Weissellicin L, a novel bacteriocin from sian-sianzih-isolated Weissella hellenica 4-7.

AIM: To identify and characterize novel bacteriocins from Weissella hellenica 4-7. METHODS AND RESULTS: Weissella hellenica 4-7, isolated from the traditional Taiwanese fermented food sian-sianzih (fermented clams), was previously found to produce a bacteriocin active against Listeria monocytogenes and some other Gram-positive bacteria. Bacteriocin activity decreased slightly after autoclaving (121°C for 15 min), but was inactivated by protease K and trypsin. Mass spectrometry analysis revealed the bacteriocin mass to be approximately 3205·6 Da. N-terminal amino acid sequencing yielded a partial sequence, NH2 -KGFLSWASKATSWLVGP, by Edman degradation. The obtained partial sequence showed high homology with leucocin B-TA33a; however, at least two different residues were observed. No identical peptide or protein was found, and this peptide was therefore considered to be a novel bacteriocin produced by W. hellenica 4-7 and termed weissellicin L. CONCLUSIONS: The findings obtained in the current study suggest a novel bacteriocin produced by W. hellenica 4-7. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriocins from Weissella remain rare, and this study is the second report of a bacteriocin produced by W. hellenica.

Off-pump coronary artery bypass grafting is a safe and effective treatment modality for Asian patients requiring coronary revascularisation.

INTRODUCTION: Off-pump coronary artery bypass grafting (OPCABG) is gaining widespread acceptance as the preferred choice for myocardial revascularisation. However, no definite data exist as to whether it is better than conventional CABG. We aimed to study the efficacy of the procedure in our patients, which constituted of a predominantly Asian population. METHODS: Between January 2000 and December 2002, 1062 patients underwent isolated coronary artery bypass in our institution. 184 patients (17.3 percent) underwent OPCABG. Patients were preoperatively prospectively risk stratified under the EuroSCORE risk assessment model under high, medium and low risk classes thereby making them comparable. Post-operative complications, intensive care unit stay, hospital stay, types of grafts done were then analysed in these different risk classes. RESULTS: The incidence of off-pump procedures showed a gradual increase over the last three years in this institution. A reduction in the number of post-operative complications, hospital stay, intensive care unit stay and mortality in the off-pump group was observed. Certain differences were found to be statistically significant. CONCLUSION: Off-pump CABG is a safe and viable alternative to conventional CABG as a treatment modality for surgical coronary revascularisation.

Measuring health-related quality of life in Singapore: normal values for the English and Chinese SF-36 Health Survey.

OBJECTIVE: To determine norms for assessing Health-related Quality of Life (HRQOL) in Singapore using the Short Form 36 Health Survey (SF-36). MATERIALS AND METHODS: Mean SF-36 scores were calculated for 24 population subgroups (categorised by age, gender, ethnicity and questionnaire language) and for subjects with self-reported co-morbid conditions using data from a community-based survey in Singapore. RESULTS: The English and Chinese SF-36 was completed by 4122 and 1381 subjects, respectively, 58% (n = 3188) of whom had self-reported co-morbid conditions. SF-36 scores varied in subgroups differing in age, gender and ethnicity. In general, subjects with self-reported co-morbid conditions had lower SF-36 scores than those without these conditions, the magnitude of which exceeded 20 points in several instances. A method for calculation of SF-36 scores adjusted for age, gender, ethnicity and questionnaire language is described. CONCLUSION: We present norms for English and Chinese SF-36 versions in Singapore and describe potential uses for these data in assessing HRQOL in Singapore.

Medical treatment of osteoporosis--increasing options.

INTRODUCTION: Many drugs are now available for the prevention and treatment of osteoporosis. They have differing levels of evidence of efficacy and each may be used according to clinical indications. METHODS: A Medline search of clinical drug trials using various therapeutic agents used for osteoporosis was carried out. RESULTS: Several randomised controlled trials have been carried out using many agents. The agents with the best data to date with regards to the prevention of spine as well as hip fractures in patients with prevalent fractures belong to alendronate and risedronate. Parathyroid hormone has been shown in one trial to reduce the risk of non-vertebral fractures. For reduction of spine fractures, in addition to the above two bisphosphonates, many agents, in particular raloxifene, have been shown to be clearly beneficial. Weaker data exist for hormone replacement, calcitonin, cyclical etidronate and the vitamin D analogues calcitriol and alfacalcidol. CONCLUSION: There are many therapeutic agents shown to be clearly effective in the treatment of osteoporosis.

Hip fracture incidence rates in Singapore 1991-1998.

