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BEDSORE HEALING: Low Level Laser Therapy- LED( Ga-Al-As 660) on Soft Tissue Healing- Review, Mechanism and A case report ( Research Paper) -

BEDSORE (SOFT TISSUE CHRONIC WOUND) HEALING- By Low Level Laser Therapy: LED ( Ga-Al-As, 660) on Soft Tissue Healing: Review, Mechanism and A case report (Research Paper) -

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LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
        On soft Tissue Healing: Review, Mechanism and A case report.



      Research Paper
      Research Panel Members:
    1 Dr. Md. Nazrul isla m, MBBS, M.Sc. (Biomedical Engineering), 2Professor Golam Abu Zaka ria, Ph D. 3Professor F. H. Sirazee, MBBS, MS. (Orthopedic).
    4 Dr. Paritosh Chandra Debena th, MBBS, MS. (Orthopedic).5 Dr. kazi Shamimuzz aman, MBBS, MS. (Orthopedic). 6Dr. Quamrul Akhter Sanju, MBBS, F CPS,
     MR CS.(Surgery). 7Dr . Ashraf Uddin Khan, MBBS, DMR D, F CPS. (Rad iology).8Dr. Md. Mostafizur Rahman,MBBS, F CPS (Surgery) 9 Dr. Sayed Shaheedul
     Isla m, MBBS, MS (Orthopedic). 1 0Sinha Abu Khalid, B. Sc. (Hons. Applied Physics & Electronics).11M uhamma d Masud Rana, M.Sc. ( Medical Physics).
      Correspondence to the Author:
      1Dr. Md Nazrul Islam .

      Resident Surgeon, Department of Or thopedic & Traumatology. Shaheed Suhraw ardyM edical College Hospita l. Dhaka - 1207 , Bangladesh.
      E-mail: abbirr@gmail.com,Tel:M: + 88- 01196133078,Office-PABX -9130800- 19-138.




                     Contents:
                     1.         Introduction
                     2.         Review
                                                                       Skin lesions and the importance of
                                                                        Healing process in treatmen t success.
                                                                       Low-level laser
                                                                       Action of Laser on Tissues and its role
                                                                        in the Healing Process.
                     3.           Mechanism of LLLT.
                                                                       Laser an d Tis sue in teraction
                                                                       Primary Mechanism- Physical
                                                                       Secondary Mechanism- Biochemical
                                                                       Tissue response & healing by LLLT
                     4.           A case report: Laser Therapy on Soft Tissue.
                                                                       Abstract
                                                                       Case Stu dy
                      5.          Discussion
                      6.          Conclusion
                      7.          References.
            1. INTRODUCTION
            Allied health professionals regularly care for a variety of skin wounds, such as abrasions, turf burns, surgical incisions, and ulcerations,
            which are perhaps the most difficult to treat.
            At present, cutaneous lesions represent a dilemma of global proportions and instigate great clinical interest because of the high morbidity
            associated with changes in the normal healing process. 1 Among the clinical aspects involving this issue, we emphasize tissue repair time
            in an effort to make the process quicker and more harmonious, reduce possible complications in lesion resolution, and allow an adequate
            choice of therapy. To do this, familiarity with the pathogenesis of tissue healing is necessary, as well as an understanding of the factors
            affecting the process and the role each one plays in its progress, always seeking a clinical treatment that optimizes skin lesion care.
            Among the methods currently available, low-level laser therapy (LLLT) stands out.
            From acute wound management to augmentation of scar tissue remodeling, the clinician seeks to optimize wound care to promote
            healing. Experimental in vitro and in vivo studies have been under development since the 1960s, and in the early 1990s, LLLT was
            approved by the Food and Drug Administration (FDA) as an important method for treating healing processes. 2-4 Recent results of a study
            demonstrated that LLLT is an effective method to modulate tissue repair, thus si gnificantly contributing to a faster and more organized
            healing process. 5
            Nevertheless, in spite of the large number of studies involving this technique and its wide use in clinical practice, the pri nciples of its
            action in cells and tissues are still not well understood. The objective of this study is to review pathogenetic aspects of soft tissue repair
            to understand the major complications in skin lesion healing. In addition, it aims at forming a concise compilation of published data from
            scientific literature to date to verify whether the use of low-level laser influences wound healing, since its mechanisms of action are not
            fully clear yet.
            2. Review
            A. Skin lesions and the importance of healing process in treatment success :
            Some of the most common cutaneous wounds include excoriations, burns, surgical incisions, and acute or chronic ulcerations.2,3
            Diabetes mellitus is one of the primary predisposing factors for skin lesion development and one of the most common reasons f or
            patients to seek health care, as it represents an important cause of disability and premature death. 6 According to Pedrosa, 7 serious
            cutaneous foot lesions in diabetic patients are the cause for hospital admission in 51% of patients in endocrinology wards of Brazilian
            university hospitals. When not properly healed, these lesions represent the main cause of morbidity, immobility and limb amputation,
            according to data from the American Diabetes Association. 6
            Burn injuries, a clinical condition resulting from direct or indirect action of heat on the human body that causes different degrees of skin
            lesions, are a significant cause of mortality, primarily due to the infections that can evolve to septicemia. According to th e Brazilian
            Society of Burn Injuries (Sociedade Brasileira de Queimaduras), there are 1 million cases each year in Brazil. 8, 9 Skin lesions have a
            great morbidity potential primarily because of complications in the normal healing process. To prevent these complications an d promote
            cure, one needs to understand the normal process of soft tissue repair, as well as the factors that determine its normal healing.
            The normal process of soft tissue repair involves the following steps: homeostasis, inflammation ("cleaning"), demolition, proliferation,
            and maturing.
            10 The homeostatic phase occurs immediately after the appearance of the lesion and depends on platelet activity and on blood

            coagulation process, which includes a complex release of vasoactive substances, adhesive proteins, and growth factors for the
            development of other stages.10,11 Later on, the inflammatory process sets in with the presence of numerous chemical mediators and
            inflammatory cells (polymorphonuclear leukocytes, macrophages, and lymphocytes). This phase is responsible for removing necrosed
            tissue and combating aggressive agents installed in the wound. Next, tissue proliferation, which is responsible for "closing" the wound,
            sets in, with re-epithelization, fibroplasia (matrix formation), and angiogenesis, essential for the supply of oxygen and nutrients needed
            for healing. Finally, there is wound contraction followed by remodeling, which takes place in the collagen of the region and has the
            objective of increasing tensile force and diminishing the scar size. 11,12
            Tissue healing highlighted as one of the main effects of LLLT, 13, 14 is characterized by three main factors.
            First, there is an increment of A TP production, (as laser is considered to raise the production of ATP, 15) leading to a boost in mitotic
            activity and to an increase in protein synthesis by mitochondria, resulting in greater tissue regeneration in the repair process. 13, 16
            Second, there is a stimulus to microcirculation, which increases the delivery of nutritional elements associated with increased spe ed of
            mitosis, facilitating cell multiplication. 13, 14
            Finally, new vessels are formed from preexisting vessels. 13, 14, and 17.



1
LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
    On soft Tissue Healing: Review, Mechanism and A case report.


     Several factors have a direct influence on tissue healing, altering this process, making it slower, thus allowing complicatio ns associated
     with wound exposure to the external environment. The table below displays the key local and systemic factors that affect tissue wound
     healing.




     We see, then, that tissue lesions become a route for the installation of problems resulting from exposure to external agents, and
     therefore there is a need to accelerate the healing process by methods that shorten its duration. Laser therapy has become an important
     treatment for patients with cutaneous lesions, and there are ongoing studies aimed at understanding and confirming the known effects of
     laser application in tissue repair.
     B. Low-level Laser:
     The origin of low-intensity laser is attributed to Albert Einstein, who in his article entitled "Zur Quantum Theories der Strahlung" (1917)
     exposed the main physical principles of stimulated emission (laser phenomenon). This emission was later classified as "high- potency"
     (with destructive potential) and "low-potency" (without destructive potential). 18, 19
     In order to be produced, laser light needs atoms, constituted by a central nucleus, that are positively charged balanced by negatively
     charged electrons that move around the nucleus in well-defined circular trajectories; in this rotational movement, there is no emission of
     energy. When the electron passes from one orbit to another, there is a release or absorption of energy called a photon 20




     The devices that produce this beam of light are comprised of three parts: a) an active laser medium (gain medium), b) an external energy
     source, and c) a resonant optical cavity. The gain medium is a gas, solid or liquid containing the atoms that enable photons to leap
     electron levels emitting photons and constituting a laser light beam. The external energy source furnishes the necessary energy to the
     system, so that elec trons leap levels releasing, and not absorbing energy.
     This energy source should be able to produce high-energy or excited states. The optical or resonator cavity makes the emerging photons
     return to the system, producing additional stimulated emissions; this phenomenon occurs by mirrors positioned at the cavity extremities,
     provoking a reflection of photons back to the sample 14, 20, 21.
     The differences between the various types of laser beams produced are determined by wavelengths: the shorter the wavelength, the
     greater its action and power of penetration. Additionally, lasers may be continuous or pulsed, and their potency is expressed in Watts
     (W), varying from deciwatts to megawatts. Energy is expressed in Joules per square centimeter (J/cm 2 ), and therefore is equal to the
     potency multiplied by the duration of application. 22 Knowledge of these parameters is vital for appropriate indication and therapeutic
     utilization of this method. 4

           Table - 1 Parameters involved in determining the                                           Table - 2. Parameters involved in determining the LLL T “dos e”
           LLLT Irradiation parameters                                                               irradiation time or energy deliver ed (th e dose)

             Irradi ation         Unit of                                                             Irradiation                   Unit
              par am eter         me asur em ent             Comment
                                                                                                                                    of
              W avel en gth       nm                 Light is electromagnetic energy whi ch
                                                     travels in discrete Packets t hat also have                          Parameter                                           Comment
                                                     a wave -like property. Wavelength is                                 measurement
                                                     measure in nanometers ( nm ) and is visible
                                                                                                      Energ y             (Joul es) J               Calculated as:
                                                     in t he 400-700 n m range.                                                                     Energy (J) = Power (W) x tim e (s).
             Ir radi anc e        W/cm2              Often called I ntensi ty, or Power Density                                                     This mixes medicin e and dose i nto a si ngle
                                                     and is calc ulated as                                                                          expression and ignores Irradiance.Using Joules
                                                     Irradiance = Power (W)/Area (cm2 )                                                             as an expression of dose is potent ially
             Pulse s tru ctu re   Peak Pow er        If the beam is p ulsed then t he Power                                                         unreliable as it assu mes reciprocit y (t he inv erse
                                  (W)                should be t he Average Power and                                                               relationship bet wee n power and ti me).
                                  Pulse freq (H z)   calculated as follows:                           Energ y D ensit y   J/cm2                     Common expression of LLLT “dose” is En ergy
                                  Pulse Width (s)    Average Power (W) = Peak Power (W )                                                            density.
                                  Duty cycl e (%)                                                                                                  This expression of dose again mixes medicin e
                                                     pulse wid th (s) pulse frequency ( Hz)                                                        and dose into a si ngle expression and is
             Cohe re nce          Coherence          Coherent ligh t produces laser speckle,                                                        potentially u nreliable as i t assum es a
                                  length             which has been depends on postulated to                                                        reciprocity relations hip bet wee n irradiance and
                                                     play a role in the p hotobiomodulation                                                         tim e.
                                                     Spectral band-widt h i nteraction wi th cells    Irradia tio n       s                         In our vie w t he safest way to record and
                                                     and subcellular organelles.                      Tim e                                         prescribe LLLT is to defi ne t he four
             Polariz atio n       Linear             Light may ha ve different effects tha n                                                        parameters of th e medicin e (see table 1.) and
                                  polarized          otherwise ligh t (or even 90-degree                                                            then defin e t he irradiation ti me as “dose”.
                                  or circular        rotated polarized polarized ligh t).             Trea tm en t        Hours, da ys or w ee ks   The effects of differen t treat men t i nter val are
                                  identi cal non-    However, it is Kno wn tha t polarized lig ht     Inter val                                     underexplored at th is ti me t hough ther e is
                                  polarized          is rapidly scrambled in hig hly scat tering                                                    sufficient evide nce to sugg est that th is is an
                                                     media such as t issue (probably in the first                                                   important paramet er.
                                                     few hundred μ m).




