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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
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.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
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.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
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 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
The Importance of Estrogen Receptors in Aetiopathogenesis of Carpal Tunnel Syndrome in Postmenopausal Women
Correspondence Address :
Dr. Ayse Nur Deger,
Department of Pathology, Kutahya Health Sciences University, Faculty of Medicine, Kutahya, Turkey.
E-mail: ayhade@yahoo.com
Introduction: Carpal Tunnel Syndrome (CTS) is a common peripheral neuropathy in postmenopausal women which is caused by compression of the median nerve in the carpal tunnel. Although mostly idiopathic, the aetiopathogenesis of CTS was not quite clear.
Aim: To verify the possible role of the estrogen surges and the presence of Estrogen Receptor (ER) in tenosynovial tissue on postmenopausal period, in the pathogenesis of idiopathic CTS.
Materials and Methods: The present study was a retrospective study conducted on, 16 patients with CTS in premenopausal group (group 1) and 18 patients with CTS in postmenopausal group (group 2). In the study, tenosynovial tissue samples of patients who had surgery due to CTS were used. Biopsy samples of 34 patients who were operated in the neurosurgery department of KSBU Medical Faculty Evliya Celebi Training and Research Hospital between January 2011 and January 2012 were included in the study. An examination was made by Haematoxylin and Eosin (H&E) in the tenosynovial tissue. ER was performed by immunohistochemistry on tissue samples. The non inflammatory fibrosis, vascular proliferation, oedema were observed. A nuclear staining for ER was observed in synovial lining cells and fibroblasts in the tenosynovial tissue.
Results: The number of positive cells for ER in the tenosyvial tissue in postmenopausal patients with CTS was found higher according to premenopausal patients with CTS (p<0.01). A high association was found among patient age, severe EMG findings and ER positivity.
Conclusion: There roles of hormonal surges in postmenopausal period and increased ER positivity in the tenosynovial tissue in the aetiopathogenesis of CTS.
Compression neuropathy, Histomorphology, Hormone receptor, Immunohistochemistry, Menopausal period
CTS is the most common peripheral compression neuropathy resulting from compression of the median nerve in the carpal tunnel.The underlying mechanism includes increased carpal tunnel pressure due to either a reduction in the size of space in the carpal tunnel or an elevation in the volume of tunnel content (1),(2),(3),(4). In addition CTS occur with mechanical damage to the median nerve. The aetiology of CTS is unknown (1).
The most cases of CTS are idiopathic (4). Some systemic diseases and conditions may be effective in the development of the syndrome. The diabetes, hypothyroidism, rheumatoid arthritis, alcoholism and renal dialysis are some of these predisposing factors (5),(6),(7),(8). CTS is more common in women. Male/female ratio is defined as 1/3 (4). The epidemiological studies showed that estrogen surges during pregnancy, oophorectomy, postmenopausal case in women are associated with idiopathic CTS (5). Hence, the present study aimed to verify the possible role of the estrogen surges and the presence of Estrogen Receptor (ER) in tenosynovial tissue on postmenopausal period, in the pathogenesis of idiopathic CTS.
The present study was a retrospective study in which tenosynovial tissue samples of 16 patient’s with idiopathic CTS in premenopausal period (group 1) and 18 patients with idiopathic CTS in post menopausal period (group 2) were evaluated. Ethics committee approval was received for this study. KSBU University (KSBU 14.06.2017, 2017-8/9) and informed consent form for this surgical procedure was obtained from all of the patients included in the study. The patients were operated in the neurosurgery department of KSBU Medical Faculty Evliya Celebi Training and Research hospital between January 2011- January 2012. The analysis of the data was done from January 2018 to July 2018.
Inclusion criteria: Idiopathic CTS patients were included in the study.
Exclusion criteria: The patients with diabetes, rheumatoid arthritis, thyroid dysfunction were excluded from the study.
To confirm the diagnosis of CTS in both groups of patients (premenopausal-group 1 and postmenopausal- group 2) paresthesia along median nerve trace, hand pain during the day or night were taken into consideration. In addition, positive findings including sensibility and provocative tests during the physical examination were used to confirm CTS (2),(4).
