Hematological Signs Research Articles

Abstract P6-13-03: Symptomatic bone marrow involvement (BMinv) in breast cancer (BC): Clinical presentation, treatment and prognosis according to BC subtype and Zoledronic acid (ZA) use. A single institution review

Abstract Background: Symptomatic BMinv occurs in a minor proportion of metastatic BC patients (pts). Few data exist regarding its clinical presentation, prognosis and optimal treatment (Tx). ZA has shown to interrupt metastatic “vicious cycle” in bone and to “clear” micrometastastic BMinv in early BC, but its role in symptomatic BMinv remains unclear. We reviewed our series of pts with proven symptomatic BMinv, focusing on Tx delivered and prognosis according to BC subtype and ZA use. Methods: Pts with histologic/cytologic evidence of BMinv from Jan2000 to Feb2012 and with any associated cytopenia were retrospectively identified from Pathology Department files. Results: Twenty-nine pts were identified. Ductal histology: 62%, lobular 24%; Luminal (Lum = HR+/HER2−):76%; HER2+:7%, Triple negative (TN):17%. Stage: II 28%, III 34.5%, IV 24%; median (M) disease free interval: 39.6 months (m) (1.3–113.4). Time BC relapse to BMinv (M): 11.5 m (0–127). At time of BMinv onset: M age 54.7 years (34.3–77.6); M systemic Tx for metastatic disease 2 (0–7). BMinv was present at time of metastatic relapse in 11 pts, including 3 without overt bone metastasis (BM1). Other involved sites at BMinv onset: bone 90% (55% prior to BMinv), nodes 28%, liver 24% and pleuropulmonar 21%. Anemia was the most prominent hematologic sign (97%) followed by thrombocytopenia (Th) (76%) and neutropenia (35%). Tx efficacy in terms of blood count improvement (BCI) and tumor response (TR) outside BM are summarized in table 1. Most pts received non-mielotoxic regimens (endocrine therapy, weekly chemotherapy or capecitabine). ZA was administered in 22 pts (with or without overt BM1). Overall survival (OS)(M) for the whole group was 5.6m (0.3–72.9); M OS in Lum, and TN groups were 9.3 (0.4–72.9) & 0.4m (0.3–20.9+), respectively, while in the 2 HER2+ pts OS was 5.6 & 44.9+ m (p = 0.023). BC subtype, ECOG (0–1 vs 2–3), ZA use after BMinv onset and Th grade (0–1 vs ≥2) were related with OS in the univariate analysis for the whole population. ZA use after BMinv onset, Th grade and presence of BMinv at time of metastatic relapse were also significantly associated with OS in the Lum subgroup. In multivariate analysis, Th remained as an independent factor for OS both in the whole group and Lum subset. ZA use after BMinv onset showed a strong prognostic trend in the Lum group (p = 0.07). Conclusions: BMinv has to be considered in BC pts with BM1 and otherwise unexplained cytopenia. Lum subtype correlates with 9 m M OS, while prognosis in TN subset appears to be particularly dismal. Severe th (<75000 platelets) independently predicts poor OS both in the whole population and in the Lum subtype. In this latter group, a strong trend to better outcome was seen by using ZA after BMinv diagnosis. Futher studies exploring the role of ZA use in pts with BC and symptomatic BMinv are warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-13-03.

Correlação dos achados clínicos e hematológicos com diagnóstico definitivo de erliquiose canina por meio de PCR

The Ehrlichiosis is a worldwide diseases of great importance in a veterinary medicine is an important infectious diseases whose prevalence has increased significant in the last year in the Brazilian states. Due to the fact that this study was designed to correlate the findings hematological clinical signs and PCR, being the most sensitive. This study evaluated twenty dogs seen at veterinary hospital UNESP – Botucatu campus during the 03 from august to September 28 2009. Animal cited 65% were positive in the PCR test. Among the most prominent clinical findings 76.92% (10/13) with anorexia, 53.84% (7/13) with hepatoesplenomegaly, 46.15% (6/13) with apathy and 38.46% (5/13) epistaxis. The thirteen animals positive PCR 92.30% (12/13) showed thrombocytopenia (<150.000 platelets) e 61.53 (8/13) anemic (<5.50 x10). Thus, we conclude that the PCR was a good method for detection differential canine ehrlichiosis may be adopted together with the clinical and hematological findings for the accurate diagnosis of the disease.

