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Biomedical subjects

Amita Aggarwal

Publications and source records attributed to Amita Aggarwal.

At least 19 recordsLinked to original sources
PubMed2006

Juvenile onset systemic sclerosis: a single center experience of 23 cases from Asia.

The aim of this paper was to study the spectrum of juvenile scleroderma (JSSc) seen at a tertiary care referral center in Asia. Retrospective analysis of case records of patients with systemic sclerosis, having age of onset less than 16 years and seen at our hospital from 1988 to 2004, was done. Patients with linear scleroderma and morphea were excluded. There were 23 patients (19 girls, 4 boys) with median age of onset of 12 years (range 5-16 years). The median age at presentation was 17 years (range 10-34 years). The median time from first symptoms to presentation was 4 years (range 0.2-26 years). Among these, 14 had diffuse systemic sclerosis (DSSc), while 9 had limited scleroderma (LSSc). The clinical features seen at presentation in patients were: Raynaud's phenomenon in 19, digital ulcers in 14, loss of finger tip pulp in 12, reflux in 8, dysphagia in 7, arthritis in 8, digital gangrene in 2, and pulmonary artery hypertension in 1. Antinuclear antibody was positive in 15 out of 18 patients tested. Interstitial lung disease was seen in 15 patients, 6 of whom had diffuse disease. The median skin score was 22 (range 7-48) . One patient died of primary pulmonary hypertension within 1 year of onset of symptoms. At a mean follow-up of 34 months, 14 patients were stable or had improvement in skin score or dyspnea on exertion. DSSc and LSSc in childhood have a clinical presentation similar to adult patients, with cardiopulmonary involvement being the major predictor of outcome. The short-term prognosis of JSSc is good.

Adolescent↗
PubMed2006

The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.

OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE). METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic. RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%. CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.

Child↗
PubMed2006

Immunomodulatory activity of Semecarpus anacardium extract in mononuclear cells of normal individuals and rheumatoid arthritis patients.

Semecarpus anacardium (SA) Linn. (family Anacardiaceae), is a plant well-known for its medicinal value in Ayurveda. The nut extracts of this plant have been traditionally used as antihelminthic, anti-fungal, anti-carcinogenic and in the treatment of nervous debilities and arthritis. In this study we have evaluated crude ethanolic extract of SA nuts for its anti-inflammatory activities in vitro using peripheral blood and synovial fluid mononuclear cells of healthy individuals and rheumatoid arthritis (RA) patients. SA extract inhibited the spontaneous and LPS induced production of proinflammatory cytokines IL-1beta and IL-12p40 but had no effect on TNF-alpha and IL-6 production, both at protein and mRNA level. The crude extract also suppressed LPS induced nuclear translocation of transcription factors, NF-kappaB and AP-1; the inhibition of NF-kappaB was through the inhibition of IkappaBalpha phosphorylation. The extract also suppressed LPS activated nitric oxide production in mouse macrophage cell line, RAW 264.7. Our results for the first time show that SA extract can inhibit proinflammatory cytokine production and demonstrate its mechanism of action.

Adult↗
PubMed2006

Anemia in rheumatoid arthritis: high prevalence of iron-deficiency anemia in Indian patients.

Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of anemia and its correlation with disease variables in RA patients. Among patients with RA anemia was defined as hemoglobin <or= 11 g/dl in females and <or= 12 g/dl in males. Iron-deficiency anemia (IDA) was defined as serum ferritin <or= 50 microg/dl. Disease activity was assessed by modified Disease Activity Score (DAS28). Of the 214 patients (183 females) anemia was found in 151 [70.6% (anemia of chronic disease--ACD in 51.6%, IDA in 48.4%)]. Except 13 all patients with anemia had active disease. mDAS-28 was higher (5.23) in anemic patients as compared to non-anemic patients (3.83; P < 0.005). Further, it was higher in patients with ACD (5.69) as compared to IDA (4.7; P < 0.001). In patients with ACD mDAS-28 had an inverse correlation with hemoglobin (r = -0.258, P < 0.05) and a positive correlation with serum ferritin (r = 0.359, P < 0.001). At 1 year 37.74% of patients with anemia had recovered. Anemia is a frequent extra-articular manifestation in RA. Significant IDA is present in nearly half the patients. Partial response to iron replacement suggests a component of ACD in these patients. Anemic patients with ACD had more active disease as compared with non-anemic patients or those with IDA.

Adult↗
PubMed2006

Low-dose methotrexate-induced pancytopenia.

Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of inflammatory rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In the present series, we have reviewed our data of five patients who developed serious pancytopenia after the use of MTX, including one who died. Two of these resulted from prescription errors by primary care physicians. The clinical, laboratory, and outcome profile of all five cases are discussed with a brief review of the literature about MTX-induced pancytopenia. There is an urgent need to increase awareness in primary care physicians, patients, and pharmacists toward informed prescribing, dispensing, and monitoring of MTX to prevent such mishaps in the future.

