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R Mukherjee

Publications and source records attributed to R Mukherjee.

At least 19 recordsLinked to original sources
PubMed2006

Histological processing variability in the determination of lateral resection margins in rectal cancer.

BACKGROUND: Involvement of the lateral resection margin (LRM) has been shown to be a reliable predictor of local recurrence of rectal cancer. Accurate determination of the LRM status is crucial in selecting patients for postoperative radiotherapy. However, variability in processing factors may affect the measurement of the LRM. AIM: To investigate how formalin fixation and laboratory processing affects the measurement of the LRM. METHODS: For this study, rectal cancer specimens (n = 9) were fixed in formalin for 4 days and then sectioned transversally, and one half of the specimen was sent for processing. The effacing tumours were placed back in formalin for another 3 days. At day 7, the effacing tumour block (mirror image) was sent for processing. The longest and the shortest perpendicular resection margins for each of the day 4 and day 7 specimens were measured. In a second experiment, control tissue (colon; n = 40), length 10 (0.05) mm, was also processed from a normal sigmoid colon. Specimens were retained in formalin for 24 h (n = 12), 48 h (n = 12), 72 h (n = 9) and 96 h (n = 7). The degree of tissue shrinkage was then recorded. Variations in the recorded LRM and length of colonic tissue are presented as a median (interquartile range) and data were compared using analysis of variance. RESULTS: In the cases of rectal cancer, the variation in measured LRM between day 4 and day 7 specimens was 3.2 (1.5-5) mm. In 30 of the 37 comparisons, the day 7 LRM increased in length, whereas in the remaining 7 it decreased. In the second experiment, control tissue of the original length 10 (0.05) mm increased in length to 10.9 (8.9-13.0) mm, p<0.01. CONCLUSION: These results suggest that the fixation period/laboratory processes result in measurable differences in the reported LRM. This degree of variation has implications for the reliable reporting of the LRM, predicting local recurrence rates and planning subsequent adjuvant radiotherapy.

Formaldehyde↗
PubMed2006

The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy.

The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple composite measure of self-reported antiretroviral therapy (ART) adherence, was compared to a standard three-day self-reported adherence measure among participants in a longitudinal, prospective cross-site evaluation of 12 adherence programs throughout the United States. The CASE Adherence Index, consisting of three unique adherence questions developed for the cross-site study, along with a three-day adherence self-report were administered by interviews every three months over a one-year period. Data from the three cross-site adherence questions (individually and in combination) were compared to three -day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence Index correlated strongly with the three-day self-reported adherence data (p < 0.001) and was more strongly associated with HIV outcomes, including a 1-log decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA < 400 copies/ml (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report when predicting CD4 count status. Participants with a CASE Index score >10 achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41 cell increase for those with scores < or =10 (p < 0.05). The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical settings.

Adult↗
PubMed2006

Observer variation in immunohistochemical analysis of protein expression, time for a change?

AIM: Immunohistochemical analysis of protein expression is central to most clinical translational studies and defines patient treatment or selection criteria for novel drugs. Interobserver variation is rarely analysed despite recognition that this is a key area of potential inaccuracy. Therefore our aim was to examine observer variation and suggest the revision of current standards. METHODS AND RESULTS: We analysed inter- and intra-observer variation, by interclass correlation coefficient (ICCC) and kappa statistics, in 8661 samples. Intra-observer assessment of nuclear, cytoplasmic and membrane staining for seven proteins in 1323 samples resulted in an ICCC of 0.94 and a kappa-value of 0.787. Interobserver reproducibility, assessed on 28 proteins by seven observer pairs in 8661 carcinomas, gave an ICCC of 0.90 and a kappa-value of 0.70. No significant effect of either antibody or cellular compartmentalization was observed. CONCLUSION: We have demonstrated that ICCC is a consistent method to assess observer variation when a continuous scoring system is used, compared with kappa statistics, which depends on a categorical system. Given the importance of accurate assessment of protein expression in diagnostic and experimental medicine, we suggest raising thresholds for observer variation: ICCC of 0.7 should be regarded as the minimum acceptable standard, ICCC of 0.8 as good and ICCC of > or = 0.9 as excellent.

Biomarkers, Tumor↗
PubMed2005

Problems with the use of self-adhesive electrode pads in neonates.