     C. Action of Laser on Tissues and its role in the Healing Process:
     Based on the understanding of the mechanism of laser light origin, we observe that when low -intensity light is used, there is no thermal effect, i.e., the
     energy from the photons absorbed is not transformed into heat, but into photochemical, photophysical, and photobiological eff ects. According to Catão,
     21 this is an important principle of the interaction between laser light and cell or tissue specimens. When it is applied at an appropriate dose, laser can

     stimulate cell functions that are vital for the progress and resolution of the he aling process via tissue biostimulation, such as increased mitochondrial
     ATP production, lymphocyte and mast cell activation, and proliferation of fibroblasts and other cells, besides promoting analgesia and anti-inflammatory
     effects.21, 23
     As previously stated, the action of laser on tissues depends on the duration of emission of the different energy densities, and on the application area.
     Therefore, if these parameters are not duly verified and/or calibrated, treatment may be ineffective, compromising th erapeutic success. 24
     According to previously established parameters, in cutaneous lesions the tissue layer to be targeted depends on type of laser, potency used and
     duration of application. Kolárová et al. 25 observed that, using high potencies or application of light for fractions of a second, the power of penetration of
     HeNe radiation with a wavelength of 632 nm could reach up to 19 mm of depth in the dermis. 25 Since the energy produced by the laser is only absorbed
     by a thin layer of adjacent tissue in addition to the spot targeted by the radiation, current recommendation is to use low -intensity laser that has a low
     power of penetration, with wavelengths between 640 and 940 nm in a punctiform application to the lesion. 26
     Several research studies have used superficial wounds to assess the effects of low -intensity laser on healing. Some have used clinical wounds such as
     ulcers of different sizes and depths3,27,28 and others have developed models of superficial wounds in animals. 19,29,30 These diverse methods have
     produced a variety of results and conclusions on the effects of LLLT.
      Cells in the wound respond to light induced reactive oxygen species (ROS) leading to the expression of growth factors, such as transforming growth
     factor beta (TGF), and platelet derived growth factor (PDGF), which encourage synthesis of more collagen, increased formation of blood vessels, and
     less inflammation, all of which increase wound healing.




2
LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
        On soft Tissue Healing: Review, Mechanism and A case report.


        3. Mechanism of Action of Laser and Action on soft Tissue Wound Healing:




         Laser Tissue Interactions:
         The primary (physical) mechanisms relate to the interaction between photons and molecules in the tissue, while the secondary mechanisms relate to the
         effect of the chemical (Bio-chemical) changes induced by primary effects.

             1). The first and commonest pathway that occurs when light is absorbed by living tissue is called internal conversion. This happens when the first
         excited singlet state of the chromophore undergoes a transition from a higher to a lower electronic state. It is sometimes ca lled "radiation less de-
         excitation", because no photons are emitted. It differs from intersystem crossing in that, while both are radiationless methods of de-excitation, the
         molecular spin state for internal conversion remains the same, whereas it changes for intersystem crossing. The energy of the electronically excited
         state is given off to vibration modes of the molecule, in other words, the excitation energy is transformed into heat.
            2). The second pathway that can occur is fluorescence. Fluorescence is a luminescence or re-emission of light, in which the molecular absorption of
         a photon triggers the emission of another photon with a longer wavelength. The energy difference between the absorbed and emitted photons ends up
         as molecular vibrations or heat. The wavelengths involved depend on the absorbance curve and Stokes shift of the particular f luorophore.
            3). The third pathway that can occur after the absorption of light by a tissue chromophore (Biochemical) represents a number of processes broadly
         grouped under an umbrella category of photochemistry.
         Among the above three, internal conversion & fluorescence are the mechanisms those are involved in Physical Mechanism of laser tissue interaction,
         and third one is recognized as Bio-chemical.
                               PHYSICAL MEC HANISMS
            There are two primary forms of physical effects generated by laser irradiation of biological tissues:
         1. Photon-absorption (the basis of photo-biological action, and generated by all forms of light ).
         2. Internal conversion & fluorescence of light also generates Speckle formation, w hich is unique to laser therapy.
         The speckle field is created when coherent laser radiation is reflected, refracted and scattered. The speckle field is not simply a phenomenon created at
         and limited to the tissue surface, but is generated within a volume of tissue, persisting to the total extent of the depth of penetration of the laser beam.
         Laser speckles formed deep in the tissue create temperature and pressure gradients across cell membranes, increasing the rate of diffusion across
         those membranes.
                                BIOCHEMICAL MEC HANISMS




                                                                    FIGURE 1&2. Schemati c diagram sh owin g th e absorpti on of red an d NIR li gh t by specific
                                                                    Cellular chromophores photoacceptors localized in the mitochondrial respiratory chain.
         The third pathway that can occur after the absorption of light by a tissue chromophore (Biochemical) represents a number of processes broadly grouped
         under an umbrella category of photochemistry. This is the basic mechanism by which way laser works in animal/ human cell/ tissue. It has been
         established by thousands of research/application, and it is recognized by World Laser Association as well as American /European associations of
         Laser/photo-biology. Bio-chemic al action of laser can be explained by“Action of photon with mitochondrial respiratory chain-Cy tochrome c ox idase enzyme”.
         Mitochondrial respiratory chain contains fiv e complexes of integral membrane proteins: NADH dehy drogenase (Complex I), succinate
         dehy drogenase (Complex II), cy tochrome c reductase(Complex III), cy tochrome c ox idase (Complex IV), and ATP synthase (ComplexV).




                                                                  FIGURE 3&4: Structure and mode of action of cytochrome c oxidase.
         The first law of photobiology states that for low power visible light to have any effect on a living biological system, the p hotons must be absorbed by
         electronic absorption bands belonging to some molecular photoacceptors, or chromophores - (Sutherland 2002). A chromophore is a molecule (or part
         of a molecule) which imparts some decided color to the compound of which it is an ingredient.
         Chromophores almost always occur in one of two forms: conjugated pi electron systems and metal complexes. Examples of such chromophores can be
         seen in chlorophyll (used by plants for photosynthesis), hemoglobin, cytochrome c oxidase (Cox), myoglobin, flavins, flavoproteins and porphyrins (Karu
         1999). Figure 1 illustrates the general concept of LLLT.
         1)   Cy tochrome c ox idase mediated increase in ATP production.
         2)   Cy tochrome c ox idase mediated singlet-oxygen production.
         3)   Cy tochrome c ox idase mediated Reactiv e oxygen species (ROS) formation.
         4)   Cy tochrome c ox idase mediated Photodiassociation.
                           Tissue response & healing by LLLT : A. Tissue response
         LLLT can prov ide the follow ing beneficial impac ts in both open surface w ounds and closed con nec tiv e or soft tissue injuries as follow s:
         1. Enhanced leukocyte infiltr ation. LLLT s timulates ac tiv ity inv olv ing neutrophils, monocy tes and ly mphocy tes.
         2. In creased macrophage activity. LLLT accelerates macrophage activ ity in phagocy tosis, grow th factor secretion and s timulation of c ollagen sy nthes is.
         3. Incr eased neovascularization. The significant angiogenesis that occurs w ith laser therapy promotes rev ascularization w ith subs equent
         im prov ement in perfusion and oxy genation. Endothelial c ell regeneration is accelerated. 3 1
         4. In creased fibroblast proliferation. LLLT s tim ulation in-creas es fibroblas t numbers and fibroblas t-m ediated collagen production. 3 2
         5. Keratinocyte proliferation. The benefic ial sy nthes is ac tivities and grow th fac tor ability of k eratinocy tes are enhanced by proliferation secondary to
         LLLT. 33
         6. Early epitheli alization. Laser-s tim ulated acc eleration of epithelial cell regeneration speeds up w ound healing, minimizes sc arring, and reduces
         infec tion opportunities.
         7. Gro wth factor increases. Tw o to fiv e fold increases in grow th-phase-specific DNA sy nthesis in normal fibroblas ts, muscle cells, osteoblas ts and
         mucosal epithelial cells irradiated w ith IR light are reported. Increases in v ascular endothelial grow th fac tor (VEGF) and fibroblas t grow th factor (FGF-2)
         secondary to IR light irradiation hav e also been reported.
         8. Enhan ced cell prolifer ation and di ffer enti ation. Laser-induc ed increases in NO, ATP and other compounds that s tim ulate higher activ ity in cell
         proliferation and differentiation into mature cells. Increased numbers of my ofibroblasts, my ofibrils, my otubes etc., as w ell as bone cell proliferation, hav e-
         been clinically documented after - LLLT. Satellite cells, the prec ursor cells in the process of muscle regeneration, show signific ant inc rease in
         proliferation w hen irradiated w ith LLLT. 3 4,3 5, 36



3
LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
    On soft Tissue Healing: Review, Mechanism and A case report.


     9. Greater heal ed wound tensil e strength. In both soft tissue and c onnec tiv e tissue injuries, LLLT can inc reas e the final tensile strength of the healed
     tissue. By increas ing the amount of c ollagen produc tion/sy n thes is and by inc reas ing the intra and inter -molecular hy drogen bonding in the c ollagen
     molecules, laser therapy contributes to improv ed tens ile strength. 37 ,3 8,3 9, 40. The preceding effec ts combine to achiev e an accelerated heal ing rate (see
     Figure 3). The time from onset of injury to mature healed w ound is reduced. 4 1 The cumulativ e effects of (physical & Bio-chemic al) laser on tis sue enhances
     physiologic al activ ities by ion-exchange, speckle formation, singlet oxygen, redox formation, ATP production & nitric ox ide formation and exerts-
                  Enhances chemiosmosis,
                  Enzyme & hormone regulation
                  Stimulates the redox activity in the mitochondria,
                  RNA synthesis and DNA production - causing mitosis and cell proliferation
                  Calcium-ion influx into the cytoplasm,
     So, Laser biostimulation may be an invaluable therapeutic modality for treating most wounds. Wound healing entails a) the process of inflammation
     during which the hematoma formed in and around the wound site is resolved; b) cellularity and protein synthesis, i.e., two processes that culminate in
     the formation of granulation tissue; and c) wound remodeling, a process that may continue long after the wound may be said to be well healed.
                                                   B. TISSUE HEALING
     One of the truly unique characteristics of LLLT is that it has the ability to actually promote and enhance healing, not just treat symptoms.
     The irradiation by low-level laser light accelerates and enhances healing activities carried out by the body. Sev eral of the unique
     characteristics of LLLT that w ork to allev iate pain and inflammation also play an important role in accelerating the healing process; the
     LLLT-mediated reduction in inflammation and pain frees the body’s natural ability to repair and heal itself.
     The effects of LLLT can vary considerably. Cells being initially at a more reduced state (low intracellular pH) have high pot ential to respond to LLLT,
     while cells at the optimal redox state respond weakly or do not respond to treatment with light.
     A s wound healing progresses through the stages of inflammation, proliferation, remodeling and maturation, laser therapy presents the
     opportunity to impact each of these phases in positive and beneficial w ays.
     The beneficial effect of LLLT on wound healing can be explained by considering several basic biological mechanisms including the induction of
     expression cytokines and growth factors known to be responsible for the many phases of wound healing.
     Firstly there is a report that laser increases both protein and mRNA levels of IL-1α and IL-8 in keratinocy tes. These are cy tokines responsible for the initial inflammatory
     phase of wound healing.
     Secondly there are reports that LLLT can upregulate cy tokines responsible for fibroblast proliferation, and migration such as bFGF, HGF and SCF.
     Thirdly it has been reported that LLLT can increase grow th factors such as VEGF responsible for the neovascularization necessary for wound healing.
     Fourthly TGF-β is a growth factor responsible for inducing collagen synthesis from fibroblasts and has been reported to be upregulated by LLLT [51].
     Fifthly there are reports that LLLT can induce fibroblasts to undergo the transformation into my ofibloblasts, a cell ty pe that ex presses smooth muscle α-actin and desmin
     and has the phenoty pe of contractile cells that hasten wound contraction.
     4. A CASE REPORT :
         Laser as an Adjunctive Modality for human Chronic Wound Healing -




