Evaluation of P16 expression in canine appendicular osteosarcoma.

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.

Structural Brain Network Reorganization in Patients with Neuropsychiatric Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Patients with neuropsychiatric systemic lupus erythematosus have worse outcomes compared with those with systemic lupus erythematosus. A better understanding of the mechanisms of neuropsychiatric systemic lupus erythematosus could potentially improve diagnosis and management. The goal of this study was to investigate the differences in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus compared with patients with systemic lupus erythematosus by using brain connectivity analysis. MATERIALS AND METHODS: We recruited 20 subjects for each patient cohort and age-matched healthy controls. The topology and efficiency of the network and the characteristics of various brain hubs were investigated by using brain connectivity analysis of diffusion MR imaging data. RESULTS: There were more extensive reorganizations in the structural brain network of patients with neuropsychiatric systemic lupus erythematosus than in patients with systemic lupus erythematosus. For example, the network of the former had significantly decreased clustering coefficient and local efficiency. They also had significantly lower nodal efficiency in the superior temporal gyrus (P = .046) and middle temporal gyrus (P = .041). CONCLUSIONS: Our results hint at a plausible relationship between the neuropsychiatric symptoms and reorganization of the structural brain network of patients with systemic lupus erythematosus. Brain connectivity analysis may be a potential tool to subtype these patients.

Systemic lupus erythematosus patients with past neuropsychiatric involvement are associated with worse cognitive impairment: a longitudinal study.

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.

Symptoms of attention deficit hyperactivity disorder in patients with systemic lupus erythematosus.

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.

Sunitinib-induced hyperammonaemia in a patient with pancreatic neuroendocrine tumour.

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.

Prognostic role of coronary calcification in patients with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVES: To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE). METHODS: A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events. RESULTS: Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events. CONCLUSIONS: Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Evaluation of performance of measurement of faecal α(1)-antitrypsin clearance and technetium-99m human serum albumin scintigraphy in protein-losing enteropathy.

BACKGROUND AND AIM: Our study aimed to compare the performance of faecal α(1)-antitrypsin clearance (AATC) and radiolabelled human serum albumin (HSA) scintigraphy in protein-losing enteropathy (PLE). METHODS: Patients studied by both AATC and technetium-99m ((99m)Tc)-labelled HSA scintigraphy were recruited and categorized into PLE and non-PLE groups based on clinical and laboratory findings. The performance of AATC and (99m)Tc-labelled HSA scintigraphy was evaluated using clinical diagnosis of PLE as a gold standard. RESULTS: 29 patients were recruited and 13 patients were considered to have definite PLE (PLE group). In the PLE group, all patients had a positive HSA scinigraphy and 10 (77%) had demonstrable positive tracing in the early phase. Conversely, only 6 of them (46%) had elevated AATC level (>13 m/day). Results of (99m)Tc-labelled HSA scan (but not AATC) showed significant agreement with the clinical diagnosis (κ 0.35, p = 0.013). (99m)Tc-labelled HSA scintigraphy carried higher sensitivity (100 vs. 46%) and negative predictive value (100 vs. 63%) compared to AATC in diagnosing PLE. The correlation between the results of these two investigations was only modest (κ 0.27, p = 0.04). The area under the receiver operating characteristic curve of AATC level showed no optimal diagnostic cut-off for PLE. CONCLUSION: (99m)Tc-labelled HSA scintigraphy was superior to AATC in diagnosing PLE.

Two missense variants in UHRF1BP1 are independently associated with systemic lupus erythematosus in Hong Kong Chinese.

UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10⁻8, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10⁻9, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.

Low circulating level of CD133+KDR+cells in patients with systemic sclerosis.

BACKGROUND: Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial. OBJECTIVES: To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients. METHODS: Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay. RESULTS: SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/µl, p<0.001) as well as FMD% (4.8% vs. 7.8%, p<0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/µl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter. CONCLUSIONS: Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

Do Asian patients have worse lupus?