Clinical and hematological findings in Leishmania braziliensis-infected dogs from Pernambuco, Brazil

Canine cutaneous leishmaniasis by Leishmania braziliensis is a neglected, but widespread disease of dogs in South America. This paper describes clinical and hematological alterations in 17 L. braziliensis-infected dogs from Brazil. The most common hematological findings were thrombocytopenia (82.4%), anemia (70.6%), low packed cell volume (52.9%) and eosinophilia (41.2%). Twelve (70.6%) dogs displayed at least one evident physical alteration; 11 dogs (64.7%) presented skin lesions, four (23.5%) had weight loss and two (11.8%) onychogryphosis. L. braziliensis-infected dogs present clinical and hematological signs often observed in dogs infected by other pathogens. This indicates that veterinarians and public health workers should not consider the presence of non-specific clinical signs as diagnostic criteria for visceral leishmaniasis in dogs living endemic areas to avoid misdiagnosis and subsequent elimination of dogs infected by L. braziliensis.

1341 The Incidence of Sepsis in Preterm Infants Delivered by Elscs for Maternal Pet Without Septic Risk Factors

BackgroundPreterm infants are at an increased risk of developing early-onset sepsis compared to term infants. The reasons for this are numerous, but mainly revolve around their inherently immature immune system...

Hematological alterations during experimental canine infection by Trypanosoma cruzi

To confirm that Beagle dogs are a good experimental model for Chagas disease, we evaluated hematological alterations during the acute and chronic phases in Beagle dogs infected with the Y, Berenice-78 (Be-78) and ABC strains of Trypanosomacruzi, correlating clinical signs with the parasitemia curve. We demonstrate that the acute phase of infection was marked by lethargy and loss of appetite. Simultaneously, we observed anemia, leukocytosis and lymphocytosis. Also,we describe hematological alterations and clinical signs that were positively correlated with the parasitemia during the experimental infection with the three strains of T.cruzi, and demonstrate that experimental infection of Beagle is a trustworthy model for Chagas disease.

Vitamin B12Deficiency With Bilateral Globus Pallidus Abnormalities

To describe a case of vitamin B(12) deficiency with classic and rare clinical features and novel radiographic features. Case report. Johns Hopkins Hospital neurology service. Middle-aged man with neuropathy, myelopathy,impaired cognition, and extrapyramidal signs. The patient had neurologic and hematologic signs of vitamin B(12) deficiency, with elevated methylmalonic acid and homocysteine levels. Brain magnetic resonance imaging showed signal abnormality in the globi pallidi, as can be seen in inherited methylmalonic acidemia.The clinical and radiographic findings reversed with vitamin B(12) administration. Vitamin B(12) deficiency can present with extrapyramidal symptoms and reversible bilateral globus pallidus abnormalities.

Late Onset Cobalamin C Disease: A Case Report of an Adolescent Presenting with Peripheral Neuropathy (P03.189)

Objective: To describe a case of late onset Cobalamin C disease presenting with peripheral neuropathy. Background Cobalamin C disease is a rare autosomal recessive disorder due to defective intracellular cobalamin metabolism. Clinical symptoms can include neurological complaints, psychiatric disturbances, and thromboembolic complications. Late onset forms of Cobalamin C disease are difficult to diagnose because they are usually lacking indicative hematological signs. There are only a few cases reported on the late onset presentation of Cobalamin C disease, and a dearth in cases describing its detailed electrophysiological findings. Design/Methods: We report on the clinical, laboratory, electrophysiological, and radiological findings of a 17 year old male who presented with bilateral lower extremity weakness, and was eventually diagnosed with methylmalonic aciduria and homocystinuria Cobalamin C type. Results: Initial neurological examination was notable for the motor examination revealing distal greater than proximal muscle weakness in patient9s bilateral lower extremities, and reflex examination revealing generalized hyperreflexia except for diminished reflexes at the left ankle, with bilateral extensor plantar responses. Additionally, patient appeared to have impairment in all sensory modalities in his distal lower extremities. Although initial laboratory values revealed a vitamin B-12 level of 908 pg/ml, diagnosis was still made with urine and plasma biomarkers which revealed an MMA level of 1980.1 mmol/mol cr, homocysteine level of 163.1 nanomol/ml, and a methionine level of 4 micromol/lit. Diagnosis was confirmed with genetic analysis showing a homozygous mutation for c.482G>A. Furthermore, nerve conduction studies revealed a sensory motor axonal neuropathy with a proximal to distal gradient. Lastly, MRI brain was notable for increased FLAIR signal within the bilateral frontal white matter. Conclusions: The clinical presentation of neurological complaints, psychiatric disturbances, and/or thromboembolic complications should prompt the evaluation of late onset Cobalamin C disease even in the presence of initially normal hematological values, given the potentially treatable nature of the disease. Disclosure: Dr. Bashir has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Gualberto has nothing to disclose. Dr. Carrasquillo has nothing to disclose.

