Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
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Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Saraswati Dental College
Lucknow
On Sep 2018




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Calcutta National Medical College & Hospital , Kolkata




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On Aug 2018




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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
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An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Original article / research
Year : 2012 | Month : August | Volume : 6 | Issue : 6 | Page : 963 - 966

The Significance of the Plasma L-Selectin Levels in Cases of Acute Myeloid Leukaemia: A Case Control Study

A.R. Subhashree, B. Shanthi, C. Revathy

1. Associate Professor, Department of Pathology, 2. Associate Professor, Department of Biochemistry, 3. Post Graduate, Department of Biochemistry, Sree Balaji Medical College & Hospital, Chrompet, Chennai, Tamil nadu, India.

Correspondence Address :
Dr. A.R.Subhashree,
Associate Professor, Department of Pathology,
Sree Balaji Medical College, Chrompet,
Chennai 600 004, India.
Phone: 9840243628
E-mail: Subhashree_sai@yahoo.in, drshanthibio@gmail.com

Abstract

Background: Acute Myeloid Leukaemia (AML) is a heterogeneous group of haematological malignancies which are characterized by malignant proliferation and the accumulation of immature myeloid progenitor cells in the bone marrow. A clinical history of myelodysplasia, the assessment of the morphology of the blast cells, cytogenetics and immunophenotyping are the important criteria which have been used in the recent WHO classification to prognosticate as well as to guide the therapy of AML. L-selectin is a cellular soluble adhesion molecule and it mediates the initial tethering of the normal leucocytes to the endothelial surface . An increase in the plasma L-selectin levels in cases of acute leukemia has been observed in many studies, but till date, this biochemical parameter has not been used as a marker in monitoring leukaemic patients. This study was conducted to compare the L-selectin levels in fresh and treated cases of AML and also with healthy controls. The assessment of the plasma L-selectin levels is expected to add more information about the disease activity and it could also serve as an adjunct to the existing immunological and genetic markers.

Aims, Settings and Design: This case control study aimed at estimating the plasma L-selectin levels in cases of acute myeloid leukaemia in comparison with those in normal healthy adults. Further, we assessed the plasma L-selectin levels during the active and the remission phases of AML.

Materials and Methods: 20 freshly diagnosed and 20 treated cases of AML were included in the study group from the Haemato Oncology Department of our institution. Forty healthy people who were the staff members of the hospital were included as the controls. The quantitation of L-selectin was done by a highly sensitive immunometric ELISA assay (Manufacturers; Bendermed systems, Vienna, Austria), by using monoclonal antibodies against L-selectin. The statistical significance was calculated by using the Bonferroni T-test and Pearson’s correlation analysis.

Results: There was a statistically significant (p=<.001) increase in the plasma L-selectin levels in the freshly diagnosed AML patients as compared to the control group. The plasma L-selectin levels in the patients who were in remission matched with that of the controls.

Conclusions: Plasma L-selectin may be used as a marker of the disease activity in AML patients. It may also be used to assess the remission status of these patients.

Abbreviations: AML=Acute Myeloid Leukaemia

Keywords

AML, Plasma L-selectin, Prognostic marker, Remission

How to cite this article :

A.R. Subhashree, B. Shanthi, C. Revathy. THE SIGNIFICANCE OF THE PLASMA L-SELECTIN LEVELS IN CASES OF ACUTE MYELOID LEUKAEMIA: A CASE CONTROL STUDY. Journal of Clinical and Diagnostic Research [serial online] 2012 August [cited: 2018 Oct 21 ]; 6:963-966. Available from
http://jcdr.net/back_issues.asp?issn=0973-709x&year=2012&month=August&volume=6&issue=6&page=963-966&id=2317

Introduction
Acute myeloid leukaemia is a group of haematological malignancies which predominantly involve the adult population. Despite intense therapies in the form of radiation and chemotherapy, relapses are common. A history of myelodysplastic syndromes or genotoxic therapy, age at diagnosis, the morphological features of the blast cells and cytogenetic aberrations are the accepted prognostic factors of AML (1), (2), (3) (4). The significance of the plasma L-selectin levels as a biochemical marker for acute leukaemias has been reported since long (5). L-selectin is an adhesion molecule which is expressed in normal leucocytes as well as in leukaemic cells, which helps in the initiation of the leucocyte attachment to the activated endothelium (6),(7).

Its proteolytic shedding facilitates the detachment of laeukocytes from the endothelial cells as they migrate through the endothelial layers. An increase in the shed L-selectin levels in leukaemic patients has been observed in a few studies (3),(8) and its significance as a prognostic marker has been observed (9), but till date, this biochemical parameter has not been used as a marker for monitoring leukaemic patients. In our study, we attempted to quantitate the levels of plasma L-selectin in fresh and treated cases of AML in comparison with healthy normal controls, to understand the importance of this biochemical marker in the follow up of AML patients.

