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

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On Sep 2018




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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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Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




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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Dr. Saumya Navit

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Professor and Head
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Saraswati Dental College
Lucknow
On Sep 2018




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Muzaffarnagar.
On Aug 2018




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"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



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




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
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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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.
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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

Important Notice

Reviews
Year : 2010 | Month : April | Volume : 4 | Issue : 2 | Page : 2325 - 2329 Full Version

Cryotherapy – A Review


Published: April 1, 2010 | DOI: https://doi.org/10.7860/JCDR/2010/.684
SUNITHA J

MDS,Assistant Professor, Department of Periodontics, College of Dental Sciences, Davangere.

Correspondence Address :
Dr. Sunitha .J,( MDS)Assistant
Professor,Department of Periodontics,
College of Dental Sciences,Davangere.
Karnataka, (India).Phone numbers: 9480177682,E-mail: dr_sunithaj@yahoo.co.in

Abstract

Technical advances in recent years have made the application of controlled low temperatures a feasible proposition in many branches of surgery. In the last decade there has been a proliferation of reports on the uses of cryotherapy; nevertheless, many of the applications are still experimental, or await the test of time. Cryotherapy is the deliberate destruction of tissue by application of extreme cold. The mouth is reasonably accessible to cryotherapy apparatus. The warm moist surface of the oral mucosa is well suited to the application of a freezing probe. Recent advances in cryotherapy equipment have brought treatment by this means within the range of the dentist.

Keywords

Cryotherapy; cryogens; ice pack; oral lesions; intraoral surgery

Introduction
Cryotherapy is the use of cold, applied locally or generally through various methods, to lower the temperature of the skin and subcutaneous tissues. It has been used in oral medicine and pathology for over 30 years. Reports of tissue destruction by freezing date back to the British physician, Arnott in 1851. Initially, its use was limited to the treatment of cancer of the lip and oral cavity. At present its applications in the head and neck region are broad (1). Also cryotherapy can be recommended after physical injuries and various surgical procedures.

Modes of cold application include ice pack, gel pack, ice chips, melted ice water, ice massage, prepackaged chemical ice pack and ice in a washcloth (2).

Cryogens
The commonly used cryogens include liquid nitrogen (-1960 C), nitrous oxide (-890 C), solidified CO2 (-780 C) (dry ice CO2 snow), chlorodifluromethane (-410 C), dimethyl ether and propane (-240 C, -420 C)(3).


Principles Of Cryotherapy
The basic technique of cryotherapy stresses rapid cooling, slow thawing and repetition of the freezing process to maximize tissue destruction. The two methods recognized are;
1) A closed system with use of probes and nitrous oxide
2) An open system with use of a liquid nitrogen spray or a cotton tip.

The probe system follows the principles of Joule-Thompson expansion which enable substances to undergo a drop in temperature when moved from a high pressure area to a low pressure area. For instance, when nitrous oxide is released from the high pressure inside the cryoprobe to the lower pressure cryotip, the drop in temperature allows freezing of the tissues to occur(1),(4),(5).

Modern cryoprobes may also be fitted with tip temperature monitors allowing for time selection and increased control. This allows clinicians to observe the effects at a certain probe temperature and use this as a basis for future treatment (1),(6).

Liquid nitrogen sprays and cotton swabs are more accessible to clinicians but not suitable for use in the oral cavity. Their disadvantage is a lack of control over the temperature achieved within cells and the area of freezing, which makes them hazardous to use intra-orally. Also, rapid evaporation of liquid nitrogen from cotton swabs requires numerous applications on the lesion. Due to direct contact between the cryogen and tissues, a more controlled and profound depth of freezing can be achieved with a nitrous oxide cryoprobe (1).

Cryotherapy Of Oral Lesions (1)
Cryotherapy is used for the treatment of keratotic, hyperplastic, granulomatous, vascular, pigmented lesions, and salivary gland lesions as well as for gingival

Stages of cryotherapy (Hocutt et al 1982) (2)
Stage 1: sensation of cold 1-3 min
Stage 2: aching or burning 2-7 min
Stage 3: local numbness 5-12 min
Stage 4: deep dilation >12 min
It has been suggested that after an injury >12 min should be used to attain stage 3.


