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1.  A novel and accurate technique of photographic wound measurement 
Context:
Wound measurement is an important aspect of wound management. Though there are many techniques to measure wounds, most of them are either cumbersome or too expensive.
Aims:
To introduce a simple and accurate technique by which wounds can be accurately measured.
Settings and Design:
This is a comparative study of 10 patients whose wounds were measured by three techniques, i.e. ruler, graph and our technique.
Materials and Methods:
The graph method was taken as the control measurement. The extent of deviation in wound measurements with our method was compared with the standard technique. The statistical analysis used was ANOVA.
Results:
The ruler method was highly inaccurate and overestimated the wound size by nearly 50%. Our technique remained consistent and accurate with the percentage of over or underestimation being 2-4% in comparison with the graph method.
Conclusions:
This technique is simple and accurate and is an inexpensive and non-invasive method to accurately measure wounds.
doi:10.4103/0970-0358.101333
PMCID: PMC3495395  PMID: 23162244
Digital planimetry; photography; wound measurement
2.  A Comparison of Wound Area Measurement Techniques: Visitrak Versus Photography 
Eplasty  2011;11:e18.
Objective: To investigate whether a cheap, fast, easy, and widely available photographic method is an accurate alternative to Visitrak when measuring wound area in cases where a non–wound-contact method is desirable. Methods: The areas of 40 surgically created wounds on porcine models were measured using 2 techniques—Visitrak and photography combined with ImageJ. The wounds were photographed with a ruler included in the photographic frame to allow ImageJ calibration. The images were uploaded to a computer and opened with ImageJ. The wound outline was defined from the photographic image using a digital pad, and the ImageJ software calculated the wound area. The Visitrak method involved a 2-layered transparent Visitrak film placed on the wound and the outline traced onto the film. The top layer containing the tracing was retraced onto the Visitrak digital pad using the Visitrak pen and the software calculated the wound area. Results: The average wound area using the photographic method was 52.264 cm2 and using Visitrak was 51.703 cm2. The mean difference in wound area was 0.560 cm2. Using a 2-tailed paired T test, the T statistic was 1.285 and the value .206, indicating no statistical difference between the two methods. The interclass correlation coefficient was 0.971. Conclusions: The photographic method is an accurate alternative to Visitrak for measuring wound area, with no statistical difference in wound area measurement demonstrated during this study. The photographic method is a more appropriate technique for clean and uncontaminated wounds, as contact with the wound bed is avoided.
PMCID: PMC3080766  PMID: 21559060
3.  Use of Standardized, Quantitative Digital Photography in a Multicenter Web-based Study 
Eplasty  2009;9:e4.
Objective: We developed a Web-based, blinded, prospective, randomized, multicenter trial, using standardized digital photography to clinically evaluate hand burn depth and accurately determine wound area with digital planimetry. Methods: Photos in each center were taken with identical digital cameras with standardized settings on a custom backdrop developed at Wake Forest University containing a gray, white, black, and centimeter scale. The images were downloaded, transferred via the Web, and stored on servers at the principal investigator's home institution. Color adjustments to each photo were made using Adobe Photoshop 6.0 (Adobe, San Jose, Calif). In an initial pilot study, model hands marked with circles of known areas were used to determine the accuracy of the planimetry technique. Two-dimensional digital planimetry using SigmaScan Pro 5.0 (SPSS Science, Chicago, Ill) was used to calculate wound area from the digital images. Results: Digital photography is a simple and cost-effective method for quantifying wound size when used in conjunction with digital planimetry (SigmaScan) and photo enhancement (Adobe Photoshop) programs. The accuracy of the SigmaScan program in calculating predetermined areas was within 4.7% (95% CI, 3.4%–5.9%). Dorsal hand burns of the initial 20 patients in a national study involving several centers were evaluated with this technique. Images obtained by individuals denying experience in photography proved reliable and useful for clinical evaluation and quantification of wound area. Conclusion: Standardized digital photography may be used quantitatively in a Web-based, multicenter trial of burn care. This technique could be modified for other medical studies with visual endpoints.
PMCID: PMC2627310  PMID: 19212431
4.  A porcine model of full-thickness burn, excision and skin autografting 
Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization.
Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring.
The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality.
doi:10.1016/j.burns.2008.03.013
PMCID: PMC2637517  PMID: 18617332
Burn; Burn excision; Wound healing; Reconstruction; Autograft
5.  A Skin Fixation Method for Decreasing the Influence of Wound Contraction on Wound Healing in a Rat Model 
Archives of Plastic Surgery  2012;39(5):457-462.
Background
The elasticity of the back skin of the rat reduced the tension around wounds during the wound healing process in that region, and thus activates wound contraction. The authors proposed two skin fixation methods using readily available materials to decrease the influence of wound contraction on wound healing and designed an experiment to determine their effects.
Methods
The authors made 36 skin wounds on the backs of 18 rats, and they divided them into three groups. Each group was treated with three different kinds of dressing materials, each with different skin fixing characteristics. Group A was a control group. Group B and group C were dressed by the first and the second skin fixation method. We measured the areas of the wounds post-surgically and calculated the wound area reduction rates.
Results
The two skin fixation methods both reduced the effect of wound contraction compared to the control group. Each of the two methods had different outcomes in reducing wound contraction.
Conclusions
The experiment demonstrated significant differences among the wound areas and the wound area reduction rates of the three groups as a result of differences in the degree of wound contraction. To obtain accurate results from wound healing experiments, appropriate skin fixation methods must be adopted.
doi:10.5999/aps.2012.39.5.457
PMCID: PMC3474401  PMID: 23094239
Wounds and injuries; Wound healing; Rats
6.  Inhibition of SDF-1α further impairs diabetic wound healing 
Objective
Impaired diabetic wound healing is associated with abnormal SDF-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound healing response and that inhibition of SDF-1α would further delay the wound-healing process.
Design of study
Db/Db diabetic mice and Db/+ non-diabetic mice were wounded with an 8mm punch biopsy and the wounds treated with a lentiviral vector containing either the GFP or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time PCR. The effect of the SDF-1α inhibitor on cellular migration was also assessed.
Results
Inhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 cm2/day versus 6.5 cm2/day in GFP-treated wounds p=0.04), and also impaired the early phase of non-diabetic wound healing. SDF-1α inhibition also resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression (IL-6 and MIP-2) in the diabetic wounds.
Conclusions
The relative level of SDF-1α in the wound plays a key role in the wound healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation.
doi:10.1016/j.jvs.2010.10.056
PMCID: PMC3058337  PMID: 21211927
7.  A High Throughput, Interactive Imaging, Bright-Field Wound Healing Assay 
Cytometry  2011;79(3):227-232.
The wound healing assay is a commonly used technique to measure cell motility and migration. Traditional methods of performing the wound healing assay suffer from low throughput and a lack of quantitative data analysis. We have developed a new method to perform a high-throughput wound healing assay that produces quantitative data using the LEAP™ instrument. The LEAP™ instrument is used to create reproducible wounds in each well of a 96-well plate by laser ablation. The LEAP™ then records bright field images of each well at several time points. A custom texture segmentation algorithm is used to determine the wound area of each well at each time point. This texture segmentation analysis can provide faster and more accurate image analysis than traditional methods. Experimental results show that reproducible wounds are created by laser ablation with a wound area that varies by less than 10%. This method was tested by confirming that neuregulin-2β increases the rate of wound healing by MCF7 cells in a dose dependent manner. This automated wound healing assay has greatly improved the speed and accuracy, making it a suitable high-throughput method for drug screening.
