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R Agarwal

Publications and source records attributed to R Agarwal.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2001

Add-on angiotensin receptor blockade with maximized ACE inhibition.

BACKGROUND: Prolonged angiotensin-converting enzyme (ACE) inhibitor therapy leads to angiotensin I (Ang I) accumulation, which may "escape" ACE inhibition, generate Ang II, stimulate the Ang II subtype 1 (AT1) receptor, and exert deleterious renal effects in patients with chronic renal diseases. We tested the hypothesis that losartan therapy added to a background of chronic (>3 months) maximal ACE inhibitor therapy (lisinopril 40 mg q.d.) will result in additional Ang II antagonism in patients with proteinuric chronic renal failure with hypertension. METHODS: Sixteen patients with proteinuric moderately advanced chronic renal failure completed a two-period, crossover, randomized controlled trial. Each period was one month with a two-week washout between periods. In one period, patients received lisinopril 40 mg q.d. along with other antihypertensive therapy, and in the other, losartan 50 mg q.d. was added to the previously mentioned regimen. Hemodynamic measurements included ambulatory blood pressure monitoring (ABP; Spacelabs 90207), glomerular filtration rate (GFR) with iothalamate clearances and cardiac outputs by acetylene helium rebreathing technique. Supine plasma renin activity and plasma aldosterone and 24-hour urine protein were measured in all patients. RESULTS: Twelve patients had diabetic nephropathy, and four had chronic glomerulonephritis. The mean age (+/- SD) was 53 +/- 9 years. The body mass index was 38 +/- 5.7 kg/m(2), and all except two patients were males. Seated cuff blood pressure was 156 +/- 18/88 +/- 12 mm Hg. The pulse rate was 77 +/- 11 per min, and the cardiac index was 2.9 +/- 0.5 L/min/m(2). Mean log 24-hour protein excretion/g creatinine or overall ABPs did not change. Mean placebo subtracted, losartan-attributable change in protein excretion was +1% (95% CI, -20% to 28%, P = 0.89). Similarly, the change in systolic ambulatory blood pressure (ABP) was 4.6 mm Hg (-5.7 to 14.9, P = 0.95), and diastolic ABP was 1.5 mm Hg (-4.5 to 7.6, P = 0.59). No change was seen in cardiac output. However, there was a mean 14% increase (95% CI, 3 to 26%, P = 0.017) in GFR attributable to losartan therapy. A concomitant fall in plasma renin activity by 32% was seen (95% CI, -15%, - 45%, P = 0.002). No hyperkalemia, hypotension, or acute renal failure occurred in the trial. These results were not attributable to sequence or carryover effects. CONCLUSIONS: Add-on losartan therapy did not improve proteinuria or ABP over one month of add on therapy. Improvement of GFR and fall in plasma renin activity suggest that renal hemodynamic and endocrine changes are more sensitive measures of AT1 receptor blockade. Whether add-on AT1 receptor blockade causes antiproteinuric effects or long-term renal protection requires larger and longer prospective, randomized controlled trials.

Adolescent↗
PubMed2001

Prediction of hypertension in chronic hemodialysis patients.

BACKGROUND: There are no universally accepted criteria for the diagnosis of hypertension in hemodialysis (HD) patients. We sought to determine the clinical performance of predialysis and postdialysis systolic and diastolic blood pressure values (BPs) in diagnosing hypertension or assessing its control. METHODS: Seventy patients [77% African American, 46% females, mean age 59 +/- 17 (SD) years, 34% diabetics] on chronic HD underwent a single 44-hour interdialytic ambulatory blood pressure monitoring (ABPM) and concomitant recording of BP by conventional syphygmomanometer in the HD unit for two weeks. Hypertension was defined as systolic BP (SBP) > or =135 mm Hg or diastolic BP (DBP) > or =85 mm Hg on an average 44-hour ABPM. RESULTS: Average ABP was 144 +/- 22/81 +/- 11 mm Hg. Seventy-three percent of the patients had systolic hypertension; 40% had diastolic hypertension, and 24% were normotensive or had well-controlled BP. Area under the curve of receiver operating characteristic (ROC) curves exceeded 80% for all BPs, but the thresholds for best sensitivity and specificity were markedly different for predialysis and postdialysis BPs. A two-week averaged predialysis BP of > 150/85 mm Hg or a postdialysis BP of > 130/75 mm Hg had at least 80% sensitivity in diagnosing hypertension. Specificity of at least 80% was achieved if predialysis BP of > 160/90 mm Hg or postdialysis BP of > 140/80 mm Hg was used. There was poor agreement between HD unit BP and ABP values. CONCLUSIONS: HD unit BP values can be used to identify the presence or absence of hypertension, although prediction of ambulatory BPs from HD unit BP values cannot be made reliably in individual patients.

