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S Agarwal

Publications and source records attributed to S Agarwal.

At least 19 recordsLinked to original sources

Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years.

OBJECTIVES: To evaluate the long-term impact on physical function of a single course of rituximab in rheumatoid factor, seropositive patients with active rheumatoid arthritis (RA) despite ongoing methotrexate treatment. METHODS: A randomized, controlled trial comparing rituximab alone [1,000 mg intravenously (iv) on days 1 and 15, n= 40], or in combination with cyclophosphamide (750 mg iv on days 3 and 7, n= 41) or oral methotrexate (> or =10 mg/week, n= 40) with placebo + methotrexate (> or =10 mg/week, n= 40), resulted in significant reductions in disease activity at weeks 24 and 48. Sustained improvements in physical function and standard effect sizes (SES) for changes in components of ACR and EULAR criteria were evaluated over 2 yrs. RESULTS: More patients receiving rituximab + methotrexate completed a 2-yr follow-up without further treatment than those receiving placebo + methotrexate (45% vs 15%, respectively), rituximab alone (10%) or rituximab + cyclophosphamide (22%). This reflected a higher percentage of patients receiving rituximab + methotrexate reporting improvements in Health Assessment Questionnaire Disability Index > or = minimum clinically important difference at 1 and 2 yrs (68% and 30%, respectively) compared with placebo + methotrexate (28% and 15%), rituximab monotherapy (43% and 10%) or rituximab + cyclophosphamide (39% and 12%). SES were high in all rituximab groups and revealed differing patterns of response over time. CONCLUSION: A single course of rituximab with continuing methotrexate in patients with active RA provided clinically meaningful improvements in physical function over 2 yrs, with lower discontinuation rates and larger SES for improvements in ACR and EULAR criteria components.

Adult↗

Biomechanical signals exert sustained attenuation of proinflammatory gene induction in articular chondrocytes.

OBJECTIVES: Physical therapies are commonly used for limiting joint inflammation. To gain insight into their mechanisms of actions for optimal usage, we examined persistence of mechanical signals generated by cyclic tensile strain (CTS) in chondrocytes, in vitro. We hypothesized that mechanical signals induce anti-inflammatory and anabolic responses that are sustained over extended periods. METHODS: Articular chondrocytes obtained from rats were subjected to CTS for various time intervals followed by a period of rest, in the presence of interleukin-1beta (IL-1beta). The induction for cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-9, MMP-13 and aggrecan was analyzed by real-time polymerase chain reaction (PCR), Western blot analysis and immunofluorescence. RESULTS: Exposure of chondrocytes to constant CTS (3% CTS at 0.25 Hz) for 4-24 h blocked more than 90% (P<0.05) of the IL-1beta-induced transcriptional activation of proinflammatory genes, like iNOS, COX-2, MMP-9 and MMP-13, and abrogated inhibition of aggrecan synthesis. CTS exposure for 4, 8, 12, 16, or 20 h followed by a rest for 20, 16, 12, 8 or 4h, respectively, revealed that 8h of CTS optimally blocked (P<0.05) IL-1beta-induced proinflammatory gene induction for ensuing 16 h. However, CTS for 8h was not sufficient to inhibit iNOS expression for ensuing 28 or 40 h. CONCLUSIONS: Data suggest that constant application of CTS blocks IL-1beta-induced proinflammatory genes at transcriptional level. The signals generated by CTS are sustained after its removal, and their persistence depends upon the length of CTS exposure. Furthermore, the sustained effects of mechanical signals are also reflected in their ability to induce aggrecan synthesis. These findings, once extrapolated to human chondrocytes, may provide insight in obtaining optimal sustained effects of physical therapies in the management of arthritic joints.

Aggrecans↗

Occult renal impairment is common in patients with peripheral vascular disease and normal serum creatinine.

