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Biomedical subjects

M Y Mok

Publications and source records attributed to M Y Mok.

At least 19 recordsLinked to original sources

Non-tuberculous mycobacterial infection in patients with systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are susceptible to opportunistic infections. To examine the clinical manifestations of non-tuberculous mycobacterial (NTM) infections with those of Mycobacterium tuberculosis (MTB) infections in SLE patients. METHODS: Medical records of a cohort of 725 SLE patients were reviewed for previous NTM infections. Demographic characteristics, predisposing factors and clinical outcomes were compared with patients who had previous MTB infections (n = 39). RESULTS: Eleven (nine female and two male) cases were identified (prevalence 1.5%). The mean +/- S.D. age at the time of infection was 42.8 +/- 13.9 yrs, 9.3 +/- 5.8 yrs after the onset of SLE. The mean +/- S.D. time taken from onset of symptoms to the diagnosis of NTM infection was 5.7 +/- 7.2 months. Sites of involvement included skin and soft tissue (n = 8), chest (n = 2) and disseminated infection (n = 1). NTM infections were more likely to involve extrapulmonary sites (P = 0.006), presented in patients with longer lupus disease duration (P < 0.001), occurred in older patients (P < 0.001) and in those who had a higher cumulative dose of prednisolone (P = 0.01) than MTB infections. Using a stepwise logistic regression, disease duration was found to be the only independent predictive factor (P = 0.005) for NTM infections. Ten (25.6%) patients with MTB infections but none of the patients with NTM infections presented concomitantly at the onset of SLE (P = 0.09). There were no differences in the recurrence rate (P = 0.64) and frequency of disseminated infections (P = 0.40) between NTM and MTB infections. CONCLUSIONS: NTM infections tended to develop in SLE patients later in their disease course than MTB infections. A high index of suspicion is required for its diagnosis.

Adult↗

Ethnic and geographical differences in systemic lupus erythematosus: an overview.

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.

Anemia, Hemolytic, Autoimmune↗

Necrotizing fasciitis in rheumatic diseases.

Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1-27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality.

Adult↗

EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis receiving prolonged methotrexate treatment.

A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.

Aged↗

Antibodies to mannose binding lectin in patients with systemic lupus erythematosus.

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 = 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.

Adult↗

Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. METHODS: Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. RESULTS: At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. CONCLUSION: The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

Adolescent↗

Interstitial lung disease in systemic sclerosis.

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.

Exercise Tolerance↗

A putative pheromone receptor gene expressed in human olfactory mucosa.

Pheromones elicit specific behavioural responses and physiological alterations in recipients of the same species. In mammals, these chemical signals are recognized within the nasal cavity by sensory neurons that express pheromone receptors. In rodents, these receptors are thought to be represented by two large multigene families, comprising the V1r and V2r genes, which encode seven-transmembrane proteins. Although pheromonal effects have been demonstrated in humans, V1R or V2R counterparts of the rodent genes have yet to be characterized.

Alleles↗

Risk factors for avascular necrosis of bone in patients with systemic lupus erythematosus: is there a role for antiphospholipid antibodies?

BACKGROUND: Avascular necrosis of bone (AVN) is a well known complication in patients with systemic lupus erythematosus (SLE). OBJECTIVE: To investigate the role of antiphospholipid antibody status (IgM and IgG anticardiolipin antibodies and lupus anticoagulant) with adjustment for corticosteroid use as risk factors for the development of AVN. METHODS: A cohort of 265 patients receiving long term follow up in our SLE clinic from 1978 to 1998 was analysed. Patients with AVN complications were detected and then matched for age, sex, ethnicity, duration of disease, and organ disease with two other patients with SLE. A further 31 patients were chosen at random for the analysis. RESULTS: Eleven patients had AVN, giving a point prevalence of 4%. There were no significant differences demonstrable in the presence of individual antiphospholipid antibodies (aPL) or their combination between the group with AVN or the two control groups. CONCLUSION: Incorporating an adjustment for corticosteroid use we were unable to show a link between the presence of aPL and the development of AVN in patients with SLE.

Adolescent↗

Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation.