Adult↗
PubMed2001

Clinical performance characteristics of hemodialysis graft monitoring.

BACKGROUND: Regular monitoring of dialysis grafts is recommended, but the value of dialysis graft blood flow monitoring and venous pressures in predicting subsequent outcomes are controversial. METHODS: Over a period of one month, we performed simultaneous flow and venous pressure monitoring in 71 dialysis patients with polytetrafluoroethylene (PTFE) grafts. These patients were prospectively followed for one year. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of the various monitoring techniques. RESULTS: During the period of follow-up, there were 71 graft failures (30 angioplasty alone and 41 thrombosis followed by interventional or surgical revisions). Failed grafts had a lower blood flow rate [799 +/- 452 (SD) mL/min] when compared with those without failure (1019 +/- 485 mL/min, P = 0.05) Single static or dynamic venous-pressure monitoring were not predictive of graft failure. ROC analysis showed poor performance of graft flows in predicting graft failures over the short (30 days, AUC = 0.726, 95% CI, 0.509 to 0.942) and long term (one year, AUC = 0.630, 95% CI, 0.499 to 0.761). An adjustment of graft flows for systolic blood pressure or classification of graft based both on flows and venous pressure did not improve test performance. CONCLUSIONS: Although dialysis graft blood flow rates are statistically different in patients who have graft failure (graft angioplasty and surgery or thrombosis) versus those who do not, the performance characteristics preclude clinical decision-making from an isolated blood flow or venous pressure study.

Aged↗
PubMed2001

Buzz in the axilla: a new physical sign in hemodialysis forearm graft evaluation.

The value of physical signs in predicting flow rates or polytetrafluoroethylene (PTFE) hemodialysis graft survival is not well known. Simultaneous physical examination and flow measurements were performed in 67 dialysis patients with PTFE grafts over a period of 1 month. Physical signs included the presence and location of a palpable thrill, location and auscultatory nature of the bruit, and presence or absence of a pulsation. Patients were followed up for 1 year to detect the time to failure defined by angioplasty, clotting, or surgical revision. There was a fair correlation between physical signs and graft flow rates. In a multivariate model, systolic blood pressure, location of the thrill, and patient age were the best predictors of graft flow. During follow-up, there were 68 graft failures (30 grafts, angioplasty alone; 38 grafts, thrombosis followed by interventional or surgical revisions). The median survival of a graft without a thrill in the axilla was 154 days compared with 321 days when a thrill was present (P = 0.05, log-rank test). Dialysis graft physical examination is a useful test to predict graft flows, as well as graft failure. The single best test is the location of the thrill along the venous limb of the graft. Average flow rates for no thrill, thrill but distal to the midarm, and axillary buzz were approximately 500, 750, and 1,000 mL/min, respectively. This single physical sign also correlated with subsequent graft failure and should be incorporated into physical examinations of all dialysis grafts.

Arteriovenous Shunt, Surgical↗
PubMed2001

Lisinopril therapy for hemodialysis hypertension: hemodynamic and endocrine responses.