OBJECTIVE: The incidence of peripheral vascular disease (PVD) and angiography/angioplasty is rising annually. The UK Small Aneurysm Trial and other trials have shown renal function is a predictor of increased mortality and failed infrainguinal bypass despite patent vessels. Renal function is classically assessed by serum creatinine (SCr). However, SCr can be normal despite significant renal impairment. A more sensitive test is creatinine clearance (CrCl) as determined by 24-hour urine collection in combination with SCr. We studied the incidence of renal impairment, as defined by CrCl, in PVD patients with normal SCr. METHODOLOGY: All patients with PVD sufficient to necessitate angiography and normal SCr (< or =120 micromol/l - men; < or =97 micromol/l - women) had their CrCl assessed prior to angiography: using both 24-hour urine collection and the Cockcroft-Gault formula. Various blood tests, a detailed history and examination were performed. A control group of arthritic patients, age and sex-matched with similar SCr, also had their CrCl determined. RESULTS: 65 of 76 patients (86%) with normal SCr had a subnormal CrCl (<100 ml/min) and 49 (65%) had a CrCl below 60 ml/min. In the control group of arthritic patients, the proportion having impaired CrCl was significantly less - 67% below 100 mls/min (p=0.0471) and only 15% below 60 mls/min (p<0.0001). The median and interquartile range CrCl of 52 [38-81] mls/min for PVD patients was significantly worse than for control patients (80 [68-119] mls/min -p<0.0001). The Cockcroft-Gault formula for calculating CrCl did not correlate well with the urinary CrCl for the control group but did for PVD patients (p<0.0001). Factors associated with a significantly reduced CrCl were age of at least 75 years, SCr of at least 85 micromol/l and a history of coronary heart disease (all p<0.05). This had a sensitivity of 88% and specificity of 82% for identifying subnormal CrCl. Statin use was associated with a significantly improved CrCl (p=0.040). CONCLUSION: Most PVD patients with normal serum creatinine have occult, significantly impaired renal function as defined by creatinine clearance. Vascular surgeons should include creatinine clearance in pre-operative assessment of renal function especially in patients over 75 years old, with a history of coronary heart disease or a serum creatinine over 85 micromol/l. The method of determining creatinine clearance could be the Cockcroft-Gault calculation or ideally 24-hour urinary creatinine clearance measurement. This would allow appropriate early referral to a nephrologist for further investigation and management. It is worth noting that statin use seems to be associated with a protective effect on renal function.

Aged↗

Pure esophageal atresia with no gap and associated intra-abdominal calcification.

Pure esophageal atresia (PEA) is characterized by a long gap in between the two pouches. Primary anastomosis is usually not feasible and various techniques have been described in the literature to bridge this gap. We describe a case of PEA where there was no gap externally in between the two pouches and associated intra-abdominal calcification.

Abdomen↗

Fentanyl-augmented MRCP.

BACKGROUND: Drugs such as secretin and morphine have been used to augment the visualization of magnetic resonance cholangiopancreatography (MRCP). This study investigated the effectiveness of intravenous administration of a synthetic opioid, fentanyl, in improving the MRCP image quality. METHODS: Thirty consecutive patients with a provisional diagnosis of benign biliary and/or pancreatic disease underwent MRCP. Coronal single-shot fast spin-echo heavily T2-weighted dynamic MRCP images were generated before and at every minute for 10 min after intravenous administration of fentanyl citrate at a dose of 1.0 mug/kg. Pre- and postinjection images were compared and analyzed qualitatively and quantitatively. RESULTS: Qualitatively, visualization of intrahepatic bile ducts, common bile duct, and main pancreatic duct improved after fentanyl injection in five (16%), 11 (37%), and 19 (63%) patients, respectively. The pancreatobiliary junction and common channel were visualized better after fentanyl injection in eight of the 18 patients (44%). Quantitatively, signal intensity and diameters of the intrahepatic ducts, common bile duct, and main pancreatic duct measured at corresponding points on pre- and postinjection images showed an increase above preinjection values in 28 (93%), 27 (90%), and 21 (70%) and in 18 (60%), 26 (86%), and 22 (73%), respectively, and these changes were highly significant at all sites (p < 0.001). CONCLUSIONS: Intravenous administration of fentanyl before MRCP improves qualitative and quantitative visualization of the ductal system anatomy that may be of value in clinical diagnosis and management.

Adolescent↗

Two simple, reliable and valid tests of proximal muscle function, and their application to the management of idiopathic inflammatory myositis.

