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R Agarwal

Publications and source records attributed to R Agarwal.

At least 19 recordsLinked to original sources
PubMed2003

Improvement in the performance of automated spike detection using dipole source features for artefact rejection.

OBJECTIVE: We evaluated the use of an efficient dipole source algorithm to improve performance of automated spike detection by identifying false detections caused by artefacts. METHODS: Automated spike detections were acquired from 26 patients undergoing prolonged electroencephalograph (EEG) monitoring. Data from 6 patients were used to develop the method and data from 20 patients were used to test the method. To provide a standard against which to evaluate the results, an electroencephalographer (EEGer) visually categorized all automated detections before the dipole models were calculated for all events. The event categories (as defined by the EEGer) were then combined with properties of the dipole model and features were identified that differentiated spike and artefact detections. The resulting method was then applied to the testing data set. RESULTS: Residual variance and eccentricity of the dipole models differentiated artefact and spike detections. A separate set of rules defining eye blink artefact was also developed. The combined criteria removed a mean of 53.2% of artefact from the testing data set. Some spike detections (4.3%) were also lost. CONCLUSIONS: The features of the dipole source of a detected event can be used to differentiate artefacts from spikes. This algorithm is computationally light and could be implemented on-line.

Electroencephalography↗
PubMed2003

Use of telemedicine in evading cholera outbreak in Mahakumbh Mela, Prayag, UP, India: an encouraging experience.

Telemedicine (TM) services a process in which expert medical advice from afar is provided using electronic signals to transfer the medical data from one site to another. As a pilot project to assess the efficacy of TM in developing countries like India, a telemedicine center was set up at the main hospital of Mahakumbh mela--a grand religious fair, at Prayag, a city in north India. The daily reporting of the in-patient and outpatient cases at the fair revealed a surge of diarrhea cases among the pilgrims at the fair. This information was communicated to the referral center at Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), which, with the help of its microbiology department, conducted microbiological examinations of stool samples and rectal swabs of patients along with various water samples. Vibrio cholerae was isolated in 22.6% (7/31) of the samples. This information was immediately relayed to the Main Hospital at the fair online, and then to the health authorities, who took strict and prompt measures to improve hygiene. Subsequently, the number of diarrhea cases decreased considerably in a matter of a few days, and thus an epidemic disaster was averted, which could have created havoc in such a large gathering.

Aged↗
PubMed2003

Absence of leukaemic fusion gene transcripts in preterm infants exposed to diagnostic x rays.

BACKGROUND: Childhood leukaemias express novel, clonotypic fusion genes that may already be present at birth before the clinical manifestation of leukaemia. Exposure of the fetus to diagnostic x rays is reported to increase the risk of childhood leukaemia, and may do so by generating leukaemic fusion genes. Advances in neonatal medicine in the past decade that have extended the limits of viability of preterm babies down to 23 weeks of gestation have resulted in the increased use of diagnostic x rays to monitor neonatal progress. AIM: To investigate whether exposure of very preterm infants to diagnostic x rays in the neonatal period leads to the development of leukaemic fusion genes. METHODS: Peripheral blood samples were collected at birth from very preterm infants (23-30 weeks gestation) and following exposure to diagnostic x rays at intervals of two weeks, until discharge. Cord blood samples from normal full term infants served as controls. Total RNA was extracted from the blood and the expression of the fusion genes TEL-AML1, MLL-AF4, and BCR-ABL, characteristic of three subtypes of childhood leukaemia, was investigated in the preterm and full term infant samples using a nested reverse transcriptase polymerase chain reaction method. Serial pre- and post-x ray samples from 42 preterm babies, pre-x ray samples from an additional 46 preterm infants, and cord blood samples from 100 normal full term infants were screened for fusion gene transcripts. RESULTS: No leukaemic fusion gene transcripts were detected in preterm infants following exposure to diagnostic x rays. A BCR-ABL transcript was identified in a single preterm infant prior to x ray exposure. TEL-AML1 transcripts were detected in cord blood samples from two full term infants. MLL-AF4 transcripts were not detected in any of the pre- or full term infants tested. CONCLUSIONS: Exposure of the preterm infants to x rays in this small series and at the doses used for diagnostic purposes did not induce leukaemic fusion gene expression, but we cannot exclude the possibility that a small proportion of preterm infants may be unusually sensitive to x rays.

