute phase protein, while an increased production of antibodies results in the increased γ-globulins. The prognosis for acute lymphoblastic leukemia is grave, as it is typically rapidLy fatal. In humans, the occurrence of hypocalcemia and large number of smudge cells in cases of acute leukemia indicates a worse prognosis. In fact, this patient died one week after her clinical presentation.

Cardiovascular disease: Monocytosis, atherosclerosis and increased cardiovascular risk in mild renal dysfunction.

Abstract: Cardiovascular disease: Monocytosis, atherosclerosis and increased cardiovascular risk in mild renal dysfunction