doi:10.1002/cyto.a.21029
PMCID: PMC3306835  PMID: 22045642
wound healing assay; quantitative image analysis; image cytometry; high-throughput screening; interactive imaging; LEAP
8.  Wound Healing Potential of Methanol Extract of Spathodea Campanulata Stem Bark Formulated into a Topical Preparation 
This study evaluated the wound healing potential of Spathodea campanulata stem bark in Sprague Dawley rats using the excision wound model. The methanol extract contained glycosides, flavonoids and tannins, and was relatively stable when stored at the room temperature for six (6) months. Solvent-free, semi-solid extract of S. campanulata was incorporated into an aqueous cream and applied (10 % w/w and 20 % w/w) on excision wounds of thirty two (32) rats. Cicatrin® cream was used as a standard wound healing agent. Prior to the remedial cream application, done later on twice daily, sixteen (16) rats had their wounds infected with Staphylococcus aureus, while in the remaining sixteen the wounds were kept clean. The surface area of the excision wounds was monitored planimetrically every four (4) days until a complete wound closure or healing took place. Excision wounds treated with 20 % w/w Spathodea cream and Cicatrin® cream showed a rapid and comparable decrease (p > 0.05) in wound size. In uninfected wounds, both 20 % w/w Spathodea cream and Cicatrin® cream application resulted in ∼ 95 %-wound closure seen on Day 20, and a complete closure seen on Day 24. In infected wounds, both 20 % w/w Spathodea cream and Cicatrin® cream administration led to ∼ 91 %-wound closure on Day 24 and a complete wound contraction on Day 28. The results of this study justify the folkloric use of S. campanulata stem bark to the effect of wound treatment.
PMCID: PMC3252224  PMID: 22468000
Spathodea campanulata; wound healing; excision wound model; Spathodea cream; Cicatrin® cream; wound contraction
9.  Epidermal wound healing in severe sepsis and septic shock in humans 
Critical Care  2009;13(3):R100.
Introduction
The effect of sepsis on epidermal wound healing has not been previously studied. It was hypothesised that epidermal wound healing is disturbed in severe sepsis.
Methods
Blister wounds were induced in 35 patients with severe sepsis and in 15 healthy controls. The healing of the wounds was followed up by measuring transepidermal water loss and blood flow in the wound, reflecting the restoration of the epidermal barrier function and inflammation, respectively. The first set of suction blisters (early wound) was made within 48 hours of the first sepsis-induced organ failure and the second set (late wound) four days after the first wound. In addition, measurements were made on the intact skin.
Results
The average age of the whole study population was 62 years (standard deviation [SD] 12). The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission was 25 (SD 8). The two most common causes of infections were peritonitis and pneumonia. Sixty-six percent of the patients developed multiple organ failure. The decrease in water evaporation from the wound during the first four days was lower in septic patients than in the control subjects (56 g/m2 per hour versus 124 g/m2 per hour, P = 0.004). On the fourth day, septic patients had significantly higher blood flow in the wound compared with the control subjects (septic patients 110 units versus control subjects 47 units, P = 0.001). No difference in transepidermal water loss from the intact skin was found between septic patients and controls. Septic patients had higher blood flow in the intact skin on the fourth and on the eighth day of study compared with the controls.
Conclusions
The restoration of the epidermal barrier function is delayed and wound blood flow is increased in patients with severe sepsis.
doi:10.1186/cc7932
PMCID: PMC2717472  PMID: 19552820
10.  Hemoglobin A1c is a Predictor of Healing Rate In Diabetic Wounds 
Lower-extremity wounds are a major complication of diabetes. Hemoglobin A1c (HbA1c) reflects glycemia over 2–3 months and is the standard measure used to monitor glycemia in diabetic patients, but results from studies have not shown a consistent association of HbA1c with wound healing. We hypothesized that elevated HbA1c would be most associated with poor wound healing. To test this hypothesis we conducted a retrospective cohort study of 183 diabetic individuals treated at the Johns Hopkins Wound Center. Our primary outcome was wound-area healing rate (cm2/day). Calibrated tracings of digital images were used to measure wound area. We estimated coefficients for healing rate using a multiple linear regression model controlling for clustering of wounds within individuals and other common clinic variables. The study population was 45% female and 41% black with mean age of 61 years. Mean HbA1c was 8.0% and there were 2.3 wounds per individual (310 wounds total). Of all measures assessed, only HbA1c was significantly associated with wound-area healing rate. Specifically, for each 1.0% point increase in HbA1c, the daily wound-area healing rate decreased by 0.028 cm2/day (95% CI: 0.003, 0.0054, p=0.027). Our results suggest that glycemia, as assessed by HbA1c, may be an important biomarker in predicting wound healing rate in diabetic patients.
doi:10.1038/jid.2011.176
PMCID: PMC3174328  PMID: 21697890
11.  The Effect of Magnetic Fields on Wound Healing 
Eplasty  2008;8:e40.