     Place of study: Shaheed Suhrawardy Medic al College Hospital, Dhaka-1 207,
     Bangladesh. Tel(Hos.):88-9130800-19 Cell: 01196133078, E-mail: abbirr@gmail.com
     Patient Particular:
     Name of the patient: Ms. Zobeda Khatun, Age: 78 Ye ars, Gender: Female.
     Ward and Bed: 6/ 1.Hospital stay: From Octo ber 14th / 2009 to January 10 th /2110.
     .
     ABSTRACT
     Background:
     Chronic wounds, particularly Bedsore/ Decubitus ulcerations in old age/ bedridden patients, are notoriously difficult to heal. Because current therapies
     are variable in their ability to induce complete healing, there remains a need to develop adjunctive treatments that can improve or accelerate the healing
     process. Low-level laser therapy is an important method for the treatment of healing processes and several experimental studies in human & animal
     models and applications has been carried out successfully in search of a greater understanding of its therapeutic possibilities.
     Objective
     The objective of this study was to review pathogenetic aspects of soft tissue repair to better understand skin lesion healing and the role of low-intensity
     laser in the progression of tissue healing.
     Methods:
     We have worked on diode laser therapy on recurrent bedsore patient, made clinical observational effects of low intensity laser therapy on constituents
     of the wound healing process.
     Results:
     A large number of in vivo studies on the effects of low intensity laser irradiation on wound healing show a lack of accuracy on dosimetric data and
     appropriate controls. Despite this fact, data from appropriately designed studies seem to indicate that this type of phototherapy should be considered a
     valuable (adjuvant) therapy for otherwise therapy -refractory wound-healing disorders.
     Conclusions:
     The use of low-energy lasers to stimulate wound healing has been pursued over many decades in studies of varying quality. This form of treatment has
     had high appeal due to its novelty, relative ease, and low morbidity profile. However, many unanswered questions demand research on the mechanism
     of action and on parameters of low-level laser use in different stages of wound repair to clarify how this method acts at a cell level in healing processes.
     High energy lasers have extensive applications in the field of surgery, ophthalmology, dermatology, medicine and oncology. The utility of low energy
     lasers for biostimulation, immune response mediation and wound healing is of relatively recent interest. The current communic ation illustrates our
     experience with low energy laser (G a-Al-As 660 laser) as an adjunct to the conventional modes of treatment for wound healing. Many studies have
     extensively covered the effects of using laser radiation in tissues, describing its beneficial aspects in tissue healing. This study consists of a concise
     review of scientific literature data on the use of low -level laser and its influence on wound healing. Further research aiming at elaborating optimal
     treatment parameters seems to be justified.
     Keywords: LLLT, Biostimulation, Soft tissue, wound healing.
     Case Study:
     Ms. Zobeda, female, Dhaka, Bangladesh, age 78, bedridden for years for spastic neurological disorder, with history of recurrent multiple large / small
     (approximately 1 -2cm deep, 6 -8cm in diameter) wound in the back, with inflammation and profuse purulent discharging infection was referred to this
     tertiary hospital from a local hospital for long lasting (More than 6 months of local management with all efforts, Fig. 1) non- healing chronic open wound.
     At the time of admission, patient’s Vital signs revealed a heart rate of 68/min, respiratory rate of 26/min, and rectal temperature of 36. 5°C. General
     examination- the patient is bedridden for years, all the system revealed normal except musculoskeletal & nervous system, which showed spastic
     muscular disorder and Parkinson disease.
     The wound was surrounded by large ulcerative skin lesion almost confluent with the spine. The surrounding areas of the lesion revealed slough and
     blackish necrotic debris.
     The total wound area covered about 6 by 8 inches (Fig. 1). The wound details are indicated in Table I.
     Investigations revealed hemoglobin- 10.7g/dl; TLC - 4700 cells/cu mm; DLC- N60 and L40; absolute Neutrophil count- 2820 cell/cu mm; μ, ESR - 16
     mm; and adequate platetets. Peripheral smear revealed microcytic red cells and mild leucopenia. Liver and Kidney profile revealed normal limit, Urine
     microscopy and cultures were positive repeatedly . Blood culture was sterile. Chest X-ray and Spine showed severe osteoporotic change.Ecg showed
     old MI, Echcadiography showed mild LVH.




4
LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
    On soft Tissue Healing: Review, Mechanism and A case report.


      Pus culture and sensitivity was performed at weekly intervals which yielded Pseudomonas initially. Subsequent cultures showed Staphylococcus
     aureus and E-coli species which is supposed to be from contamination with urine. Appropriate antibiotics were given time to time, throughout the
     hospital stay including intravenous Ciprofloxacillin (100 mg/ kg/day) and amikacin (15 mg/kg/day) for 15 days. Antibiotics were subsequently changed
     both for wound and urine infection, to netilmycin (6 mg/kg/ day for 7 days), cefotaxime (100 mg/kg/day for 10 days), Kenamycin (500 mg 12 hourly for 7
     days) and Clindamycin (300mg 12 hourly for 10 days duration). Alternate day cleaning and dressing of the wound was done with Betadine, E-usol and
     Hexisol.
                                                                           TABL E -3


                                                                        Morphology of the Wounds Before and After Therapy-
                                                                         Wound                Before debridement                                                                      After debridement/ closure
                                                                          Wound                                         Prior to Therapy                      End of Therapy          Prior to                 End of
                                                                          parameters-                                                                                                 Therapy                  Therapy
                                                                           Margin                                       Irregular & indurated                 Partially Regular
                                                                                                                                                                                      Sutured                  In tacked skin

                                                                                Floor                                   Unhealthy,                            Almost Healthy
                                                                                                                         Necrotic Oozing Tissue               granulation tissue      Covered                  Covered
                                                                                Base                                    Spine bone Exposed                    Partially Clear         Spine
                                                                                                                                                               granulation tissue     bone covered             Covered
                                                                                Surrounding skin/Contraction            Inflamed and scared                   Partially Healthy       Healthy                  Up to
                                                                                                                                                                                                               mark He althy
                                                                                Discharge                               Profuse purulent Oozing pus           Serous Discharge        No discharge
                                                                                                                                                                                                               No d ischar ge

         Irradiance Parameters
         LE D App aratu s: BioLux MD
                               Beam source (Incoherent- Ga- Al- As)
                               Irradiance dose: 4- 8 J/cm2/min.
                               Irradiance ti me: 1- 2 minutes
                               Mode: Continuous wave
                               Wavelengths Used: 660 nm
                               Total session: 35.
     The parameters which have been found to be most effective are in the range of 90 sec/cm2 of open wound surface, with the laser beam set at a pulsed
     rate of 40-80 pulses per second (PPS), depending upon the chronicity of the lesion. The more chronic, the slower the pulse rate suggested.
     The optimum distance from probe tip to target surface was 1-4 mm. Probe motion during lasing was a slow, circling movement over each square
     centimeter of open lesion, timed to permit the suggested dosages. As the lesion is large, i.e., 4-6 cm in diameter, a change in technique is adopted
     which involves a slow, traversing of the perimeter of the lesion, allowing approximately 90 sec per linear centimeter of the perimeter, at the suggested
     distances (1-4 cm). This technique apparently provides sufficient exposure to the laser beam to stimulate healing effectively, compared with non-treated
     areas and previously experienced wound management of a similar nature.
                                                                  T ABL E - 4

                                                                     Treatment Schedule (Dose duration and wound parameter
                                                                     Per iod/               Frequency      Wound                    Irradia tion                                    En ergy
                                                                     W ee k                                A rea /siz e             Source                             W av e       Fluenc e           Point              T im e
                                                                                                                    2                                                                              2
                                                                     1-2 week               5/ week        6.8 cm                   LED-660 nm (G a-Al -As)            Continuous   6 joules/c m       2                  8 joules/min.
                                                                                                                    2                                                                              2
                                                                     3- 5 week              3/ week        5.7 cm                   LED-660 nm (G a-Al -As)            Continuous   4 joules/cm        2                  8 joules/min.
                                                                                                                        2                                                                          2
                                                                     4-6 week               3/ week        4.4 cm                   LED-660 nm (G a-Al -As)            Continuous   4 joules/cm        1                  8 joules/min.
                                                                                                                    2                                                                              2
                                                                     7-8 week               2/week         2.2 cm                   LED-660 nm (G a-Al -As)            Continuous   3 joules/ cm       1                  8 joules/min.
                                                                                                                                                                                                   2
                                                                     9-10 week              2/ week        Closed                   LED-660 nm (Ga -Al -As)            Continuous   3 joules/ cm       1                  8 joules/min.



       Low energy Ga-Al laser provides infrared rays in the wave length of around 660 nm by continuous mode.
     An average power of 5-8 mw was provided through a fiber optic delivery system around the wound margin for about 8-10 min at each point at a distance
     of one cm. Since the center of the ulcer was deep, it was decided to give laser therapy concentrating maximum irradiance ther e (Fig. 1).
     At the end of 2nd week there was an improvement in laser irradiated side with respect to ulcer size and wound margin and there was serous disch arge
     after eight exposures (Table I). Surgical debridement was done 2 times: at 3rd & 5th week and finally secondary closure given at the end of 8th week,
     within in the treatment period (two and half months).
     A healthy granulation tissue appeared by 6-7th week. Fig. 6/7 reveals the post laser therapy ulcer on 6-7th week. At this stage, the center of the ulcer
     was still unhealthy and significant signs of healing. It was decided to irradiate the center of ulcer also with maximum permitted irradiance dose. At the
     end of 8th week the wound looked pretty healthy, we decided to do secondary closure instead of skin grafting, as because of old age, we could mobiles
     the wound adjacent skin without tension and closed the wound by four point suture.
     And next two weeks we observed the wound surface with a keen observation, and continued to two days interval laser therapy ( Total treatment 25),
     and medications properly. Enhancement of healing processes with open lesions is described. The effective parameters were determined to be a pulsed
     beam at 40-80 PPS, administered at a target distance of 4 mm, for 90 sec/cm2 of open lesion surface. In addition, lasing along the perimeter of the larger
     wound was indicated to overcome the diminished penetration of the laser beam through the hardened eschar overlaying the lesion. No untoward
     reactions or side effects were reported by the patient.