The use of hands free self-adhesive electrode pads for monitoring and defibrillation, rather than using defibrillation paddles, has been widely adopted in many hospitals. This system can be used on automated external defibrillators as well as manual defibrillators. We describe two cases where we could not cardiovert neonates safely using self-adhesive electrode pads (SAEP) with a manual defibrillator and why we had to revert to using standard paediatric defibrillator paddles.

Adhesives↗
PubMed2005

Raf-1 expression may influence progression to androgen insensitive prostate cancer.

BACKGROUND: Recent evidence has implicated the MAP kinase pathway with the development of androgen insensitive prostate cancer (AIPC). We have previously reported gene amplification of critical members of this pathway with the development of androgen insensitive disease. METHODS: Protein expression of Raf-1 was analyzed using immunohistochemistry (IHC) in a database of 65 paired tumor specimens obtained before and after the development of AIPC and correlated with other members of the pathway. RESULTS: Patients whose Raf-1 expression rose with development of AIPC had a significantly shorter median time to biochemical relapse compared to those whose expression fell or remained unchanged (1.16 vs. 2.62 years, P = 0.0005). In AIPC tumors, expression of Raf-1 correlated significantly with expression of HER2 and with expression of c-fos. CONCLUSIONS: We conclude that the HER2/Raf-1/AP-1 axis may promote the development of AIPC, leading to early relapse. Members of the pathway may act as novel therapeutic targets for patients.

Androgens↗
PubMed2005

Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice.

The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole-brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy-three patients were treated with WBRT for cerebral metastases over a 12-month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7-4.1), with 6- and 12-month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0-2 (P = 0.015), Medical Research Council neurological functional status 0-1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.

Aged↗
PubMed2005

Epidemiology of HIV infection among brothel-based sex workers in Kolkata, India.

A cross-sectional study was carried out during January-June 2004 to assess the status of HIV infection among brothel-based sex workers in Kolkata city, India. Six hundred and twenty-two sex workers, selected from six brothels, were included in the study to assess their HIV status, and 362 sex workers, a subset of the above population, were interviewed to study their risk behaviour and practices. Blood samples were collected from each sex worker for testing HIV by an unlinked anonymous method. The prevalence of HIV infection was 9.6%, but was much higher among younger sex workers aged 20 years or less (27.7%) compared to the older age group (8.4%). This difference was statistically significant, indicating an association of younger ages with HIV infection [p = 0.006 and odds ratio (OR) = 4.18; (95% confidence interval (CI) 1.2-13.8)]. HIV was not associated with duration of sex work, average number of clients entertained per day, condom use, practice of sex during menstruation, pre-coital examination of penis for visible ulcer/discharge, suffering from sexually transmitted infections, and entertaining clients outside the brothel. There was a big gap between the reported and the evaluated condom use by sex workers. The results suggest that there is a need to develop suitable HIV intervention strategies, considering the socioeconomic and cultural aspects of city sex workers, with a provision for continuous monitoring and evaluation.

Adolescent↗
PubMed2004

An evaluation of Beam cath in the verification process for prostate cancer radiotherapy.

AIMS: As the trend towards more conformal treatment continues, the accuracy of treatment delivery becomes more important. Conventionally, treatment set-up for prostate cancer patients is verified in relation to the bony anatomy. However, there can be prostate movement independent of bony anatomy. This study tested the feasibility of using Beam cath to enable online correction of treatment set-up in relation to the prostate position, and to assess inter-fraction and intra-fraction prostate movement. MATERIALS AND METHODS: Beam cath is a urethral catheter containing radio-opaque markers, which can be seen on electronic portal imaging, enabling verification of prostate rather than bony anatomy position. The Beam cath was used for planning and treatment of a boost phase of 10 Gy in 5 fractions, delivered before the conventional conformal plan of 60 Gy in 30 fractions. Patients were scanned by computed tomgography (CT), with and without the catheter, and a radio-opaque marker in the catheter was used as the isocentre of the boost phase to enable accurate and rapid pre-treatment isocentre adjustment. The set-up errors between the Beam Cath and bony images were compared to identify the magnitude of prostate movement, independent of bony anatomy. Post-treatment portal images were taken to assess intra-fraction prostate movement. RESULTS: Of 29 patients approached to take part in the study, 18 patients gave informed consent, but only five completed the intended 5 fractions of the boost phase using Beam cath. Pre- and post-treatment portal images were obtained for a total of 29 fractions in six patients. Inter-fraction prostate movement, independent of bony anatomy, was identified. The mean movements were 0.2 mm (standard deviation [SD] 1.2 mm), 2.9 mm (SD 3.1 mm) and 0.7 mm (SD 2.3 mm) in the right left (RL), cranio-caudal (CC) and anterior posterior (AP) direction, respectively. The mean intra-fraction movement was 0.2 mm (SD 1.2 mm), 2.9 mm (SD 3.1 mm) and 0.7 mm (SD 2.3 mm) in the RL, CC and AP direction, respectively. CONCLUSION: Although independent prostate movement was identified, the use of Beam cath was poorly tolerated. Alternative methods of identifying and correcting for prostate movement should be investigated.