Study procedure: All those patients with clinical complaints and examination findings in support of CTS, underwent Electromyography (EMG), to further confirm the diagnosis. After confirmation, they were divided into the premenopausal group (group 1) consisted of patients between the ages of 20 and 25 and postmenopausal group (group 2) consisted of patients between the ages of 50 and 75. Patients in the postmenopausal group (group 2) were selected from individuals who have been in menopause for five years or more.The majority of patients, who were diagnosed with CTS as a result of physical examination mentioned above and laboratory findings, had received splints, non-steroidal anti-inflammatory drugs, vitamin B12 treatment. Patients with unresolved complaints, despite drug therapy, were operated. About 0.5 mm3 tenosynovial tissue was excised from each case. About 1 cc saline solution was given to perineurium to decrease the hydrostatic pressure. Thus carpal tunnel was decompressed.
Connective tissue samples within 10% buffered formalin were immediately sent to histopathology laboratory. Paraffin-embedded blocks were prepared from tissue samples and 4 micron-thick sections were taken. H&E staining was performed to evaluate the histomorphological changes caused by CTS in the subsynovial tissue. The procedure was performed at room temperature. Immunohistochemical examinations with ER to subsynovial connective tissue samples were made in both premenopausal (group 1) and postmenopausal (group 2) groups to evaluate ER of the fibroblasts and synovial lining cells (Clone SP 1 Thermo scientific).
In immunohistochemical procedure, micro polymer system kit was used. Mature breast tissue was used for positive external control and mesenchymal cells were used for internal control. Negative control for immunohistochemistry was processed without the primary antibody. Olympus CX41 light microscope was used in the assessment of H&E stained preparations and immunohistochemical studies and to get an image of the preparations. H&E stained sections were evaluated histomorphologically in both patient groups.
Positively stained fibroblasts (the cells with collagenous stroma and spindle, stellate nuclei) and synovial lining cells (the cells located in the periphery of tissue samples with oval nuclei) were counted in eight randomly selected areas per slide at X400 objective for ER assessment (4). Complete nuclear immunostaining was considered to be positive. Percentages of immunoreactive cells among all cells counted per field were calculated.
Statistical Analysis
Mann-Whitney U test was used for statistical analysis to compare cell staining in fibroblasts and synovial lining cells between both of patient groups. The association between patient age and ER positivity in fibroblasts and synovial lining cells in both of patient groups was evaluated. Along with the evaluation of association between EMG finding and ER positivity in fibroblasts and synovial lining cells.
Tissue samples of both patient groups exhibited non inflammatory fibrosis in tenosynovial tissue. With H&E staining, tissue oedema, vascular proliferation, vascular hypertrophy in varying degrees were seen (Table/Fig 1), (Table/Fig 2).
In the immunohistochemical analysis performed with ER, the staining for ER in tenosynovial tissue was seen to be in intranuclear attributes (Table/Fig 3), (Table/Fig 4).
Intranuclear staining was seen in vascular endothelial cells, in fibroblasts and synovial lining cells in both of patient groups (Table/Fig 5), (Table/Fig 6).
On comparing the number of fibroblasts and number of synovial lining cells giving positivity for ER in premenopausal and postmenopausal patient groups, it was observed that increased number of fibroblasts and synovial lining cells gave positivity for ER in postmenopausal patient and the difference of both cell types (fibroblast and synovial lining cell) amongst both groups was statistically significant (p<0.01) (Table/Fig 7), (Table/Fig 8).
The relationship between patient age and EMG findings with ER positivity was evaluated with Eta coefficient. On evaluation in both groups, showed strong relationship of 94% between EMG changes with positivity for ER in fibroblasts and of 95% between EMG changes with positivity for ER in synovial lining cells was observed. There was strong relationship of 87% between patient age with positivity for ER in fibroblasts and of 89% between patient age with positivity for ER in synovial lining cells.
CTS is caused by compression of median nerve of wrist, hence impacts the functioning of hand and an important cause of morbidity (9). It is important to know the aetiology of CTS firstly for effective treatment of CTS. The increased pressure within carpal tunnel causes median nerve neuropathy. Although there are numerous studies about the CTS, it is not known exactly the reason of increase in pressure in the carpal tunnel and aetiology of CTS (10),(11). Increased pressure in the carpal tunnel and the median nerve damage can occur the result of mechanical factors. Another reason is that ischaemia reperfusion injury causes CTS (3),(12). It recently focuses on the histomorphologic changes in tenosynovial tissues in carpal tunnel in the aetiopathogenesis of CTS. Increase in the size of the collagen fibrils, fibroblast proliferation, vasculary proliferation, vasculary hypertrophy, intimal thickening are histomorphological changes seen in the tenosynovial tissue in CTS (2).