OBJECTIVE: To develop objective, isotonic, reliable and valid tests of upper (UL) and lower (LL) limb proximal muscle function for use in the management of idiopathic inflammatory myositis (IIM). METHODS: The '1 kg arm lift' test was devised to assess UL function and the '30 s chair stand' test was used for LL function. The tests were performed in 30 control subjects to determine short (24 h) and long (2 week) interval test-retest reliability. Thirty-two patients with IIM were assessed over a period of 2 yr. RESULTS: In the control group both tests showed excellent test-retest reliability; Spearman correlation >0.8 for both tests over both time intervals. Twenty-four of the 32 IIM patients remained in remission over a mean period of 20.7 months throughout which scores varied by <5 for the '1 kg arm lift' test and <3 for the '30 s chair stand' test from each patient's mean score. Eight patients relapsed with scores falling by >5 for the '1 kg arm lift' test and by >3 for the '30 s chair stand' test from the mean remission score in each case. Both UL and LL scores correlated inversely with serum creatinine kinase. CONCLUSION: Two isotonic tests of proximal muscle function are described. They exhibit excellent test-retest reliability and demonstrate construct validity in IIM. Both tests are responsive to changes in disease activity, offer physiological and practical advantages over existing tests of muscle function and are suitable for use in clinical practice.

Adult↗

Doppler Adson's test: predictor of outcome of surgery in non-specific thoracic outlet syndrome.

INTRODUCTION: Outcome of surgery in non-specific thoracic outlet syndrome (TOS) is variable. Duplex imaging of the subclavian artery during Adson's maneuvre may help predict outcome. PATIENTS AND METHODS: A retrospective study of 16 cases of non-specific TOS who had pre-operative duplex imaging of the subclavian artery during Adson's maneuvre was done and their outcomes following surgical decompression of the thoracic outlet studied. RESULTS: Of the eight cases with a positive Adson's test, seven (87.5%) had a complete response of symptoms following surgery while in the eight cases with a negative test, only four (50%) had a favorable response to surgery. CONCLUSION: Duplex scanning of the thoracic outlet during Adson's maneuvre may help predict outcome of thoracic outlet decompression surgery in cases of non-specific TOS.

Decompression, Surgical↗

Radiological classification of anterior skull base anatomy prior to performing medial orbital wall decompression.

PURPOSE: To study a radiological classification, originally described by Keros in 1965, which provides an objective assessment of anterior skull base anatomy relevant in patients undergoing external medial orbital decompression. MATERIALS AND METHODS: The classification is based on anatomical landmarks measured via coronal CT-scan. The patients are divided into 3 Keros categories based on their olfactory fossa depth; Keros 1 (1-3 mm), Keros 2 (4-7 mm) and Keros 3 (8-16 mm). A cross-sectional group of 32 consecutive patients on the hospital radiology database with coronal CT scans were classified according to the Keros system. RESULTS: All the patients fell into one of the three Keros categories. Anatomical associations of the Keros classification suggest that Keros 1 patients have the least risk of intracranial entry whilst Keros 3 patients carry the greatest risk. CONCLUSION: Keros classification provides an objective assessment of anterior skull base anatomy and can therefore guide the surgeon on the superior extent of medial wall bone removal during orbital decompression. This may help improve the safety profile of the procedure.

Decompression, Surgical↗

Ultra-low dose CSE.

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Anesthesia, Epidural↗

Female pattern hair loss, sebum excretion and the end-organ response to androgens.

BACKGROUND: Although female pattern hair loss can be a feature of hyperandrogenism, many women with hair loss show no clinical or biochemical features of androgen excess. It is possible that hair loss in nonhyperandrogenic women is due to a high level of response to androgens by scalp hair follicles. In this study we explored this idea using sebum excretion as a marker of the cutaneous end-organ response to androgens. OBJECTIVES: To test the hypothesis that hair loss in nonhyperandrogenic women is due to an increased cutaneous end-organ response to androgens. METHODS: We studied 100 women, 41 with female pattern hair loss (without hirsutism), 29 with hirsutism (with and without scalp hair loss) and 30 subjects without hair problems. We measured hair density on the frontal scalp, forehead sebum excretion, serum free androgen index (FAI), and body mass index (BMI). RESULTS: The mean FAI was significantly raised in hirsute women compared with nonhirsute women (P < 0.001), but there was no difference in FAI levels between nonhirsute women with and without hair loss. The mean BMI was also significantly elevated in hirsute women (P < 0.01) but there was no difference in BMI between nonhirsute women with and without hair loss. The mean sebum excretion was higher in hirsute women than nonhirsute women but the difference was not statistically significant. There was no difference in sebum excretion between nonhirsute women with and without hair loss. There was no correlation between hair density and sebum excretion. CONCLUSIONS: Our results show that sebum excretion is not elevated in women with female pattern hair loss. This may indicate that different androgen-response pathways operate in controlling hair growth and sebum excretion. The alternative explanation is that nonandrogenic mechanisms are involved in mediating hair loss in some women.

