I, DR.S.VIGNESH, solemnly declare that this dissertation, titled “ROLE OF C-REACTIVE PROTEIN AS A SEVERITY MARKER IN ACUTE PANCREATITIS” is a bonafide record of work done by me in the Department of General Surgery, Government Stanley Medical College and Hospitals, Chennai under the guidance of my unit chief PROF.DR. C.BALAMURUGAN, M.S., Assoc. Prof. of surgery, This dissertation is submitted to The Tamilnadu DR.M.G.R. Medical University, Chennai in partial fulfillment of regulations for the award of M.S. (General Surgery) examination to be held in April 2013.
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In the study conducted by Abha Gupta, Umesh Dubay, et,.al.. titles “Correlation of serum calcium levels with severity and functional outcome in acute ischemic stroke patients “ stated that patients with high calcium had significantly less severity of the stroke and during follow up after 7 days the prognosis is better in patients with high calcium compared to the lower levels of calcium, which was statistically significant(p-value 0.01).
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It is well known that the recognition receptor “RAGE” and HMGB-1 play a central role in the innate immune system with an impact on its perpetuation and amplifica- tion . RAGE stimulation results in sustained NF- B activation, which may be a predictor of severity in sepsis . Conditions that induce NF- B also increase RAGE expression, which in turn produces sustained inflamma- tion; this is seen in CAP, where RAGE ligands are abun- dantly present. Angus et al. found that CAP patients had higher HMGB-1 concentrations, and this correlated with mortality . Gaini et al. also found higher levels of HMGB-1 in CAP . Studies of severe influenza CAP demonstrated an association between excessive release of cytokines and increased mortality [34,35]. However, Alleva et al. found in a murine model of severe influenza that HMGB-1 concentrations were not increased in plasma at the time of peak mortality, and peak levels of HMGB1 did not occur until relatively late in infection .
a-SMA: alpha smooth muscle actin; ANOVA: analysis of variance; BrdU: 5- bromo-2 ′ -deoxyuridine; CD: cluster of differentiation; DAB: diaminobenzidine; DMEM: Dulbecco ’ s modified Eagle ’ s Medium; DNA: deoxyribonucleic acid; Dnase: deoxyribonuclease; ECM: extracellular matrix; ELISA: enzyme-linked immunosorbent assay; EMT: epithelial-mesenchymal transition; FCS: fetal calf serum; FEV1: forced expiratory volume in 1 s; FITC: fluorescein-isothiocianate; FVC: forced vital capacity; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; IHC: immunohistochemistry; ILD: interstitial lung diseases; IPF: idiopathic pulmonary fibrosis; KD: knock-down; MFI: median fluorescent intensitíy; NHLF: Normal Human Lung Fibroblasts; NHS: National Health Service; PCR: polimerase chain reaction; PDGF: platelet-derived growth factor; qPCR: quantitative polimerase chain reaction; r2: r squared; RNA: ribonucleic acid; siRNA: silencing ribonucleic acid; TEM-1: tumour endothelial marker-1; TGF- β 1: transforming growth factor beta 1; TLC: total lung capacity; TLCO: transfer factor for carbon monoxide; VATS: video-assisted thoracoscopy.
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In conclusion, DHF patients showed an increased soluble Fas ligand level compared to DF patients and the healthy people. This result suggests that the soluble Fas ligand may play important roles in the severity of dengue infection, and it can be used as a marker for the severity of dengue infection. However, a larger number of samples will need to be tested before its potential as a diagnostic severity marker can be evaluated.