Aged↗
PubMed2004

HER2 and COX2 expression in human prostate cancer.

COX2 and HER2 expression are associated with a poor prognosis in prostate cancer and HER2 has been linked to COX2 expression in colorectal cancer. The association between COX2 and HER2 expression was investigated in 117 patients with prostate cancer (89) or Benign prostatic hyperplasia (BPH) (28). Tissue was analysed for HER2 amplification by fluorescent in situ hybridisation, and HER2 and COX2 protein expression by immunohistochemistry (IHC). All tumours analysed expressed COX2 at a significantly higher level than BPH tissue (P=0.041). Only low levels of HER2 gene amplification (8%, 7/89) and HER2 protein expression (12%, 11/89) were observed. HER2 protein expression was rarely observed and did not correlate with HER2 amplification or COX2 expression. Although HER2 does not drive COX2 expression in prostate cancer, this study identified high levels of COX2 expressed in locally advanced prostate cancer, suggesting COX2 could be a potential therapeutic target. COX2 inhibitors are currently being used in clinical trials for the treatment of other tumour types.

Aged↗
PubMed2004

The activity of milk leukocytes in response to a water-soluble fraction of Mycobacterium phlei in bovine subclinical mastitis.

The effect of a water-soluble fraction (WSF) of a non-pathogenic strain of Mycobacterium phlei was studied in bovine subclinical mastitis (SCM) by measuring the myeloperoxidase and acid phosphatase enzyme levels in the milk leukocytes. Forty-five cows were divided into three equal groups. Group I, consisting of 15 healthy cows, served as the control, whereas groups II and III each contained 15 cows with subclinical mastitis on the basis of a positive reaction in the California mastitis test (CMT). The cows in group II received 100 microg of WSF in 5 ml sterile phosphate-buffered saline, pH 7.4 (PBS) once only, while those in group III received 5 ml sterile PBS daily for 7 days, both treatments being given by the intramammary route. Observations were made up to 30 days after treatment (AT). The CMT of the healthy milk was negative (0), whereas it ranged between 1 and 2 points in SCM. The somatic cell count (SCC) increased significantly (p < 0.05) on day 3, then fell steeply from day 7 up to day 30 AT in the cows in group II. A steady decrease in the total bacterial count (TBC) was observed in the group treated with WSF but the bacterial counts remained high in the groups treated with PBS. The mean acid phosphatase level was enhanced by 119% on day 3 AT in group II but only by 18.7% in the cows in group III. The mean myeloperoxidase level was enhanced by 100% in the cows in group II but only by 18% in those in group III on day 3 AT. This significant reduction in the bacterial load in infected cows caused by intramammary infusion of WSF may be due to activation of the microbicidal activity of the neutrophils, but this requires confirmation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2004

Improvement of dry matter digestibility of water hyacinth by solid state fermentation using white rot fungi.

Feeding value of water hyacinth biomass colonized by three species of white rot fungi during solid-state fermentation was investigated. All three organisms proved to be efficient degraders and enhanced dry matter digestibility. Loss of organic matter was maximum (23.6+/-0.1% dry wt) after 48 days by P. ostreatus. C. indica showed maximum cellulose degradation (18.5+/-0.1% dry wt) than other two fungi after 48 days of incubation. In all cases, an extensive removal of hemicellulose at the initial growth period and a delayed degradation of lignin were observed. Hemicellulolysis was maximum (46.3+/-0.1% dry wt) by C. indica, but delignification (14.2+/-0.2% dry wt) by P. sajor-caju after 48 days. The amount of reducing sugar in the degraded biomass decreased at early stages, but increased as degradation progressed in all three cases (maximum 1.1+/-0.05% dry wt after 48 days by C. indica). Soluble nitrogen content increased only during 16-32 days of incubation (highest 1.1+/-0.1% dry wt after 32 days by P. sajor-caju). Crude protein of the bioconverted biomass increased gradually up to 32 days but decreased thereafter (maximum 10.3+/-0.1% dry wt after 32 days by P. sajor - caju). Per cent change in in vitro dry matter digestibility of degraded substrates enhanced gradually after 8 days and reached maximum after 32 days but thereafter decreased (highest + 20.4+/-0.3% dry wt by P. sajor-caju). The results demonstrated the efficient degrading capacity of the test fungi and their potential use in conversion of water hyacinth biomass into mycoprotein-rich ruminant feed, more so by P. sajor-caju.

