609 research outputs found
Characterization of Ionizing Radiation Sensitive (IRS) Mutants of Deinococcus Radiodurans R1.
Deinococcus radiodurans is extremely resistant to ionizing radiation and can withstand 5 kGy radiation without loss of viability or evidence of mutation. Available evidence argues that an efficient DNA repair mechanism is responsible for the resistance these organisms possess to ionizing radiation. The enzymes which coordinate DNA repair in D. radiodurans are poorly characterized. Two new loci have been detected in D. radiodurans, namely, irrB and irrI which provide resistance. Mutational inactivation of either locus resulted in a partial loss of resistance to ionizing radiation. The extent of sensitivity was locus specific and differentially affected by inactivation of the uvrA gene product. An irrB uvrA double mutant was more sensitive to ionizing radiation than was an irrB mutant. In contrast, an irrI uvrA double mutant and irrI single mutant were equally sensitive to ionizing radiation. irrB and irrI mutations also reduced resistance to UV radiation in D. radiodurans which was more pronounced in the presence of an uvrA\sp+ background. Subclones derived from each gene were generated and the loci of each gene were mapped relative to each other. The irrB and irrI genes were separated by approximately 20 kb of intervening sequence in which the uvrA and pol genes are located. A mutation which inactivates the irrB gene does not impair repair of transforming DNA which has been damaged and contains thymine glycol or 8-hydroxyguanosine lesions. Examination of irrB cell extracts for novel DNA binding proteins revealed little information. irrB strains do produce a 23 kD novel protein (IrrB*) in large amounts but IrrB* did not bind to either ssDNA or dsDNA in the presence of 50 mM NaCl. A mutation which impairs the function of the irrI gene product did not affect its potential to reactivate 8-hydroxyguanosine containing transforming DNA, but it failed to reactivate thymine glycol containing transforming DNA. In the absence of the irrI gene product D. radiodurans was extremely sensitive to UV radiation and its DNA underwent extensive degradation. The irrI gene product appears to regulate endonuclease mediated DNA degradation which occurs following exposure to UV radiation
Study of correlation between EGFR mutation status and P-AKT, TTF 1 in adenocarcinoma lung and to compare the quality of life between patients on TKI and Chemotherapy
BACK GROUND:
Treatment of advanced carcinoma lung has been disappointing till last decade. The discovery of TKI’s has changed the natural history of this disease especially in patients who are EGFR mutation positive. Data regarding EGFR mutation testing and response to treatment depending on EGFR mutation status is limited from India. EGFR mutation testing by RT-PCR is expensive and time consuming. Surrogate tests which are less expensive and less time consuming, which can replace RT- PCR of EGFR mutation analysis will be of great importance especially in countries with limited resources. P-AKT and TTF-1 by IHC have shown some significant promise in detecting EGFR mutation.
METHOD:
This is a prospective single institution study where 73 patients with adenocarcinoma of lung were studied for EGFR mutation and treatment response, in which treatment was started on the basis of EGFR mutation status, that is in patients who were EGFR mutation positive were started on TKI and those who were negative were started on chemotherapy. 101 patients were included for analysis of correlation between EGFR mutation status and P-AKT and TTF-1. The quality of life (QOL) was also assessed in TKI and chemotherapy group by using questionnaire which was standardized to Indian population.
RESULTS:
EGFR mutation in our study population was 48.5%. The one year OS and PFS of study population was 72.6% and 51.1 % respectively. The patients in TKI group had better one year PFS and OS (61.2% and 80.7% respectively) compared chemotherapy group (42.4% and 55.9% respectively) even though it was statistically not significant. The major toxicity in TKI group was skin toxicity which was much higher with erlotinib compared to gefitinib. In the correlation study of EGFR mutation status and IHC, negative predictive value of TTF-1 and P-AKT was very high (>90%). In our study, QOL was better in TKI group compared to chemotherapy group.
CONCLUSION:
EGFR mutation based treatment approach resulted in improved survival in both TKI and chemotherapy group, which emphasis the impotence of doing EGFR mutation testing in upfront setting. TKI arm compared to chemotherapy group had increased PFS and OS, and also had better quality of life. TTF-1 and P-AKT has high negative predictive value in detection of EGFR mutation, indicating that in patients who are above IHC negative, EGFR mutation testing can be avoided and started on chemotherapy, if the treatment needs to be started urgently
Drug package inserts: how accessible is the information?