Several limitations of our study should be mentioned. First, this was a single-center study and the sample size was relatively small. Second, the elevation of immature granulocytes is not specific for infection and may be observed in various other conditions, including myeloproliferative disorders, chronic inflammatory dis- eases, tissue damage, acute hemorrhage, and neoplasia . Because DNI is also one of the leukocyte-related parameters, there may be a lack of sensitivity or speci- ficity for DNI as a severity marker of sepsis in this group. Third, we did not evaluate the comparative advantage of using DNI over procalcitonin which may have a role in reducing antibiotic exposure of critically ill patients  and serve as a useful complementary comparator for prediction of survival outcome in post- operative patients with severe sepsis . Because the
Abstract: This study aims to investigate the potential of microRNA126 (miRNA126) as a molecular marker for the early diagnosis of H5N1 influenza. This study included a total of 16 H5N1 virus-infected children. The patients were given an intravenous injection of cephalosporins (0.03-0.05 g/day) for 3 consecutive weeks. The serum in- terleukin-6 (IL-6) levels were measured to determine the effectiveness of the treatment. Sixteen healthy children were used as controls. The pre- and post-treatment levels of miRNA126 in the blood cells of the patient group were compared with the control group. The association between the miRNA126 levels in the blood cells and the severity of H5N1 influenza was analyzed using Pearson’s correlation test. The pre-treatment miRNA126 levels in the H5N1 group were significantly higher compared with the levels in the control group (P < 0.05). The miRNA126 levels in the severe H5N1 group (defined as IL-6 > 32.1 ng/L) were significantly higher than the levels in the mild/moder- ate H5N1 group (defined as 11.8 ≤ IL-6 < 32.1 ng/L) before the treatment (P < 0.05). After the 3-week treatment, the miRNA126 levels in the patients were significantly reduced (P < 0.05). The miRNA126 level in blood cells was positively correlated with the severity of H5N1 influenza (r = 0.94, P < 0.05). The positive correlation between the miRNA126 level and the severity of H5N1 influenza suggests that the miRNA126 level in blood cells might be a molecular marker for evaluating the severity of pediatric H5N1 influenza and might be used in the early diagnosis of the disease.
(100% sensitivity). Thus, most children with normal CRP values probably could be safely considered not suffering from acute pyelonephritis and would not require either DMSA scintigraphy or early parenteral antibiotic therapy. However, a number of children with elevated CRP values show no renal lesion, and this low specificity (26.1%) limits its clinical useful- ness and leads, in our current practice, to unneces- sary hospital admissions and costs. Furthermore, when analyzing the severity of renal involvement, we found a borderline correlation to CRP that con- trasted with a highly significant correlation to ele- vated PCT values. The specificity of PCT was found much higher (82.6%) than that of CRP. The sensitiv- ity of an elevated PCT value was calculated at 70.3%, 11 children being found with very mild or mild lesions (grades 1 and 2) despite a normal PCT value. This was not explained by previous antibiotic treat- ment, which none of the children received, or by a shorter duration of symptoms. They also were not explained by infection with different microorgan- isms (E coli in all the cases). Thus, PCT alone cannot be used to identify all renal lesions because 30% of patients had normal PCT levels despite grades 1 and 2 lesions on DMSA scans. However, PCT represents the first biological parameter found to correlate with the severity of renal lesions at time of diagnosis, and possibly also with the risk of permanent scarring. It
In the current study the predictive values of WBC and CRP for infection and sepsis are comparable with those identified in previous studies, in which a low AUROC of 0.55–0.66 for WBC (sensitivity 65–91 %; specificity 35– 54 %) and an intermediate AUROC of 0.64–0.77 for CRP (sensitivity 82–100 %; specificity 40–64 %) was re- ported [4, 5, 10, 11]. Large reviews report an AUROC of 0.78 – 0.81 for PCT (sensitivity 42 – 100 %; specificity 48 – 100 %), comparable to our study [7, 9]. The reported predictive value of ICIS in this study is lower compared with two previous studies, in which AUROC of 0.79 (sensitivity 70 %; specificity 79 %) and 0.85 (sensitivity 80 %; specificity 75 %) were reported, respectively [12, 13]. Both studies investigated a relatively small number of pa- tients or investigated postoperative critically ill patients only [12, 13]. They were pilot studies to define the cutoff values of ICIS as a marker of infection in critically ill patients and recommended determination of the suit- ability and effectiveness of this score in a prospective trial [12, 13].