Cell Line↗
PubMed2003

Resting energy expenditure in chronic kidney disease: relationship with glomerular filtration rate.

BACKGROUND: The kidneys may account for up to 20% of resting energy expenditure (REE), but there is controversy regarding the relationship between severity of renal impairment and REE. Furthermore, reduction in protein intake is associated with declining glomerular filtration rate (GFR) that contributes to malnutrition. If a selective aversion to protein intake or a global reduction in food intake takes place is not known. METHODS: To define the relationship between REE and its relationship to GFR, we measured REE with indirect calorimetry, GFR with iothalamate clearance, and body composition with creatinine kinetics and skin-fold measurements in 16 patients with mild to moderate renal failure due to type 2 diabetes mellitus (n = 12) or glomerulonephritides (n = 4). RESULTS: In univariate analysis, age, weight, height, body mass index, lean body mass, urine urea nitrogen but not hemoglobin or albumin correlated with REE. In multivariate analysis, lean body mass emerged as the strongest predictor of REE followed by GFR. A lower GFR was associated with a lower REE. Also, we found reduced REE, but not a fall in GFR, was associated with a fall in dietary protein intake. This supports the hypothesis that patients with CKD have no selective aversion to protein; reduction in dietary protein intake with progressive CKD is due to global reduction in food intake. CONCLUSIONS: We conclude that REE falls with declining renal function in patients with CKD. This is likely secondary to combination of reduced energy expenditure of kidneys, adaptation to decreased energy intake or alteration in cellular energy metabolism.

Body Composition↗
PubMed2002

Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis.

Prostate cancer (PCA) is one of the most common invasive malignancies of men in the US, however, there have been limited successes so far in its therapy. Even most potent agents (e.g. TNFalpha) are ineffective in killing human PCA cells possibly due to constitutive activation of NF-kappaB that subsequently activates a large number of anti-apoptotic genes. In such a scenario, strong apoptotic agent TNFalpha, further induces NF-kappaB activation rather than inducing apoptosis. In several recent studies, we have demonstrated both cancer preventive and anti-cancer efficacy of silymarin and its constituent silibinin in a variety of experimental tumor models and cell culture systems. Here we examined whether silibinin is effective in inhibiting constitutive NF-kappaB activation in human PCA cells, which would help in overcoming TNFalpha-insensitivity. Our studies reveal that silibinin effectively inhibits constitutive activation of NF-kappaB in advanced human prostate carcinoma DU145 cells. Consistent with this, nuclear levels of p65 and p50 sub-units of NF-kappaB were also reduced. In the studies assessing molecular mechanism of this effect, silibinin treatment resulted in a significant increase in the level of IkappaBalpha with a concomitant decrease in phospho-IkappaBalpha. Kinase assays revealed that silibinin dose-dependently decreases IKKalpha kinase activity. The effect of silibinin on IKKalpha seemed to be direct as evidenced by the in vitro kinase assay, where immunoprecipitated IKKalpha was incubated with silibinin. This shows that silibinin does not necessarily need an upstream event to bring about its inhibitory effect on IKKalpha and downstream effectors. Additional studies showed that silibinin also inhibits TNFalpha-induced activation of NF-kappaB via IkappaBalpha pathway and subsequently sensitizes DU145 cells to TNFalpha-induced apoptosis. These results indicate that silibinin could be used to enhance the effectiveness of TNFalpha-based chemotherapy in advanced PCA.

Active Transport, Cell Nucleus↗
PubMed2002

Fabric-staining properties and washability of a novel liposomal dithranol formulation.