The predisposition to and clinical phenotype of systemic lupus erythematosus, an autoimmune disease that is associated with significant morbidity and mortality, are affected by genetic and environmental factors. This article aims to examine whether Asians have worse lupus by reviewing the literature on genetic predisposition and clinical outcomes, including major organ involvement, damage score and mortality in Asian populations compared with other ethnicities. A number of lupus nephritis susceptibility genes have been identified in Asians and White patients, with further variations among different Asian populations. Meta-analysis studies on various Fcγ receptor subtypes revealed that FcγRIIIA-F158 allele, which is associated with low binding affinity to IgG1 and IgG3, predisposed to lupus nephritis in Asian patients. Asian patients were reported to have higher rates of lupus nephritis-associated autoantibodies, lupus nephritis and more active glomerulonephritis compared with White patients. Renal outcome and the level of immunosuppressant use in Asians were comparable to Afro-American Blacks in some studies. Asians were also found to have higher overall damage scores compared with Whites. The difference in mortality between Asian patients and other ethnicities in different geographical regions was found to vary depending on socioeconomic factors such as access to health care. Poverty, education level, cultural and behavioural factors are confounders to ethnicity in determining clinical outcome of systemic lupus erythematosus.

Disseminated penicilliosis, recurrent bacteremic nontyphoidal salmonellosis, and burkholderiosis associated with acquired immunodeficiency due to autoantibody against gamma interferon.

Acquired immunodeficiency due to autoantibody against gamma interferon has recently been associated with opportunistic nontuberculous mycobacteriosis, especially among Southeast Asians. We report another 8 cases, all except one apparently immunocompetent hosts who suffered from concomitant or sequential infections by other intracellular pathogens causing penicilliosis, extraintestinal nontyphoidal salmonellosis, and burkholderiosis. The only case with an underlying immunodeficiency syndrome had systemic lupus erythematosus that was quiescent throughout the multiple infective episodes. Eight out of 10 (80.0%) patients with serological evidence of penicilliosis, 5 out of 7 (71.4%) with culture-positive extraintestinal nontyphoidal salmonellosis, 5 out of 28 (17.9%) with serological evidence of melioidosis, and 7 out of 13 (53.8%) with culture-positive nontuberculous mycobacteriosis possessed autoantibody against gamma interferon, whereas only 1 out of 100 patients with systemic lupus erythematosus did. Our study represents the first and largest case series linking this emerging immunodeficiency syndrome with these atypical infections in apparently immunocompetent hosts. Thus, we advocate that any patient with unexplained recurrent or polymicrobial infections due to these intracellular pathogens should be screened for acquired immunodeficiency due to autoantibody against gamma interferon.

Defective phenotype of mesenchymal stem cells in patients with systemic lupus erythematosus.

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.

Diffuse large B-cell lymphoma of the central nervous system in mycophenolate mofetil-treated patients with systemic lupus erythematosus.

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.

Coronary atherosclerosis using computed tomography coronary angiography in patients with systemic sclerosis.

BACKGROUND: Impaired coronary artery reserve has previously been demonstrated in patients with systemic sclerosis (SSc). Both micro- and macrovascular factors are probably contributory to the underlying pathogenesis. OBJECTIVES: To examine the frequency of coronary atherosclerosis in a series of SSc patients by computed tomography coronary angiography (CTCA), a less invasive method than conventional coronary angiography, the current gold standard in the detection of coronary atherosclerosis, and to explore its clinical associations. METHODS: Nineteen consecutive SSc patients [six with diffuse (dSSc) and 13 with limited disease (lSSc)] with disease duration of >or= 3 years were recruited. Coronary calcium score and contrast angiography were examined by CT scan. Conventional cardiovascular factors and inflammatory markers were measured and correlated with CT findings. RESULTS: The mean+/-SD age of these patients was 52.5+/-12.5 years with median disease duration of 12.5 years. Six (31.6%) patients were found to have coronary artery calcification (calcium score 13-2008). Coronary calcium was detected in one dSSc patient but contrast angiography was not performed because of interference from an in situ implantable cardiac device. Some parts of the coronary arteries were not assessable in two patients who had ectopic cardiac rhythm. Five lSSc patients had calcified plaques causing variable coronary luminal stenosis. All patients were asymptomatic. Patients with abnormal CTCA findings were more likely to be older (p < 0.001) and were less likely to have serum anti-Scl70 antibodies (p = 0.003) than those without, after Bonferroni correction. CONCLUSIONS: Coronary atherosclerosis is not uncommon in asymptomatic SSc patients. CTCA is a convenient and non-invasive method for studying coronary atherosclerosis.

Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA). BACKGROUND: Patients with RA are prone to premature atherosclerosis; nonetheless the prevalence and extent of atherosclerosis in different vascular beds and their relationship to each other remain unknown. METHODS: We studied the distribution and extent of arterial calcification in 85 RA patients and 85 age-and sex-matched controls. Arterial calcification as determined by calcium score (CS) were measured using multi-detector computed tomography in thoracic aorta, coronary and carotid arteries. RESULTS: Compared with controls, RA patients had a significantly higher average CS and prevalence of CS > 0 in aorta, coronary and carotid arteries and overall arteries (all P < 0.05). After adjusting for age and sex, RA patients had a significantly higher relative risk of developing calcification in the aorta [Odds Ratio (OR) = 19.5, 95% Confidence Interval (CI): 8.0-47.6], followed by the carotid arteries (OR = 5.7, 95% CI:1.7-18.7) and coronary arteries (OR = 5.0, 95% CI:2.2-11.1) compared with controls (all P < 0.01). Amongst RA patients aged >60, 90% had diffuse arterial calcification, especially over the thoracic aorta, compared with 55% of controls who had arterial calcification clustered in the coronary arteries (P < 0.05). RA patients with total CS > 0 were older with a higher urea level and C-reactive protein than those without arterial calcification, no factor was found to be independently predictive for arterial calcification (all P > 0.05). CONCLUSIONS: Our results demonstrated that RA patients had earlier onset, more diffuse arterial calcification over multiple vascular beds and more preferential involvement of thoracic aorta, rather than coronary artery when compared with control.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 x 10(-9); TNFSF4, rs844648, OR=1.22, P=2.47 x 10(-3); TNFSF4, rs2205960, OR=1.30, P=2.41 x 10(-4)). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 x 10(-8), respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.

In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.

The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study.

Cevimeline hydrochloride, a specific agonist of the M3 muscarinic receptor, is beneficial in the treatment of symptoms of xerostomia and xerophthalmia associated with Sjögren's syndrome (SS). Cevimeline has not been evaluated in southern Chinese patients. Furthermore, the effects of cevimeline on health-related quality of life and oral health status are not known. In this randomised, double-blind, placebo-controlled crossover study, patients received cevimeline 30 mg or matched placebo three times per day over 10 weeks followed by a 4-week washout period before treatment crossover. Participants self-completed the following questionnaires: Xerostomia Inventory (XI), the General Oral Health Assessment Index (GOHAI), the Ocular Surface Disease Index (OSDI) and the Medical Outcomes Short Form (SF-36). Clinical assessments included sialometry, examination of the oral cavity for the degree of xerostomia and dental complications of xerostomia. Fifty patients (22 primary SS and 28 secondary SS) were enrolled in the trial. Forty-four patients completed the study. There was a significant improvement in the XI and GOHAI scores as well as the objective rating of xerostomic signs of the oral cavity after treatment with cevimeline. However, there was no improvement in salivary flow rates and dry eye symptoms. SS patients had lower SF-36 scores, but these did not improve after treatment with cevimeline.

Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension.

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.