Increasing podiatry referrals for patients with inflammatory arthritis at a tertiary hospital in Singapore: A quality improvement project.

BACKGROUND: Foot disease is highly prevalent in people with inflammatory arthritis and is often under-recognized. Podiatry intervention can significantly reduce foot pain and disability, with timely access being the key factor. The aim of this study was to plan and implement a quality improvement project to identify the barriers to, and improve, uptake of podiatry services among patients with inflammatory arthritis-related foot problems seen at a tertiary hospital in Singapore. METHOD: A 6-month quality improvement program was conducted by a team of key stakeholders using quality improvement tools to identify, implement and test several interventions designed to improve uptake of podiatry services. The number of patients referred for podiatry assessment was recorded on a weekly basis by an experienced podiatrist. The criterion for appropriate referral to podiatry was those patients with current or previous foot problems such as foot pain, swelling and deformity. RESULTS: Interventions included education initiatives, revised workflow, development of national guidelines for inflammatory arthritis, local podiatry guidelines for the management of foot and ankle problems, routine use of outcome measures, and introduction of a fully integrated rheumatology-podiatry service with reduced cost package. Referral rates increased from 8% to 11%, and were sustained beyond the study period. Complete incorporation of podiatry into the rheumatology consultation as part of the multidisciplinary team package further increased referrals to achieve the target of full uptake of the podiatry service. CONCLUSION: Through a structured quality improvement program, referrals to podiatry increased and improved the uptake and acceptance of rheumatology-podiatry services.

Prevalence of foot problems in people with inflammatory arthritis in Singapore.

BACKGROUND: Foot problems are highly prevalent in people with inflammatory arthritis reported from studies in the UK, Europe and New Zealand, but there is limited evidence from Southeast Asia. The study aim was to evaluate the prevalence of foot problems in people with inflammatory arthritis in Singapore. METHODS: People with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a tertiary hospital in Singapore. Disease and clinical characteristics included age, sex, disease duration, current blood tests and medications. The Leeds Foot Impact Scale was used to evaluate foot impairment/disability and the Modified Health Assessment Questionnaire was used to assess global function. RESULTS: We recruited 101 people with inflammatory arthritis, of which 50 % were female. The majority of participants were Chinese (70 %). The mean (SD) age was 52 (15) years, and the mean (SD) disease duration was 9.3 (0.3) years. The most commonly reported inflammatory arthritic conditions were rheumatoid arthritis (46), gout (31) and spondyloarthritis (15 %). The mean (SD) of the total Leeds Foot Impact Scale was 17 (13) indicating moderate to severe levels of foot impairment and activity limitation. Over 80 of participants reported foot pain during the course of their condition, and 48 % reported current foot pain. Despite the high prevalence of foot pain, only 21 participants (21 %) had been referred to a podiatrist. CONCLUSION: This is the first study to investigate the prevalence of foot problems in people with inflammatory arthritis from Singapore. The majority of the participants reported foot problems, but had not been referred to a podiatry service.

Footwear characteristics in people with inflammatory arthritis in Singapore.

BACKGROUND: Foot problems are common in people with inflammatory arthritis. Despite suitable footwear having the potential to alleviate pain, improve mobility and maintain independence, previous studies have found many people with inflammatory arthritis wearing poorly fitting and inappropriate footwear. Footwear styles and characteristics have not been reported in a Singapore inflammatory arthritis population. The objective of this study was to identify current footwear styles and characteristics of footwear worn by people with inflammatory arthritis in Singapore. METHODS: One-hundred-and-one participants with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a large public hospital in Singapore. Disease and clinical characteristics were recorded. A patient-reported outcome included current foot pain. An objective footwear assessment of style, age of shoe, fit and construction was conducted. RESULTS: The majority of participants were Chinese women with a mean (SD) age was 52.0 (15.0) years old and a mean (SD) disease duration of 9.3 (0.3) years. We found 50 % of participants (n = 51) reported footwear problems. Sandals (n = 27, 26 %), flip-flops (n = 19, 19 %) and moccasin type (n = 19, 19 %) was the most common footwear choice. Evaluation of footwear characteristics found that there was a lack of motion control features. Only 32 (32 %) participants had correctly fitting footwear with regard to length, width and depth. No participant was wearing therapeutic footwear. CONCLUSION: This study provides the first insight into footwear preferences of people with inflammatory arthritis in Singapore. Use of slip-on and poorly fitting footwear was found to be common in people with inflammatory arthritis. Further research on footwear preferences in Southeast-Asian communities needs to take into account cultural habit and preference, socio-economic status, footwear options and affordability.