AIM: To test the staining potential of a novel liposomal dithranol gel on different types of fabrics and compare it with the only commercially available dithranol preparation in India, Derobin. METHODS: Pure cotton, pure polyester and four blends of the two fabrics were tested for staining and washability. RESULTS: Both products showed the least staining and spreading on pure cotton with progressively worse stains as the proportion of polyester in the fabric increased. When compared with each other the liposomal dithranol gel showed markedly lighter staining than Derobin on all fabrics. It also washed off completely with water whereas the Derobin stains could not be washed off, even with detergent. CONCLUSION: The liposomal gel due to its superior staining properties may potentially increase the acceptability of dithranol amongst psoriasis patients.

Administration, Topical↗
PubMed2002

Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants.

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.

Analysis of Variance↗
PubMed2002

Anaesthetic management of a patient with Emery-Dreifuss muscular dystrophy.

Emery-Dreifuss muscular dystrophy is a rare form of muscular dystrophy associated with cardiac implications such as cardiomyopathy and arrhythmias leading to sudden death. We describe the anesthetic management of a patient with Emery-Dreifuss muscular dystrophy who presented for orthopaedic surgery and discuss the disorder and its potential anaesthetic implications.

Achilles Tendon↗
PubMed2002

Tamoxifen-related porphyria cutanea tarda.

We report a case of porphyria cutanea tarda (PCT) in a patient with breast cancer following adjuvant tamoxifen. Cessation of tamoxifen resulted in a prompt decline in urinary porphyrins suggestive of a causative role. Tamoxifen is known to be hepatotoxic; however, its association with PCT is unclear. In this report, we discuss the porphyrinogenicity of tamoxifen and potential mechanisms.

Anticarcinogenic Agents↗
PubMed2002

Is continuous veno-venous hemofiltration for acetaminophen-induced acute liver and renal failure worthwhile?

We describe a patient with acute liver and renal failure secondary to acetaminophen and chronic alcohol abuse who was treated aggressively with oral acetylcysteine, continuous renal replacement therapy, glucose and branched-chain amino acid intravenous feeding and ventilatory support. The patient had a predicted mortality of > 95% without liver transplantation however, with intensive ventilatory, renal, and nutritional support he made a complete recovery. We discuss the benefits of aggressive supportive therapy and suggest that continuous renal replacement therapy may allow gentle fluid removal, excellent control of cerebral edema and intravenous feeding that may favorably influence prognosis.

Acetaminophen↗
PubMed2002

How to diagnose hypertension in hemodialysis patients?

An accurate measurement of BP is essential for the diagnosis and treatment of hypertension in any hypertensive patient. Although hypertension is a big public health burden in hemodialysis patients and is characterized by elevated systolic and pulse pressure, assessment of blood pressure in these patients is often difficult. Some problems unique in this hypertensive population include interdialytic weight gain, occurrence of sleep-apnea and consequent nocturnal hypertension, and the inability to take BP in both arms in patients who have hemodialysis angioaccess in the arm. The problems of accurate assessment of BP are compounded by the lack of standardized BP measurements and the occurrence of white coat effect in about 1 in 5 patients. Precise measurement of BP in hemodialysis patients requires interdialytic ambulatory BP monitoring. However, when ambulatory BP monitoring is not possible, BP obtained in the dialysis unit can be used in a qualitative sense for prediction of hypertension in these patients. A 2-week averaged predialysis BP of >150/85 mmHg or a postdialysis BP of >130/75 mmHg has at least 80% sensitivity in diagnosing hypertension. Specificity of at least 80% can be achieved if predialysis BP of >160/90 mmHg or postdialysis BP of >140/80 mmHg are used. However, poor agreement between HD unit BPs and ABPs precludes their use for the precise prediction of BP. Improving the measurement technique in the dialysis unit, averaging multiple BP, using a 20 min postdialysis reading, or home BP monitoring can improve BP determination when interdialytic BP monitoring is not possible.

Blood Pressure Determination↗
PubMed2001

Preparation and in vitro evaluation of liposomal/niosomal delivery systems for antipsoriatic drug dithranol.