Cryolesion Dimensions
Cryolesion dimensions are dependent upon three variables; the temperature of the cryotip, the period of contact and the area of contact between the tip and tissue. The temperature of the probe tip contributes to the size of the freeze-ball as well as determining the velocity of freezing within cells. Since lethal effects are observed with rapid freezing, a high velocity of freezing is desired. Growth patterns of the cryolesion in vitro suggest that the duration of freezing is proportional to the lesion size in the first 1-7 minutes.1 After this time no further increase in size is observed and no added benefit is gained by continuous exposure. In addition, since it is difficult to freeze tissue ,2-3 cm away from the probe, multiple freeze sites in large lesions may be warranted. This is especially true when freezing bony tissue but freezing times are in the order of 20-30 seconds when dealing with most oral soft tissue lesions. The area of contact of the probe can be varied by tip diameter. Larger tip diameters correspond to an increasing size in the freeze-ball. However, diameter size also compromises the efficiency of the cryoprobe. Another factor to consider is that moisture in the vicinity of the lesion may enhance the area of contact, thus creating a larger freeze-ball (1).

Current protocols suggest that for most benign mucosal lesions a 1-2 min freeze/thaw cycle using a cryoprobe is sufficient. Premalignant/malignant lesions are recommended to undergo three 2 min freeze/thaw cycles. For smaller lesions, shorter freeze cycles (20-30 seconds) are adequate. In cases where hyperplastic tissue exists, freezing of the mass and then removing the bulk of tissue, followed by further freezing of the tissue base results in higher success rates (1).

Mechanisms Of Tissue Damage In The Cryolesion
At present, the optimal temperature of cell death is unclear, however, it has been determined that most tissues freeze at -2.2oc and that the temperature must fall below -20oc for cell death to occur. On this basis, dermatological guidelines suggest that temperatures of -30oc may be effective for small cancers. The treatment of more aggressive cancers in the oral cavity may require repetitive freeze cycles at temperatures of at least -50oc or more for tissue necrosis to occur (1),(7).

Tissue destruction following cryotherapy is believed to be a multifactoral process. Accumulation of damage occurs as the lesion undergoes repetitive freeze and thaw cycles. Immediately following treatment, cryolesions are indistinguishable from original tissue. However, latent damage is produced which progresses to severe damage and subsequent necrosis of the tissues in the following days (1),(7).

During the freeze cycle as the temperature drops, it is believed that extracellular water undergoes crystallization. In addition, membrane lipids harden at low temperatures decreasing cell resistance to shrinkage. As extracellular stores of water diminish, the electrolyte concentration increases. In order to counteract this concentration gradient, intracellular water moves out of the cell, and this water becomes involved in the crystallization process. Also, the intracellular ice formed remains trapped within the cellular membrane. As a result of these processes, intracellular electrolytes reach toxic levels, which become lethal to the cell. During a slow thaw cycle, cells at the periphery of the cryolesion will take up excess electrolytes. To equalize this gradient, water enters the cell and this can lead to swelling and lysis. Further re-crystallization may contribute to cellular damage; however, this phenomenon may be avoided if cells are thawed rapidly (1),(7).

Cold Therapy After Intraoral Surgical Procedures
The therapeutic use of cold is applied locally or generally through various methods, to lower the temperature of the skin and subcutaneous tissues (2).Clinicians often recommend that patients apply ice for therapeutic purposes after physical injuries and various surgical procedures (2),(8). THE Physiological and clinical effects of cryotherapy have been widely studied but there is still dearth of scientific information with respect to the best mode of application, optimal time interval for therapy (time on and off), and total duration of cryotherapy. To establish a basis for discussion the basic physiological responses to cold subsequent to oral surgery was reviewed (2).