Therapeutic efficiency of everolimus and lapatinib in xenograft model of human colorectal carcinoma with KRAS mutation

KRAS mutation is a negative predictive prognostic factor during metastatic colorectal cancer treatment with antiepidermal growth factor receptor antibodies. For affected patients, new therapeutics must be explored. Our objective was to study efficacy of two drugs with different mechanisms of action, everolimus (mTOR inhibitor) and lapatinib (tyrosine kinase inhibitor), in a mouse xenograft model. We chose a model obtained after engraftment of a tumor originating from a human tumor collection. The patient was affected by a metastasis colorectal carcinoma resistant to cetuximab with KRAS mutation. From a previous study in mice, we know that everolimus is a P-glycoprotein (P-gp) substrate and that a lapatinib pretreatment increases significantly (2.6-fold) everolimus AUC by inhibiting its intestinal P-gp efflux. We hence tested the effect of these drugs alone or combined. Mice bearing the xenografts were divided in four groups: control, lapatinib, everolimus, and L/E group (L/E: 2 days of lapatinib 200 mg/kg and then 3 days of everolimus 1 mg/kg). Tumor volumes and treatment toxicities were evaluated. Sixteen days after treatment initiation, the group L/E was the first one in which tumor volume average was significantly lower than the one of control group (193 ± 90 vs. 395 ± 171 mm(3) ; P = 0.0025). After 4 weeks of treatment, inhibition of tumor growth in lapatinib, everolimus, and L/E groups reached, respectively, 49, 53, and 57%. Each drug showed significant antitumor activity. Only moderate hematologic toxicity signs were observed. These results lead to new perspectives for new oral drugs in metastatic KRAS-mutated colorectal cancer resistant to standard chemotherapy.

Blastic plasmacytoid dendritic cell neoplasm: a report of four cases and review of the literature

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular CD4(+) /CD56(+) haematodermic neoplasm (CD4/CD56 HN), is a rare distinct form of lymphoma-like entity known of dermatologists because of its marked predilection for cutaneous involvement, and its aggressive behaviour. Moreover, the association or the evolution to an acute leukaemia entity that still expresses CD4 and CD56 markers is almost systematic. This new described entity of 'CD4(+) /CD56(+) leukaemia' or 'leukaemia of plasmacytoid dendritic cell lineage' has a poor prognostic and may lead to include haematopoietic stem cell transplantation in the treatment strategy as early as possible. We report here four cases presenting with skin lesions and haematological signs. One of the patients underwent allogeneic stem cell transplantation, with a relapse-free survival of 40 months. We discuss the diagnosis features as well as the treatment options. A collaborative work between dermatologists and onco-haematologists is essential to give patients the best chance of complete and long-term response.

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

BackgroundPoikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients.ResultsWe characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain.Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase.According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding.Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect.ConclusionsIn cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients.