Adolescent↗

Assessment of total thrombus load in symptomatic patients with venous thromboembolism.

Pulmonary embolism (PE) and Deep vein thrombosis (DVT) are separate but related aspects of the same dynamic process termed as venous thrombembolism (VTE). The existing Asian literature has shown a wide variation in the prevalence of VTE, with very limited data from the Indian subcontinent. Between January 2001 and July 2004, 1,552 patients with clinically suspected lower limb DVT underwent a combined ascending radionuclide venogram and lung perfusion scan for assessment of the total thrombus burden. Of 744 patients with radionuclide venography proven DVT, 294 (40%) had a high probability lung scan. Nearly half of these patients were asymptomatic for pulmonary embolism. The high prevalence of PE in patients with DVT suggests the need for evaluation of thrombus load in the venous as well as pulmonary circulation. A combination radionuclide ascending venography with lung perfusion scan is a useful and reliable single test for this purpose.

Adult↗

Application of the polymerase chain reaction on formalin-fixed, paraffin-embedded tissue in the recognition of tuberculous osteomyelitis.

A retrospective series of 45 cases of chronic osteomyelitis collected over a period of 14 years was histologically classified into tuberculous osteomyelitis (25) and chronic non-granulomatous osteomyelitis (20). The tuberculous osteomyelitis group was divided into three subgroups: a) typical granulomas (13 cases); b) ill-defined granulomas (seven cases), and c) suspected granulomas (five cases). An in-house polymerase chain reaction amplifying the 245 bp nucleotide sequence, and capable of detecting 10 fg of DNA of Mycobacterium tuberculosis, was used on the DNA extracted from the paraffin blocks. The polymerase chain reaction was positive in 72% of cases (18) of tuberculous osteomyelitis, but when typical cases of tuberculous osteomyelitis with confirmed granulomas were considered (13), this increased to 84.6% (11). The chronic non-granulomatous osteomyelitis group gave positive polymerase chain reaction results in 20% of the cases (4). Our preliminary study on tuberculous osteomyelitis shows that the polymerase chain reaction can be a very useful diagnostic tool, since a good correlation was seen between typical granulomas and polymerase chain reaction with a sensitivity of 84.6% and a specificity of 80%. In addition, our study shows that tuberculous osteomyelitis can be diagnosed in formalin-fixed paraffin-embedded tissues in the absence of typical granulomas.

Chronic Disease↗

Effect of biopolymer on the dewatering characteristics of autothermal thermophilic aerobic digestion of sludges.

Autothermal thermophilic aerobic digestion of sludge is known to produce poorly dewatering sludges. Laboratory studies were conducted to investigate the reasons for the poor dewatering. It was found that, during digestion, proteins and polysaccharides were released into solution, and that these could be linked to the deterioration in dewatering. The biopolymer release was accompanied by an increase in the monovalent-to-divalent (M/D) cation ratio. The degree to which the M/D caused deterioration of the sludges depended on the presence of iron in sludge. When the iron content was high, the release of protein and polysaccharides was low. When iron was low, the release of protein and polysaccharides increased linearly with the M/D ratio. The dose of conditioning chemicals, cationic polymer or ferric chloride, was related to the amount of colloidal biopolymer present in solution. The findings suggest that the addition of iron during the digestion process has the potential to produce better dewatering sludges.

Aerobiosis↗

Nonstarter lactic acid bacteria biofilms and calcium lactate crystals in Cheddar cheese.