Animal Feed↗
PubMed2003

HIV-related knowledge and adherence to HAART.

Near perfect adherence is considered essential for patients on HAART, yet adherence to medical recommendations is rarely so high. Supportive services and reminder tools may help individuals to become adherent, yet it is difficult to determine who may need such interventions. In this study, based on data from the NYSDOH/AIDS Institute Treatment Adherence Demonstration Program, we look at the association between HIV-related knowledge and adherence, hypothesizing that a better understanding of HIV and its treatment is associated with better adherence. In analyses based on 997 participants, knowledge, as measured by five true/false questions, was significantly associated with self-reported adherence. In multivariate analysis, compared to persons with four or five items answered correctly, persons with fewer correct answers were more likely to report missed doses (OR = 1.72 for 2-3 correct, p < 0.01; OR = 2.92 for 0-1 correct, p < 0.05). Our data suggest that providers should include questions focused on knowledge of HIV in their assessments of medication readiness and need for adherence support. Similarly, providers should be diligent with respect to patient education, ensuring that each patient has the information needed to support reasoned decision making and adequate adherence.

Adolescent↗
PubMed2003

Regulation of type 1 diabetes by a self-MHC class II peptide: role of transforming growth factor beta (TGF-beta).

The present study was undertaken to analyze the regulatory T cells generated in response to class I derived self-I-A beta(g7) (54-76) peptide. It was observed T cells from young unprimed type 1 diabetes (T1D) prone NOD mice did not respond to self-I-A beta(g7) (54-76) peptide although T cells from primed young NOD mice showed a strong response. T cells from young unprimed BALB/c mice responded to self-I-A beta(d) (62-78) peptide. However, a breakdown of tolerance to these peptides was observed with age in both the strains. Culture supernatant from I-A beta(g7) (54-76) peptide-primed cells secreted large amounts of TGF-beta and inhibited T cell responses in allogeneic-MLR. Further, I-A beta(g7) (54-76) peptide specific T cell lines from young (I-A.Y) and diabetic (I-A.D) NOD mice were established. I-A.Y secreted IL-4, TGF-beta and IL-10 while I-A.D T cell line secreted IL-10 and IFN-gamma. We found that I-A.D T cell line induced diabetes when transferred in NOD/SCID mice but I-A.Y T cell line did not induce disease. These results show that immunization of NOD mice with I-A beta(g7) (54-76) peptide at a younger age induces a regulatory T cell response suggesting that correcting the defects in immunoregulatory mechanisms using self-MHC peptides may be one of the approaches to prevent autoimmune diseases like T1D.

Animals↗
PubMed2003

Hepatoprotective effect of Himoliv, a polyherbal formulation in rats.

The effect of Himoliv (HV) was evaluated in carbon tetrachloride or paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of either carbon tetrachloride (CCl4, 1 ml/kg, 50% v/v with olive oil, s.c.) or paracetamol (PC, 1 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and serum alkaline phosphatase (ALP) and hepatic thiobarbituric acid reacting substances (TBARS) and superoxide dismutase (SOD). HV pretreatment (0.5 and 1.0 ml/kg, p.o.) significantly (P < 0.001) reduced CCl4 or PC-induced elevations of the levels of SGOT, SGPT, ALP and TBARS, while the reduced concentration of SOD due to CCl4 or PC was reversed. Silymarin (25 mg/ kg, p.o.), a known hepatoprotective drug showed similar results.

Acetaminophen↗
PubMed2002

Unnecessary peripheral intravenous catheterisation on an acute medical admissions unit: a preliminary study.