Benefits Of Cold Application On Inflammatory Response
Historically, five cardinal signs of inflammation were identified: pain, swelling, heat, redness and loss of function. However, signs of inflammation are not inflammatory response. The inflammatory reaction consists of overlapping stages that can impair tissue function or structure (8). The r reason for applying cold therapy (e.g., ice) after an injury is to cool tissues to accomplish the following physiological objectives: decrease inflammation, inhibit swelling (edema), diminish blood supply (vasoconstriction), decrease hemorrhage, inhibit temperature elevation, reduce metabolic alterations (cold decreases the metabolic rate, thereby lessening secondary injuries due to lack of oxygen), assuage pain (cold decreases nerve conduction speed), and, ultimately, speed up the recovery of the patient to resume normal functions (1),(10).

Physiological Effects
Temperature Changes
Cold or ice packs work on the Principle of conduction. Heat is transferred between molecules from warmer to cooler areas. Thus, cryotherapy does not convey cold to tissues because cold is not transferable. In contrast, tissues lose heat because they warm the cold agent. Following the same principle, deeper structures lose heat to more superficial tissues that were cooled. The amount of temperature change in treated areas depends on various factors: differences in temperature, size & shape of pack, duration, tissue thickness, anatomic location and mode of therapy. The temperature declines gradually until skin warmth plateaus a few degrees above the temperature of the applied cold agent (1),(11). Ebrall et al (1992) used wet ice pack of 37ÂșC to 7.6ÂșC in 5 min and to 5ÂșC within 10 min and found no change in skin warmth 1 cm proximal or medial to ice pack.2 After cessation of cold therapy, Bugaj (1975) noted the skin readjusted at 1.9ÂșC per minute. The target temperatures that need to be reached to accomplish the desired physiological endpoint remained unsolved. In conclusion, temperatures to inhibit signs of inflammatory response range between 10ÂșC and 15ÂșC. Ice and cold packs reduced skin temperature by 10ÂșC to 15ÂșC within 15 minutes (2).

Hemodynamics (Blood Flow)
Studies indicated that cold application initially resulted in vasoconstriction of blood vessels. After an injury, this reduced the hemorrhage and perfusion of fluids, and ultimately resulted in decreased edema. Subsequent to vasoconstriction, there may be vasodilatation, despite continued use of cold. This is believed to occur as a result of reactive hyperthermia. The vasodilatation is referred to as a “hunting response” and represents the flow of blood through arteriovenous anastomoses. This may be a compensatory mechanism that prevents injury caused by extreme cold temperatures. The hunting response was reported to occur after 20-30 minutes (2) which is refuted completely by Knight who called it a measurement artifact. However, the controversy has not yet been resolved (2).

Edema
Swelling can be caused by hemorrhage and/or edema. After an injury, bleeding usually stops within 5 minutes because of clotting; therefore, swelling is usually caused by edema. Decreased temperature also reduces tissue metabolism and permeability. Depressed metabolism results in less tissue debris, a diminished amount of free protein and subsequently, less osmotic pressure for fluid to exit cells. In addition, reduced cell death because of tissue hypoxia results in fewer mediators (e.g., bradykinin) being released; therefore, there is less vascular permeability and edema. Cold could help prevent swelling from occurring, but it does not decrease edema that is already present (2).

Pain Reduction
Decreased pain was caused by cold-induced diminished nerve conduction velocity. Alterations of nerve transmission were due to thermal effects on nerve fibre membranes. Superficial nerves demonstrated the greatest nerve velocity reduction, and cold temperature blocked sensory fibres before motor fibres. Cold affected the small myelinated fibres first, then the large myelinated fibres and finally, the small unmyelinated fibres. The critical temperature at which alterations of nerve velocity commenced were 27ÂșC, while analgesia began after skin temperature decreased to 13.6ÂșC (pin-prick test) (2).

Metabolic Processes
Reducing tissue temperature suppresses the injured tissue’s metabolic rate and enzymatic processes. But some studies demonstrated that cooling diminished the demand for ATP and the need for oxygen; therefore, tissues survived well during hypoxia induced by injury. To diminish skin metabolic rates, the temperature needed to be around 10ÂșC for a period of about 15 min (2).