A sanitized cheese plant was swabbed for the presence of nonstarter lactic acid bacteria (NSLAB) biofilms. Swabs were analyzed to determine the sources and microorganisms responsible for contamination. In pilot plant experiments, cheese vats filled with standard cheese milk (lactose:protein = 1.47) and ultrafiltered cheese milk (lactose:protein = 1.23) were inoculated with Lactococcus lactis ssp. cremoris starter culture (8 log cfu/mL) with or without Lactobacillus curvatus or Pediococci acidilactici as adjunct cultures (2 log cfu/mL). Cheddar cheeses were aged at 7.2 or 10 degrees C for 168 d. The raw milk silo, ultrafiltration unit, cheddaring belt, and cheese tower had NSLAB biofilms ranging from 2 to 4 log cfu/100 cm2. The population of Lb. curvatus reached 8 log cfu/g, whereas P. acidilactici reached 7 log cfu/g of experimental Cheddar cheese in 14 d. Higher NSLAB counts were observed in the first 14 d of aging in cheese stored at 10 degrees C compared with that stored at 7.2 degrees C. However, microbial counts decreased more quickly in Cheddar cheeses aged at 10 degrees C compared with 7.2 degrees C after 28 d. In cheeses without specific adjunct cultures (Lb. curvatus or P. acidilactici), calcium lactate crystals were not observed within 168 d. However, crystals were observed after only 56 d in cheeses containing Lb. curvatus, which also had increased concentration of D(-)-lactic acid compared with control cheeses. Our research shows that low levels of contamination with certain NSLAB can result in calcium lactate crystals, regardless of lactose:protein ratio.

Animals↗

Cheese pH, protein concentration, and formation of calcium lactate crystals.

The occurrence of calcium lactate crystals (CLC) in hard cheeses is a continual expense to the cheese industry, as consumers fail to purchase cheeses with this quality defect. This research investigates the effects of the protein concentration of cheese milk and the pH of cheese on the occurrence of CLC. Atomic absorption spectroscopy was used to determine total and soluble calcium concentrations in skim milk (SM1, 8.7% total solids), and skim milk supplemented with nonfat dry milk (CSM1, 13.5% total solids). Calcium, phosphorus, lactic acid, and citrate were determined in cheeses made with skim milk (SM2, 3.14% protein), skim milk supplemented with ultrafiltered milk (CSM2, 6.80% protein), and nonfat dry milk (CSM3, 6.80% protein). Supplementation with nonfat dry milk increased the initial total calcium in CSM1 (210 mg/100 g of milk) by 52% compared with the total calcium in SM1 (138 mg/100 g of milk). At pH 5.4, soluble calcium concentrations in CSM1 were 68% greater than soluble calcium in SM1. In cheeses made from CSM2 and CSM3, total calcium was 26% greater than in cheeses made from SM2. As the pH of cheeses made from SM2 decreased from 5.4 to 5.1, the concentration of soluble calcium increased by 61.6%. In cheeses made from CSM2 and CSM3, the concentrations of soluble calcium increased by 41.4 and 45.5%, respectively. Calcium lactate crystals were observed in cheeses made from SM2 at and below pH 5.1, whereas CLC were observed in cheeses from CSM2 and CSM3 at and below pH 5.3. The increased presence of soluble calcium can potentially cause CLC to occur in cheese manufactured with increased concentrations of milk solids, particularly at and below pH 5.1.

Animals↗

Methylenetetrahydrofolate reductase gene polymorphism in Indian stroke patients.

BACKGROUND AND AIMS: In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR) C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T gene polymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy) and conventional risk factors. SETTINGS AND DESIGN: Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital. MATERIALS AND METHODS: Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done. STATISTICAL ANALYSIS: MTHFR gene polymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test. RESULTS: There were 58 patients with ischemic stroke, whose mean age was 50 (4-79) years; among them, 10 were females. MTHFR gene polymorphism was present in 19 (32.8%) patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50%) patients and Hcy in 48 (83%). Hypertension was present in 28 (48%) patients, diabetes in 12 (21%), hyperlipidemia in 52 (90%), smoking in 17 (29%), obesity in 1 (1.7%) and family history of stroke in first-degree relatives in 13 (22.4%). There was no significant relationship of MTHFR gene polymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians (P<0.003). In 3 patients with MTHFR TT alleles, Hcy was elevated in all 3, low folic acid in 2 and family history of stroke in 1 patient. CONCLUSION: MTHFR gene polymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.

Adolescent↗