BACKGROUND: The ability to secure peripheral intravenous access is regarded as a basic medical skill that is often required for the management of patients admitted to acute medical admission wards. The decision to insert a peripheral intravenous catheter (PIC) is usually taken by relatively inexperienced members of the acute medical team and is primarily based on 'traditional' or 'routine' practice, rather than on an assessment of need. Furthermore, there appears to be little recognition of the potentially serious adverse events associated with PIC insertion. METHOD: We conducted a prospective study to evaluate unnecessary PIC insertion in a United Kingdom teaching hospital's acute medical admissions unit. RESULTS: Of the 338 patients included in the study, 272 (80.5%) received a PIC. Of these, 179 patients (66%) received a PIC that had been used by the post-on-call ward round. Of the 93 patients (34%) with an unused PIC, 30 patients (11%) had been catheterised inappropriately by the study criteria. CONCLUSIONS: Despite our use of conservative criteria for PIC insertion, a notable level of inappropriate peripheral intravenous catheterisation was identified. A hypothetical cost-minimisation analysis is presented and a care pathway for best practice proposed.

Journal Article↗
PubMed2001

Usefulness of calcium scoring using electron beam computed tomography and noninvasive coronary angiography in patients with suspected coronary artery disease.

The aim of this study was to investigate the reliability of calcium scoring (CS) and electron beam computed tomographic angiography (EBCTA) as a noninvasive tool in the diagnosis of coronary artery disease (CAD): 93 consecutive patients (aged 59 +/- 9 years) with symptoms suspicious for CAD underwent CS. In 87 of these subjects, an additional EBCTA investigation was performed. Using receiver-operating characteristic curve analysis, we determined a calcium score cut point providing an overall sensitivity of 80% and a specificity of 72% in detecting patients with CAD. For clinical purposes the use of cut points is difficult. We therefore determined score ranges providing >80% specificity (high score range) and >85% sensitivity (low score range) and determined the scores between these ranges as equivocal borderline scores. Calculated on a per-segment basis in assessable proximal and midcoronary segments, the sensitivity for detecting coronary stenoses >50% was 78%, and the specificity was 93%. Thus, 32 of 44 patients with significant CAD and 24 of 49 patients without CAD were correctly classified. The combination of CS and EBCTA predicted CAD in 77% (72 of 93) of patients. No or low calcium scores provided high specificity for ruling out CAD. The addition of EBCTA in those patients improved sensitivity. In patients with high calcium scores, accuracy of EBCTA was not significantly different from CS alone (72% vs 83%), whereas in patients with borderline scores it was significantly superior (80% vs 58%, p <0.03). Thus, the complementary use of CS and EBCTA appears beneficial, particularly in patients with borderline scores, and could improve sensitivity in the low score range. In the presence of high scores, no major diagnostic gain from an additional EBCTA versus CS alone could be observed.

Calcinosis↗
PubMed2001

Treatment with a growth hormone secretagogue in a model of developing heart failure: effects on ventricular and myocyte function.

BACKGROUND: Exogenous administration of growth hormone (GH) and subsequently increased production of insulin-like growth factor-1 can influence left ventricular (LV) myocardial growth and geometry in the setting of congestive heart failure (CHF). This study determined the effects of an orally active GH secretagogue (GHS) treatment that causes a release of endogenous GH on LV function and myocyte contractility in a model of developing CHF. METHODS AND RESULTS: Pigs were randomly assigned to the following treatment groups: (1) chronic rapid pacing at 240 bpm for 3 weeks (n=11); (2) chronic rapid pacing and GHS (CP-424,391 at 10 mg x kg(-1) x d(-1), n=9); and (3) sham controls (n=8). In the untreated pacing CHF group, LV fractional shortening was reduced (21+/-2% versus 47+/-2%) and peak wall stress increased (364+/-21 versus 141+/-5 g/cm(2)) from normal control values (P:<0.05). In the GHS group, LV fractional shortening was higher (29+/-2%) and LV peak wall stress lower (187+/-126 g/cm(2)) than untreated CHF values (P:<0.05). With GHS treatment, the ratio of LV mass to body weight increased by 44% from untreated values. Steady-state myocyte velocity of shortening was reduced with pacing CHF compared with controls (38+/-1 versus 78+/-1 microm/s, P:<0.05) and was increased from pacing CHF values with GHS treatment (55+/-7 microm/s, P:<0.05). CONCLUSIONS: The improved LV pump function that occurred with GHS treatment in this model of CHF was most likely a result of favorable effects on LV myocardial remodeling and contractile processes. On the basis of these results, further studies are warranted to determine the potential role of GH secretagogues in the treatment of CHF.

Animals↗