Dithranol is one of the mainstays in the topical treatment of psoriasis. However, the use of dithranol in psoriatic condition is inconvenient and troublesome, as it has irritating, burning, staining and necrotizing effect on the normal as well as the diseased skin. The entrapment of drug in vesicles is viewed to help in the localized delivery of the drug and an improved availability of the drug at the site will reduce the dose and in turn, the dose-dependent side effects like irritation and staining. The investigations deal with critical parameters controlling the formulation and stabilization of dithranol loaded liposomes and niosomes. The entrapment efficiency of dithranol in liposomes was optimized by altering the proportion of phosphatidyl choline and cholesterol, and in case of niosomes it was between Span 60 and cholesterol. Hydration and permeation mediums were also established keeping in view the poor solubility and stability of dithranol. The mean liposome and niosomes sizes were 4+/-1.25 and 5+/-1.5 microm, respectively. The drug-leakage study carried out at different temperatures of 4-8, 25+/-2 and 37 degrees C for a period of two months affirms that the drug leakage increased at a higher temperature. The in vitro permeation study using mouse abdominal skin shows significantly enhanced permeation with vesicles as indicated by flux of dithranol from liposomes (23.13 microg/cm(2)/h) and niosomes (7.78 microg/cm(2)/h) as compared with the cream base (4.10 microg/cm(2)/h).

Administration, Topical↗
PubMed2001

Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells.

BACKGROUND: Targeting epigenetic events associated with autonomous growth of advanced prostate cancer (PCA) is a practical approach for its control, prevention, and treatment. Recently we showed that treatment of prostate carcinoma DU145 cells with cancer preventive flavonoid silymarin at 100-200 microM doses inhibits erbB1-Shc mitogenic signaling and modulates cell cycle regulators leading to a G1 arrest and inhibition of cell growth and anchorage-independent colony formation. Here, we asked the question whether these important findings could be extended to other cancer preventive flavonoids and isoflavones such as epigallocatechin 3-gallate (EGCG) and genistein. METHODS: DU145 cells were treated with similar doses (100-200 microM) of silymarin, genistein or EGCG, cell lysates prepared, and levels of activated signaling molecules (erbB1-Shc-ERK1/2) and cell cycle regulators (CDKIs, CDKs, and cyclins) analyzed employing immunoprecipitation and/or immunoblotting techniques. Cell growth studies were done by cell counting during 5 days of treatment with these agents, and cell death was determined by Trypan blue staining. RESULTS: Treatment of cells with silymarin, genistein or EGCG at 100-200 microM resulted in a complete inhibition of TGFalpha-caused activation of erbB1 followed by a moderate to strong inhibition (10-90%) of Shc activation without an alteration in their protein levels. Silymarin and genistein, but not EGCG, also inhibited (10% to complete) ERK1/2 activation suggesting that these agents impair erbB1-Shc-ERK1/2 signaling in DU145 cells. In other studies, silymarin, genistein or EGCG caused a strong induction of Cip1/p21 (up to 2.4-fold) and Kip1/p27 (up to 150-fold), and a strong decrease in CDK4 (40-90%) but had moderate effect on CDK2, and cyclins D1 and E. An enhanced level of CDKIs also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein or EGCG also resulted in 50-80% cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein showed cytotoxic effect causing 30-40% cell death. A more profound cytotoxic effect was observed with EGCG accounting for 50% cell death at lower doses and complete loss of viability at higher doses. CONCLUSIONS: These results suggest that similar to silymarin, genistein and EGCG also inhibit mitogenic signaling pathway(s) and alter cell cycle regulators, albeit at different levels, leading to growth inhibition and death of advanced and androgen-independent prostate carcinoma cells. More studies are, therefore, needed with these agents to explore their anti-carcinogenic potential against human prostate cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Inhibitory effect of silibinin on ligand binding to erbB1 and associated mitogenic signaling, growth, and DNA synthesis in advanced human prostate carcinoma cells.