In this population-based study, we determined the incidence rates of hip fracture among Singapore residents aged 50 years and above. Information was obtained from a centralized database system which captured admissions with the primary diagnosis of a closed hip fracture (ICD-9 codes 820, 820.0, 820.2 and 820.8, n = 12,927) from all health care establishments in the country from 1991 to 1998 inclusive. After removing duplicates, hospital transfers, readmissions and non-acute care admissions, the total number of hip fractures was 9406. Based on the national population census 1990 (n = 464,100) and yearly population estimates, the age-adjusted hip fracture rates for 1991-1998 (per 100,000) were 152 in men and 402 in women. This was 1.5 and over 5 times higher than corresponding rates in the 1960s. From 1991 to 1998, these hip fracture rates tended to increase by 0.7% annually in men and by 1.2% annually in women. Among the three major racial groups, in men, the Chinese had significantly higher age-adjusted hip fracture rates (per 100,000): 168 (95% confidence interval (CI) 158-178) compared with 128 (95% CI 105-152) for Indians and 71 (95% CI 54-88) for Malays. A similar pattern occurred in women: 410 (95% CI 395-425), for Chinese compared with 361 (95% CI 290-432) for Indians and 264 (95% CI 225-303) for Malays. Since the 1960s, the main increases in hip fracture rates have been seen in the Chinese and Malays, with the rates in Indians appearing to decrease. Hip fracture incidence rates in Singapore have risen rapidly over the past 30-40 years, particularly in women, and are now among the highest in Asia. Significant racial differences in hip fracture rates occur within the same community. Time trends in hip fracture rates differed between races.

A comparative study of the clinical manifestations of systemic lupus erythematosus in Caucasians in Rochester, Minnesota, and Chinese in Singapore, from 1980 to 1992.

OBJECTIVE: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively. METHODS: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors. RESULTS: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively). CONCLUSION: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Central serous retinopathy complicating systemic lupus erythematosus: a case series.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with widespread manifestations including the eye. Central serous retinopathy (CSR) has been associated as a complicating event in SLE, although it is uncommon. We present a case series of four female Chinese SLE patients who developed CSR during the course of their systemic disease. All four presented clinically with typical CSR. Angiographic findings did not show evidence of choroidal ischaemia or delayed choroidal filling. Resolution of the serous retinal detachment occurred in all four patients. Recovery of vision was seen in three patients. The clinical outcome was similar to that occurring in the usual male population. Central serous retinopathy as a manifestation of SLE may be caused by various factors. These include SLE-associated choroidopathy, systemic hypertension, renal disease, retinal pigment epithelial dysfunction and glucocorticoid therapy.

Accuracy of medical record scoring of the SLICC/ACR damage index for systemic lupus erythematosus.

OBJECTIVE: To study the accuracy of medical record scoring of the SLICC/ACR Damage Index (DI) for SLE. METHODS: Medical record DI (MDI) scoring of 60 SLE patients by one physician was compared with prospective direct DI (DDI) scoring a median of 2 y earlier. Agreement between DDI and MDI total and organ system scores was compared using Cohen's kappa, the degree of misclassification by MDI and the significance of differences between DDI and MDI scores. RESULTS: The mean duration of SLE at DDI scoring was 5.2 y. The median/mean (SD) DDI and MDI total scores were 0/0.78 (1.38) and 0/0. 85 (1.44). Damage was present on DDI and MDI scoring in 36.7% (22/60) and 38.3% (23/60) of patients. Qualitative MDI and DDI total scores (damage present/absent) showed good agreement (kappa=0.61, 95% CI=0.40-0.82, 18.3% misclassification). Quantitative MDI and DDI total scores (degree of damage) showed moderate agreement (kappa=0. 47, 95% CI=0.28-0.66, 36.7% misclassification). 9 of 12 MDI organ system scores misclassified <10% of subjects. There was no statistically significant difference between DDI and MDI total or organ system scores. CONCLUSION: MDI total scoring is a good qualitative and moderate quantitative reflection of SLE related damage. MDI organ system scores are more accurate than MDI total scores.

A prospective study of factors affecting quality of life in systemic lupus erythematosus.

OBJECTIVE: To prospectively identify factors influencing quality of life (QOL) over 6 months in patients with systemic lupus erythematosus (SLE). METHODS: Ninety ethnically diverse patients with SLE completed questionnaires administered 6 months apart assessing QOL (using the Medical Outcomes Study Short Form-36) and demographic, socioeconomic, psychosocial, and behavioral factors. Disease activity, damage, and treatment were recorded at both evaluations. Multiple linear regression (adjusting for baseline health status) was used to identify factors influencing mental and physical health. RESULTS: Improved physical health after 6 months was associated with reductions in learned helplessness (p = 0.034), improved mental health (p<0.001), longer disease duration (p = 0.009), and better physical health at baseline (p = 0.027). Improved mental health after 6 months was associated with better family support (p = 0.002), improvements in physical health (p<0.001), disease activity, and prednisolone dose (interaction term p = 0.019), less disease related damage (p<0.001), non-use of cytotoxic drugs (p = 0.02), and older age at diagnosis (p = 0.007). CONCLUSION: Potentially modifiable psychosocial, disease, and therapy related factors influence QOL in patients with SLE.