     Chronology of management & improvement:
     At the 5th day of her adm ission in our ward, we simu ltaneously s tar ted conservative treatment and He-Ne l aser therapy. After wound cleaning, s tandardized digi tal photos were
     recorded weekly.
          At the end of 2 nd week of treatment; the outlook of the wound looked better, and signs of increased vascularity in the surrounding
           area noted. But serous discharge continued.
          At the end of 3rd week of treatment, we did wound debridement, and continued alternate d ay dressing and as well as laser therapy.
          At the 4 th week of treatment, we continued to care the wound by alternate day dressing and medications, and noticed formation of
           granulation tissue at the margin of the wound.
          At the end of 5 th week of treatment, we again debrided the center of the wound with care so that the adjacent healthy tissue could
           be preserved.
          At the end of 6 th week of treatment, we observed marked improvement in the wound and at the same time si gns of vascular marking
           noted at the wound margin.
          At the 7 th week of treatment, we noticed general condition of the wound healthy, and signs of healthy granulation tissue all over the
           wound, we continued to two days interval dressing. No discharge noted.
          At the end of 8 th week of treatment, we did surgical toileting and secondary closure of the wound, and continued to give conservative
           & laser therapy twice weekly until 10 th week of treatment.
          At the end of 9 th week of treatment we observed a nice and healthy wound margin, and reddish vascular marking all over the wound
           surface area.
          At the end of 10 th week of treatment of her admission we assessed her wound and surround areas for any sign of wound dehiscence,
           infection, vascularity of the wound as well as adjacent areas was up to mark, and being satisfied discharged her with smile. Our
           purpose was to assess potenti al changes in healing due to LLLT over time using a human experimental wound model. Healing was
           measured in terms of wound contraction and changes in chromatic red and luminance. Chromatic red is an indication of wound healing
           as a wound changes in color from dark red to pale pink over time. Luminance refers to the homogeneity of a wound as the tissue
           heals and becomes more smooth and consistent.
           In addition to laser therapy (Led) and surgical intervention , adjacently she was also given the following management :
     o     Pneumatic Bed support.
     o     Catheterization.
     o     High protein diet,
     o     Antibiotics (according to c ulture and s ensitivity test),
     o     Pain killer (Non-NSI D)
     o     H2 Blocker- Pantoprazole and Ranitidine.
     o     Tab- Perkinil, 5mg 12 ho urly,
     o     Tab- Ecosporin(Aspirin)
     o     Vitamin B-complex , anti-ox idant, Vitamin D3 ,
     o     Iron, Folic acid and Zinc supplements,
     o     Calcium,
     o     Fresh blood transfusion.



5
LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy –
    On soft Tissue Healing: Review, Mechanism and A case report.




                                                                    Chronological Picture View:
                           1ST DAY, 24TH OCTOBER/2009
                           Pretreatment photograph of wound showing irregular margins, Necrotic tissue and pus discharge.




          F-1: At the end of 1 st Week                     F-2: At the end of 2 nd week.                      F-3a: At the end of 3 rd week.                   F-3b: At the end of 3 rd week.




          F-4: At the end of 4 th week.                     F-5: At the end of 5 th week.                    F-6: At the end of 6 th week                      F-7: At the end of 7 th week




        F- 8b: At 9th week                                   F-10a: At 10t h week .                          F-10b: At The End Of 10t h Wk.                   F-10c: At The End Of 10t h Wk
         (9rd post operative day)                             (12rd post op. day)

     5. Discussion
     Our patient demonstrated a significant benefit of Ga-Al-As 660 laser for rapid healing of skin wound. The comparis on betw een the laser and conventionally treated
     prev iously treated wounds of the same patient at about same size clearly highlighted that despite uniformity of host factors, local factors and systemic state, the w ound
     healing process was stimulated on the laser exposed side. Healing of wounds is an im portant problem faced by general & orthopedic surgeons. The possible
     biostimulatory role of laser light in wound healing is of recent interest (42). Small sub destructiv e repetitiv e doses of laser light are claim ed to be useful for trophic ulcers and
     indolent wounds (43). The proposed mechanisms of action include local leukocy te proliferation), neovascularization, fibroblastic proliferation and rapid epithelialization (44, 45).
     All these mechanisms possibly lead to more rapid closure of wounds and stronger scar formation. In an experim ental study, wounds treated with Ga-Al-As 660 laser
     rev ealed significantly more granulation tis sue. This study establis hed the biostimulatory effects of low intensity laser radiation (46). Many reports now indicate benefit to non
     healing w ounds and trophic ulc ers by low-intensity laser irradiation. Out of 351 patients thus treated, 236 showed complete epithelialisation of the wound surface (47). A
     44% increase in healthy granulation tis sue was observed, 2/12 ulc ers healed completely while 27% rev ealed reduction in siz e of the remaining ulc ers indic ating
     considerable benefit (48). Nussbaum et al. (49) in a study compared- the effect of ultraviolet-C and laser for treatm ent of pressure ulc ers in adults w ith spinal cord injury.
     They used 660-980 nm w ave length light at an energy density of 4 J/cm2. Weekly percentage changes in wound area were compared.
     The authors concluded ex posure to UV-C decreased healing time and allowed faster return to rehabilitation programs. The UV-C light was better than the laser (50). Another
     nonrandomized study of laser and UV lamp on chronic skin ulc ers suggested that wounds whic h fail to respond to topical treatm ents benefit from either modality (51).
     Ev aluations of different approaches to wound healing are complic ated by the large number of factors that influence wound healing. Although there are anecdotal reports of
     successful therapy, there are few well controlled studies. The use of lasers for healing wounds is becoming increasingly attractiv e to surgeons. A number of animal and in
     vitro studies (52, 53) have demonstrated that laser irradiation has a significant effect on components of tissue repair.
     6. Conclusion
     This study results efficacy of LLLT on wound healing in human model, and indicates that it can be a very important adjective tool /modality for chronic
     intractable wound management, and in any way it is not harmful to human being.
     In the past Laser / LED were shown to be effective in wound management b ut in different degrees, some of those applications showed significant
     improvement some less effective others no effect. Probably laser/ LED Irradiation parameters are vital for its Biostimulative effects. Inference of those
     results summaries that irradiation parameters are of vital to laser therapy. We used an optimal dose of irradiance which proved to be most effective
     biostimulation on human application
     Application and research of LLLT on cell responses of wounded skin fibroblasts demonstrate that correct energy density or fluence and number of
     exposures can stimulate cell responses of wounded fibroblast and promote cell migration and cell proliferation by stimulating mitochondrial activity and
     maintaining viability without causing additional stress or damage to wounded cells. Results indicate that the cumulative effect of lower doses determines
     the stimulatory effect, whereas multiple exposure at higher doses result in an inhibitory effect with more damage. 39
     Although various studies have extensively covered the effects of laser radiation on tissue, many unanswered questions remain. The mechanisms
     effectively responsible for cell mitotic activity has not been clarified yet, and there is no standardized ideal dose for stimulating tissue healing. Therefore,
     we noted that there is a need for research on the action and parameters of low -intensity laser use in cutaneous lesions during the different stages of
     repair, as an attempt to elucidate how this method acts at a cell level in healing processes.
     Elucidation of these issues will enable the establishment of criteria on the true benefits of laser therapy in diseases that need he aling stimulation,
     minimizing healing time and the complications that may occur during the clinical progress of these wounds. In addition, experimental studies indicated
     that the LLLT may be an important therapeutic tool to stimulate wound healing in decubitus ulcer patients.
     In conclusion, the present report highlights the possible utility of Galliium-Aluminium laser at 660 wavelengths is as effective as Helium-Neon laser as
     an adjunctive modality for wound healing in skin/general & orthopedic practices.
     7. References:
     1. Snyder RJ. Trea        tment of nonhealing ulcers with allografts. Clin Dermatol. 2005; 23:388-95.
     2. Sugrue ME, Carolan J, L            een EJ, Feeley TM, Moore DJ, Shanik GD. The use of infrared laser therapy in the tr                            eatment of venou s ulceration. Ann VascSurg. 1990; 4:179-81.
     3. Chromey PA. The efficacy of carbon dioxide laser surgery for adjunct ulcer therapy. Clin Podiatr MedSurg. 1992; 9:709-19.
     4. NussbaumEL, Zuylen JV, Baxter GD. Specific atio n of treatment dosage in laser therapy: unreliable equip ment and radiant power determination as confounding factors. Phy       siotherapy Can. 1999; 157-167.
     5. Rocha Jr. AM, de Oliveira RG, Farias RE, de Andrade LCR, Aarestrup FM. Modulation of fibroblast proliferatio n and inflammatory response by low-intensity laser therapy in tissue repair process. An Bras Dermatol. 2006; 81:150-6.
     6. Economic consequences of diabetes mellitus in the U.S in 1997. AmericanDiabetes Association. Diabetes Care. 1998 ; 21:296-309.
     7. Pedrosa HC. Pé diabético: aspectos histopatológicos, trata                         mentoe pr      evenção. Rev Bras Neurol Psiqu ia 1997; 1:131-5.
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     8. Ramos-e-Silva M, Ribeiro de Castro MC. New dressings, including tissue-engineered living skin. ClinDerma                                          tol. 2002; 20:715-23.
     9. Sheridan RL, Thompkins RG. Wha new in burns and metabolism? J Am Coll Surg. 2004; 198:243-63.
                                                        t's
     10. Contran RS, Kumar V, Collins T. Robbins. Pa                    tologia estrutural e funcional. Rio de Janeiro: Guanabara Koogan; 2001. p. 44 -100.
     11. Mandelbaum SH, Di Santis EP,Mandelba MHS.Cica             um               trização: conceitos atuais e recursos auxiliaries: parte I.An Bras Der                     matol. 2003;78:393-408.
     12. Tanaka A, Ha       toko M, Tada H, Iioka H, Niitsuma K, Miyagawa S. Expression of p53 family in scars. J Dermatol Sci. 2004 ; 34:17-24.                                             ]
     13. Silva EC, Filho AH, Musskopf DE. Radiação laser. In: Rodrigues EM. Manual de r                                 ecursosterapêuticos. Rio de Janeiro: Revinter; 1998. p. 17-35.
     14. Tavares MR,Mazzer N,Pa                torello M.Efeito do laser terapêutico na cicatrização tendinosa:estudo experimental em ratos.F                                   isioterBras.2005;6:96-100.
     15. KaruT,Pya      tibrat L,KalendoG.Irradiation with He-Ne laser incr                    easesATP level in cells cultivated in vitro.J Photochem PhotobiolB.1995;27:219-23.
     16. Herrero C. Los efectosterapeuticos. Bol Sociedad Española Láser Médico Quirúrgico. 1988 ; 15:22-6.
     17. Bibikova A, Belkin V, Oron U. Enhancement of angio genesis in regenerating gastrocnemiu s muscle of the toad (Bufo viridis) by low-energy laser irradiation. Anat Embryol (Berl). 1994; 190:597-602.
     18. Mester AF, Mester A. Wound healing. Laser Ther. 1989; 1:7-15.
     19. Hopkins JT, McLoda TA, Seegmiller JG, Baxter GD. Low-lev laser therapy facilites superficialwound healing in humans: a triple-blind, sham- controlled study. J Athl Train. 2004; 39:223-9.
                                                                      el
     20. Bagnato VS. Os fundamentos da luz laser. Fís Esc. 2001; 2:4-9.
     21. Catão MHCV. Os benefícios do laser de baixa intensidade na clínica odontológica na estomatologia. Rev Bras Pa Oral. 2004;3:214-8.                         tol
     22. Da   llan LAO, Oliveira SA. Cirurgia de r             evascularização transmiocárdica a laser de CO2. Rev Bras Cir Cardiovasc. 2000; 15:89-104.
     23. Gomez-Villamandos RJ, Santisteban Valenzuela JM, Ruiz Calatrava I, Gomez-Villamandos JC, Avila Jurado I. He-Ne laser therapy by fibroendoscopy in the mucosa of the equine upper airway. Lasers Surg Med. 1995; 16:184-
     24. Weis LC,Arieta A,Souza J,Guirro RRJ.Utilização do laser de baixa potência nas clínicas de fisioterapia de Piracicaba,SP.Fisioter Bras.2005; 6:124-9.
     25. Kolárová H, Ditr        ichová D, Wagner J. Penetration of the laser light into the skin in vitro. Lasers Surg Med. 1999; 24:231-5.
     26. Parizotto NA, Baranauskas V. Structural analysis of colla gen fibrils after HeNe laser photostimulated regenerating rat tendon. In: 2o Congress World Association for Laser Therapy; Sep 2-5. Kansas City. Proceedin gs. Kansas City; 1998. p. 66.
     27. Gogia PP, Hurt BS,ZirnTT.Wound management with whir                               lpool a infrared cold laser trea
                                                                                                     nd                                 tment. A clinical repor Phys Ther. 1988 ; 68:1239-42.
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     28. Lundeberg T, Malm M. Low-power HeNe laser tr                         eatment of venous leg ulcers. Ann Plast Surg. 1991; 27:537-9.
     29. Allendorf JD, Bessler M, Huang J, et al. Helium-neon laser irradiatio n at fluences of 1, 2, and 4 J/cm2 failed to accelerate wound healin g as assessed by wound contracture rate and tensile strength. Lasers Surg Med. 1997 ; 20:340-5.
     30. Lucas C, Criens-Poublo n LJ, Cockrell CT, de Haan RJ. Wound healing in cell studies and animal model experiments by Low Level Laser Therapy; w ere clinical studies justified? a systematic review. Lasers Med Sci. 2002; 17:110-34.
     31. Y. Moriyama, E.H. Moriyama, K. Blackmore,M.K. Akens and L. Lilge, In Vivo Study of the Infla mmatory Modula ting Effects of Lo w-lev Laser Therapy on iNOS Expression Using Biolumin escence Imaging, Photochem Photobiol 81 (2005) 1351-5.
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6