Platelet-activating factor promotes motility in breast cancer cells and disrupts non-transformed breast acinar structures.

A plethora of studies have demonstrated that chronic inflammatory microenvironment influences the genesis and progression of tumors. Such microenvironments are enriched with various lipid mediators. Platelet activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is one such lipid mediator that is secreted by different immune cell types during inflammation and by breast cancer cells upon stimulation with growth factors. Overexpression of PAF-receptor has also been observed in many other cancers. Here we report the possible roles of PAF in tumor initiation and progression. MCF10A, a non-transformed and non-malignant mammary epithelial cell line, when grown as 3D 'on-top' cultures form spheroids that have a distinct hollow lumen surrounded by a monolayer of epithelial cells. Exposure of these spheroids to PAF resulted in the formation of large deformed acinar structures with disrupted lumen, implying transformation. We then examined the response of transformed cells such as MDA-MB 231 to stimulation with PAF. We observed collective cell migration as well as motility at the single cell level on PAF induction, suggesting its role during metastasis. This increase in collective cell migration is mediated via PI3-kinase and/or JNK pathway and is independent of the MAP-kinase pathway. Taken together this study signifies a novel role of PAF in inducing transformation of non-tumorigenic cells and the vital role in promotion of breast cancer cell migration.

Use of rituximab in the treatment of refractory systemic lupus erythematosus: Singapore experience.

We performed a retrospective study of 10 patients with refractory systemic lupus erythematosus treated with rituximab to determine the efficacy, safety and impact on hospitalization days. Patients received rituximab according to a standardized protocol, all achieved B-cell depletion with clinical improvement in nine patients. At 12 months, BILAG scores improved significantly from a median of 13.5 (range 3-20) at baseline to 1 (range 0-27) (p < 0.05). There was significant reduction in urinary total protein excretion with stabilization of renal function in patients with nephritis. Two out of three patients with thrombocytopenia had normalization of platelet counts. The median duration of B-cell depletion was 6 months (range 6-18). Two patients required retreatment and responded well. There were no adverse outcomes following rituximab therapy. Patients with lupus nephritis spent a median of 17.1 days per year (range 1.9-49) in hospital on conventional treatment which was reduced to 0 days (range 0-14.8, p = 0.027) post-rituximab treatment. The cost of hospitalization was 5989 Singapore dollars per patient-year while on conventional treatment and 5792 Singapore dollars per patient-year post-rituximab. This study adds to the growing literature of rituximab efficacy with potential cost saving in lupus nephritis.

Nitric oxide decreases motility and increases adhesion in human breast cancer cells.

Our previous results have suggested that increasing aggressiveness of breast tumour cells is associated with the down-regulation of the expression of nitric oxide synthase (NOS). As increasing aggressiveness is associated with a propensity for metastasis, this study aimed to investigate whether our theory applied to the processes of motility and invasion. Although the well-established dual roles of nitric oxide (NO) were evident, most of the results are consistent with our theory. We demonstrated that basal motility is higher in the MCF-7-ADR multidrug-resistant variant cell line compared to the MCF-7 parent cell line and that treatment with NOS inhibitors increased motility in MDA-MB-231 and T47D cells. Exogenous NO was associated with a trend to increase adhesion in the MCF-7 and MDA-MB-231 cell lines. These results are consistent with the theory that loss of NOS expression may be associated with the progression of breast cancers via increase in motility and loss of adhesion.

Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy.

OBJECTIVE: Atherogenic serum lipid profile possesses pro-inflammatory properties and is associated with more active RA. While prevalent in patients with gout, whether atherogenic lipid profile is associated with gouty flares is unknown. This study aims to investigate whether atherogenic serum lipid predicts gouty flares in patients with gout. METHODS: Adult patients (age > or =21 yrs) who suffered from gout were prospectively followed between September 2006 and November 2007 and their demographic, clinical and laboratory data were collected. Episodes of gouty flares over this observation period were recorded and factors predictive of gouty flares were studied by regression models. RESULTS: Of the 100 patients, 80 were men, 65 were ethnic Chinese, 31 were Malay and the rest were Indian and Caucasian. The mean age and duration of gout (+/-S.D.) were 61.9 +/- 14.0 and 6.6 +/- 7.8 yrs, respectively. The mean serum uric acid and creatinine levels were 537.6 +/- 142.8 and 173.6 +/- 119.9 micromol/l, respectively. In univariate analysis, longer duration of gout, higher adjusted mean serum creatinine, lower adjusted mean fasting serum, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were associated with gouty flares. After adjustment for potential confounders in multivariate regression models, longer duration of gout and lower adjusted mean fasting serum HDL-C level remained independently predictive of gouty flares. CONCLUSIONS: Low serum high-density lipoprotein cholesterol level was an independent predictor for gouty flares. Whether optimizing serum HDL-C level can benefit patients with gout in terms of reducing gouty flares needs to be addressed by controlled trials.

