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Background: Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. Results: We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval.Conclusions: The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study. [ABSTRACT FROM AUTHOR]

Longitudinal studies on cognitive impairment in patients with past history of neuropsychiatric lupus (NPSLE) are scant. In this study, NPSLE patients and matched disease and healthy controls were examined with a full battery of neuropsychological tests that covered eight cognitive domains at two time-points 12 months apart. Confounders, including depressive and anxiety symptoms, were measured by the Hospital Anxiety and Depression Scale. Eighteen NPSLE, 18 patients with systemic lupus erythematosus (SLE) who had no previous cerebral involvement (non-NPSLE) and 16 healthy subjects were recruited. NPSLE patients consistently reported more cognitive and anxiety symptoms than non-NPSLE patients over both time-points. NPSLE patients had significantly worse memory, simple and complex attention compared to non-NPSLE patients, among which memory remained significantly impaired after adjustment for confounders. NPSLE patients demonstrated a trend of higher raw scores of some neurocognitive tests upon re-evaluation over 12 months, but NPSLE patients did not demonstrate any practice effect. In conclusion, NPSLE patients had significantly worse and persistently impaired memory and learning deficits compared to non-NPSLE patients over the 12-month re-assessment period. [ABSTRACT FROM AUTHOR]

Objectives Cognitive function and mood disturbance are common in patients with systemic lupus erythematosus (SLE). This study aims to examine whether SLE patients have more features of adult attention deficit hyperactivity disorder (ADHD) and their relation to anxiety and depressive symptoms. Methods Symptoms and clinically significant items of the inattention and hyperactivity/impulsivity domains of ADHD were examined in Part A and Part B by the screening instrument of the ADHD Self-Reported Scale (ASRS), respectively. Anxiety and depressive symptoms were measured by HADS-A and HADS-D, respectively. Results There were no differences in symptom scores of inattention and hyperactivity/impulsivity between inactive SLE patients (n = 117) and age- and sex-matched controls (n = 64). However, SLE patients had more clinically significant items in the inattention domain compared with controls (p = 0.006), particularly among those who had previous cerebral involvement (p = 0.004). Patients who had psychiatric diseases had more clinically significant items in the hyperactivity/impulsivity domain (p = 0.006). Possible ADHD was found in 7.7% of SLE and 6.3% of healthy individuals (p = 1.00) by the screening tool. Patients with higher inattention symptom scores were more likely to be unemployed but not for duration of education and smoking habit. Anxiety and depressive symptoms correlated with ADHD symptoms. HADS-A was an independent predictive factor for clinically significant symptoms of inattention (p < 0.001) and hyperactivity/impulsivity (p = 0.04) by logistic regression. Conclusion Inactive SLE patients, particularly those who had previous cerebral lupus, had more clinically significant symptoms of inattention but not hyperactivity/impulsivity reflecting underlying cognitive impairment. Anxiety and depressive symptoms were common confounders for ADHD-like symptoms. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) has been considered as stem cell disorder. The objective of this study was to examine the phenotype, growth and immunomodulatory effect of mesenchymal stem cells (MSCs) from SLE patients compared with those from age- and sex-matched healthy donors. MSCs were expanded from bone marrow aspirate and were examined for morphological appearance, quantified in different passages to determine growth rate and evaluated for ability of adipogenesis and osteogenesis. Telomerase activity was measured by telomerase repeat amplification protocol. The immunomodulatory effect of MSCs was evaluated by mixed lymphocyte reaction. MSCs from SLE patients were found to be bigger and flattened in appearance after passage 3 and demonstrated slower growth rate compared with fibroblast-like MSCs from normal controls. These cells were not able to reach confluence after passage 4. Telomerase activity was upregulated in five SLE patients mostly with active disease compared with two with negative expression with lesser activity. MSCs from SLE patients were, otherwise, comparable to normal controls in terms of their surface marker (CD73, CD90 and CD105) expression and extent of suppression on proliferation of allogeneic T lymphocytes. In conclusion, MSCs from SLE demonstrated early signs of senescence which may be a corollary of active lupus or a contributory factor to disease pathogenesis. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythematosus (SLE) are susceptible to the development of lymphoproliferative disorders and postulated causes include intrinsic defects in immune surveillance and iatrogenic administration of immunosuppressants. Since the introduction of mycophenolate mofetil (MMF) to the immunosuppressive regimen for the management of post-organ transplantation, there have been reports of primary lymphoma of the central nervous system (PCNSL). MMF has been widely used to treat active SLE patients with Class IV lupus nephritis. In addition to two previously reported cases of PCNSL among SLE patients on long-term MMF, we report a third patient who has been on treatment with MMF for 8 years. The histology showed features compatible with diffuse large B-cell lymphoma with strong immunohistochemical staining for CD20 and positive signal for Epstein-Barr virus (EBV)-encoded RNA by in-situ hybridization that is similar to other case reports, suggesting EBV driven B-cell lymphoproliferative disease. The patient responded to withdrawal of MMF, intravenous methotrexate, rituximab and whole brain radiotherapy. With the increasing use of MMF in active renal as well as non-renal exacerbations of SLE, PCNSL should be included in the differential diagnosis in patients who present with gradual onset of focal neurological deficit. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan, a dual endothelin-1 receptor antagonist, on symptomatology, haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD), NYHA functional class, Borg Dyspnoea Index (BDI) and SF-36 were measured at 0, 3, 6, 9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero, six and 12 months. Clinical parameters were analysed, pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m, +26.2 m, +54 m and +62.7 m at three (P = 0.001), six (P = 0.001), nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class, BDI, transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health, vitality, social function and general health. Significantly deranged liver function was found in one patient. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is one of the most heterogeneous autoimmune disorders known. There is production of a variety of autoantibodies and patients present with a wide range of symptoms due to multiple organ involvement by the disease process. The underlying cause is not fully understood but it may involve genetic and environmental factors. It is interesting to note that while SLE is found worldwide, it is more commonly found in some countries, and within a country certain ethnic groups appear to be more susceptible to develop this condition than others. Additionally, the presentation and course of SLE appear highly variable between patients of different ethnic origins. For example, African-Americans and Orientals are believed to have a more severe disease than Caucasian whites. But are these ethnic and geographical differences real? If yes, they may provide investigators insight into the underlying pathoaetiology of this condition and pave the way to future research directions in lupus. [ABSTRACT FROM AUTHOR]