Objective: Magnets are purported to aid wound healing despite a paucity of scientific evidence. The purpose of this study was to evaluate the effect of static magnetic fields on cutaneous wound healing in an animal model. The literature was reviewed to explore the historical and scientific basis of magnet therapy and to define its current role in the evidence-based practice of plastic surgery. Methods: Standardized wounds were created on the backs of 33 Sprague-Dawley rats, which were divided into 3 groups with either a 23 gauss magnet (group 1), a sham magnet (group 2), or nothing (group 3) positioned over the wound. The rate of wound closure by secondary intention was compared between the groups. Literature review was conducted through searches of PubMed and Ovid databases for articles pertinent to magnets and wound healing. Results: Wounds in the magnet group healed in an average of 15.3 days, significantly faster than those in either the sham group (20.9 days, P = .006) or control group (20.3 days, P < .0001). There was no statistically significant difference between the sham and control groups (P = .45). Conclusions: An externally applied, low-power, static magnetic field increases the rate of secondary healing. Review of the literature reveals conflicting evidence regarding the use of magnetic energy to aid the healing of bone, tendon, and skin. Level I studies are lacking and difficult to execute but are needed to define conclusively the role of magnets in clinical practice.
PMCID: PMC2490801  PMID: 18725953
12.  Viability of split-thickness skin grafts attached with fibrin glue. 
Full-thickness, circular, cutaneous wounds (4 cm diameter) were created on metacarpi and metatarsi of 5 horses. On day 6, all 4 wounds on each horse received a stored autogenous split-thickness sheet graft. Grafts were obtained from the horse's ventrolateral thorax with a pneumatic dermatome at the time the cutaneous wounds were created. Grafts were coapted to the granulation bed of 2 wounds of each horse with fibrin glue. Grafts were coapted to the cutaneous margin of all 4 wounds of each horse with cyanoacrylate glue. Bandages were changed daily until the study ended at 14 d. When the bandages were changed, ointment containing neomycin, polymyxin B, and bacitracin was applied to all wounds. The viable area of graft was measured on post-grafting d 14 and calculated with a micro-processor. Split-thickness sheet-grafts attached to granulation beds on the metacarpi and metatarsi with fibrin glue had no greater survival than did grafts attached without fibrin glue (P > 0.05).
PMCID: PMC1263823  PMID: 8785723
13.  Modalities for the Assessment of Burn Wound Depth 
Objective: Burn wound depth is a significant determinant of patient treatment and morbidity. While superficial partial-thickness burns generally heal by re-epithelialization with minimal scarring, deeper wounds can form hypertrophic or contracted scars, often requiring surgical excision and grafting to prevent a suboptimal result. In addition, without timely intervention, more superficial burn wounds can convert to deeper wounds. As such, the rapid and accurate assessment of burn wound depth is a priority in treating burn-injured patients. The object of this article is to review current research on modalities useful in the assessment of burn wound depth with emphasis on the relative costs and benefits of each technique. Methods: PubMed and Cochrane computerized databases were used for data retrieval, using the search terms “burns,” “burn wounds,” “burn depth,” “burn depth measurement,” and “burn depth progression.” In addition, bibliographic references from prior reviews of burn depth were reviewed. All peer-reviewed, English-language articles relevant to the topic of burn depth measurement were reviewed, including those focusing on animal and human populations. Where appropriate, conclusions drawn from review articles and expert analyses were included. Results: Although bedside evaluation remains the most common modality of diagnosing the depth of burn wounds, recent technological advances have broadened the scope of depth assessment modalities available to clinicians. Other depth assessment techniques include biopsy and histology, and perfusion measurements techniques such as thermography, vital dyes, indocyanine green video angiography, and laser Doppler techniques. Conclusion: Of the depth assessment modalities currently used in clinical practice, LDI and ICG video angiography offer the best data-supported estimates of accuracy. Until the future of new modalities unfolds, a combination of clinical evaluation and another modality—thermography, biopsy, or, ideally, ICG video angiography or LDI—is advised to best assess the depth of acute burn wounds.