Adult↗
PubMed2006

Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA.

INTRODUCTION: Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. MATERIALS AND METHODS: A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. RESULTS: The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). CONCLUSION: Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.

Adult↗
PubMed2006

Aneurysm of the internal carotid artery in a female patient of Behcet's disease: a rare presentation.

Behcet's disease is a systemic inflammatory disease characterized commonly by oral and genital ulcerations, with skin and eye involvement. Unlike other manifestations, involvement of the central nervous system and vascular manifestations can be late in the course and are the leading causes of death. Aneurysms are relatively common in visceral vessels but extremely rare in intracranial arteries, being limited to few case reports. Moreover, vascular involvement is significantly less common in female than in male patients. In this paper, we report a case of aneurysm of internal carotid artery in a female patient of Behcet's disease who had presented with subarachnoid hemorrhage and was treated successfully by a brief course of corticosteroids followed by endovascular treatment.

Adult↗
PubMed2006

Subclinical atherosclerosis in rheumatoid arthritis in India.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have high cardiovascular morbidity and mortality as compared to the general population. Indians are also at increased risk of developing early and severe atherosclerotic coronary artery disease. Carotid intima-media thickness as measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in Indian patients with RA. METHODS: Common carotid IMT (CCA IMT) was measured at the level of carotid bifurcation along with fasting lipid profile in 57 RA patients and 45 age and sex matched controls. Values of mean CCA IMT above mean + 2 SD of the control group were defined as abnormal IMT. Variables of disease activity and severity were measured in RA patients. Patients and controls with known traditional cardiovascular risk factors were excluded from the study. Student t test and chi-square test for proportion were used for statistical analysis. A logistic regression analysis was done to find out independent predictors of abnormal IMT. RESULTS: Nineteen RA patients (33.3%) and 2 controls (4.44%) had abnormal IMT values. RA patients had significantly increased mean CCA IMT (0.558 +/- 0.137 mm) as compared to controls (0.416 +/- 0.002 mm; p < 0.0001). Age > or = 42 years, duration of disease > or= 6 years, and tender joint count > or = 5 predicted increased risk of having abnormal CCA IMT in a logistic regression analysis. CONCLUSION: One-third of Indian RA patients had subclinical atherosclerosis. Age and tender joint count were independent predictors of abnormal CCA IMT.

Adult↗
PubMed2006

Low prevalence of IgA deficiency in north Indian population.

BACKGROUND AND OBJECTIVES: IgA deficient patients are at risk of severe anaphylactic reaction on being transfused blood and blood products, and its prevalence varies in different parts of the world. No data are available from India. We did a blood donor survey to look for prevalence of IgA deficiency in north India. METHODS: A sensitive enzyme linked immunosorbent assay developed in-house was used to detect IgA deficiency in a total of 3818 blood donors. Complete IgA deficiency was defined as value less than 5 mg/dl whereas partial IgA deficiency was defined as value between 5-30 mg/dl. RESULTS: Of the 3818 blood donors screened, 3640 (95.3%) were males with a mean age of 31.2 yr. No donor was found to have complete IgA deficiency; however, 257 (6.7%) had partial IgA deficiency. INTERPRETATION AND CONCLUSION: Our study shows that IgA deficiency is rare in north India.

Adolescent↗
PubMed2006

Osteopenia is common in adult male patients with active juvenile idiopathic arthritis.

OBJECTIVE: To assess the prevalence of osteopenia in Southeast Asian men with active juvenile idiopathic arthritis (JIA) and to identify predictors of reduced bone mineral density (BMD). METHODS: BMD of 30 men with active JIA and 23 healthy men was assessed by dual energy x-ray absorptiometry scans. Clinical variables that influence bone mass were also analyzed. T scores were calculated based on Caucasian normative data. RESULTS: Absolute BMD (g/cm(2)) was significantly lower in men with active JIA compared to controls at all measured sites, i.e., lumbar spine (p = 0.018), hip (p = 0.018), and distal third of forearm (p = 0.044). More subjects in the JIA group had low BMD (T score <or= -1.0) than controls at hip (22/30 vs 9/23; p < 0.05) and distal third of forearm (27/30 vs 10/23; p < 0.001), while at lumbar spine region the difference was not statistically significant (22/30 vs 13/23). A significant negative correlation of BMD was found with joint deformities, limitation of joint movement, Health Assessment Questionnaire score, and erythrocyte sedimentation rate. BMD at the hip and distal third of forearm was significantly lower in patients having arthritis at these sites. A positive correlation of BMD was found with body mass index. CONCLUSION: A majority of Southeast Asian men with active JIA have reduced BMD. More patients in our cohort had low BMD compared to reports from Western countries. This finding may be attributed to use of Caucasian normative data, uncontrolled disease activity, severity of disease, poor nutritional status, or an ethnic variation.