Hyperlipidemia was defined according to the National Cholesterol Education Program (NCEP) Guidelines (total cholesterol ≥ 200 mg/dl or LDL ≥ 130 mg/dl or triglycerids ≥ 150 mg/dl)  and by the intake of lipid- lowering drugs (statines or fibrates). Patients were considered diabetic in case of insuline therapy, oral anti- diabetics or HbA1c ≥ 6.5% . The presence of a hepa- titis B surface antigen defined active hepatitis B disease. Patients were considered hepatitis C positive if anti- hepatitis C antibodies were present. An analysis of data from the CASCADE collaboration demonstrated that in- dividuals co-infected with HIV and hepatitis C have a higher risk of death from HIV or liver disease than pa- tients infected with only HIV . As a validated indir- ect marker of liver fibrosis the FIB-4 index was calculated according to the following formula: FIB-4 = age (years) × AST [U/L]/(platelets [10 9 /L] × (ALT [U/ L]) 1/2 ) . A cut-off > 3.25 was used because it predicts a significant liver fibrosis with a positive predictive value of 65% and a specificity of 97% . The FIB-4 index has recently been shown to be an independent predictor of liver-related death in HIV infected patients initiating antiretroviral therapy .
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It is very clear from our study that level of serum procalcitonin among patients with SSI was found to be elevated on post op day 1 with a significant continuous increase on post op day 3 unlike among patients without SSI where its serum level shows initial rise followed by rapid fall on post op day 3.This persistent elevation of PCT levels make the presence of a complicating bacterial infection likely and once again, stresses the importance of follow-up measurement (Christ-Crain and Muller, 2006; Christ-Crain et al., 2004). So we conclude that persistent elevation of procalcitonin levels during post operative period is indicative of SSI and wound complication. So a serial estimation of marker is highly reliable in early detection of SSI as compared to single measurement. But this study is having its own limitations as our sample size is small and also due to lack of funds to measure PCT in all patientsone important drawback of PCT is its high cost, so that serial measurement of the same becomes difficult as compared to conventional infective markers.
AgNOR is strictly related to the rapidity of cell proliferation. Therefore, AgNOR can be considered to represent a marker of cell proliferation rate.A number of studies carried out in different tumour types indicates the expression of AgNOR PROTEINS FOUND TO BE GREATER COMPARED TO NON MALIGNANT CELLS. Beningn cells tend to have a regular nucleolus with tight clustering of silver proteins and malignant cells show dispersal of NORs through the nucleus.
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Both ionized Ca (iCa) and Albumin adjusted Ca were significantly higher in PTB patients (4.71±0.69 mg/dl ; 8.81± 1.3 mg/dl) than controls (4.2±0.56 mg/dl ; 7.5±1.1 mg/dl) respectively (Table 2). Only few of our PTB patients showed symptoms related to high Ca level. Serum Phosphorus did not show significant difference between PTB patients and controls (p=0.765) and poor correlation to disease severity. Phosphorus is a widely distributed element with skeleton as the major reservoir providing phosphate for both intracellular and extracellular pools. Since PTB is associated with muscle wasting, there may be slightly high serum phosphorus level in patients than controls. Further Phosphorus tends to be higher in those with elevated polymorphs suggesting its association with active phase of disease and tissue destruction. Both ionized Ca (iCa) and Albumin adjusted Ca showed some correlation to disease severity i.e r=0.297 and 0.300 (Figure 1 & 2) respectively (Table 5).
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becomes <1 when the HMW- multimer ratio is reduced. The CT- ADP was measured using the Platelet Function Analyzer (PFA)−100 (Siemens Medical Solutions Diag- nostics, Netherlands), vWF multimers were analysed on a Hydrasys 2 system using ‘Hydragel von Willebrand Multimers’ and ‘von Willebrand Multimers Visualisation’ kits (all from SEBIA, Belgium). Analysis of CT- ADP with the point- of- care assay PFA-100 is used as a surrogate marker of vWF loss. Higher values correspond to a longer closure time and more loss of vWF. All assessments were done in our tertiary hospital laboratory with laboratory personnel blinded to clinical data.