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BEDSORE HEALING: Low Level Laser Therapy- LED( Ga-Al-As 660) on Soft Tissue Healing- Review, Mechanism and A case report ( Research Paper) -

  • 1. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. Research Paper Research Panel Members: 1 Dr. Md. Nazrul isla m, MBBS, M.Sc. (Biomedical Engineering), 2Professor Golam Abu Zaka ria, Ph D. 3Professor F. H. Sirazee, MBBS, MS. (Orthopedic). 4 Dr. Paritosh Chandra Debena th, MBBS, MS. (Orthopedic).5 Dr. kazi Shamimuzz aman, MBBS, MS. (Orthopedic). 6Dr. Quamrul Akhter Sanju, MBBS, F CPS, MR CS.(Surgery). 7Dr . Ashraf Uddin Khan, MBBS, DMR D, F CPS. (Rad iology).8Dr. Md. Mostafizur Rahman,MBBS, F CPS (Surgery) 9 Dr. Sayed Shaheedul Isla m, MBBS, MS (Orthopedic). 1 0Sinha Abu Khalid, B. Sc. (Hons. Applied Physics & Electronics).11M uhamma d Masud Rana, M.Sc. ( Medical Physics). Correspondence to the Author: 1Dr. Md Nazrul Islam . Resident Surgeon, Department of Or thopedic & Traumatology. Shaheed Suhraw ardyM edical College Hospita l. Dhaka - 1207 , Bangladesh. E-mail: abbirr@gmail.com,Tel:M: + 88- 01196133078,Office-PABX -9130800- 19-138. Contents: 1. Introduction 2. Review  Skin lesions and the importance of Healing process in treatmen t success.  Low-level laser  Action of Laser on Tissues and its role in the Healing Process. 3. Mechanism of LLLT.  Laser an d Tis sue in teraction  Primary Mechanism- Physical  Secondary Mechanism- Biochemical  Tissue response & healing by LLLT 4. A case report: Laser Therapy on Soft Tissue.  Abstract  Case Stu dy 5. Discussion 6. Conclusion 7. References. 1. INTRODUCTION Allied health professionals regularly care for a variety of skin wounds, such as abrasions, turf burns, surgical incisions, and ulcerations, which are perhaps the most difficult to treat. At present, cutaneous lesions represent a dilemma of global proportions and instigate great clinical interest because of the high morbidity associated with changes in the normal healing process. 1 Among the clinical aspects involving this issue, we emphasize tissue repair time in an effort to make the process quicker and more harmonious, reduce possible complications in lesion resolution, and allow an adequate choice of therapy. To do this, familiarity with the pathogenesis of tissue healing is necessary, as well as an understanding of the factors affecting the process and the role each one plays in its progress, always seeking a clinical treatment that optimizes skin lesion care. Among the methods currently available, low-level laser therapy (LLLT) stands out. From acute wound management to augmentation of scar tissue remodeling, the clinician seeks to optimize wound care to promote healing. Experimental in vitro and in vivo studies have been under development since the 1960s, and in the early 1990s, LLLT was approved by the Food and Drug Administration (FDA) as an important method for treating healing processes. 2-4 Recent results of a study demonstrated that LLLT is an effective method to modulate tissue repair, thus si gnificantly contributing to a faster and more organized healing process. 5 Nevertheless, in spite of the large number of studies involving this technique and its wide use in clinical practice, the pri nciples of its action in cells and tissues are still not well understood. The objective of this study is to review pathogenetic aspects of soft tissue repair to understand the major complications in skin lesion healing. In addition, it aims at forming a concise compilation of published data from scientific literature to date to verify whether the use of low-level laser influences wound healing, since its mechanisms of action are not fully clear yet. 2. Review A. Skin lesions and the importance of healing process in treatment success : Some of the most common cutaneous wounds include excoriations, burns, surgical incisions, and acute or chronic ulcerations.2,3 Diabetes mellitus is one of the primary predisposing factors for skin lesion development and one of the most common reasons f or patients to seek health care, as it represents an important cause of disability and premature death. 6 According to Pedrosa, 7 serious cutaneous foot lesions in diabetic patients are the cause for hospital admission in 51% of patients in endocrinology wards of Brazilian university hospitals. When not properly healed, these lesions represent the main cause of morbidity, immobility and limb amputation, according to data from the American Diabetes Association. 6 Burn injuries, a clinical condition resulting from direct or indirect action of heat on the human body that causes different degrees of skin lesions, are a significant cause of mortality, primarily due to the infections that can evolve to septicemia. According to th e Brazilian Society of Burn Injuries (Sociedade Brasileira de Queimaduras), there are 1 million cases each year in Brazil. 8, 9 Skin lesions have a great morbidity potential primarily because of complications in the normal healing process. To prevent these complications an d promote cure, one needs to understand the normal process of soft tissue repair, as well as the factors that determine its normal healing. The normal process of soft tissue repair involves the following steps: homeostasis, inflammation ("cleaning"), demolition, proliferation, and maturing. 10 The homeostatic phase occurs immediately after the appearance of the lesion and depends on platelet activity and on blood coagulation process, which includes a complex release of vasoactive substances, adhesive proteins, and growth factors for the development of other stages.10,11 Later on, the inflammatory process sets in with the presence of numerous chemical mediators and inflammatory cells (polymorphonuclear leukocytes, macrophages, and lymphocytes). This phase is responsible for removing necrosed tissue and combating aggressive agents installed in the wound. Next, tissue proliferation, which is responsible for "closing" the wound, sets in, with re-epithelization, fibroplasia (matrix formation), and angiogenesis, essential for the supply of oxygen and nutrients needed for healing. Finally, there is wound contraction followed by remodeling, which takes place in the collagen of the region and has the objective of increasing tensile force and diminishing the scar size. 11,12 Tissue healing highlighted as one of the main effects of LLLT, 13, 14 is characterized by three main factors. First, there is an increment of A TP production, (as laser is considered to raise the production of ATP, 15) leading to a boost in mitotic activity and to an increase in protein synthesis by mitochondria, resulting in greater tissue regeneration in the repair process. 13, 16 Second, there is a stimulus to microcirculation, which increases the delivery of nutritional elements associated with increased spe ed of mitosis, facilitating cell multiplication. 13, 14 Finally, new vessels are formed from preexisting vessels. 13, 14, and 17. 1
  • 2. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. Several factors have a direct influence on tissue healing, altering this process, making it slower, thus allowing complicatio ns associated with wound exposure to the external environment. The table below displays the key local and systemic factors that affect tissue wound healing. We see, then, that tissue lesions become a route for the installation of problems resulting from exposure to external agents, and therefore there is a need to accelerate the healing process by methods that shorten its duration. Laser therapy has become an important treatment for patients with cutaneous lesions, and there are ongoing studies aimed at understanding and confirming the known effects of laser application in tissue repair. B. Low-level Laser: The origin of low-intensity laser is attributed to Albert Einstein, who in his article entitled "Zur Quantum Theories der Strahlung" (1917) exposed the main physical principles of stimulated emission (laser phenomenon). This emission was later classified as "high- potency" (with destructive potential) and "low-potency" (without destructive potential). 18, 19 In order to be produced, laser light needs atoms, constituted by a central nucleus, that are positively charged balanced by negatively charged electrons that move around the nucleus in well-defined circular trajectories; in this rotational movement, there is no emission of energy. When the electron passes from one orbit to another, there is a release or absorption of energy called a photon 20 The devices that produce this beam of light are comprised of three parts: a) an active laser medium (gain medium), b) an external energy source, and c) a resonant optical cavity. The gain medium is a gas, solid or liquid containing the atoms that enable photons to leap electron levels emitting photons and constituting a laser light beam. The external energy source furnishes the necessary energy to the system, so that elec trons leap levels releasing, and not absorbing energy. This energy source should be able to produce high-energy or excited states. The optical or resonator cavity makes the emerging photons return to the system, producing additional stimulated emissions; this phenomenon occurs by mirrors positioned at the cavity extremities, provoking a reflection of photons back to the sample 14, 20, 21. The differences between the various types of laser beams produced are determined by wavelengths: the shorter the wavelength, the greater its action and power of penetration. Additionally, lasers may be continuous or pulsed, and their potency is expressed in Watts (W), varying from deciwatts to megawatts. Energy is expressed in Joules per square centimeter (J/cm 2 ), and therefore is equal to the potency multiplied by the duration of application. 22 Knowledge of these parameters is vital for appropriate indication and therapeutic utilization of this method. 4 Table - 1 Parameters involved in determining the Table - 2. Parameters involved in determining the LLL T “dos e” LLLT Irradiation parameters irradiation time or energy deliver ed (th e dose) Irradi ation Unit of Irradiation Unit par am eter me asur em ent Comment of W avel en gth nm Light is electromagnetic energy whi ch travels in discrete Packets t hat also have Parameter Comment a wave -like property. Wavelength is measurement measure in nanometers ( nm ) and is visible Energ y (Joul es) J Calculated as: in t he 400-700 n m range. Energy (J) = Power (W) x tim e (s). Ir radi anc e W/cm2 Often called I ntensi ty, or Power Density This mixes medicin e and dose i nto a si ngle and is calc ulated as expression and ignores Irradiance.Using Joules Irradiance = Power (W)/Area (cm2 ) as an expression of dose is potent ially Pulse s tru ctu re Peak Pow er If the beam is p ulsed then t he Power unreliable as it assu mes reciprocit y (t he inv erse (W) should be t he Average Power and relationship bet wee n power and ti me). Pulse freq (H z) calculated as follows: Energ y D ensit y J/cm2 Common expression of LLLT “dose” is En ergy Pulse Width (s) Average Power (W) = Peak Power (W ) density. Duty cycl e (%)  This expression of dose again mixes medicin e pulse wid th (s) pulse frequency ( Hz) and dose into a si ngle expression and is Cohe re nce Coherence Coherent ligh t produces laser speckle, potentially u nreliable as i t assum es a length which has been depends on postulated to reciprocity relations hip bet wee n irradiance and play a role in the p hotobiomodulation tim e. Spectral band-widt h i nteraction wi th cells Irradia tio n s In our vie w t he safest way to record and and subcellular organelles. Tim e prescribe LLLT is to defi ne t he four Polariz atio n Linear Light may ha ve different effects tha n parameters of th e medicin e (see table 1.) and polarized otherwise ligh t (or even 90-degree then defin e t he irradiation ti me as “dose”. or circular rotated polarized polarized ligh t). Trea tm en t Hours, da ys or w ee ks The effects of differen t treat men t i nter val are identi cal non- However, it is Kno wn tha t polarized lig ht Inter val underexplored at th is ti me t hough ther e is polarized is rapidly scrambled in hig hly scat tering sufficient evide nce to sugg est that th is is an media such as t issue (probably in the first important paramet er. few hundred μ m). C. Action of Laser on Tissues and its role in the Healing Process: Based on the understanding of the mechanism of laser light origin, we observe that when low -intensity light is used, there is no thermal effect, i.e., the energy from the photons absorbed is not transformed into heat, but into photochemical, photophysical, and photobiological eff ects. According to Catão, 21 this is an important principle of the interaction between laser light and cell or tissue specimens. When it is applied at an appropriate dose, laser can stimulate cell functions that are vital for the progress and resolution of the he aling process via tissue biostimulation, such as increased mitochondrial ATP production, lymphocyte and mast cell activation, and proliferation of fibroblasts and other cells, besides promoting analgesia and anti-inflammatory effects.21, 23 As previously stated, the action of laser on tissues depends on the duration of emission of the different energy densities, and on the application area. Therefore, if these parameters are not duly verified and/or calibrated, treatment may be ineffective, compromising th erapeutic success. 