To evaluate the antihypertensive effects of lisinopril, a renally excreted angiotensin-converting enzyme inhibitor, we assessed supervised administration of the drug after hemodialysis (HD) three times weekly. Blood pressure (BP) was assessed by interdialytic 44-hour ambulatory BP (ABP) monitoring, and endocrine responses were assessed by plasma renin activity (PRA) before and after dialysis. Lisinopril dose was titrated at biweekly intervals. If this was not effective after full titration (lisinopril to 40 mg three times weekly), ultrafiltration was added to reduce dry weight. The primary outcome variable was change in BP from the end of the run-in period to the end of the study. No change in mean ABP was noted during run-in. However, mean 44-hour ABP decreased from 149 +/- 14 (SD)/84 +/- 9 to 127 +/- 16/73 +/- 9 mm Hg, a decrease of 22/11 mm Hg (P < 0.001) at final evaluation. Of 11 patients who completed the trial, only 2 patients had systolic hypertension (>/=135 mm Hg) and 1 patient had diastolic hypertension (>/=85 mm Hg) at the final visit. Four patients were administered 10 mg of lisinopril; 5 patients, 20 mg; and 2 patients, 40 mg; only 1 of these patients required ultrafiltration therapy. There was a persistent antihypertensive effect over 44 hours. BP reduction was achieved without an increase in intradialytic symptomatic or asymptomatic hypotensive episodes. PRA increased in response to dialysis, as well as lisinopril. In conclusion, supervised lisinopril therapy is effective in controlling hypertension in chronic HD patients. This may be related to blockade of angiotensin II generation by kidneys despite the loss of excretory function.

Adult↗
PubMed2001

Expression profiles of interleukin-15 in early and late gestational human placenta and in pre-eclamptic placenta.

The presence of interleukin-15 (IL-15) mRNA in human placenta has been demonstrated previously. The present study was undertaken to investigate the expression profiles of IL-15 mRNA and protein in early and late gestational placental tissues, and also the effect of labour on its production. Levels of placental IL-15 expression were also determined in patients presenting with pre-eclampsia. An explant culture system was used to study the release of immunoreactive IL-15 by the placental tissues. Enzyme-linked immunosorbent assays were employed to quantify concentrations in the culture medium. The results showed that placental tissues from all groups released immunoreactive IL-15 into the culture medium. Moreover, the level of secretion by the term placental tissues was much higher than that by first trimester tissues. The presence of labour at term resulted in a further increase in placental IL-15 production. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the expression of IL-15 mRNA in these tissues. The results confirmed the expression of IL-15 in placenta from all the groups and the mRNA levels in the samples was highly correlated with the respective protein concentrations. Levels of both IL-15 mRNA and protein were significantly reduced in the pre-eclamptic placental tissue compared with the normal controls. The present study suggests an important role for this novel cytokine in human pregnancy.

Culture Media↗
PubMed2001

Management of soft-tissue problems in leg trauma in conjunction with application of the Ilizarov fixator assembly.

Forty-five patients presenting with high-energy open grade III tibial diaphyseal fractures were treated with the Ilizarov technique. Of these patients, 28 required plastic surgical intervention for achieving wound closure. Most of the injuries were complicated by initial neglect and inadequate primary soft-tissue coverage resulting in osteitis, sequestration, and segmental diaphyseal tibial defects, often in combination with skin-envelope deficits of various types in and around the fracture perimeter. The unique soft-tissue problems encountered while using the Ilizarov fixator have not been focused on in previous reports on the management of segmental bone defects. Four basic local flap procedures: the transposition flap, rotation flap, adipofascial turnover flap, and Z-plasty are useful and versatile for managing most types and grades of soft-tissue defects associated with a segmental bone loss with the Ilizarov technique.

Adolescent↗
PubMed2001

Computer-assisted sleep staging.

To address the subjectivity in manual scoring of polysomnograms, a computer-assisted sleep staging method is presented in this paper. The method uses the principles of segmentation and self-organization (clustering) based on primitive sleep-related features to find the pseudonatural stages present in the record. Sample epochs of these natural stages are presented to the user, who can classify them according to the Rechtschaffen and Kales (RK) or any other standard. The method then learns from these samples to complete the classification. This step allows the active participation of the operator in order to customize the staging to his/her preferences. The method was developed and tested using 12 records of varying types (normal, abnormal, male, female, varying age groups). Results showed an overall concurrence of 80.6% with manual scoring of 20-s epochs according to RK standard. The greatest amount of errors occurred in the identification of the highly transitional Stage 1, 54% of which was misclassified into neighboring stages 2 or Wake.

Adolescent↗
PubMed2001

Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic fever.

During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean+/-S.D.=36+/-20 U ml(-1)) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean+/-S.D.=5+/-2 U ml(-1); P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the 'cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1-4, 5-8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator.

Autoantibodies↗