PMCID: PMC1687143  PMID: 16921415
14.  Use of Platelet Rich Plasma Gel on Wound Healing: A Systematic Review and Meta-Analysis 
Eplasty  2011;11:e38.
Objective: Autologous platelet rich plasma is an advanced wound therapy used in hard-to-heal acute and chronic wounds. To better understand the use and clinical outcomes of the therapy, a systematic review of the published literature in cutaneous wounds was performed. Methods: Electronic and hand searches for randomized controlled trials and comparative group studies using platelet rich plasma therapy in cutaneous wounds and published over the last 10 years was conducted. Eligible studies compared the treatment to standard care or other interventions. All citations were screened and eligible studies were assessed for validity, quality, and bias using accepted scoring methods. The primary outcomes were effect of platelet rich plasma and control wound care on wound healing and related healing measurements. Secondary outcomes related to healing such as infection, pain, exudate, adverse events, and quality of life were also considered. The meta-analysis utilized appropriate statistical methods to determine the overall treatment effect on chronic and acute wound healing and infection. Results: The search terms resulted in 8577 citations and after removing duplicates and screening for protocol eligibility, a total of 24 papers were used. The meta-analysis of chronic wound studies revealed platelet rich plasma therapy is significantly favored for complete healing. The meta-analysis of acute wounds with primary closure studies demonstrated that presence of infection was reduced in platelet rich plasma treated wounds. Conclusions: This systematic review and meta-analysis of platelet rich plasma therapy in cutaneous wounds showed complete and partial wound healing was improved compared to control wound care.
PMCID: PMC3174862  PMID: 22028946
15.  ABC/2 for Rapid Clinical Estimate of Infarct, Perfusion and Mismatch Volumes 
Neurology  2009;72(24):2104-2110.
Background
Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometrical models generated accurate estimates of these volumes.
Methods
Acute diffusion weighted image (DWI) and perfusion (mean transit time, MTT) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as (MTT-DWI)/DWI ≥ 0.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B and C. Geometrical estimates of sphere, ellipsoid, bicone and cylinder were compared to planimetric volume by least-squares linear regression.
Results
The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16 95% confidence interval (95%CI) 0.94 to 1.38; R2 = .91, p=0.001) and MTT (slope 1.11, 95%CI 0.99 to 1.23; R2 = .89, p=0.001). The intra-rater and inter-rater reliability for ABC/2 was high for both DWI (.992 and .965) and MTT (.881 and .712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95%CI 0.98 to 1.19; R2 = .74, p=0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%
Conclusions
Of the models tested, ABC/2 is reproducible, accurate and provides the best simple geometric estimate of infarction and MTT volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment.
doi:10.1212/WNL.0b013e3181aa5329
PMCID: PMC2697964  PMID: 19528517
Cerebrovascular Accident; Infarction; Estimation Techniques; Computed Tomography Scanners; Magnetic Resonance Imaging
16.  ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes 
Neurology  2009;72(24):2104-2110.
Background:
Rapid and easy clinical assessments for volumes of infarction and perfusion mismatch are needed. We tested whether simple geometric models generated accurate estimates of these volumes.
Methods:
Acute diffusion-weighted image (DWI) and perfusion (mean transit time [MTT]) in 63 strokes and established infarct volumes in 50 subacute strokes were measured by computerized planimetry. Mismatch was defined as MTT/DWI ≥ 1.2. Observers, blinded to planimetric values, measured lesions in three perpendicular axes A, B, and C. Geometric estimates of sphere, ellipsoid, bicone, and cylinder were compared to planimetric volume by least-squares linear regression.
Results:
The ABC/2 formula (ellipsoid) was superior to other geometries for estimating volume of DWI (slope 1.16, 95% confidence interval [CI] 0.94 to 1.38; R2 = 0.91, p = 0.001) and MTT (slope 1.11, 95% CI 0.99 to 1.23; R2 = 0.89, p = 0.001). The intrarater and interrater reliability for ABC/2 was high for both DWI (0.992 and 0.965) and MTT (0.881 and 0.712). For subacute infarct, the ABC/2 formula also best estimated planimetric volume (slope 1.00, 95% CI 0.98 to 1.19; R2 = 0.74, p = 0.001). In general, sphere and cylinder geometries overestimated all volumes and bicone underestimated all volumes. The positive predictive value for mismatch was 92% and negative predictive value was 33%.