Factors Affecting Brain Metabolism Measured with <sup>18</sup>FDG

An observational finding found a large variation in the brain SUV in patients with multiple myeloma undergoing PET/CT. The first hypothesis considered a toxic effect of chemotherapeutic agents, but no correlation was found with hematological signs of toxicity. Low brain FDG uptake has been described with anesthesia, but this was not relevant in this case. An alternative is the presence of a large FDG avid mass, but that was excluded. Since there was a question of chemotherapy toxicity, the metrics used for comparison were Hemoglobin levels (Hgb, g/dl), Erythrocyte count (RBC, M/μL), Lymphocytes absolute counts (Lymph#, K/μL) and % (lymph, %), Granulocytes Neutrophils, K/μL), age and C-reactive protein levels (CRP, g/L). The liver SUV (standardized uptake value) was included to eliminate unexpected global effects on the SUV values, since FDG uptake is a competitive system with a single source (plasma FDG levels). There was in fact no correlation between brain SUV and hepatic SUV, eliminating the so-called super scan effect. Further analysis, however, revealed a strong positive correlation with hemoglobin or RBC levels, but an inverse effect with Neutrophils, C-reactive proteins and age (in years). The results suggest that brain metabolism strongly depends on oxygen supply and may be depressed by general inflammatory diseases and independently with age. If the variation of glucose metabolism correlates with cognitive deficits (CD), considering general measures of good health may be a first step for relief of age related CD.

In vitro and in vivo toxicity studies of Agrobacterium radiobacter k84 biopolymer (ARB)

Sugar cane molasses is a cheaper carbon source alternative than glucose traditionally used in fermentation processes. In the present study a biopolymer soluble from Agrobacterium radiobacter k84 (ARB) was obtained by fermentation using sugar cane molasses as a carbon source in a process with yield of 10.0 g.L-1. The ARB is composed by minerals (40%), carbohydrate (35%) and protein (15%). In vitro test of the cytotoxic effect of ARB at concentrations 2.5 mg/mL, 5.0 mg/mL and 10.0 mg/mL in LLC MK2 (Rhesus Monkey Kidney) cells revealed a 50% cytotoxic concentration (CC50) of 9.32 mg/mL. In a 30-day in vivo oral toxicity study, Swiss mice were administered ARB by gavage at 5 mg/mL, 15 mg/mL, 50 mg/mL and 150 mg/mL (approximately 25 mg/kg/day, 75 mg/kg/day, 250 mg/kg/day and 750 mg/kg/day). The results did not present any hematological or histopathological signs of adverse effects, leading us to define the no observed adverse effect level (NOAEL) as 150 mg/mL (approximately 750 mg/kg/day).

Two-Year Safety and Tolerability of Velaglucerase Alfa in Patients with Type 1 Gaucher Disease, Including Patients Switched From Imiglucerase: Phase III Trial HGT-GCB-039 and Extension,