Validation of the medical outcomes study family and marital functioning measures in SLE patients in Singapore.

OBJECTIVE: To validate the Medical Outcomes Study Family and Marital Functioning Measures (FMM and MFM) in a multi-ethnic, urban Asian population in Singapore. METHODS: English speaking Chinese, Malay or Indian SLE patients (n=120) completed a self-administered questionnaire containing the FFM and MFM at baseline, after 2 weeks and after 6 months. Lupus activity, disease-related damage and quality of life were assessed using the British Isles Lupus Assessment Group (BILAG), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and SF-36 Health Survey respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's alpha, quantifying test-retest differences and known-groups construct validity. RESULTS: Factor analysis of scores obtained at baseline and after 6 months identified 3 factors corresponding to the FFM (1 factor) and the MFM (2 factors). Both scales showed acceptable internal consistency, with Cronbach's alpha of 0.95 for the FFM and 0.70 for the MFM. Mean (s.d.) test-retest differences were -0.31 (3.82) points for the FFM and -0.70 (4.26) points for the MFM. Eleven out of 13 a priori hypotheses relating both the FFM and MFM to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. CONCLUSION: The FFM and MFM are valid and reliable measures of family and marital functioning in a multi-ethnic cohort of Asian SLE patients in Singapore.

The Rheumatology Attitudes Index and its helplessness subscale are valid and reliable measures of learned helplessness in Asian patients with systemic lupus erythematosus.

OBJECTIVE: To assess the internal consistency, reliability, and construct validity of the Rheumatology Attitudes Index (RAI) and its subscales in a cohort of Asian patients with systemic lupus erythematosus (SLE). METHODS: English speaking ethnic Chinese, Malay, or Indian patients with SLE (n = 120) seen at a rheumatology unit completed a questionnaire containing the RAI twice within a 2 week period. Lupus activity was assessed using the British Isles Lupus Activity Group (BILAG) score, disease related damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, and quality of life using the Medical Outcome Survey Short Form 36 Health Survey (SF-36). Factor analysis and Cronbach's alpha were used to study the psychometric properties of the RAI. The magnitude of test-retest differences was assessed using the method of Bland and Altman. Relationships between the RAI, its helplessness (HS) and internality (IS) subscales, and BILAG, SLICC/ACR damage index and SF-36 scores were studied using Spearman's rank correlation. RESULTS: Factor analysis (n = 105) identified 2 factors corresponding to the HS and IS subscales of the RAI. All scales showed acceptable internal consistency, with Cronbach's alpha of 0.64 for the HS, 0.77 for the IS, and 0.74 for the RAI. Mean (SD) test-retest differences were 0.85 (3.96) points for the HS (n = 86), 0.81 (4.44) points for the IS (n = 85), and 1.46 (7.88) points for the RAI (n = 74). Six of 10 hypotheses relating the RAI and HS to demographic, disease, and quality of life variables were confirmed, supporting the construct validity of these scales. CONCLUSION: The RAI and its helplessness subscale are valid and reliable measures of learned helplessness in a multiethnic cohort of Asian patients with SLE in Singapore.

Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma.

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.

Clonality of isolated eosinophils in the hypereosinophilic syndrome.

The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration. In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES. Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin. Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation. In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia. Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting. Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation. Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation. After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis. The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis. Further, the method described can be used to monitor disease progression.

Validation of the MOS SF-36 for quality of life assessment of patients with systemic lupus erythematosus in Singapore.

OBJECTIVE: To assess the reliability and construct validity of the Medical Outcomes Study Short Form 36 Health Survey (SF-36) in a multiracial cohort of Asian patients with lupus in Singapore. METHODS: A cross sectional study was performed on 118 English speaking patients with lupus attending a specialist rheumatology unit between March and August 1996. Patients completed a questionnaire containing the UK standard version of the SF-36 twice within a 14 day period. All patients were assessed for disease activity using the British Isles Lupus Assessment Group score (BILAG), and for disease related damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (DI). Relationships between SF-36, BILAG, and DI scores were studied using Spearman's rank correlation. Internal consistency of the SF-36 was assessed using Cronbach's alpha, and stability using the repeatability coefficient of Bland and Altman. RESULTS: SF-36 subscales showed high internal consistency, with Cronbach's alpha coefficient ranging from 0.84 to 0.94. Test-retest reliability was acceptable, with Spearman's rank correlation >0.70 for all subscales except role-physical, and mean differences in test scores of <2 points for 5 of 8 subscales. SF-36 subscale scores were weakly correlated with BILAG scores (Spearman's p -0.37 to 0.15) and SLICC/ACR DI scores (Spearman's p -0.25 to 0.23), suggesting divergent construct validity of the SF-36. CONCLUSION: These data suggest the SF-36 is a reliable and valid measure of the quality of life of patients with lupus in Singapore.