We recently showed the inhibitory effect of a flavonoid antioxidant, silymarin, on erbB1-Shc activation in prostate cancer (PCA) DU145 cells. In the present study, we performed more detailed mechanistic and molecular modeling studies with pure silibinin to assess and define its effect on membrane signaling related to erbB1 activation in human PCA LNCaP and DU145 cells. Studies also were performed to establish the biologic responses toward extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation, cell growth, and DNA synthesis. Treatment of serum-starved cells with various doses of silibinin for 2 h followed by (125)I-epidermal growth factor (EGF) showed 30-75% inhibition in ligand binding and 55-95% inhibition in its internalization in LNCaP cells and 20-64% and 12-27% inhibition in these two events in DU145 cells. Time-response studies showed similar effects. In further studies, treatment of serum-starved cultures with silibinin followed by EGF showed strong inhibitory effects on membrane and cytoplasmic signaling molecules. In the case of erbB1 activation, silibinin showed a 58-75% decrease in LNCaP and a 40-100% decrease in DU145 cells at 50, 75, and 100-microg/mL doses. Inhibitory effects of silibinin also were evident on ERK1/2 activation (20-80% inhibition) in both cell lines. Treatment of serum-starved cultures with silibinin resulted in 20-40% and 30-55% inhibition of LNCaP and DU145 cell growth, respectively, at similar doses after 1-3 d of treatment, and 10-50% cell death in both cell lines. Under 10% serum conditions, identical silibinin treatments resulted in 20-65% inhibition of cell growth in LNCaP and DU145 cells but did not cause any cell death. Similar doses of silibinin treatments for 24 h also resulted in 25-60%, 35-40%, and 36-50% inhibition of DNA synthesis when cells were cultured in 10% serum, totally serum starved, and serum starved plus stimulated with EGF, respectively. Molecular modeling of silibinin showed that it is a highly lipophilic compound, suggesting that it interacts with lipid-rich plasma membrane, including binding with erbB1, thereby competing with the EGF-erbB1 interaction. Because the ligand-erbB1 autocrine-loop is causally involved in advanced and androgen-independent PCA, the observed effects of silibinin and its strong lipophilic nature could be useful in developing this agent for the prevention and therapy of PCA.

Antioxidants↗
PubMed2001

Minimal enteral nutrition.

Although parenteral nutrition has been used widely in the management of sick very low birth weight (VLBW) infants, a smooth transition to the enteral route is most desirable. Animal studies have shown that long periods of starvation are associated with mucosal atrophy and reduction of enzymatic activity. Studies have shown that giving small volumes of feeds frequently exerts a trophic effect on the gut mucosa. This concept has been termed as Minimal Enteral Nutriton (MEN). Clinical benefits of MEN include faster progression to full enteral feeds, lesser episodes of feed intolerance and reduction in hospital stay without a concomitant increase in the risk of necrotizing enterocolitis. MEN may be commenced in neonates on ventilation and total parenteral nutrition. A protocol for giving MEN has been described.

Animals↗
PubMed2001

Mutation analysis of codons 345 and 347 of rhodopsin gene in Indian retinitis pigmentosa patients.

More than 100 mutations have been reported till date in the rhodopsin gene in patients with retinitis pigmentosa. The present study was undertaken to detect the reported rhodopsin gene point mutations in Indian retinitis pigmentosa patients. We looked for presence or absence of codon 345 and 347 mutations in exon 5 of the gene using the technique of allele-specific polymerase chain reaction by designing primers for each mutation. We have examined 100 patients from 76 families irrespective of genetic categories. Surprisingly, in our sample the very widely reported highly frequent mutations of codon 347 (P --> S/A/R/Q/L/T) were absent while the codon 345 mutation V --> M was seen in three cases in one family (autosomal dominant form) and in one sporadic case (total two families). This is the first report on codon 345 and 347 mutation in Indian retinitis pigmentosa subjects.

Apoptosis↗