Adult↗
PubMed2006

Lack of clinical association with antibodies to ribosomal P proteins in Indian patients with systemic lupus erythematosus.

OBJECTIVE: We examined the prevalence and clinical association of the antiribosomal antibodies in our cohort of patients with systemic lupus erythematosus (SLE). METHODS: IgG antiribosomal P protein (anti-P) antibodies were detected in 202 consecutive patients with SLE and 212 age and sex matched healthy subjects by an in-house ELISA, using the 22-mer C-terminal peptide. In 13 patients, IgG anti-P antibodies were also tested in paired cerebrospinal fluid (CSF) and sera samples. Clinical variables were compared in the antibody-positive and negative groups using appropriate statistical tests. RESULTS: Of the 202 patients, 15 were male. Their median age was 30 years and the median disease duration was 36 months. Thirty-one patients (15.35%) were positive for IgG anti-P antibodies, of which 24 were also positive by Western blot. No association with SLE Disease Activity Index, nervous system disease, nephritis, hepatitis, skin disease, arthritis, and juvenile onset disease could be demonstrated. Levels of IgG anti-P antibodies in CSF were 100-fold less compared to levels in serum, and correlated well with the latter (r = 0.86; p < 0.01). CONCLUSION: The prevalence of IgG anti-P antibodies is similar in Indian and Caucasian patients with SLE. No association with specific organ involvement or age at onset could be demonstrated.

Adolescent↗
PubMed2006

Cytokine generation in stored platelet concentrate: comparison of two methods of preparation.

BACKGROUND & OBJECTIVES: Contaminating white blood cells (WBCs) in stored platelet concentrates (PC) are the main source of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin- 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) that are implicated in transfusion reactions. We compared the levels of these cytokines in stored platelet preparations prepared by two methods. Effect of pre-storage leucofiltration on these cytokine levels was also studied. METHODS: Twelve units of pooled PCs were prepared by platelet rich plasma (PRP) method and buffy-coat (BC) method each and stored for 5 days. IL-6, IL-8 and TNF-alpha levels were measured in platelet supernatants on day 0, 1, 3 and 5 of the storage using commercially available immunoassays. Pre-storage leucofiltration was done in 4-pooled units of PRP-PC and cytokine levels compared with unfiltered PCs. RESULTS: Median IL-6 levels increased from day 0 to day 5 in both PRP-PC and BC-PC. In PRP-PC, IL-8 increased from <3 pg/ml on day 0 to 817 pg/ml on day 5, while in BC-PC the corresponding levels were 10 and 346.5 pg/ml, respectively. No significant increase in levels of TNF-alpha was observed in BC-PC during storage period, while levels increased significantly in PRP-PC on day 1 only. There was no significant change in the levels of all three cytokines in leucofiltered PCs over 5 days of storage. INTERPRETATION & CONCLUSION: Findings of our study showed that method of preparation and WBC content are the critical factors in determining the cytokine levels in stored PCs.

Blood Platelets↗
PubMed2006

Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation.

BACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. RESULTS: The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation. Forty two per cent (63/150) of the patients had C677T polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The baseline characteristics of the patients with or without polymorphism were comparable. The frequency of adverse events was not increased in patients with C677T polymorphism with 11 patients experiencing adverse events as compared to 19 in the group without polymorphism (of whom 4 and 7 patients respectively discontinued treatment). The C677T polymorphism was not associated with any difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation. Further studies need to be done to look at polymorphisms in other enzymes that may have association with MTX clinical efficacy and toxicity.

Adult↗
PubMed2005

Outer membrane protein of salmonella is the major antigenic target in patients with salmonella induced reactive arthritis.