The effects of ethnicity on disease patterns in 472 Orientals with systemic lupus erythematosus.

OBJECTIVE: To determine the effects of ethnicity on disease manifestations in Oriental patients with systemic lupus erythematosus (SLE) and to describe the risk of developing renal or central nervous system (CNS) involvement with time. METHODS: A retrospective study of 472 patients with SLE seen at the only Rheumatology Unit in Singapore. The effect of ethnicity on selected disease manifestations at diagnosis was assessed after adjusting for demographic variables using multiple logistic regression. The probability of developing selected disease manifestations with time was determined using the Kaplan-Meier product limit method. RESULTS: At diagnosis, Malays had a higher risk of renal or CNS involvement than Chinese (OR 2.26, 95% CI 1.21 to 4.21, and OR 3.07, 95% CI 1.01 to 9.34, respectively), and Indians a lower risk of malar rash and a higher risk of oral ulcers than Chinese (OR 0.30, 95% CI 0.13 to 0.68, and OR 2.90, 95% CI 1.45 to 7.34, respectively). The prevalence of renal or CNS involvement in the entire cohort increased with time, reaching 75.6% (95% CI 66.1% to 85.0%) and 16.7% (95% CI 11.7% to 21.6%), respectively, after 18 years of disease. CONCLUSION: Ethnicity influenced disease manifestations at diagnosis in this cohort of Oriental patients with SLE. Renal or CNS involvement developed in previously unaffected patients up to 18 years after diagnosis, highlighting the need for continued vigilance in patients with lupus.

Clinical predictors of nephritis in systemic lupus erythematosus.

We identified clinical predictors of lupus nephritis presenting more than 6 months after the diagnosis of lupus in a cohort of 335 lupus patients. Almost 24% (80/335) of patients developed nephritis more than 6 months after the diagnosis of lupus. Using a Cox proportional hazards model, we found hypertension, thrombocytopaenia and leukopaenia to be associated with lupus nephritis presenting more than 6 months after diagnosis, with adjusted relative risks of 2.5 (95% CI 1.3 to 4.7), 4.3 (95% CI 1.7 to 10.8) and 3.2 (95% CI 1.7 to 6.2) respectively. In this cohort, hypertension, thrombocytopaenia and leukopaenia were associated with lupus nephritis presenting more than 6 months after the diagnosis of lupus.

Lipid disorders and rheumatic diseases.

Lipid abnormalities can exist in patients with rheumatic diseases. Many mechanisms give rise to these abnormalities and include treatment with corticosteroids and upregulation of certain cytokines in active rheumatic disease. Premature atherosclerosis can occur in these patients with significant morbidity and mortality. Greater awareness and earlier treatment of these lipid problems may lead to better outcomes.

Osteoporosis--the need for a paradigm shift.

Osteoporosis is a potentially devastating illness and causes morbidity and mortality from fragility fractures at the wrist, spine and hip. Currently, the illness can be detected before the fractures occur using dual energy X-ray absorptiometry and many preventive and therapeutic options exist. Efforts should be directed at helping the population at large achieve a healthy peak bone mass and adopt lifestyle habits which benefit bone mass. For those at high risk of fractures or who have already suffered an osteoporotic fracture, many pharmacological agents have been shown to reduce the risk of subsequent fractures. Hormone replacement therapy and bisphosphonates have the best efficacy data at present but there are likely to be more options in the near future. Hence, there is a need for a paradigm shift in that osteoporosis should not be thought of as an illness that starts at the point of fracture. Instead, it should be actively assessed and treated before fractures occur.

DNA vaccination against virus infection and enhancement of antiviral immunity following consecutive immunization with DNA and viral vectors.

Recent demonstrations of the immunogenicity of antigens encoded in DNA plasmids following delivery by various routes have heralded a new era in vaccine development. In this article, we review progress in DNA-based antiviral immunoprophylaxis. Preclinical studies have already established the immunogenicity of DNA plasmids encoding protective antigens from a wide variety of viral pathogens and work published in recent months has raised real prospects of broadly protective DNA vaccination against infections with influenza virus and HIV. We also describe a consecutive immunization protocol consisting of a priming dose of vaccine antigen encoded in DNA plasmids followed by a booster with the same antigen encoded in recombinant fowlpox virus vectors. We have used this strategy to generate protective antiviral cell-mediated immunity and sustained, high-level antibody responses both systemically and at mucosae, and to elucidate immunological mechanisms underlying the development of immunity to antigens delivered in DNA vectors.