Material and Methods

20 freshly diagnosed cases of acute myeloid leukaemia, 20 cases of AML who had undergone treatment with two to three cycles of chemotherapy and were clinically remitted and 40 healthy controls were included in the study, based on the inclusion and exclusion criteria.

Exclusion criteria:
• Acute infection or inflammation • Diabetes mellitus • Connective tissue disorders • Post-operative deep vein thrombosis

Inclusion criteria:
Group A (Fresh cases of AML) The 20 patients who were selected were of the age group of 18-60 years and they were diagnosed as the cases of AML, based on the following criteria (10): • Complete blood count, differential count • Peripheral smear study and cytochemistry • Bone marrow aspiration cytology • Cytogenetics • Immunophenotyping Among these, 50% were women.

Group B (Treated cases of AML)
20 patients (different set of cases from Group A) who had undergone treatment with two to three cycles of chemotherapy with Cytarabine + Daunorubicin (7+3 regimen) and were clinically remitted11 were included. The clinical remission was assessed by using the following criteria (11): • Normalization of the neutrophil counts (at least 1.5 X 109/L). • Platelet counts of more than 100 X 109/L. • Marrow aspirates that demonstrated at least 20% cellularity and less than 5% blasts with no Auer Rods. • Absence of extra medullary leukaemia. They were of the age group of 18-60 years. Among these, 50% were women.

Group C (Control)
40 age and sex matched healthy people were selected as the controls. The controls were chosen from among the staff of Sree Balaji Medical College. A written consent was obtained from each subject. Ethical clearance and an approval to conduct the study were obtained from our institutional human ethical committee. The plasma samples (in EDTA) and the serum samples were collected. A complete haemogram, liver function tests, renal function tests and serum uric acid tests were performed. As bone marrow aspiration was already done for all the fresh cases of AML, it was not repeated for the Group A cases, though the procedure was done for all the treated cases (Group B). The quantitation of L-selectin in the plasma samples was done by a highly sensitive immunometric ELISA assay (Manufacturers; Bendermed systems, Vienna, Austria) by using monoclonal antibodies (murine) against L-selectin.

Results

The plasma L-selectin levels ranged from 963 ng/ml to 2500 ng/ml in the freshly diagnosed AML patients, from 98 ng/dl to 683 ng/ml in the treated cases of AML which were under remission and from 110 ng/ml to 423 ng/ml in the healthy controls. (Table/Fig 1) gives the mean levels and the standard deviation of various parameters in the 3 groups and (Table/Fig 2) gives the statistical significance p(<.001) which was obtained from the comparison.

The significance of the differences in the values of the parameters among the Groups I, II and III was evaluated by using the Bonferroni T-test. The Pearson’s correlation analysis was employed to find out the correlations between the L-selectin levels and the bone marrow blast percentage (Table/Fig 3). (Table/Fig 4) and (Table/Fig 5) show the increasing levels of L-selectin from the controls to the treated cases to the fresh cases of AML. (Table/Fig 2)shows the statistical correlation of the plasma L selectin values among the three groups. The fresh cases of AML (Group A) showed a statistically significant increase in the plasma L-selectin levels as compared to those in the treated cases (GroupB) and in the control group (Group C), (p =000). There was no significant change in the values between the Groups B and C.

(Table/Fig 6) demonstrates that only the freshly diagnosed cases of AML showed an elevation in the blast cell count in the marrow. There was no significant overlap in the marrow blast cell count between the fresh and the treated cases. This could be reasoned by the fact that the patients in the treated category had undergone a clinical remission. There was a statistically significant correlation between the percentage blasts in the marrow and the L-selectin levels, as was noted in the Pearson’s correlation analysis (Table/Fig 3). (Table/Fig 4)highlights that there was no gender based difference in the levels of plasma L-selectin in the leukaemic patients.

Discussion

Under normal conditions, L-selectin plays an important role in inflammation by mediating leucocyte rolling along the activated endothelium (12). It also increases the recruitment of leucocytes into the tissues by mediating leucocyte rolling on the already adherent leucocytes (13). Soon after the endothelial adhesion, this receptor gets shed from the white cell surface due to a proteolytic cleavage and it circulates in the plasma. In acute leukaemias, it is observed that there is an increase is the shedding of L-selectin, which probably inhibits the binding of leukaemic cells to the vascular endothelium, thereby influencing the migration of the leukaemic blast cells. The shed L-selectin probably would protect the leukaemic cells from cell death by immune surveillance, by either interfering with the lymphocyte homing or by inhibiting the cytotoxic lymphocytes to interact with the blast cells (3). On the other hand, the over expression of L-selectin in the leulaemic cells might help these cells in attaching to the vascular endothelium, leading to transmigration and organ infiltration (2).