Deficiency of mannose binding lectin (MBL), a C-type lectin with structural similarities to C1q, has been shown to predispose to the development of systemic lupus erythematosus (SLE). Some patients have low serum MBL levels which cannot be explained by either structural gene mutations or promoter polymorphisms. The objective of this study was to detect the presence of autoantibodies against MBL and to evaluate their relationship to serum MBL levels. Anti-MBL antibodies of IgM and IgG classes from consecutive SLE patients (n ¼ 135) and healthy subjects (n = 50) were measured by an in-house ELISA. Using the 90th percentile of controls as a cutoff, more SLE patients [23.7% (32/135)] were found to have IgG anti-MBL antibodies than normal controls [10.0% (5/50)] (P = 0.04). The same trend was observed when ethnicity was taken into account by analysing Caucasians alone (n = 90). IgM anti-MBL antibodies were only found in two SLE patients (2/22, 9.1%) who had no concomitant IgG anti-MBL antibodies. Serum levels of IgG anti-MBL antibodies were found to correlate with serum MBL levels (r = 0.55, P = 0.049). However, the levels of anti-MBL antibodies did not correlate with overall disease activity. Thus the production of anti-MBL antibodies is likely to be a specific antigen-driven process. Its role in lupus pathogenesis remains to be elucidated. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance.Material and Methods: 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters.Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function.Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively. [ABSTRACT FROM AUTHOR]

What is known and objective Sunitinib can improve progression-free survival and overall survival in patients with advanced pancreatic neuroendocrine tumor ( PNET). From clinical trial, most commonly reported adverse events of sunitinib were neutropenia (12%), diarrhea (10%), asthenia (7%), erythrodysesthesia (7%), hypertension (7%) and thrombocytopenia (6%). Case summary We report a patient with PNET with liver metastases who developed hyperammonemia with a low dosage of sunitinib probably contributed by the presence of liver metastases. What is new and conclusions We would like to draw attention to the potential risk of sunitinib induced hyperammonemic encephalopathy even with a low dosage of sunitinib. The absence of sunitinib-induced hyperammonemia during its initial course does not rule out this possibility if there is increased in liver metastases. We suggest checking the ammonia level if patient on sunitinib presented with altered sensorium even if the liver function is normal. [ABSTRACT FROM AUTHOR]