A novel multiplex RT-PCR system detects human endogenous retrovirus-K in breast cancer.

Human endogenous retrovirus HERV-K like-sequences have been implicated in certain cancers. We developed a novel multiplex RT-PCR system for HERV-K that yielded a 533 bp product together with a smaller sized product (319 bp) of the house keeping gene, histidyl tRNA synthetase (HtRNAS). The latter spanned an intron that also served to validate target cDNA. PCR amplicons of HERV-K and HtRNAS were visualised using a gel documentation system and the pixel intensity used to derive semi-quantitative levels of viral expression. Our data showed that HERV-K10 was significantly elevated in MCF-7 cells treated with estrogen. Interestingly, HERV-K expression was higher in MCF-7 cells selected with adriamycin. RT-PCR combined with Southern blotting also detected HERV-K from breast cancer tissue using laser capture microscopy. This study highlights the presence of HERV-K in the breast cancer cell lines MCF-7 and MCF-7 ADR and confirms HERV-K10 transcripts in the cell line T47D. We believe this study to be a novel approach in determining levels of HERV-K expression and for detecting this virus in cancer cell lines and tissues.

Reduced expression of endothelial and inducible nitric oxide synthase in a multidrug resistant variant of the MCF-7 human breast cancer cell line.

The purpose of the present study was to investigate expression of endothelial and inducible nitric oxide synthase in the MCF-7 human breast cancer cell line compared to a multidrug resistant variant, MCF-7-ADR. Immunohistochemical investigations demonstrated 51% of MCF-7 cells stained positive for endothelial nitric oxide synthase, with 46% positive for inducible nitric oxide synthase. However, in the breast cancer cell line that was multidrug resistant there was a much lower positive staining for endothelial nitric oxide synthase at 20% and for inducible nitric oxide synthase at 15%. For the multidrug resistant variant, there was also lower nitric oxide production and the band intensity for immunoblotting for endothelial nitric oxide synthase was weaker than for the parent cell line. These results lend further support to the proposal that expression of NOS is negatively associated with human breast cancer progression.

Risk factors for pneumonia in infants and young children and the role of solid fuel for cooking: a case-control study.

We evaluated the risk factors for childhood pneumonia with particular reference to indoor air-pollution associated with solid fuel use for cooking (e.g. coal, wood, dung), using a case-control study in a children's hospital in Calcutta. Cases were 127 children aged 2-35 months of either sex admitted with pneumonia and controls were 135 children attending their immunization clinic. Solid fuel use (odds ratio = 3.97, CI = 2.00-7.88), history of asthma in the child (OR = 5.49, CI = 2.37-12.74), poor economic status indicator (OR = 4.95, CI = 2.38 to 10.28), keeping large animals (OR = 6.03, CI = 1.13-32.27) were associated with high risk of pneumonia after adjusting for confounding (logistic regression analysis). Nearly 80% of people in India use such smoke producing fuel and the population attributable risk would be very high. This finding has important health policy implications. Furthermore, history of asthma is a useful prognostic indicator for early action for prevention of severe pneumonia.

Flowcytometric and histopathological correlation of primary intracranial neoplasms.

DNA ploidy and synthetic phase fraction (SPF) of 52 cases of primary intracranial neoplasms have been determined from fresh tissues and the data was correlated with histopathological typing and grading. Fresh tumour tissues from 52 random surgical biopsies (28 malignant and 24 benign) were obtained from neurosurgical operations during the period 1994-1996. The cells were analysed in Becton Dickinson flowcytometer fitted with Consort 30 programme and 'Sober' software. Percentage of diploid cells, proliferative cells and DNA aneuploidy were evaluated. The tumours were classified and graded according to WHO classification (1993). On histology, there were 28 malignant (grade II to IV) and 24 benign cases (grade I). All the histologically benign tumours in this study showed diploid DNA content with the exception of a pituitary adenoma which had a heterogeneous population of cells. The S phase fraction in all the benign cases was less than 10% except in the case of choroid plexus papilloma (S-phase 54%) and an atypical meningioma (S-phase 14%). Out of the 28 malignant tumours, 12 cases were aneuploid (43%) and the rest were diploid (57%). Among the 16 diploid tumours, SPF was more than 10% in eight cases. DNA aneuploidy and high SPF are more common in histologically malignant tumours than benign tumours. SPF is a reflection of proliferation potential of a tumour and may have some role in prognostication of brain tumours.