Rett syndrome (RTT) is a rare, progressive neurodevelop- mental disorder occurring almost exclusively in females that is caused by a mutation in the X-linked methyl-CpG binding protein 2 (MECP2) gene . The disorder is gen- erally marked by a period of seemingly typical develop- ment until 6 to 18 months of age followed by a developmental regression and the emergence of features such as stereotypies, motor dysfunction, loss of expressive language, intellectual disability, and epilepsy [2–4]. The objective assessment of brain function in individuals with RTT, including cognition and sensory processing, can be difficult due to problems with purposeful hand use and verbal communication, and there remains a need for ob- jective biomarkers to assess cortical function and disease severity in this population.
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susceptibility allele for ADHD. The a priori hypothesis arises principally from the pharmacology of stimulant medications, such as methylphenidate (MPH), which inhibit the action of the transporter. A number of studies suggest that DAT1 is a gene of minor effect for ADHD with an average odds ratio of around 1.2 (Brookes et al, 2006; Cook et al, 1995; Daly et al, 1999; Gill et al, 1997). More recently, a number of studies have attempted to link allelic variation in DAT1 to intermediate constructs (Bellgrove et al, 2005a, b; Loo et al, 2003), or endophenotypes, and to both clinical (Kirley et al, 2003) and physiological measures of stimulant response (Gilbert et al, 2006; Loo et al, 2003). These studies could provide important collateral evidence regarding the functional effects of risk variants and highlight the potential clinical utility of molecular genetics for identifying sub- populations of children with ADHD that might respond better or more poorly to stimulant medication. Here, we report an association between a neurocognitive phenotype- spatial attentional bias and DAT1 genotype in 96 children and adolescents with ADHD. We also show that spatial bias relates to symptom severity and is modified, as a function of Received 25 July 2007; revised 18 October 2007; accepted 27 October
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lated with MELD scores in cirrhosis patients . Therefore, they suggested that the RDW might be a predictor of the severity of HBV- related hepatic disease. Furthermore, they found that the RDW could independently pre- dict the presence of cirrhosis. Chen considered that elevated RDW and RPR could predict liver cirrhosis in chronic HBV . They showed that RDW and platelet could strongly predict the presence of severe fibrosis or cirrhosis in chronic HBV patients. Few studies have report- ed the relationship between RDW, as well as RPR, and the stage of liver cirrhosis. In our study, an increased RDW value and thrombocy- topenia can bring about an elevated RPR in cir- rhosis patients. The RPR and RDW presented prominent performance in the prediction of decompensated cirrhosis.
C-reactive protein (CRP) is a marker of inflam- mation, and serum CRP concentration reflects disease activity in patients with CD . CRP is a pentameric protein produced almost exclu- sively by hepatocytes in response to stimula- tion by Interleukin 6, Interleukin 1α, and tumor necrosis factor β . CRP is the most impor- tant acute-phase protein. The baseline concen- tration of CRP is 1 mg/l and levels are partially genetically regulated. Levels of CRP increase dramatically in the presence of an acute-phase inflammation or infection. CRP concentrations also quickly decrease when the inflammation process is treated .
Fractalkine may not be merely a marker of disease severity in sepsis. Animal studies have suggested an important functional role for fractalkine in the patho- genesis of sepsis. In accordance with our human data, abdominal sepsis induced by CLP in mice was associated with elevated plasma fractalkine levels [14, 15]. Elimin- ation of the biological activity of fractalkine, achieved by studying mice deficient for its receptor CX3CR1, has been shown to exaggerate organ damage and increase lethality . During murine abdominal sepsis, fractalk- ine mRNA levels are elevated in the heart, lung, kidney, and liver, indicating that many organs contribute to elevated plasma concentrations .
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The values were expressed as mean ± SD, the median and interquartile range for continuous variables and number and percentage for nominal variables. Normality of the data was tested by Kolmogorov–Smirnov test. Statistical analysis of differences within and between the study groups was carried out using the Student’s t-test and one-way post hoc ANOVA. Pearson’s correlation coefficients were used to determine the relationships between variables. Multiple linear regression models were used for association of independent variables with the disease severity as per Psoriasis Area and Severity Index (PASI) score. The analysis was done by using SPSS ver- sion 16.0. P < 0.05 was considered as statistically significant.