The physical changes noted were that; the collagen became stiffer and was not able to stretch, motion was decreased temporarily, and the tissue became pallid (2),(12).

Psychological benefits can be achieved by giving patients a task which will distract them from focusing on their discomfort, causing a placebo effect (2),(12).

Contraindications include a history of frost bite or arteriosclerosis, hypertension, local limb ischemia, paroxysmal cold hemoglobulinuria, Raynaud’s disease, rheumatoid arthritis and cryoglobulinemia (2),(3).

Advantages
The merits of cold therapy include relative lack of discomfort and pain (decreases nerve conduction speed), the absence of bleeding(vasoconstriction), minimal to no scarring, ease of application, preservation of inorganic structures of bone, very low incidence of infection(decreases the metabolic rate, thereby lessening secondary injuries due to lack of oxygen), no permanent side effects and being more localized in action . Perhaps its greatest advantage is its usefulness in candidates for whom surgery is contraindicated (1),(2),(7).

Disadvantages
But cold therapy has its own limitations. These include the unpredictable degree of swelling, lack of precision with depth and area of freezing and its high dependence on operator skill and experience (1),(2),(7).


Length Of Therapeutic Intervals & Duration Of Ice Application
Therapeutic intervals are prescribed for the time cold is applied and the subsequent rest periods. Duration of therapy denotes the overall time (cycles of cold therapy and rest periods) that treatment is continued. In many of the studies related to oral surgical procedures, there has been a great deal of variation with respect to the length of intervals and durations of time recommended for cold therapy. LaVelle & Synder (1985) limited therapy time to 10 min intervals instead of 20 min as it may achieve the same skin temperature but with less hunting response. But Knight (1995) proposed a protocol for cooling and rewarming tissues at a 1:2 ratio. Accordingly ice was applied for 30-45 min at 1-2 hr intervals for the first 12-24 hrs after injury. Another investigator suggested that cold should be applied post-surgically until response to trauma is stabilized, which could be between 24 to 72 hours.

But, there are no clear clinical guidelines based on dental or physiotherapy literature for the optimal time that ice should be applied to achieve specific clinical objectives (2).

Intermittent V/S Continuous Application
The efficacy of intermittent versus continuous cold therapy has not been resolved. Intra orally investigators recommend continuous ice therapy. Many studies recommend continuous therapy for 2 – 24 hours but fail to provide significant benefits compared to no cold therapy. No clinical trials have compared these two parameters after intraoral surgical procedures (2),(14).

Conclusion

Currently, cryotherapy is an effective treatment method for intraoral surgeries. By reviewing various physiological responses to cold application it is expected that ice therapy would provide several benefits. However clinical trials are required to provide a strong evidence to prove the therapeutic efficacy of cryotherapy.

References

1.
Farah CS, Savage NW. Cryotherapy for treatment of oral lesions. Aus Dent Journal 2006;51(1):2-5
2.
Greestein G. Therapeutic efficacy of cold therapy after intraoral surgical procedures: A literature review. J periodontal 2007;78:790-800
3.
Sharma V.K, Kandhpur S. Guidelines for cryotherapy. Indian J Dermatol Venerol Leprol 2009;75(2):90-100
4.
Pogrel MA. The use of liquid nitrogen cryotherapy in the management of locally aggressive bone lesions. J Oral Maxillofac Surg 1993;22:353-55
5.
Salmassy DA, Pogrel MA. Liquid nitrogen cryosurgery and immediate bone grafting in the management of aggressive primary jaw lesions.
6.
Leopard PJ, Poswillo DE. Practical cryosurgery for oral lesions. Br Dent J. 1974;136:185-96
7.
Leopard PJ. Cryosurgery and its application to oral surgery. Br J Oral Surg. 1975 Nov;13(2):128-52.
8.
Olson JE, STravino VD. A review of cryotherapy. Phys Ther 1972;52;840-53
9.
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