Conclusions:
Of the models tested, ABC/2 is reproducible, is accurate, and provides the best simple geometric estimate of infarction and mean transit time volumes. ABC/2 has a high positive predictive value for identifying mismatch greater than 20% and might be a useful tool for rapid determination of acute stroke treatment.
GLOSSARY
= cerebral blood flow;
= cerebral blood volume;
= confidence interval;
= diffusion-weighted image;
= field of view;
= intracerebral hemorrhage;
= middle cerebral artery;
= mean transit time;
= perfusion-weighted imaging;
= region of interest;
= echo time;
= repetition time.
doi:10.1212/WNL.0b013e3181aa5329
PMCID: PMC2697964  PMID: 19528517
17.  CICATRIZATION OF WOUNDS  
1. A method for measuring the area of a wound not geometric in form is described. 2. The rate of cicatrization of a wound is greater at the beginning than at the end of the period of repair. It depends on the area rather than on the age of the wound. There is a constant relation between the size of a wound and the rate of cicatrization. The larger the wound the greater is the rate of cicatrization. Two wounds of different size have a tendency to become equal. 3. The rate is proportional to the area, but diminishes less rapidly than the area. 4. The process of contraction is the more important factor in the repair of a wound. Epidermization completes the work of contraction. After the wound is healed, the cicatrix as a rule expands. 5. The curve representing the diminution of the size of an aseptic wound while it cicatrizes is regular and geometric.
PMCID: PMC2125470  PMID: 19868052
18.  A Comparison of Survival and Secondary Contraction in Expanded Versus Conventional Full-Thickness Skin Grafts: An Experimental Study in Rats 
Eplasty  2012;12:e20.
Aim: The aim of this experimental study is based on a comparison between the effect of expanded versus nonexpanded full-thickness skin grafts (FTSGs) on survival and secondary wound contraction. Methods: A total of 20 quadrangular-shaped, full-thickness skin defects with dimensions of 2 × 3 cm were created on the backs of 10 rats. Two groups were specified in this study depending on the coverage of the aforementioned defect areas using expanded versus conventional full-thickness grafts (n = 10 per group). The survival area of each graft and the amount of graft/wound contraction (secondary contraction) were measured by computerized planimetry on days 0, 7, 30, and 90. Results: The mean graft areas achieved were 5.8 ± 0.6, 4.2 ± 1.5, and 1.2 ± 1.1 cm2 (P < .001) in the expanded FTSGs group and 5.3 ± 0.9, 3.3 ± 1.3, and 0.98 ± 0.8 cm2 (P < .001) in the nonexpanded FTSGs group on days 7, 30, and 90, respectively. Graft area reductions (secondary contraction) were 1.7 ± 0.9 and 2.1 ± 1.2 cm2 (P = .8) on day 30 and 2.1 ± 1.3 and 2.86 ± 0.8 cm2 (P = .3) on day 90 in the expanded and nonexpanded groups, respectively. Conclusion: According to this study, FTSGs that were harvested from tissue expansion revealed biological behaviors that were comparable with those of conventional grafts.
PMCID: PMC3346212  PMID: 22582117
19.  The Effects of Supplemental Zinc and Honey on Wound Healing in Rats 
Objective(s)
Clinicians have long been searching for ways to obtain "super normal" wound healing. Zinc supplementation improves the healing of open wounds. Honey can improve the wound healing with its antibacterial properties. Giving supplemental zinc to normal rats can increase the wound tensile strength. This work is to study the concurrent effects of zinc and honey in wound healing of normal rats.
Materials and Methods
One hundred and seventy two young rats were randomly divided into four groups: control, zinc-supplement, applied honey, zinc-supplement and applied honey. Two areas of skin about 4 cm² were excised. The wound area was measured every 2 days. After 3 weeks, all animals were killed and tensile strength of wounds, zinc concentration of blood and histological improvement of wounds were evaluated. The results were analyzed using two-way ANOVA and the mean differences were tested.