Humoral immune responses in different clinical forms of tuberculosis.

To assess the antibody responses in different clinical forms of tuberculosis in an attempt to ascertain the specificity of such a response, so that it may be used as a diagnostic tool, 93 tuberculosis cases and 62 normal healthy controls were included in the study. All the cases were diagnosed as tuberculosis by clinical picture including radiological findings, blood picture, fine needle aspiration cytology (FNAC) or histopathological features, sputum examination or urine culture for acid-fast bacilli. IgM and IgG antibodies in the cases and controls were detected by ELISA using A60 antigen from M. bovis and compared with common diagnostic parameters of tuberculosis like presence of acid-fast bacilli in smear and tuberculin response. Antibody responses with A60 antigen has not been found to be specific and often failed to detect a new case.

O-ethylphosphatidylcholine: A metabolizable cationic phospholipid which is a serum-compatible DNA transfection agent.

1,2-dioleoyl-sn-glycero-3-ethylphosphocholine was prepared in a one-step reaction from phosphatidylcholine by reaction with ethyl trifluoromethanesulfonate. This and related O-alkyl phosphatidylcholines constitute the first chemically stable triesters of biological lipid structures and the first cationic derivatives of phospholipids consisting entirely of biological metabolites linked with ester bonds. The complex of cationic phospholipid and plasmid DNA transfected cells with high efficiency. Maximum efficiency of transfection was obtained with complexes in which the positive charge was a few percent in excess over the negative charge. Modest stimulation of transfection of common cell lines was obtained by continuous culture in the presence of 10% serum. Incubation of the phospholipid complex for at least 2 h at 37 degrees C in nearly pure serum had no deleterious effects on transfection efficiency. The lipid has low toxicity; BHK cells tolerated amounts of 2 mg/2 x 10(6) cells at concentrations of 1 mg/mL. The lipid is biodegradable; it was hydrolyzed by phospholipase A(2) in vitro and was metabolized with a half-life of a few days in cells in culture. The synthetic route to cationic phospholipids is well suited to the preparation of derivatives that are tailor-made to have a wide variety of different properties.

Poisoning in children: Indian scenario.

The retrospective data on childhood poisoning from eight regional hospitals in India has been reviewed. The demographic features and types of poisonings encountered have been compared. The analysis of the data indicated that pediatric poisonings constituted 0.23-3.3% of the total poisoning. The mortality ranged from 0.64-11.6% with highest being from Shimla. Accidental poisoning was common involving 50-90% of children below 5 years of age and males outnumbered the females. Suicidal poisoning was seen after 13 years of age and was due to drugs and household chemicals. One of the hospitals in Delhi recorded a very high incidence (66.6%) of drug poisoning in children. The drugs consumed belonged to phenothiazines, antiepileptics and antipyretics. Iron poisoning was seen in younger children. Kerosene was one of the causes of accidental poisoning at all hospitals except Shimla and rural Maharashtra were probably wood charcoal is widely used. Pesticide poisoning was more prevalent in Punjab and West Bengal whereas plant poisoning was very common in Shimla. Significant number of snake envenomation has been recorded from rural Maharashtra. Other less common accidental poisonings in children included alcohol, corrosives, heavy metals, rodenticides, detergents and disinfectants. Thus various regions in the country showed some variation in types and frequency of childhood poisoning which could be attributed to different geographical and socio-economic background.

Protective effect of food additives on aflatoxin-induced mutagenicity and hepatocarcinogenicity.

Food additives such as turmeric (Curcuma longa), and active ingredient curcumin (diferuloyl methane), asafoetida (flavouring agent), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and ellagic acid were found to inhibit the mutagenesis induced by aflatoxin B1 (AFB1) (0.5 microg/plate) in Salmonella tester strains TA 98 and TA 100. Turmeric and curcumin, which were the most active, inhibited mutation frequency by more than 80% at concentrations of 2 microg/plate. Other food additives were also significantly effective. Dietary administration of turmeric (0.05%), garlic (0.25%), curcumin and ellagic acid (0.005% each) to rats significantly reduced the number of gammaglutamyl transpeptidase-positive foci induced by AFB1 which is considered as the precursor of hepatocellular neoplasm. These results indicate the usefulness of antioxidant food additives in ameliorating aflatoxin-induced mutagenicity and carcinogenicity.