OBJECTIVES: To document intestinal pseudo-obstruction (IpsO) as a recognised clinical manifestation of systemic lupus erythematosus (SLE) and a possible new clinical entity with its apparent association with ureterohydronephrosis. METHODOLOGY: We report six lupus patients who presented with IpsO and review 12 other cases from an English literature search. IpsO is defined as the presence of clinical features suggestive of intestinal obstruction but without organic obstruction, namely absence of bowel sounds, presence of multiple fluid levels on plain abdominal X-rays and exclusion of organic obstruction by imaging or surgical procedure. Other clinical characteristics related to the underlying lupus, serological and histological findings, treatment modalities and outcomes of these patients were reviewed. RESULTS: All 18 patients fulfilled the ACR revised classification criteria for SLE. None showed any clinical features of scleroderma or overlap syndrome. The mean age of onset of IpsO was 29.0 (15-47) y. The female to male ratio was 16:2. Nine patients had IpsO as the initial presentation of their underlying lupus. Coexisting lupus involvement of other organ systems included glomerulonephritis (n=7), thrombocytopenia (n=5) and cerebral lupus (n=3). The serology data and autoantibody profile of some of the previously reported patients were incomplete. In our series, anti-Ro antibody was positive in 5/6 while anti-RNP was found in 1/6 patients only. All our patients had active lupus serology at presentation. 17/18 patients required the use of high dose systemic corticosteroid therapy while one patient responded to topical adrenocorticotrophin hormone treatment. Response was good and was observed early after commencement. Azathioprine was used as maintenance therapy in 6/18 patients with good effects. An apparent association with the presence of bilateral ureterohydronephrosis was found in 12/18 patients. These patients presented with dysuria without positive bacterial culture though features of chronic interstitial cystitis were not invariably found in these patients. CONCLUSION: IpsO is an uncommon but important manifestation of SLE. The underlying pathology is not fully understood but it may be related to immune complex deposition. The finding of coexisting ureterohydronephrosis suggests that there may also be a central smooth muscle motility problem of neuropathic or myogenic pathophysiology which may or may not be secondary to vasculitis. Early recognition and treatment of IpsO in SLE is important.

Adult↗

Pulmonary hypertension secondary to systemic lupus erythematosus: prolonged survival following treatment with intermittent low dose iloprost.

Pulmonary hypertension (PHT) associated with systemic lupus erythematosus (SLE) has a dismal prognosis. Vasodilators and immunosuppressive therapy have been tried over the years with discouraging results. Prostacyclin (PGI2) which has potent vasodilatatory and anti-platelet effects has been demonstrated to significantly decrease pulmonary arterial pressure and pulmonary vascular resistance during acute infusion. Satisfactory response has been reported in SLE patients with PHT treated with short-term intravenous continuous PGI2 infusion. We report here a 48-month experience of the use of monthly low dose infusion of a PGI2 analogue, iloprost, in a SLE patient with pulmonary hypertension in New York Heart Association functional Class III. There was an initial haemodynamic response to an acute infusion of iloprost. Repeated infusions were followed by marked improvement in her functional status and her mean pulmonary arterial pressure dropped from 80 mmHg in the first few months and remained static at around 55 mmHg for the subsequent years.

Adult↗

Features of spondyloarthritis around the world.

This article elucidates the prevalence and pathogenic roles of the MHC and microbial infections and clinical features and treatment of SpA across different populations from the arctic and subarctic regions to Central America, Asia, and Africa. Preliminary evidence suggests significant genetic and environmental influences on the onset and presentation of SpA, particularly AS, in these populations, which are different than those reported in white Caucasians; however, community surveys and longitudinal and case control studies are difficult to undertake in many of the developing countries. Thus, most of the currently available data have been devised from short-term and retrospective studies and should be treated with caution. Differences in referral and follow-up practices and the availability of rheumatology expertise and relevant resources may explain some of the differences observed in the populations discussed in this article. Furthermore, widely accepted criteria for the classification of SpA may not be applicable to non-Caucasians and need to be evaluated in these subjects. With gradual improvement in the economic status in many of the developing countries in Asia and Africa, it is hoped that with improvement in medical services, more physicians and specialty clinics in rheumatology, and changing referral patterns, better documentation of the various aspects of different SpA can be achieved. Future research should focus on the evaluation of specific risk or protective factors in population groups to better delineate the relative importance of genetic and environmental effects in the pathogenesis of SpA.

Arthritis, Psoriatic↗

Safety of hormonal replacement therapy in postmenopausal patients with systemic lupus erythematosus.

It remains controversial whether administration of exogenous estrogens is safe in systemic lupus erythematosus (SLE). The current study was undertaken to determine the effect of hormone replacement therapy (HRT) on the rate and magnitude of flares in a cohort of postmenopausal SLE patients. Thirty-four patients were prospectively followed. The frequency and severity of disease exacerbations in 11 patients who received HRT was compared with 23 patients who did not receive HRT. Our results showed that both users and non-users of HRT had a comparable age of disease onset, duration of disease, clinical manifestations, and duration of follow-up. No significant increase in the rate (0.12 relapses/patient-year in HRT group vs 0.16 relapses/patient-year in the non-HRT group, p = 0.90) or magnitude (total SLEDAI score increase during flares/patient-year in the HRT and non-HRT groups were 0.55 and 1.22, respectively, p = 0.57) of flares could be demonstrated in patients who received HRT over a median follow-up period of 35 months. We concluded that HRT appeared to be well tolerated and safe in postmenopausal SLE patients. Its potential beneficial effect may outweigh its deleterious effect on disease activity.