Results
It was found that honey could inhibit the bacterial growth in skin excisions. The tensile strength was increased significantly in the second to fourth groups at 21st day (P< 0.001). Also there was a significant increase in tensile strength at the same time in the fourth group. The results of the histological study showed a considerable increase in the collagen fibers, re-epithelialization and re-vascularization in the second to fourth groups.
Conclusion
The results of the present study indicate that zinc sulfate could retard re-epithelialization, but when used with natural honey (administered topically) it could have influent wound healing in non-zinc-deficient subjects as well.
PMCID: PMC3586837  PMID: 23493488
Honey; Spectrophotometry; Tensile strength; Wound healing; Zinc Sulfate
20.  Healing of cutaneous wounds in the common garter snake (Thamnophis sirtalis). 
Healing of cutaneous wounds was studied in groups of common garter snakes (Thamnophis sirtalis) held at 13.5 degrees C, 21 degrees C and 30 degrees C. Linear unsutured incisions and circular excisional wounds were evaluated two, five, and ten days after surgery, while linear sutured and unsutured incisions and circular and square excisional wounds were studied three and six weeks after wound production. The sequence of events during healing was the same for all experimental situations. The epithelial margins of the wounds moved freely over exposed epaxial muscle until an exudate of fibrin and inflammatory cells caused adhesion. Heterophils and macrophages were present two days after wounding. Heterophils were present throughout the wound while macrophages were concentrated in areas containing fibrin and proteinaceous exudate. Fibroblasts moved laterally into the wound from the adjacent dermis producing a flat dermal scar oriented parallel to the wound surface. Epithelial cell hypertrophy and hyperplasia occurred in a zone extending up to 1.5 mm from the margin of the wound. A tongue of flattened epithelial cells extended across the wound surface, mingling with the superficial crust and migrating over eosinophilic fibrillar material. Maturation of the new epithelium, indicated by formation of a distinct basal layer, rounding of superficial cells and keratin production, began at the wound margins before the epithelial spurs linked. The epithelium over healed wounds appeared normal, but the dermis did not reorganize to form scales. Reptilian and mammalian healing differ in the character of the inflammatory reaction, the pattern of fibroplasia, and the interaction between epithelial and dermal repair.
Images
PMCID: PMC1255409  PMID: 3349388
21.  Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers 
Wound Repair and Regeneration  2011;19(3):302-308.
We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5–10.0 cm2 chronic diabetic neuropathic foot ulcers that healed <30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (−0.06±0.32 to 0.78±1.53, p=ns) but both FCG (−0.08±0.61 to 1.97±1.77, p<0.002) and GAM501 (−0.02±0.58 to 1.46±1.37, p<0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.
doi:10.1111/j.1524-475X.2011.00669.x
PMCID: PMC3443373  PMID: 21371164
22.  Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves. 
British Heart Journal  1992;67(2):193-199.
Orifice areas calculated by the continuity and Gorlin equations have been shown to correlate well in vivo. The continuity equation, however, gives underestimates compared with the Gorlin formula and it is not clear which is the more accurate. Both equations have therefore been tested against maximal orifice area measured by planimetry in eight prepared native aortic valves and four bioprostheses. A computer controlled, ventricular flow simulator (cycled at 70 beats/min) was used at five different stroke volumes that gave cardiac outputs of 2.8 to 7.0 l/min. The mean difference between measured and estimated orifice area was zero for the continuity equation, but -0.14 cm2 for the conventional Gorlin formula. Thus the Gorlin formula tended to give overestimates compared with both measured area and area estimated by the continuity equation, probably because of the effect of pressure recovery. When predictive equations derived from these data were tested, residual standard deviations were around 0.3 cm2 at all stroke volumes for the continuity equation, around 0.2 cm2 for the invasive Gorlin formula, and between 0.2 and 0.4 cm2 for the modified Gorlin formula. These results suggest that estimates of orifice area in an individual valve as judged by any of the equations tested should be seen as a guide to rather than as a precise measure of actual orific area.
Images
PMCID: PMC1024754  PMID: 1540443
23.  Evaluation of Wound Healing Effect of Topical Phenytoin on Excisional Wound in Albino Rats 
Objectives:
Wound healing is a significant healthcare problem in today’s medical practice. Despite extensive treatment modalities that are supposed to hasten the wound healing process, the outcomes of existing methods are far from optimal. One such agent that has been tried previously and found controversial in wound healing is phenytoin. In this study, the wound-healing efficacy of phenytoin was investigated in albino rats.