24 According to previously established parameters, in cutaneous lesions the tissue layer to be targeted depends on type of laser, potency used and duration of application. Kolárová et al. 25 observed that, using high potencies or application of light for fractions of a second, the power of penetration of HeNe radiation with a wavelength of 632 nm could reach up to 19 mm of depth in the dermis. 25 Since the energy produced by the laser is only absorbed by a thin layer of adjacent tissue in addition to the spot targeted by the radiation, current recommendation is to use low -intensity laser that has a low power of penetration, with wavelengths between 640 and 940 nm in a punctiform application to the lesion. 26 Several research studies have used superficial wounds to assess the effects of low -intensity laser on healing. Some have used clinical wounds such as ulcers of different sizes and depths3,27,28 and others have developed models of superficial wounds in animals. 19,29,30 These diverse methods have produced a variety of results and conclusions on the effects of LLLT. Cells in the wound respond to light induced reactive oxygen species (ROS) leading to the expression of growth factors, such as transforming growth factor beta (TGF), and platelet derived growth factor (PDGF), which encourage synthesis of more collagen, increased formation of blood vessels, and less inflammation, all of which increase wound healing. 2
  • 3. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. 3. Mechanism of Action of Laser and Action on soft Tissue Wound Healing: Laser Tissue Interactions: The primary (physical) mechanisms relate to the interaction between photons and molecules in the tissue, while the secondary mechanisms relate to the effect of the chemical (Bio-chemical) changes induced by primary effects. 1). The first and commonest pathway that occurs when light is absorbed by living tissue is called internal conversion. This happens when the first excited singlet state of the chromophore undergoes a transition from a higher to a lower electronic state. It is sometimes ca lled "radiation less de- excitation", because no photons are emitted. It differs from intersystem crossing in that, while both are radiationless methods of de-excitation, the molecular spin state for internal conversion remains the same, whereas it changes for intersystem crossing. The energy of the electronically excited state is given off to vibration modes of the molecule, in other words, the excitation energy is transformed into heat. 2). The second pathway that can occur is fluorescence. Fluorescence is a luminescence or re-emission of light, in which the molecular absorption of a photon triggers the emission of another photon with a longer wavelength. The energy difference between the absorbed and emitted photons ends up as molecular vibrations or heat. The wavelengths involved depend on the absorbance curve and Stokes shift of the particular f luorophore. 3). The third pathway that can occur after the absorption of light by a tissue chromophore (Biochemical) represents a number of processes broadly grouped under an umbrella category of photochemistry. Among the above three, internal conversion & fluorescence are the mechanisms those are involved in Physical Mechanism of laser tissue interaction, and third one is recognized as Bio-chemical.  PHYSICAL MEC HANISMS There are two primary forms of physical effects generated by laser irradiation of biological tissues: 1. Photon-absorption (the basis of photo-biological action, and generated by all forms of light ). 2. Internal conversion & fluorescence of light also generates Speckle formation, w hich is unique to laser therapy. The speckle field is created when coherent laser radiation is reflected, refracted and scattered. The speckle field is not simply a phenomenon created at and limited to the tissue surface, but is generated within a volume of tissue, persisting to the total extent of the depth of penetration of the laser beam. Laser speckles formed deep in the tissue create temperature and pressure gradients across cell membranes, increasing the rate of diffusion across those membranes.  BIOCHEMICAL MEC HANISMS FIGURE 1&2. Schemati c diagram sh owin g th e absorpti on of red an d NIR li gh t by specific Cellular chromophores photoacceptors localized in the mitochondrial respiratory chain. The third pathway that can occur after the absorption of light by a tissue chromophore (Biochemical) represents a number of processes broadly grouped under an umbrella category of photochemistry. This is the basic mechanism by which way laser works in animal/ human cell/ tissue. It has been established by thousands of research/application, and it is recognized by World Laser Association as well as American /European associations of Laser/photo-biology. Bio-chemic al action of laser can be explained by“Action of photon with mitochondrial respiratory chain-Cy tochrome c ox idase enzyme”. Mitochondrial respiratory chain contains fiv e complexes of integral membrane proteins: NADH dehy drogenase (Complex I), succinate dehy drogenase (Complex II), cy tochrome c reductase(Complex III), cy tochrome c ox idase (Complex IV), and ATP synthase (ComplexV). FIGURE 3&4: Structure and mode of action of cytochrome c oxidase. The first law of photobiology states that for low power visible light to have any effect on a living biological system, the p hotons must be absorbed by electronic absorption bands belonging to some molecular photoacceptors, or chromophores - (Sutherland 2002). A chromophore is a molecule (or part of a molecule) which imparts some decided color to the compound of which it is an ingredient. Chromophores almost always occur in one of two forms: conjugated pi electron systems and metal complexes. Examples of such chromophores can be seen in chlorophyll (used by plants for photosynthesis), hemoglobin, cytochrome c oxidase (Cox), myoglobin, flavins, flavoproteins and porphyrins (Karu 1999). Figure 1 illustrates the general concept of LLLT. 1) Cy tochrome c ox idase mediated increase in ATP production. 2) Cy tochrome c ox idase mediated singlet-oxygen production. 3) Cy tochrome c ox idase mediated Reactiv e oxygen species (ROS) formation. 4) Cy tochrome c ox idase mediated Photodiassociation. Tissue response & healing by LLLT : A. Tissue response LLLT can prov ide the follow ing beneficial impac ts in both open surface w ounds and closed con nec tiv e or soft tissue injuries as follow s: 1. Enhanced leukocyte infiltr ation. LLLT s timulates ac tiv ity inv olv ing neutrophils, monocy tes and ly mphocy tes. 2. In creased macrophage activity. LLLT accelerates macrophage activ ity in phagocy tosis, grow th factor secretion and s timulation of c ollagen sy nthes is. 3. Incr eased neovascularization. The significant angiogenesis that occurs w ith laser therapy promotes rev ascularization w ith subs equent im prov ement in perfusion and oxy genation. Endothelial c ell regeneration is accelerated. 3 1 4. In creased fibroblast proliferation. LLLT s tim ulation in-creas es fibroblas t numbers and fibroblas t-m ediated collagen production. 3 2 5. Keratinocyte proliferation. The benefic ial sy nthes is ac tivities and grow th fac tor ability of k eratinocy tes are enhanced by proliferation secondary to LLLT. 33 6. Early epitheli alization. Laser-s tim ulated acc eleration of epithelial cell regeneration speeds up w ound healing, minimizes sc arring, and reduces infec tion opportunities. 7. Gro wth factor increases. Tw o to fiv e fold increases in grow th-phase-specific DNA sy nthesis in normal fibroblas ts, muscle cells, osteoblas ts and mucosal epithelial cells irradiated w ith IR light are reported. Increases in v ascular endothelial grow th fac tor (VEGF) and fibroblas t grow th factor (FGF-2) secondary to IR light irradiation hav e also been reported. 8. Enhan ced cell prolifer ation and di ffer enti ation. Laser-induc ed increases in NO, ATP and other compounds that s tim ulate higher activ ity in cell proliferation and differentiation into mature cells. Increased numbers of my ofibroblasts, my ofibrils, my otubes etc., as w ell as bone cell proliferation, hav e- been clinically documented after - LLLT. Satellite cells, the prec ursor cells in the process of muscle regeneration, show signific ant inc rease in proliferation w hen irradiated w ith LLLT. 3 4,3 5, 36 3
  • 4. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. 9. Greater heal ed wound tensil e strength. In both soft tissue and c onnec tiv e tissue injuries, LLLT can inc reas e the final tensile strength of the healed tissue. By increas ing the amount of c ollagen produc tion/sy n thes is and by inc reas ing the intra and inter -molecular hy drogen bonding in the c ollagen molecules, laser therapy contributes to improv ed tens ile strength. 37 ,3 8,3 9, 40. The preceding effec ts combine to achiev e an accelerated heal ing rate (see Figure 3). The time from onset of injury to mature healed w ound is reduced. 4 1 The cumulativ e effects of (physical & Bio-chemic al) laser on tis sue enhances physiologic al activ ities by ion-exchange, speckle formation, singlet oxygen, redox formation, ATP production & nitric ox ide formation and exerts-  Enhances chemiosmosis,  Enzyme & hormone regulation  Stimulates the redox activity in the mitochondria,  RNA synthesis and DNA production - causing mitosis and cell proliferation  Calcium-ion influx into the cytoplasm, So, Laser biostimulation may be an invaluable therapeutic modality for treating most wounds. Wound healing entails a) the process of inflammation during which the hematoma formed in and around the wound site is resolved; b) cellularity and protein synthesis, i.e., two processes that culminate in the formation of granulation tissue; and c) wound remodeling, a process that may continue long after the wound may be said to be well healed. B. TISSUE HEALING One of the truly unique characteristics of LLLT is that it has the ability to actually promote and enhance healing, not just treat symptoms. The irradiation by low-level laser light accelerates and enhances healing activities carried out by the body. Sev eral of the unique characteristics of LLLT that w ork to allev iate pain and inflammation also play an important role in accelerating the healing process; the LLLT-mediated reduction in inflammation and pain frees the body’s natural ability to repair and heal itself. The effects of LLLT can vary considerably. Cells being initially at a more reduced state (low intracellular pH) have high pot ential to respond to LLLT, while cells at the optimal redox state respond weakly or do not respond to treatment with light. A s wound healing progresses through the stages of inflammation, proliferation, remodeling and maturation, laser therapy presents the opportunity to impact each of these phases in positive and beneficial w ays. The beneficial effect of LLLT on wound healing can be explained by considering several basic biological mechanisms including the induction of expression cytokines and growth factors known to be responsible for the many phases of wound healing. Firstly there is a report that laser increases both protein and mRNA levels of IL-1α and IL-8 in keratinocy tes. These are cy tokines responsible for the initial inflammatory phase of wound healing. Secondly there are reports that LLLT can upregulate cy tokines responsible for fibroblast proliferation, and migration such as bFGF, HGF and SCF. Thirdly it has been reported that LLLT can increase grow th factors such as VEGF responsible for the neovascularization necessary for wound healing. Fourthly TGF-β is a growth factor responsible for inducing collagen synthesis from fibroblasts and has been reported to be upregulated by LLLT [51]. Fifthly there are reports that LLLT can induce fibroblasts to undergo the transformation into my ofibloblasts, a cell ty pe that ex presses smooth muscle α-actin and desmin and has the phenoty pe of contractile cells that hasten wound contraction. 