Adult↗

Systemic lupus erythematosus patients with respiratory symptoms: the value of HRCT.

Ten Chinese patients with systemic lupus erythematosus (SLE) and with persistent respiratory symptoms were evaluated with high resolution computed tomography (HRCT), chest radiographs and lung function tests. Fourteen of 15 HRCT scans performed were abnormal. The predominant disease pattern, seen in 60% of patients, was one of chronic interstitial lung disease with honeycombing, architectural distortion, parenchymal bands, pleural irregularity, and a lower zone predominance. Three of 10 patients had histological evidence of either lung fibrosis or interstitial pneumonitis. Airways disease and pleural thickening were seen in 20% and 87% of scans, respectively. Pleural thickening and honeycombing were present in 53% and 20% of chest radiographs, respectively. All concurrent lung function tests were abnormal. Reduced diffusion capacity of carbon monoxide (DLCO/VA) was observed in 60% of lung function tests. There was no correlation between duration of disease and DLCO/VA. However, pathological reduction of DLCO/VA was seen in 71% of patients with honeycombing, and 88% of patients with ground glass opacity. Our study has documented a high incidence of HRCT features of chronic lung destruction and a lower zone predominance in SLE patients with persistent respiratory symptoms.

Adult↗

Safety of disease modifying anti-rheumatic agents in rheumatoid arthritis patients with chronic viral hepatitis.

OBJECTIVE: To examine the safety of the use of disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with chronic viral hepatitis (CVH). METHODS: Records of 600 Chinese patients satisfying the ARA criteria for RA in two rheumatology centers were reviewed. Patients with CVH were studied. Liver enzymes were checked before (baseline) and during DMARD use at 3-month intervals or more frequently if necessary. Drug-episodes (D-Ep), defined as the continuous use of DMARD, singly or in combination, for more than 6 months in a patient, were analysed. Changes in serum liver alanine transaminase (ALT) levels as multiples of the upper range of normal were taken to reflect the severity of hepatotoxicity. Changes of ALT to > or = 1.5 times the upper range of normal if they were measured at baseline or > or = 2 times the upper range of normal if they were measured during and after the use of DMARD were considered as abnormal. Control patients included those with CVH alone (n = 623) or RA without CVH (n = 62) matched for age, sex and D-Ep. RESULTS: 30 RA patients were found to have concomitant CVH. One patient was excluded because of use of NSAID alone (n = 1). Among the 29 patients, 23 were HBsAg +ve and 6 were anti-HCV Ab +ve. A total of 47 D-Ep were analysed. 20/47 (42.6%) of D-Ep in 16/29 (55.2%) RA + CVH patients developed abnormal ALT levels after a mean 1.9-year duration of DMARD use. This was statistically significant when compared with 13/94 (13.8%) of D-Ep which ended with abnormal ALT levels in 13/62 (21%) patients with RA alone (p < 0.0001 for D-Ep which ended up with abnormal ALT, and p < 0.02 for the number of patients who developed abnormal ALT) and 128/623 (20.5%) patients with CVH alone (p < 0.005). 53% (9/17) of hydroxychloroquine (HCQ) D-Ep were associated with an abnormal outcome. Corresponding figures for sulphasalazine (SAZP) and oral or intramuscular gold preparations were 55.6% (5/9) and 0% (0/3) respectively. Two patients on methotrexate, used either singly or in combination, had normal ALT levels throughout the study period. One patient on azathioprine developed reactivation of hepatitis B infection. When D-Ep of the RA + CVH group were further analysed, 16/43 (37.2%) and 4/4 (100%) D-Ep which started with normal and abnormal baseline ALT respectively developed further liver enzyme derangement. CONCLUSION: The use of DMARD in RA + CVH patients is associated with a high incidence of hepatotoxicity. The effect is likely to be synergistic. This includes drugs such as HCQ, which is generally believed to be less hepatotoxic.

Adult↗

Lymphoepithelioma-like carcinoma of the parotid gland in a patient with rheumatoid arthritis.

Lymphoepithelioma-like carcinoma (LELC) is an Epstein-Barr virus (EBV) related malignancy. It is not a common condition and is usually found in the head and neck region. We describe the development of LELC involving the parotid gland in a patient with rheumatoid arthritis (RA) who had been receiving long-term azathioprine. A brief review is also made on the clinical presentation and histological features of LELC and the association of RA with EBV related diseases. The latter may be attributed to an increase in risk of malignancy associated with RA or as a result of the long-term immunosuppressive used.

Antirheumatic Agents↗