Abstract 3214 BACKGROUNDType 1 Gaucher disease (GD1) is a chronic, multisystem disease that varies considerably among individuals with regard to organ involvement, presentation, severity, and progression rate. Because hematologic signs and symptoms are common (e.g., anemia, thrombocytopenia, splenomegaly, and hepatomegaly), treatment is often guided by a hematologist. OBJECTIVETo describe the safety and tolerability of velaglucerase alfa after 15 months of treatment in an ongoing, open-label extension study (HGT-GCB-044 [ClinicalTrials.gov identifier, NCT00635427]) in GD1 patients who received either velaglucerase alfa or imiglucerase in a preceding 9-month, double-blind, randomized, Phase III trial (HGT-GCB-039 [NCT00553631]). METHODSIn HGT-GCB-039, treatment-naïve GD1 patients aged ≥2 years were randomized to velaglucerase alfa or imiglucerase as a continuous 60-minute intravenous infusion (60 U/kg body weight every other week [EOW]; 9 months). HGT-GCB-039 completers could enroll in extension study HGT-GCB-044, receiving velaglucerase alfa (60 U/kg EOW; ongoing). Safety and tolerability were assessed after 15 months of participation in HGT-GCB-044 (i.e., after a total of 2 years of enzyme replacement therapy).RESULTS Of 35 patients enrolled in HGT-GCB-039, 34 received study drug and 32 completed the trial (1 velaglucerase alfa patient was lost to follow-up after a serious adverse event [AE] of life-threatening convulsion, which was considered unrelated to treatment; 1 imiglucerase patient withdrew consent because of AEs). This analysis included only the 32 patients completing HGT-GCB-039 who enrolled in the HGT-GCB-044 extension phase: 16 had received velaglucerase alfa (median age, 38 years [range, 8–60 years]; 50% [n=8] male; 56% [n=9] splenectomized) and 16 had received imiglucerase (median age, 27 years [range, 4–59 years]; 44% [n=7] male; 63% [n=10] splenectomized). These patients had received velaglucerase alfa for 24 months (continuous velaglucerase alfa group) or imiglucerase for 9 months + velaglucerase alfa for 15 months (imiglucerase-switch group) at the time of the current analysis. No differences were observed between the safety profiles of the continuous velaglucerase alfa and imiglucerase-switch treatment arms (Table). AEs most commonly reported (≥20% of patients) during the extension phase were nasopharyngitis and arthralgia in the continuous velaglucerase alfa group and headache and upper respiratory tract infection in the imiglucerase-switch group. Most AEs were mild or moderate in severity and, apart from the patient who was lost to follow-up in HGT-GCB-039 after a convulsion, there were no other life-threatening AEs. None of the serious AEs were considered drug related. The proportion of patients with infusion-related AEs remained low in HGT-GCB-044. Anti-imiglucerase antibodies developed in 4 patients receiving imiglucerase in trial HGT-GCB-039, 1 of whom discontinued following multiple infusion-related AEs and did not enter HGT-GCB-044. This patient also had anti-velaglucerase alfa antibodies, which was attributed to assay cross-reactivity, as he had never been exposed to velaglucerase alfa. No patients developed anti-velaglucerase alfa antibodies during the first 9 or subsequent 15 months of drug exposure.Patients, n (%)*0–9 months (HGT-GCB-039)9–24 months (HGT-GCB-044)DescriptionVelaglucerase alfa(n=16)Imiglucerase → velaglucerase alfa(n=16)Velaglucerase alfa(n=16)Imiglucerase → velaglucerase alfa(n=16)Experienced ≥1 AE15 (94)15 (94)15 (94)13 (81)Experienced ≥1 drug-related AE8 (50)5 (31)2 (13)4 (25)Experienced ≥1 infusion-related AE5 (31)3 (19)2 (13)1 (6)Experienced ≥1 severe AE2 (13)1 (6)3 (19)2 (13)Drug-related2 (13)000Experienced ≥1 serious AE2 (13)03 (19)3 (19)Experienced ≥1 life-threatening AE0000*Patients who completed HCT-GCB-039 and entered HCT-GCB-044; the 2 patients who discontinued HCT-GCB-039 are not included. CONCLUSIONSVelaglucerase alfa was generally well tolerated in both the continuous velaglucerase alfa and imiglucerase-switch arms of these controlled clinical trials. Although 4 patients had anti-imiglucerase antibodies in trial HGT-GCB-039, no patient has developed anti-velaglucerase alfa antibodies over the course of the trials to date. Disclosures:Mehta:Shire HGT: Consultancy. Giraldo:Shire HGT: Consultancy. Kisinovsky:Shire Argentina: Consultancy. Kishnani:Shire HGT: Honoraria; Genzyme: Honoraria; Pfizer: Honoraria. Barton:Shire HGT: Employment. Wang:Shire HGT: Employment. Crombez:Shire HGT: Employment. Bhirangi:Shire HGT: Employment. Zimran:Shire HGT: Consultancy; Protalix: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding; Actelion: Honoraria; Pfizer: Honoraria.

Objetivos terapéuticos en la enfermedad de Gaucher

Gaucher's disease (GD) occurs because of deficiency of the enzyme beta-glucocerebrosidase that results in accumulation of this glycolipid compound in the cells of the macrophage-monocyte system. There are 3 types: type 1 is non-neuronopathic with primarily visceral signs and symptoms which range tremendously in severity; infantile-onset type 2 and later-onset type 3 involve the central nervous system. More than 300 mutations have been described in the gene, partially explaining phenotypic heterogeneity. Commercialization in 1991 of the first enzyme replacement therapy, alglucerase, resulted in a revolution in the management of patients with symptomatic GD (i.e., by improving the hematological and visceral signs and symptoms). Within the first 5 years of alglucerase, its safety and efficacy in improving hemoglobin levels and platelet counts, and in reducing splenic and hepatic enlargement were confirmed albeit recognizing its inability to impact neurological symptoms and signs because of its large molecular size. Recombinant imiglucerase soon replaced alglucerase as the standard of care for GD. The therapeutic targets recently defined as treatment goals were: normalization of cell counts; reduction of liver and spleen volume; elimination of the infiltration in the bone marrow to prevent the complications, and improvement in surrogate biomarkers.