Background: Information given in drug package inserts is often not easily accessible by patients and practitioners. Presentation of important information in an easily accessible manner fulfills the very purpose of inserts. In the present study, accessibility of important information in drug package inserts is evaluated.Methods: We evaluated 110 package inserts. Accessibility to important information was noted under following headings: use of box, use of special/bigger font or color, use of table of contents and information in front sheet. Each of these parameters was given a point. Cumulative accessibility score of more than three considered as accessible. Provision of toll free numbers and internet addresses of the companies noted.Results: Information in inserts regarding posology, method of administration, precautions under special conditions, contraindications, pharmacokinetics, interactions, pregnancy and lactation, driving, and machine use precautions were adequate and orderly in most. Only seven drug inserts mentioned important information with special font/different color. 18 drug inserts had used boxes. About 13 inserts used bigger font size for revealing important information. We observed a mean accessible score was 0.37 a insert. Only two inserts carried toll free numbers.Conclusion: Important information in drug package inserts is not easily accessible. Display of toll free numbers and internet addresses for queries and reporting adverse drug reactions is highly recommended
CAVASS: A Computer-Assisted Visualization and Analysis Software System
The Medical Image Processing Group at the University of Pennsylvania has been developing (and distributing with source code) medical image analysis and visualization software systems for a long period of time. Our most recent system, 3DVIEWNIX, was first released in 1993. Since that time, a number of significant advancements have taken place with regard to computer platforms and operating systems, networking capability, the rise of parallel processing standards, and the development of open-source toolkits. The development of CAVASS by our group is the next generation of 3DVIEWNIX. CAVASS will be freely available and open source, and it is integrated with toolkits such as Insight Toolkit and Visualization Toolkit. CAVASS runs on Windows, Unix, Linux, and Mac but shares a single code base. Rather than requiring expensive multiprocessor systems, it seamlessly provides for parallel processing via inexpensive clusters of work stations for more time-consuming algorithms. Most importantly, CAVASS is directed at the visualization, processing, and analysis of 3-dimensional and higher-dimensional medical imagery, so support for digital imaging and communication in medicine data and the efficient implementation of algorithms is given paramount importance
BORTEZOMIB INDUCED SUBCONJUNCTIVAL HEMORRHAGE
Many drugs are used in the treatment of multiple myeloma but Thalidomide, Lenalidomide, Bortezomib, dexamethasone and their combination remains the main stay of treatment. The molecular formula of bortezomib is C19H25BN4O4 and its chemical IUPAC name is [3-methyl-1-(3-phenyl-2-pyrazin-2-ylcarbonylamino-propanoyl) amino-butyl] boronic acid. Mechanisms by which it acts is usually by 26 SProteasome inhibition leading to degradation of anti-apoptotic proteins. Bortezomib is known to cause many side effects. So hence we report a rare case of Bortezomib induced subconjunctival hemorrhage in our tertiary care hospital.KEYWORDS: Bortezomib, Adverse effect, Proteosome inhibition, Subconjunctival Hemorrhag
Study on epidemiology of endometriosis in North East India
Background: Endometriosis is the presence of endometrial glands and/or stroma outside the uterus, predominantly in reproductive age. The prevalence is around 10% in women of reproductive age and is caused by combination of multiple genetic and environmental factors. Characterization of endometriosis can be learnt from epidemiological factors of the patients which influence on disease development and thus helpful in clinical diagnosis. Histological pictures after surgery may vary considerably and sometimes over diagnosis of the disease is not uncommon. The purpose of the study was to study the epidemiology of endometriosis in North East population of India and correlation of clinical and histopathological diagnosis.
Methods: It was a hospital based observational descriptive study carried out in Department of Obstetrics and Gynecology, AMCH, Dibrugarh, Assam, India. Detailed history and clinical presentations were elicited and relevant investigations were done. Operative findings and biopsy reports were correlated. All the findings were tabulated and statistically analyzed.
Results: Women in age group 30-39 years (48.31%) with mean BMI of 24.44±4.06 kg/m2, nulliparous (31.46%) or para 1(33.71%) formed the majority of study population. Majority had early age at menarche (11.45±1.24), irregular cycles, shorter cycle length, longer duration of flow. Majority (79.78%) had dysmenorrhea followed by dyspareunia (59.55%). Only 62.92% had biopsy proven endometriosis.
Conclusions: Epidemiological factors and clinical presentations guide in diagnosing endometriosis and should be given importance. Clinical diagnosis of endometriosis may not always correlate with histopathologic diagnosis and many other pathologies mimic endometriosis
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