Some cytokines and growth factors are responsible from changes seen in the tenosynovial tissue in patients with CTS, whereas they aren’t seen in non-CTS induviduals.The non inflammatory fibrosis is seen in the tenosynovial tissue in CTS. Transforming growth factor β(TGF-β) is one of basic mediators responsible from fibrosis in tissues. The increase in TGF-β expression in the tenosynovial tissue is seen in CTS. The inhibition of TGF-β expression is seen as a treatment target in CTS (13),(14),(15),(16). Hirata H et al., specified that Matrix metallo proteinase (MMP)-2 is produced in the tenosynovial tissue in early period in CTS. MMP-2 may be responsible from narrowing of the arteries and pain resulting in CTS (17). In another study, Hirata H et al., showed that there were increased Vascular Endothelial Growth Factor (VEGF) and prostoglandin E2 expression in intermediate phase in CTS. These two molecules may be responsible for increasing vasculary permeability and the formation of oedema in CTS (18).
Although the majority of patients with CTS are idiopathic, some systemic diseases and conditions were to ease occurrence of the disease. The diabetes, obesity, thyroid diseases, renal dialysis are some of these diseases. CTS is more common in women. The incidence is increased in pregnancy and menopausal period. The hormone replacement treatment, oophorectomy are systemic factors that facilitate the development of the disease (5),(19),(20).
It is known that estrogen has anti-inflammatory properties.The amount of some inflammatory cytokines such as interleukin 1(IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha increases due to estrogen fluctuations in menopause. The estrogen shows its anti-inflammatory affect by repressing genes which regulate inflammation. The surges in estrogen level in menopausal period eliminate anti-inflammatory feature of estrogen. This condition result with cellulary proliferation, angiogenesis, increased capillary permeability, oedematous changes in tissues (4). The apperance of these changes in carpal tunnel contributes to the devolopment of CTS. It is believed that hormonal affects and oestrogen surges have a role in CTS that frequently seen in women. It is believed that oestrogen surges cause histomorphological changes in tissues by causing it to lose its anti-inflammatory properties (4),(21).
It is shown that estrogen shows anti-inflammatory affect by suppressing proinflammatory cytokines in study Amelia T et al., and Anneleen L and Neven P, (5),(22).
Anneleen L and Neven P showed that estrogen has an affect preventing from arthritis by this way. It is specified that aromatase inhibitors, used in ER positive breast cancer, increase AI induced musculoskeletal syndrome (AIMSS) (arthralgia, carpal tunnel syndrome, start pains, stiffness, etc) in same study (22).
Histomorphological studies on the impact of hormonal factors on the CTS is very few number in the literature. The presence of estrogen in target tissue is a prerequisite for acting via ER. Amelia T et al., investigated the ER and PR positive cells in transverse carpal ligament biopsies and showed that positive cell numbers for ER and PR receptors in patients seen CTS findings are higher than non CTS individuals (5). Kim JK et al., evaluated ER receptors in tenosynovial tissue in postmenopausal women. They determined higher ER positivity, cells in tenosynovial tissue in postmenopausal women with idiopatic CTS according to postmenopausal individuals, not seen in clinical CTS findings (4).
Present study examined ER in the tenosynovial tissue in patients with idiopathic CTS in premenopausal group (between 20-35 years) and patients with idiopathic CTS in postmenopausal group (between 50-75 years). ER expression was observed in the tenosynovial tissue in patients with CTS in both groups. This study showed that positive cell number in both fibroblasts and synovial lining cells in postmenopausal CTS cases is higher according to premenopausal CTS cases. A strong relationship was seen between ER positivity and patient age in fibroblasts and synovial lining cells. A strong relationship was seen between ER positivity and EMG findings in fibroblasts and synovial lining cells also.
Limitation(s)
Due to the insufficient number of patients, a small number of tissue samples were studied. Further studies in larger patient samples are recommended in future for better contributions to literature.
The increased ER in tenosynovial tissue cells in postmenopausal period with increased incidence of CTS is to support role of hormones in aetiopathogenesis of CTS. It is believed that the surges of estrogen level in postmenopausal period eliminate anti-inflammatory feature of estrogen. It is possible that the loss of anti-inflammatory feature increases the incidence of CTS. Even so, the role of estrogen in the aetiopathogenesis of CTS is not understood exactly. Further studies are needed about the role of estrogen in the occurrence of symptoms and in the aetiopathogenesis of CTS.
DOI: 10.7860/JCDR/2022/54978.16857
Date of Submission: Jan 15, 2022
Date of Peer Review: Feb 17, 2022
Date of Acceptance: Jun 03, 2022
Date of Publishing: Sep 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: This research hereby is supported through the DPU University (DPU BAP 2012/17)
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
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