The effect of HBB:c.+96TC (3UTR 1570 TC) on the mild b-thalassemia intermedia phenotype

Hemoglobin beta (HBB): c.*+96T>C substitution is very rare among β-globin gene mutations and its clinical significance remains to be clarified. The present study aimed to investigate the role of HBB: c.*+96T>C in the β-thalassemia intermedia phenotype in a Turkish family. The proband and parents were screened for β-globin gene mutations via direct sequencing. Hematological and physical examination results were recorded, and correlated according to genotype. The proband was compound heterozygous for Cod 8 (-AA) and HBB: c.*+96T>C, whereas his mother and father were heterozygous for Cod 8 (-AA) and HBB: c.*+96T>C, respectively. The father had almost normal hematological findings, whereas the mother had the typical β-thalassemia trait phenotype. The proband was diagnosed as mild β-thalassemia intermedia based on hepatosplenomegaly and hematological findings. To the best of our knowledge this is the first report of HBB: c.*+96T>C mutation in a Turkish family. HBB: c.* 96T>C substitution is a very rare, but clinically relevant β-globin gene mutation. Additionally, we think that if 1 spouse is a carrier for β-globin gene mutation the other should be screened for silent mutations, such as HBB: c.*+96T>C mutation of the β-globin gene, even if she/he does not have any clinical or hematological signs of the β-thalassemia trait phenotype.

Hematologic and immunologic signs of the lupus disease: The experience of the Dakar's hospital

The systemic erythematosus lupus (SEL) or lupic disease is a systemic auto-immune pathology, characterized primarily by the presence of antibodies directed against native antibodies anti-DNA. The circumstances of discovery are variable and polymorphic. The hematologic signs and the immunological disorders constitute criteria of diagnosis of lupic disease. It is a multicentric retrospective study from January 1, 1997 to September 30, 2006. Patients were followed up in Internal medicine of Dakar. We appreciate the hematologic and immunological aspects appreciate their prognosis prevalence and their implications with the course the lupic disease. 142 lupic patients were included with 125 women and 17 men; the sex ratio is 0.13. The average age was 34 years with extremes of 6 and 72 years. Our patients had hematologic manifestations average in 32,4 % of the cases and immunological in 76,8 % of the cases. The immunological tests showed the presence, of antinuclear antibodies in 97,9 % of the cases, of native antibody anti-DNA in 45,7 % of the cases, the anti-ECT in 86,95 % (with the anti-RNP in 78,3 % of the cases, anti-Sm in 56,5 % and of anti-SSA in 87 % of the cases). Antibodies anti-DNA and anti-ECT were associated with the hematologic demonstrations respectively in 92,0 % and 95 % of the cases (p = 0,08). Total survival in 96 % of the cases is estimated to 7 years. The circumstances of discovery of the lupic disease are variable. The hematologic signs constitute criteria diagnosis of lupic disease. The accessibility of the hematologic and immunological assessment is necessary for an early diagnosis and an early treatment.

Technique of extracting a compression intramedullary nail that preserves knee arthrodesis

Intramedullary compression nails have recently been developed for knee arthrodesis. These implants have given fusion in 90–100% of cases regardless of the initial diagnosis or experience of the user (Domingo et al. 2004, McQueen et al. 2006, De et al. 2008). However, many clinicians have been reluctant to use this technique due to the perceived difficulty in or impossibility of removing these nails without disrupting the fusion, to allow the management of associated complications such as infection. We present the case of a patient who required removal of a compression intramedullary fusion nail for recurrent infection, in order to describe an easily performed extraction technique that does not disrupt the arthrodesis and that allows definitive management of infection. A 48-year-old man was referred with a painful failed knee arthrodesis that had originally been attempted for failed primary knee arthroplasty secondary to infection. There were no clinical or hematological signs of residual infection, so we proceeded to attempt fusion with an intramedullary compression nail (Wichita Fusion Nail; Stryker). He developed recurrent infection, which was managed with appropriate antibiotics until solid fusion was achieved. We then proceeded to remove the nail 8 months after the fusion procedure and to manage the infection more definitively (Figure 1). Figure 1. A. 8 months after fusion. B. 1 month after nail removal.