OBJECTIVE: We previously reported that Salmonella typhimurium was the triggering agent in one-third of our patients with sporadic enteric reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA). The antigens recognized by the synovial T cells in Salmonella induced ReA are not known. We investigated the immunodominant antigens in Salmonella ReA. METHODS: Synovial fluid mononuclear cells (SFMC) from 53 patients with ReA/uSpA were cultured with crude lysate of S. typhimurium. In 20 patients, the triggering agent was found to be Salmonella (stimulation index, SI, > 2.5). For cell fractionation of S. typhimurium, the sonicated crude lysate was separated by ultracentrifugation into a cytoplasmic supernatant (CYT) and membrane pellet (OMP). The CYT was further separated on SDS-PAGE and blotted onto nitrocellulose membrane for proliferation assays. SFMC from 20 patients with Salmonella ReA/uSpA were stimulated with OMP, CYT, and cytosolic fractions of S. typhimurium, and proliferation was measured by thymidine incorporation. Quantitation of antigen-specific cells in SF was by intracellular interferon-g staining in 7 patients and paired peripheral blood (PB) in 5 patients after stimulation with crude Salmonella lysate, CYT, and OMP. RESULTS: Out of 20 patients with Salmonella ReA/uSpA, the SFMC showed a significant proliferation to OMP in 19 patients and CYT in 17 patients. The median SI of OMP (8.2, range 2.8-52.5) was significantly higher (p < 0.0005) than for the CYT (4.9, 2.7-18.8). Fifty percent of the patients showed proliferative response to cytosolic fractions of < 60 kDa. The mean antigen-specific T cell frequency was also higher with OMP (0.68% +/- 0.59%) than CYT (0.53% +/- 0.62%) but this was not statistically significant. Compared to PB, the OMP-specific cells were 7.5 times more numerous in the SF (p < 0.05). CONCLUSION: The cellular immune response in Salmonella ReA/uSpA is directed predominantly against the OMP and low molecular weight proteins in the cytosolic fraction.

Adolescent↗
PubMed2005

Elevated concentrations of monocyte derived cytokines in synovial fluid of children with enthesitis related arthritis and polyarticular types of juvenile idiopathic arthritis.

OBJECTIVE: Cytokines are the major mediators of joint damage in chronic arthritis. Data on synovial fluid (SF) cytokine concentrations in patients with juvenile idiopathic arthritis (JIA), especially enthesitis related arthritis (ERA), are limited. We measured levels of different monocyte derived cytokines, T cell derived cytokines, and a proinflammatory chemokine in SF specimens from children with ERA or polyarticular (Poly) rheumatoid factor (RF)-negative JIA. METHODS: Macrophage products [tumor necrosis factor-a (TNF-a), interleukin 1ss (IL-1ss), IL-6, IL-12p40)], T lymphocyte products [IL-2, IL-4, interferon-g (IFN-g)], and a proinflammatory chemokine (IL-8) were assayed using ELISA in SF specimens from 53 patients with JIA [ERA 34, polyarticular RF-negative 19] and 40 patients with rheumatoid arthritis (RA). RESULTS: In the ERA group, median SF cytokine levels were higher compared to RA (all values are pg/ml): IL-1ss [< 15.6 (< 15.6-213) vs < 15.6 (< 15.6-41); p < 0.01], IL-12p40 [236 (< 15.6-1714) vs 21 (< 15.6-520); p < 0.0001], and IL-6 [1139 (< 4.6-2187) vs 835 (< 4.6-875); p < 0.0001]. TNF-a and IFN-g levels were similar to RA. IL-8 levels were significantly less than RA (p < 0.0001). The median levels of IL-1ss [39.4 (< 15.6-558) vs < 15.6 (< 15.6-41); p < 0.0001] and IL-12p40 [209 (< 15.6-849) vs 21 (< 15.6-520); p < 0.0001] were higher in patients with Poly-JIA compared to RA. TNF-a, IL-6, and IL-8 levels in Poly-JIA were comparable to RA. IL-2 and IL-4 were not detectable in any patient with JIA. Cytokine profile comparison between the 2 subsets revealed that the median IL-6 [1139 (< 4.6-2187) vs 790 (17.4-2119); p < 0.01] and IFN-g levels [235 (< 4.6-600) vs < 4.6 (< 4.6-412); p < 0.0001] were higher in ERA than in Poly-JIA. In contrast, median IL-8 levels were higher in Poly-JIA [200 (3.8-200)] compared to ERA [74.6 (4-200); p < 0.001]. However, there was no difference in levels of TNF-a, IL-1ss, and IL-12p40 between patients with these 2 subtypes of JIA. CONCLUSION: SF levels of IL-1ss and IL-12p40 are increased in both Poly-JIA and ERA as compared to RA. IL-6 levels were higher in ERA compared to RA. Levels of TNF-a were comparable to RA in both Poly-JIA and ERA. This suggests that joint inflammation in JIA is mediated predominantly by monocytes. In ERA the levels of IL-6 and IFN-g are higher than in Poly-JIA. The increase in IFN-g in children with ERA with undetectable IL-4 suggests a Th1-dominant immune response in this disease subset.

Adolescent↗
PubMed2005

Angiomatous malformation: a rare cause of recurrent swelling of the knee joint.

Angiomatous malformation of the muscle around the knee joint is an extremely uncommon cause of recurrent swelling of the joint. We report a case of a 13-year-old boy who presented with recurrent episodes of knee joint swelling. Though the history and physical examination was typical, magnetic resonance imaging clinched the diagnosis.

Adolescent↗