The present study observed an increase in the plasma L-selectin levels in fresh cases of AML as compared to those in those who were treated. A statistically significant correlation was observed965between the blast percentage in the marrow and the L-selectin levels in the fresh and treated patients. These findings added value to the aim of our study, of establishing L-selectin as a biochemical marker for the disease activity in AML. The findings of the study which was done by Exterman et al., (3). were in agreement with our findings. The observed values of L-selectin and its correlative findings in comparison with the percentage blasts, were in concordance with the findings which were observed by Spertinii O, and Callegari P et al., (8).

Conclusion

Our study emphasized the fact that plasma L-selectin was a marker for the disease activity in AML patients. It can be used as an indicative marker for the remission status of the patient. An important challenge in the management of AML is to distinguish the patients with a high risk of relapse, who may benefit from high dose chemotherapy, followed by BMT, from those cases in which such treatments can be delayed. Though cytogenetic aberrations can affect the prognosis of such cases in a greater way, it can be suggested that L-selectin can still be used as a marker for serially monitoring the disease activity and as a prognostic marker of AML in future.

FUTURE PERSPECTIVES AND RECOMMENDATIONS: A comparative study of the plasma L-selectin levels can be done with immuno phenotyping and cyto genetic analysis to ascertain whether L-selectin could be an adjunct to the other prognostic markers. The serial monitoring of the plasma L-selectin values in fresh cases of AML during the course of the treatment and following up their remission may also give therapeutic suggestions and options.

Acknowledgement

The authors are grateful to Professor B.O. Parijatham, Head of the Department of Pathology, for her valuable guidance in the accomplishment of this study.

References

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Kumar, Abbas, Fausto, Aster. Robbins and Cotran Pathologic Basis of Disease. 8th edition. Elsevier; 2010; 622.
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Vardiman J W , Harris N L, Brunning R D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood .2002; 100: 2292-302.
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Heilmeier B, Buske C, Spiekermann K, Bohlander S, Feuring-Buske M, Hiddemann W, et al. The diagnostics, classification and the prognostic criteria of acute myeloid leukemia. Med Klin (Munich). Apr 2007; 102(4):296-308.
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Extermann M., Bacchi M.,Monai N, Fopp M., Fey M., Tichelli A, et al.Schapira M, Spertinii O. The relationship between the cleaved L-selectin levels and the outcome of acute myeloid leukemia. Blood. 1998; 92: 3115-22.
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Tatewaks M, Yamaguchi, K.Matsuoka M, .Ishi T. The constitutive over expression of the L-selectin gene in the fresh leukemic cells of adult T cell leukemia can be transactivated by the human T cell Lymphotropic virus type I-Tax. Blood. Oct 1995; 86 (8): 3109-17.
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Osborn L. Laeukocyte adhesion to the endothelium in inflammation. Cell .1990 ; 62:3-6.
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Spertini O, Callegari P, Cordey A-S, Hauert J, Joggi J, Von Fliedner V, et al. High levels of the shed form of L-selectins are present in patients with acute leukemia and they inhibit blast cell adhesion to the activated endothelium. Blood. 1994; 84:1249-56.
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Aref S, Salama O, Al-Tonbary Y, Fouda M, Menessy A, El-Sherbiny M. L, El-Sherbiny MLE. Selections in acute myeloid leukaemia: expression, clinical relevance and relationship with the patient outcome. Hematology. Apr 2002; 7(2):83-7.
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Döhner H, Estey E H, Amadori S, Appelbaum F R., Büchner T, Alan K. The diagnosis and management of acute myeloid leukaemia in adults: Recommendations from an international expert panel. On behalf of the European Leukaemia Net. Blood.2010; 115: 453-474.
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Greer J P, Foerrster J, Rodgers G, Paraskevas F, Glader B, Arber DA, et al., Jr. Wintrobe’s Clinical Hematology. 11th edition. Lippincott Williams and Wilkins; 2008; 2120.
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Tedder TF, Steeber DA, Pizcueta P. L-selectin-deficient mice have an impaired laeukocyte recruitment into the inflammatory sites. J Exp Med. 1995; 181:2259-64.
13.
Alon R, Fuhlbrigge RL, Finger EB, Springer TA. The interactions through L-selectin between the laeukocytes and the adherent leukocytes can nucleate the rolling adhesions on the selectins and VCAM-1 in the shear flow. J Cell Biol. 1996; 135:849-65.

DOI and Others

ID: JCDR/2012/4636:2317

Financial OR OTHER COMPETING INTERESTS:
None.

Date of Submission: Jun 04, 2012
Date of Peer Review: Jun 18, 2012
Date of Acceptance: Jul 05, 2012
Date of Publishing: Aug 10, 2012

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2016: 132.37
  • SCOPUS
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • EBSCOhost
  • Embase & EMbiology
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com