An outbreak of haemolytic anaemia associated with infection of Theileria orientalis in naïve cattle

CASE HISTORY: An outbreak of haemolytic anaemia occurred when 87 cattle were introduced from a presumed non-infected herd from south Otago to a herd in Northland (n=580 cows), New Zealand, where theileriosis is endemic. CLINICAL FINDINGS: Clinical signs associated with Theileria spp. infection included lethargy, anorexia, inappetance, pale mucous membranes, and varying severity of anaemia. In the naïve imported cattle, 11/29 (38%) of those tested showed haematological signs of anaemia (haematocrit (HCT) <0.25 L/L). A negative association was present between the HCT and the number of Theileria spp. organisms counted using light microscopy (correlation coefficient=−0.4; p<0.05). Haemoparasites consistent with Theileria spp. were observed on examination of a blood smear. Theileria orientalis group (Theileria buffeli/orientalis) species was confirmed using PCR and DNA sequencing, and other causes for anaemia were excluded in the most clinically severely affected cow. The 18S sequence data and phylogenetic analysis of the CoxIII sequences showed samples had the greatest similarity to T. orientalis Chitose from Japan. DIAGNOSIS: Haemolytic anaemia associated with infection of T. orientalis. CLINICAL RELEVANCE: Previous reports have suggested that T. orientalis group species may be non-pathogenic in healthy cattle, and an incidental finding in blood samples. However, this investigation provided evidence that in New Zealand, this pathogen is capable of causing clinical disease in cattle not necessarily debilitated by another disease. The potential for disease should be considered when naïve cattle are brought in from non-endemic to endemic regions, for instance cattle from the South Island moved to regions where the vector for T. orientalis group species, Haemaphysalis longicornis, is active, and T. orientalis is present.

Effect of atorvastatin in a case of feline multicentric lymphoma — Case report

A case of feline multicentric lymphoma is reported in an 8-year-old male cat weighing 4.7 kg. At the time of the clinical consultation the animal presented weight loss, anorexia and generalised lymphadenomegaly. After careful clinical observation and a detailed laboratory workup, the diagnosis of small cleaved cell lymphoma was established. It was classified as a stage III b multicentric lymphoma. Chemotherapy was initiated according to a classical COP protocol to which atorvastatin was added. After 34 months, the cat continues to enjoy an excellent quality of life with no clinical or haematological signs of lymphoma. This is the first report in clinical veterinary medicine about a new effective adjuvant therapy in feline multicentric lymphoma. Further studies are needed to confirm that the addition of atorvastatin can provide a regular, safe and improved treatment in feline lymphoma cases.

Clinical, Biological, and Skin Histopathologic Effects of Ionic Macrocyclic and Nonionic Linear Gadolinium Chelates in a Rat Model of Nephrogenic Systemic Fibrosis

the purpose of this study was to compare the clinical, pathologic, and biochemical effects of repeated administrations of ionic macrocyclic or nonionic linear gadolinium chelates (GC) in rats with impaired renal function. rats submitted to subtotal nephrectomy were allocated to single injections of 2.5 mmol/kg of gadodiamide (nonionic linear chelate), nonformulated gadodiamide (ie, without the free ligand caldiamide), gadoterate (ionic macrocyclic chelate), or saline for 5 consecutive days. Blinded semi-quantitative histopathologic and immunohistochemical examinations of the skin were performed, as well as clinical, hematological, and biochemical follow-up. Rats were killed at day 11. Long-term (up to day 32) follow-up of rats was also performed in an auxiliary study. epidermal lesions (ulcerations and scabs) were found in 4 of the 10 rats treated with nonformulated gadodiamide. Two rats survived the study period. Inflammatory signs were observed in this group. No clinical, hematological, or biochemical signs were observed in the saline and gadoterate- or gadodiamide-treated groups. Plasma fibroblast growth factor-23 levels were significantly higher in the gadodiamide group than in the gadoterate group (day 11). Decreased plasma transferrin-bound iron levels were measured in the nonformulated gadodiamide group. Histologic lesions were in the range: nonformulated gadodiamide (superficial epidermal lesions, inflammation, necrosis, and increased cellularity in papillary dermis) > gadodiamide (small superficial epidermal lesions and signs of degradation of collagen fibers in the dermis) > gadoterate (very few pathologic lesions, similar to control rats). repeated administration of the nonionic linear GC gadodiamide to renally impaired rats is associated with more severe histologic lesions and higher FGF-23 plasma levels than the macrocyclic GC gadoterate.