4. A CASE REPORT : Laser as an Adjunctive Modality for human Chronic Wound Healing - Place of study: Shaheed Suhrawardy Medic al College Hospital, Dhaka-1 207, Bangladesh. Tel(Hos.):88-9130800-19 Cell: 01196133078, E-mail: abbirr@gmail.com Patient Particular: Name of the patient: Ms. Zobeda Khatun, Age: 78 Ye ars, Gender: Female. Ward and Bed: 6/ 1.Hospital stay: From Octo ber 14th / 2009 to January 10 th /2110. . ABSTRACT Background: Chronic wounds, particularly Bedsore/ Decubitus ulcerations in old age/ bedridden patients, are notoriously difficult to heal. Because current therapies are variable in their ability to induce complete healing, there remains a need to develop adjunctive treatments that can improve or accelerate the healing process. Low-level laser therapy is an important method for the treatment of healing processes and several experimental studies in human & animal models and applications has been carried out successfully in search of a greater understanding of its therapeutic possibilities. Objective The objective of this study was to review pathogenetic aspects of soft tissue repair to better understand skin lesion healing and the role of low-intensity laser in the progression of tissue healing. Methods: We have worked on diode laser therapy on recurrent bedsore patient, made clinical observational effects of low intensity laser therapy on constituents of the wound healing process. Results: A large number of in vivo studies on the effects of low intensity laser irradiation on wound healing show a lack of accuracy on dosimetric data and appropriate controls. Despite this fact, data from appropriately designed studies seem to indicate that this type of phototherapy should be considered a valuable (adjuvant) therapy for otherwise therapy -refractory wound-healing disorders. Conclusions: The use of low-energy lasers to stimulate wound healing has been pursued over many decades in studies of varying quality. This form of treatment has had high appeal due to its novelty, relative ease, and low morbidity profile. However, many unanswered questions demand research on the mechanism of action and on parameters of low-level laser use in different stages of wound repair to clarify how this method acts at a cell level in healing processes. High energy lasers have extensive applications in the field of surgery, ophthalmology, dermatology, medicine and oncology. The utility of low energy lasers for biostimulation, immune response mediation and wound healing is of relatively recent interest. The current communic ation illustrates our experience with low energy laser (G a-Al-As 660 laser) as an adjunct to the conventional modes of treatment for wound healing. Many studies have extensively covered the effects of using laser radiation in tissues, describing its beneficial aspects in tissue healing. This study consists of a concise review of scientific literature data on the use of low -level laser and its influence on wound healing. Further research aiming at elaborating optimal treatment parameters seems to be justified. Keywords: LLLT, Biostimulation, Soft tissue, wound healing. Case Study: Ms. Zobeda, female, Dhaka, Bangladesh, age 78, bedridden for years for spastic neurological disorder, with history of recurrent multiple large / small (approximately 1 -2cm deep, 6 -8cm in diameter) wound in the back, with inflammation and profuse purulent discharging infection was referred to this tertiary hospital from a local hospital for long lasting (More than 6 months of local management with all efforts, Fig. 1) non- healing chronic open wound. At the time of admission, patient’s Vital signs revealed a heart rate of 68/min, respiratory rate of 26/min, and rectal temperature of 36. 5°C. General examination- the patient is bedridden for years, all the system revealed normal except musculoskeletal & nervous system, which showed spastic muscular disorder and Parkinson disease. The wound was surrounded by large ulcerative skin lesion almost confluent with the spine. The surrounding areas of the lesion revealed slough and blackish necrotic debris. The total wound area covered about 6 by 8 inches (Fig. 1). The wound details are indicated in Table I. Investigations revealed hemoglobin- 10.7g/dl; TLC - 4700 cells/cu mm; DLC- N60 and L40; absolute Neutrophil count- 2820 cell/cu mm; μ, ESR - 16 mm; and adequate platetets. Peripheral smear revealed microcytic red cells and mild leucopenia. Liver and Kidney profile revealed normal limit, Urine microscopy and cultures were positive repeatedly . Blood culture was sterile. Chest X-ray and Spine showed severe osteoporotic change.Ecg showed old MI, Echcadiography showed mild LVH. 4
  • 5. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. Pus culture and sensitivity was performed at weekly intervals which yielded Pseudomonas initially. Subsequent cultures showed Staphylococcus aureus and E-coli species which is supposed to be from contamination with urine. Appropriate antibiotics were given time to time, throughout the hospital stay including intravenous Ciprofloxacillin (100 mg/ kg/day) and amikacin (15 mg/kg/day) for 15 days. Antibiotics were subsequently changed both for wound and urine infection, to netilmycin (6 mg/kg/ day for 7 days), cefotaxime (100 mg/kg/day for 10 days), Kenamycin (500 mg 12 hourly for 7 days) and Clindamycin (300mg 12 hourly for 10 days duration). Alternate day cleaning and dressing of the wound was done with Betadine, E-usol and Hexisol. TABL E -3 Morphology of the Wounds Before and After Therapy- Wound Before debridement After debridement/ closure Wound Prior to Therapy End of Therapy Prior to End of parameters- Therapy Therapy Margin Irregular & indurated Partially Regular Sutured In tacked skin Floor Unhealthy, Almost Healthy Necrotic Oozing Tissue granulation tissue Covered Covered Base Spine bone Exposed Partially Clear Spine granulation tissue bone covered Covered Surrounding skin/Contraction Inflamed and scared Partially Healthy Healthy Up to mark He althy Discharge Profuse purulent Oozing pus Serous Discharge No discharge No d ischar ge Irradiance Parameters LE D App aratu s: BioLux MD  Beam source (Incoherent- Ga- Al- As)  Irradiance dose: 4- 8 J/cm2/min.  Irradiance ti me: 1- 2 minutes  Mode: Continuous wave  Wavelengths Used: 660 nm  Total session: 35. The parameters which have been found to be most effective are in the range of 90 sec/cm2 of open wound surface, with the laser beam set at a pulsed rate of 40-80 pulses per second (PPS), depending upon the chronicity of the lesion. The more chronic, the slower the pulse rate suggested. The optimum distance from probe tip to target surface was 1-4 mm. Probe motion during lasing was a slow, circling movement over each square centimeter of open lesion, timed to permit the suggested dosages. As the lesion is large, i.e., 4-6 cm in diameter, a change in technique is adopted which involves a slow, traversing of the perimeter of the lesion, allowing approximately 90 sec per linear centimeter of the perimeter, at the suggested distances (1-4 cm). This technique apparently provides sufficient exposure to the laser beam to stimulate healing effectively, compared with non-treated areas and previously experienced wound management of a similar nature. T ABL E - 4 Treatment Schedule (Dose duration and wound parameter Per iod/ Frequency Wound Irradia tion En ergy W ee k A rea /siz e Source W av e Fluenc e Point T im e 2 2 1-2 week 5/ week 6.8 cm LED-660 nm (G a-Al -As) Continuous 6 joules/c m 2 8 joules/min. 2 2 3- 5 week 3/ week 5.7 cm LED-660 nm (G a-Al -As) Continuous 4 joules/cm 2 8 joules/min. 2 2 4-6 week 3/ week 4.4 cm LED-660 nm (G a-Al -As) Continuous 4 joules/cm 1 8 joules/min. 2 2 7-8 week 2/week 2.2 cm LED-660 nm (G a-Al -As) Continuous 3 joules/ cm 1 8 joules/min. 2 9-10 week 2/ week Closed LED-660 nm (Ga -Al -As) Continuous 3 joules/ cm 1 8 joules/min. Low energy Ga-Al laser provides infrared rays in the wave length of around 660 nm by continuous mode. An average power of 5-8 mw was provided through a fiber optic delivery system around the wound margin for about 8-10 min at each point at a distance of one cm. Since the center of the ulcer was deep, it was decided to give laser therapy concentrating maximum irradiance ther e (Fig. 1). At the end of 2nd week there was an improvement in laser irradiated side with respect to ulcer size and wound margin and there was serous disch arge after eight exposures (Table I). Surgical debridement was done 2 times: at 3rd & 5th week and finally secondary closure given at the end of 8th week, within in the treatment period (two and half months). A healthy granulation tissue appeared by 6-7th week. Fig. 6/7 reveals the post laser therapy ulcer on 6-7th week. At this stage, the center of the ulcer was still unhealthy and significant signs of healing. It was decided to irradiate the center of ulcer also with maximum permitted irradiance dose. At the end of 8th week the wound looked pretty healthy, we decided to do secondary closure instead of skin grafting, as because of old age, we could mobiles the wound adjacent skin without tension and closed the wound by four point suture. And next two weeks we observed the wound surface with a keen observation, and continued to two days interval laser therapy ( Total treatment 25), and medications properly. Enhancement of healing processes with open lesions is described. The effective parameters were determined to be a pulsed beam at 40-80 PPS, administered at a target distance of 4 mm, for 90 sec/cm2 of open lesion surface. In addition, lasing along the perimeter of the larger wound was indicated to overcome the diminished penetration of the laser beam through the hardened eschar overlaying the lesion. No untoward reactions or side effects were reported by the patient. Chronology of management & improvement: At the 5th day of her adm ission in our ward, we simu ltaneously s tar ted conservative treatment and He-Ne l aser therapy. After wound cleaning, s tandardized digi tal photos were recorded weekly.  At the end of 2 nd week of treatment; the outlook of the wound looked better, and signs of increased vascularity in the surrounding area noted. But serous discharge continued.  At the end of 3rd week of treatment, we did wound debridement, and continued alternate d ay dressing and as well as laser therapy.  At the 4 th week of treatment, we continued to care the wound by alternate day dressing and medications, and noticed formation of granulation tissue at the margin of the wound.  At the end of 5 th week of treatment, we again debrided the center of the wound with care so that the adjacent healthy tissue could be preserved.  At the end of 6 th week of treatment, we observed marked improvement in the wound and at the same time si gns of vascular marking noted at the wound margin.  At the 7 th week of treatment, we noticed general condition of the wound healthy, and signs of healthy granulation tissue all over the wound, we continued to two days interval dressing. No discharge noted.  At the end of 8 th week of treatment, we did surgical toileting and secondary closure of the wound, and continued to give conservative & laser therapy twice weekly until 10 th week of treatment.  At the end of 9 th week of treatment we observed a nice and healthy wound margin, and reddish vascular marking all over the wound surface area.  At the end of 10 th week of treatment of her admission we assessed her wound and surround areas for any sign of wound dehiscence, infection, vascularity of the wound as well as adjacent areas was up to mark, and being satisfied discharged her with smile. Our purpose was to assess potenti al changes in healing due to LLLT over time using a human experimental wound model. Healing was measured in terms of wound contraction and changes in chromatic red and luminance. Chromatic red is an indication of wound healing as a wound changes in color from dark red to pale pink over time. Luminance refers to the homogeneity of a wound as the tissue heals and becomes more smooth and consistent. In addition to laser therapy (Led) and surgical intervention , adjacently she was also given the following management : o Pneumatic Bed support. o Catheterization. o High protein diet, o Antibiotics (according to c ulture and s ensitivity test), o Pain killer (Non-NSI D) o H2 Blocker- Pantoprazole and Ranitidine. o Tab- Perkinil, 5mg 12 ho urly, o Tab- Ecosporin(Aspirin) o Vitamin B-complex , anti-ox idant, Vitamin D3 , o Iron, Folic acid and Zinc supplements, o Calcium, o Fresh blood transfusion. 5
