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.

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.

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.

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.

Effect of four plant phenols, beta-carotene and alpha-tocopherol on 3(H)benzopyrene-DNA interaction in vitro in the presence of rat and mouse liver postmitochondrial fraction.

The modulatory effect of beta-carotene, alpha-tocopherol and the four plant phenols eugenol, hydroxychavicol, curcumin and catechin on mouse and rat liver postmitochondrial fraction (S9 mix)-mediated 3(H)benzopyrene (B(a)P)-DNA interaction in vitro was studied. All the plant phenolics significantly inhibited 3(H)B(a)P-DNA interaction in the presence of both mouse and rat liver S9 fractions. In contrast, alpha-tocopherol proved to be ineffective in the presence of both types of S9 mix, whereas beta-carotene inhibited only mouse S9 mix-mediated 3(H)B(a)P-DNA interaction.

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.

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.

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.

Clinical & bacteriological profiles of shigellosis in Calcutta before & after an epidemic (1984-87).

Patients below 5 yr of age, hospitalised for shigellosis over a period of four years (1984-87), were studied. During the epidemic of bacillary dysentery (1984) isolation of different Shigella spp. as well as Shigella dysenteriae type 1 was high. Decreased isolation of Sh. dysenteriae type 1 and increased isolation of Sh. flexneri was observed during post-epidemic years (1985-87). Isolation of different Shigella spp. was always above 25 per cent from patients with dysentery and greater than 7 per cent from those with watery diarrhoea during the post-epidemic years. Higher incidence of shigellosis was observed amongst older children (greater than 3 yr). Most of the shigellosis patients complained of blood and mucus in stools. Vomiting was common among shigellosis patients presenting with watery diarrhoea whereas fever was commonly seen in patients with both dysentery and watery diarrhoea. Most patients of shigellosis presenting with blood and mucus in stools had no dehydration.

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.

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.

Serosurvey of chikungunya antibody in Calcutta metropolis.

Since its first isolation in Calcutta, in 1963, there have been many reports about epidemis of chikungunya virus infection in different parts of India. Calcutta experienced a concurrent epidemic of dengue and chikungunya between 1963 and 1965. But after that there is no report about any chikungunya infection in Calcutta. During routine investigations it is found that chikungunya antibody is on the wane. The present survey for chikungunya antibody showed only 4.37% (n = 17) seropositivity out of 389 sera tested. The highest (12.5%) seropositivity was observed in the age group of 51-55 years and no chikungunya antibody was detected in young and young adults. The findings suggest that chikungunya virus is disappearing from the Calcutta population.

Effect of protein rich diet during acute phase of dysentery.

Ninety six children upto the age of five years suffering from uncomplicated acute dysentery of less than 3 days' duration were studied to find out the impact of feeding of extra-protein rich diet during their acute phase of illness. These children were randomly allocated to either control group (receiving only hospital diet) and study group (receiving hospital diet and extra milk which constituted 30% of ideal total calorie requirement of patients. Patients in the two groups were comparable on admission. Forty percent reduced food intake was observed among the children of both the groups due to severe anorexia which was reflected by no significant differences in clinical outcome, anthropometrical measurements and haematological parameters between the two groups on day 7 of hospitalisation and on day 15 after discharge.

PIP: Health practitioners admitted 96 7-25 month old children with uncomplicated acute dysentery to the Dr. B.C. Roy Memorial Hospital for Children in Calcutta, India and randomly allocated them into either the group that received only the hospital diet (control group) or the group that received the hospital diet and extra milk (3.1 g of protein/100 g milk) comprising 30% of ideal calorie requirement of the patient (case group). They treated all the children with nalidixic acid (55 mg/kg/day). They conducted this clinical study to examine the effect of an extra protein rich diet during the acute phase of dysentery. 37.5% of the patients tested positive for Shigella species. No enteroinvasive pathogens were isolated from the remaining patients, however. Food intake of both groups was 40% less than recommended intake. Therefore it was difficult to give the food to the children. No statistically significant differences in clinical outcomes, anthropometrical measurements, and hematological values existed on day 7 of hospitalization and day 15 after discharge between cases and controls. Anorexia may have been responsible for the study's inability to demonstrate any advantage of increase protein in the diet. Further this study was done in a hospital rather in the children's home where they may have been more willing to eat more food. Yet children still had reduced food intake during the 2nd week of discharge from the hospital.