Tumour M2-pyruvate kinase: a gastrointestinal cancer marker

BACKGROUND: Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. 'Tumour M2-pyruvate kinase' was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate kinase converted to an inactive dimeric form by direct interaction with oncoproteins to channel glucose carbons into DNA synthesis. This review summarizes the current knowledge of this unique tumour marker with regard to its biochemistry, assay and potential use as a diagnostic and screening tool in gastrointestinal cancer. METHODS: A literature search was conducted for entries from 1980 to 2005 using PubMed and NeLH databases using tumour M2-pyruvate kinase, faecal tumour M2-pyruvate kinase, tumour metabolism, tumour markers and carcinoembryonic antigen as keywords. A total of 56 references relevant to tumour M2-pyruvate kinase were retrieved. Eighteen references were clinical studies involving plasma/faecal tumour M2-pyruvate kinase and gastrointestinal cancer. The remaining 38 references were clinical/nonclinical trials and reviews on tumour metabolism and plasma/faecal tumour M2-pyruvate kinase assay. Seven of the 18 clinical studies involved faecal M2-pyruvate kinase. Three of the 11 plasma tumour M2-pyruvate kinase studies were non-English language and were excluded. The sensitivity, specificity, positive predictive and negative predictive value for plasma/serum tumour M2-pyruvate kinase in the detection of gastrointestinal cancer was determined for each of the remaining eight studies. Data for gastrointestinal cancer M2-pyruvate kinase were compared with other gastrointestinal cancer markers. Data from three of the eight studies using a diagnostic cut-off value of 15 U/ml for ethylenediaminetetraacetic acid (EDTA) plasma tumour M2-pyruvate kinase were analysed together as a small meta-analysis. RESULTS: At a diagnostic cut-off value of 15 U/ml for tumour M2-pyruvate kinase in EDTA plasma the sensitivity, specificity, positive predictive and negative predictive value was 57.3, 89, 85.7 and 64.8%, respectively, for colorectal cancers, 62.1, 89, 88 and 64%, respectively, for gastric/oesophageal cancers and 72.5, 89, 58 and 94%, respectively, for pancreatic cancers. As a faecal marker for colorectal cancers, faecal tumour M2-pyruvate kinase has a sensitivity of 73-92% at a cut-off value of 4 U/ml as against 50% sensitivity for Guaiac faecal test. CONCLUSION: Circulating tumour M2-pyruvate kinase is more commonly elevated in oesophageal, gastric and colorectal cancer patients than conventional tumour markers. Faecal M2-pyruvate kinase is a sensitive marker of colorectal cancer. The clinical role of tumour M2-pyruvate kinase in gastrointestinal cancer management should be investigated in large-scale clinical trials.     

Liver biochemistry profile, significance and endoscopic management of biliary tract complications post orthotopic liver transplantation

AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Patients who developed biliary complications were analysed in detail for the clinical information,laboratory tests,treatment offered,response to it,follow up and outcomes. The profile of liver enzymes was determined. The safety,efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed. RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 ± 70.9 U/mL vs 168.5 ± 34.2 U/L,P = 0.007) and SAP > 2 times (345.1 ± 59.1 U/L vs 152.7 ± 21.4 U/L,P = 0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients. CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early,non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.     

Implications of chronic obstructive pulmonary disease (COPD) on patients' health status: a western view

AIM: To assess and compare health status among chronic obstructive pulmonary disease (COPD) patients presenting for treatment in six countries and in two healthcare settings using a generic health status instrument. METHODS: A population based cross-sectional survey was conducted among 2703 patients and their physicians (1381 in primary and 1322 in specialty care) in five EU countries and the USA. Information was collected on demographic and clinical characteristics, exacerbations and health status estimated using EQ-5D. RESULTS: The mean EQ-5D score for COPD patients was similar between primary and specialty settings in all countries except Italy. Approximately, half of the patients indicated some impairment in health status on mobility, usual activities, pain/discomfort and anxiety/depression domains of EQ-5D. Approximately, 5% of patients in EU countries except UK had health status valued as worse than death based on valuations of the general population. Patients suffering from severe breathlessness, experiencing > or =3 exacerbations in the previous year, categorised as severe according to GOLD criteria, and experiencing day-time and night-time symptoms had significantly impaired health status. CONCLUSION: COPD patients classified as moderate/severe in clinical practice have worse health status compared to mild patients. This impairment is similar in primary and specialty setting across western countries.     

Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) has a negative effect on patients' daily functioning. Thus far, no study has investigated the effect of treatment-related improvement in cognitive functions on health-related quality of life (HRQOL). We measured psychometric performance by number and figure connection tests parts A and B, picture completion, and block design tests and HRQOL by the Sickness Impact Profile (SIP) of 90 patients with cirrhosis on inclusion into the study and 3 months later. A Z score less than -2 on the neuropsychological (NP) tests was considered abnormal. Sixty-one (67.7%) patients had MHE. They were randomly assigned in a 1:1 ratio to receive treatment (lactulose) for 3 months (n=31) or no treatment (n=30) in a nonblinded design. The mean number of abnormal NP tests decreased significantly in patients in the treated group (baseline, 2.74 [95% CI 2.40-3.08]; after 3 months, .75 [95% CI .36-1.16]) compared with patients in the untreated group (baseline, 2.47 [95% CI 2.19-2.74]; after 3 months, 2.55 [95% CI 2.16-2.94]); multivariate analysis of variance (MANOVA) for time and treatment, P=0.001. The mean total SIP score improved among patients in the treated group (baseline, 10.39 [95% CI 9.36-11.43]; after 3 months, 3.77 [95% CI 2.52-5.02]) compared with patients in the untreated group (baseline, 10.36 [95% CI 8.98-11.73]; after 3 months, 10.39 [95% CI 8.36-12.42]); MANOVA for time and treatment, P=0.002. Improvement in HRQOL was related to the improvement in psychometry. CONCLUSION: Treatment with lactulose improves both cognitive function and HRQOL in patients with cirrhosis who have MHE.     

Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions

Background: Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA-IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). Results: Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 ± 41.8 vs. 118 ± 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 ± 26.8 vs 74.3 ± 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. Conclusions: Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.     

Amplification of four genes of influenza A viruses using a degenerate primer set in a one step RT-PCR method

We designed a degenerate primer set that yielded full-length amplification of hemagglutinin (HA), neuraminidase (NA), matrix (M), and non-structural protein (NSP) genes of influenza A viruses in a single reaction mixture. These four genes were amplified from 15 HA (1–15) and 9 NA (1–9) subtypes of influenza A viruses of avian (n = 16) origin. In addition, 272 field isolates of avian origin were tested by this method. Full-length amplification of HA, NA, M, and NSP genes was obtained in 242 (88.9%), 254 (93.4%), 268 (98.5%), and 268 (98.5%) isolates, respectively. No gene was amplified in four isolates. Of these four isolates, two were subtyped as H4N6, one as H7N7, and one as H10N7. Amplification was successful for all 4 genes of H1N1, H2N3, and H3N2 isolates of swine influenza. Also, all four genes were amplified in one equine influenza (H3N8) isolate and seven isolates of human origin (H1N1 and H3N2). This appears to be the first study using degenerate primer set for full-length amplification of four genes of influenza A viruses in a single reaction. Further studies are needed to determine if this primer set can be used for subtyping of influenza virus isolates.     

Our Experience with Split Electrode Array Implant for Obliterated Cochlea

To study the outcomes of split electrode array cochlear implantation in ossified cochlea using the CAP scoring system. Retrospective case study. Tertiary referral center. Six cochleae in three adult and three pediatric patients with ossification. Intervention(s): All Patients underwent cochlear implantation with a split electrode array system. Major outcome parameter(s): Number of electrodes inserted during surgery, number of functioning electrodes on follow-up and auditory performance evaluation using the CAP score—Category of Auditory Perception [TSC Revised Version, based on Nottingham CI Program, 1995]. Six patients (three children and three adults) had insertion of split electrode array system. The mean number of electrodes inserted were 18.3 (range 15–21) and functioning electrodes at follow-up were mean of 14.3 (range 7–21). Auditory performance was measured using CAP score at 1 year post implant follow up, mean score in children was six and that in adult was eight. One pt had facial nerve twitching which was corrected by switching off the concerned electrode. No complications in sort of facial palsy or vestibular disorder were observed. Patients of ossified cochlea having profound deafness do well with split electrode array cochlear implantation as evaluated with CAP scoring system. The split electrode array results in more number of electrodes within the cochlear lumen. Retro graded apical array insertion has less chances of facial nerve stimulation as it is placed away from the nerve.     

Whole genome sequence of colistin-resistant Escherichia coli from western India

BackgroundWith virtually dried out new antibiotic discovery pipeline, emergence and spread of antimicrobial resistance is a cause for global concern. Colistin, a cyclic polypeptide antibiotic, often regarded as last resort for multi drug resistance gram-negative bacteria, is also rendered ineffective by horizontal transfer of resistance genes. Surveillance of colistin resistance in GNB is essential to ascertain molecular epidemiology.MethodsWhole genome sequencing (WGS) of an unusual colistin resistant urinary isolate of Escherichia coli was performed using Illumina MiSeq platform using 2x250bp V2 chemistry by following the manufactures protocol (Illumina Inc. USA). Multiple web-based bio-informatic tools were utilized to ascertain antibiotic resistant genes.ResultsAn approximate 5.4 Mb of genome of the urinary isolate AFMC_UC19 was sequenced successfully. Mobile colistin resistance gene (mcr) on the plasmid responsible for horizontal spread was absent in the isolate.ConclusionColistin resistance has been reported previously in Klebsiella pneumoniae and it is a rare occurrence in Escherichia coli in Indian setting. Although the isolate lack mcr mediated colistin resistance, emergence and spread of colistin resistant in gram-negative bacteria pose a threat.