  • 6. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. Chronological Picture View: 1ST DAY, 24TH OCTOBER/2009 Pretreatment photograph of wound showing irregular margins, Necrotic tissue and pus discharge. F-1: At the end of 1 st Week F-2: At the end of 2 nd week. F-3a: At the end of 3 rd week. F-3b: At the end of 3 rd week. F-4: At the end of 4 th week. F-5: At the end of 5 th week. F-6: At the end of 6 th week F-7: At the end of 7 th week F- 8b: At 9th week F-10a: At 10t h week . F-10b: At The End Of 10t h Wk. F-10c: At The End Of 10t h Wk (9rd post operative day) (12rd post op. day) 5. Discussion Our patient demonstrated a significant benefit of Ga-Al-As 660 laser for rapid healing of skin wound. The comparis on betw een the laser and conventionally treated prev iously treated wounds of the same patient at about same size clearly highlighted that despite uniformity of host factors, local factors and systemic state, the w ound healing process was stimulated on the laser exposed side. Healing of wounds is an im portant problem faced by general & orthopedic surgeons. The possible biostimulatory role of laser light in wound healing is of recent interest (42). Small sub destructiv e repetitiv e doses of laser light are claim ed to be useful for trophic ulcers and indolent wounds (43). The proposed mechanisms of action include local leukocy te proliferation), neovascularization, fibroblastic proliferation and rapid epithelialization (44, 45). All these mechanisms possibly lead to more rapid closure of wounds and stronger scar formation. In an experim ental study, wounds treated with Ga-Al-As 660 laser rev ealed significantly more granulation tis sue. This study establis hed the biostimulatory effects of low intensity laser radiation (46). Many reports now indicate benefit to non healing w ounds and trophic ulc ers by low-intensity laser irradiation. Out of 351 patients thus treated, 236 showed complete epithelialisation of the wound surface (47). A 44% increase in healthy granulation tis sue was observed, 2/12 ulc ers healed completely while 27% rev ealed reduction in siz e of the remaining ulc ers indic ating considerable benefit (48). Nussbaum et al. (49) in a study compared- the effect of ultraviolet-C and laser for treatm ent of pressure ulc ers in adults w ith spinal cord injury. They used 660-980 nm w ave length light at an energy density of 4 J/cm2. Weekly percentage changes in wound area were compared. The authors concluded ex posure to UV-C decreased healing time and allowed faster return to rehabilitation programs. The UV-C light was better than the laser (50). Another nonrandomized study of laser and UV lamp on chronic skin ulc ers suggested that wounds whic h fail to respond to topical treatm ents benefit from either modality (51). Ev aluations of different approaches to wound healing are complic ated by the large number of factors that influence wound healing. Although there are anecdotal reports of successful therapy, there are few well controlled studies. The use of lasers for healing wounds is becoming increasingly attractiv e to surgeons. A number of animal and in vitro studies (52, 53) have demonstrated that laser irradiation has a significant effect on components of tissue repair. 6. Conclusion This study results efficacy of LLLT on wound healing in human model, and indicates that it can be a very important adjective tool /modality for chronic intractable wound management, and in any way it is not harmful to human being. In the past Laser / LED were shown to be effective in wound management b ut in different degrees, some of those applications showed significant improvement some less effective others no effect. Probably laser/ LED Irradiation parameters are vital for its Biostimulative effects. Inference of those results summaries that irradiation parameters are of vital to laser therapy. We used an optimal dose of irradiance which proved to be most effective biostimulation on human application Application and research of LLLT on cell responses of wounded skin fibroblasts demonstrate that correct energy density or fluence and number of exposures can stimulate cell responses of wounded fibroblast and promote cell migration and cell proliferation by stimulating mitochondrial activity and maintaining viability without causing additional stress or damage to wounded cells. Results indicate that the cumulative effect of lower doses determines the stimulatory effect, whereas multiple exposure at higher doses result in an inhibitory effect with more damage. 39 Although various studies have extensively covered the effects of laser radiation on tissue, many unanswered questions remain. The mechanisms effectively responsible for cell mitotic activity has not been clarified yet, and there is no standardized ideal dose for stimulating tissue healing. Therefore, we noted that there is a need for research on the action and parameters of low -intensity laser use in cutaneous lesions during the different stages of repair, as an attempt to elucidate how this method acts at a cell level in healing processes. Elucidation of these issues will enable the establishment of criteria on the true benefits of laser therapy in diseases that need he aling stimulation, minimizing healing time and the complications that may occur during the clinical progress of these wounds. In addition, experimental studies indicated that the LLLT may be an important therapeutic tool to stimulate wound healing in decubitus ulcer patients. In conclusion, the present report highlights the possible utility of Galliium-Aluminium laser at 660 wavelengths is as effective as Helium-Neon laser as an adjunctive modality for wound healing in skin/general & orthopedic practices. 7. References: 1. Snyder RJ. Trea tment of nonhealing ulcers with allografts. Clin Dermatol. 2005; 23:388-95. 2. Sugrue ME, Carolan J, L een EJ, Feeley TM, Moore DJ, Shanik GD. The use of infrared laser therapy in the tr eatment of venou s ulceration. Ann VascSurg. 1990; 4:179-81. 3. Chromey PA. The efficacy of carbon dioxide laser surgery for adjunct ulcer therapy. Clin Podiatr MedSurg. 1992; 9:709-19. 4. NussbaumEL, Zuylen JV, Baxter GD. Specific atio n of treatment dosage in laser therapy: unreliable equip ment and radiant power determination as confounding factors. Phy siotherapy Can. 1999; 157-167. 5. 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  • 7. LLLT, Low Level Laser (LED- Ga-Al- As 660) Therapy – On soft Tissue Healing: Review, Mechanism and A case report. 39. Y. Fujimaki, T. Shimoyama, Q. Liu, T. Umeda, S. Nakaji and K. Sugawara, Low-level laser irradia tion attenuates production of reactive oxygen species by human neutrophils, J Clin Laser Med Surg 21 (2003) 165-70. 40. Y.S. Chen, S.F. Hsu, C.W. Chiu, J.G. L C.T. Chen a C.H. Yao, Effect of low-power pulsed laser on per in, nd ipheral nerve regeneration in rats, Microsurgery 25 (2005) 83-9. 41. M. Miloro, L.E. Halkias, S. Mallery, S. Travers and R.G. Rashid, Low-level laser effect on neural regeneration in Gore-Tex tubes, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93 (2002) 27-34. 42. Gogoa PP, Margue RR. Effects of Hellium-Neon laser on wound healing. Osteomy Wound Manag 1992; 38: 33-41. 43. Koshelev VN, Arkhangel AV, Glukhov El. Effect of low intensity carbon dioxide laser on reparative regeneration of experimen talwounds. Byulleten Eksperimental noi Biologii Meditriny 1985; 99: 338-341. 44. Kana JS, Hutschenreiter G, Haina D, Waidelich W. Effect of low power density laser radiation on healing of open skin wounds in rats. Arch Surg 1981; 116: 293- 295. 45. Avevbakh MM, Sorkin MZ, Dobkin VG, Kosarev II, Osta pehenkoEP. Effect of Helium- Neon laser on the healing of aseptic experimenta wounds. EKSP Khir Anaesteziol 1976; 3: 56-61. l 46. Mester E, Spiry T, Szends B. Effect of laser rays on wounds healing. Bull Soc Int Chir 1973; 32:169 -172. 47. Bisht D, Gupta SC, Misra V, Mittal VP, Sharma P. Effect of low intensity laser radia tion on healing of open skin woundsin rats. Indian J Med Res 1994; 100: 43- 46. 48. Georgadze AK, Karpov VI, Kuznetsov EV, Solda tov AV, Rukosuev VP. Tr eatment of non -hea ling wounds and trophic ulcers by low-intensity laser irradia tion in 49. Sugrue ME, Careolan J, Leen EJ, F eeley TM, Moore DJ, Shanik GD. The use of infrared laser therapy in the treatment of venous ulceration. Ann Vase Surg 1990; 179-181. 50. Nussbaum E L, Biemann I, Mustard B. Comparison of ultrasound/ultraviolet-c and laser for trea tment of pressure ulcers in patients with spina cord injury. Physical Therapy 1994; 74: 812-823. l 51. Crous L, Malherbe C. Laser a ultraviolet light irradiation in the treatment of chronic ulcers. Physiotherapy 1988; 44: 73-77. nd 52. Young S. Dyson M, Bottom P. Effect of light on Calcium uptake by macrophages. Pr esented at a Seminar on Laser Biomodula tion a Guy's Hospital, London, 1991. t 53. El Sayed S, Dyson M. Comparison of the effect of multiw avele ngth light produced by a cluster of semiconductor diodes and of each individual dio de on mast cell number and degranulation in intact and injured skin. Laser Surge Med 1990; 10: 559-568. Research Panel Members: 1. Dr. Md. Nazrul islam, MBBS, M.Sc.(Biomedical Engineering). Resident Surgeon, Department of Orthopaedics’ & Traumatology, Shaheed Suhrawardy Medical College Hospital, Dhaka-1207. Bangladesh (BD). 2. Professor Golam Abu Zakaria, ph. D, Dept.of Medical Radi ation Physics,Kreiskrankenhaus Gummersbach, Teaching Hospital of the University of Cologne,51643 ,Germany. And Prof.- Dept. of Medical Physics and Biomedical Engineering, Gono - Bishwabidyalay (Gono University), Nayarhat, Savar, Dhaka-1344, Bangladesh. 3. Professor F. H. Sirazee, MBBS, MS, Department of Orthopedic and Traumatology, Shaheed Suhrawardy Medic al College Hospital, Dhaka-1207, Bangladesh. 4. Dr. Paritosh Chandra Debenath, MBBS, MS, Associate Prof.,Department of Orthopedic and Traumatology, Shaheed Suhrawardy Me dical College Hospital, Dhaka-1207, BD. 5. Dr. kazi Shamimuzzaman, MBBS, MS, Assistant Prof., Department of Orthopedic and Traumatology, Shaheed Suhrawardy Medical College Hospital, Dhaka-1207, B angladesh. 6. Dr. Quamrul Akhter sanju, MBBS, FCPS, MRCS, Assistant prof., Department of Surgery, Shaheed Suhrawardy Medical College Hospital, Dhaka-1207, Bangl adesh. 7. Dr. Ashraf Uddin Khan, MBBS, DMRD, FCPS, Assistant Prof., Department of Radiology & I maging, Shaheed Suhrawardy Me dical College Hospital, Dhaka-1207, Bangladesh. 8. Dr. Md. Mostafizur Rahman, MBBS, FCPS (Surgery), Assistant prof., Department of Surgery, Shaheed Suhrawardy Medic al College Hospital, Dhaka-1207, Bangladesh. 9. Dr. Sayed Shaheedul Islam MBBS, MS (Orthope dic), Assistant prof., NITOR- National Institute of Traumatology And Rehabilitation, Dhaka-1207, Bangladesh. 10.Sinha Abu Khalid, B. Sc. (Hons.,) Applied Physics & E lectronics, Dhaka University, Member, American Society for Laser Medicine & Surgery, CEO, LabNucelon CTS, Dhaka,BD. 11. Muhammad Masud R ana,M.Sc.(Medical Physics),National Institute of Cancer Research and Hospital,Dhaka,Bangladesh.General Secretary-Bangladesh Medical Physics Society. 7