Materials and Methods:
20 male Wistar albino rats were subjected to excisional wounds measuring 500 mm2 on the back and then randomized to two groups (n = 10): Control group (A) and treatment group (B). The control group received no drug treatment till the end of the study. 1% Phenytoin cream was applied to the wounds of rats in the group B and continued till the 16th day of the study. The areas of wounds were measured on the Days 4, 8, 12, and 16 of the experiment. The percentages of the healing wounds were calculated by Walker formula after measurement of the wound area. The total number of days required for complete epithelization of wounds was noted in each group.
Results:
Statistically significant reduction (P < 0.05) in average wound area was seen in Group B (P value=0.0017, 0.0001, 0.0001, 0.0001), respectively, on Days 4, 8, 12, and 16 of the experiment in comparison to Group A. The average number of days required for complete epithelization of wound area was less in Group B as compared to Group A (P=0.0120). The difference was statically significant
Conclusion:
In the present study, topical phenytoin accelerated healing of excisional wound in albino rats.
doi:10.4103/0975-1483.62215
PMCID: PMC3035887  PMID: 21331193
Phenytoin cold cream; area of wound healing; percentage healing of wound area; complete epithelization
24.  In vivo analysis of wound healing by optical methods 
The analysis of wound healing is important for the therapy control and for the development of drugs stimulating the healing process. Wounds cause damage to the skin barrier. A damaged stratum corneum leads to an increased water loss through the skin barrier. The standard measuring procedure for characterization of wound healing is the measurement of transepidermal water loss (TEWL). The disadvantage of this method is that it can be easily disturbed by the perspiration of the volunteers and by topically applied substances, for instance wound healing creams.
In the study presented, in vivo laser scanning microscopy and optical coherent tomography were compared concerning the application for their analysis of wound healing processes. The laser scanning microscopy allows the analysis of the healing process on a cellular level. The course of wound healing determined by laser scanning microscopy was correlated with numerical values, allowing the numerical characterization of the wound healing process.
PMCID: PMC2831523  PMID: 20204112
in vivo laser scanning microscopy; optical coherent tomography; transepidermal water loss; suction blister technique; wound healing analysis
25.  The Cdk5 inhibitor olomoucine promotes corneal debridement wound closure in vivo 
Molecular Vision  2008;14:542-549.
Purpose
To investigate the effect of the Cdk5 inhibitor olomoucine on corneal debridement wound healing in vivo.
Methods
Corneal debridement wounds of 1.5 mm were made on the ocular surface of CD-1 mice. A 20 μl drop of 15 µM olomoucine in 1% DMSO was applied to the wound area immediately after wounding and again after 6 h. Control mice received identical applications of 1% DMSO. Mice were euthanized after 18 h, two weeks, and three weeks for evaluation of wound healing and restratification. Corneas were stained with Richardson’s dye, photographed, and processed for histology and immunofluorescence as whole mounts or paraffin sections. The remaining wound area at 18 h was measured by image analysis. Scratch wounded cultures of human corneal-limbal epithelial cells (HCLE) were used to examine the effect of olomoucine on matrix metalloproteinase (MMP) expression in vitro. MMP-2 and MMP-9 were detected by immunofluorescence and immunoblotting.
Results
Olomoucine treatment significantly enhanced corneal wound closure without increasing inflammation or infiltration of polymorphonuclear leukocytes 18 h after wounding (p<0.05). The increased localization of MMP-9 within epithelial cells at the wound edge was further enhanced by olomoucine while the expression of MMP-2 was reduced. Olomoucine treatment of scratch wounded HCLE cells produced similar changes in MMP-9 and MMP-2 expression. The examination of treated corneas two and three weeks after wounding showed normal epithelial restratification with no evidence of inflammation or stromal disorganization.
Conclusions
Topical application of olomoucine in 1% DMSO significantly enhances closure of small epithelial debridement wounds without increasing inflammation or impairing reepithelialization.
PMCID: PMC2274924  PMID: 18385789

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