| Background:Refractory chronic skin ulcer is caused by the factors, such as injury, burn, infections, long oppressed, diabetes, vascular lesions, neuropathy, and long-term radiation. With a long time of wound, it has necrosis and defects of the skin, subcutaneous tissue, and even muscle, bone, complicated by chronic infection. In general, elderly adults suffer form this disease easier than the young, and lower limbs its high risk site.Refractory chronic skin ulcer is a clinical common disease. According to one research on more than30000cases of hospitalized patients in our country,1.5%-3.0%of the patients need hospital treatment. A large number of refractory chronic skin ulcer patients are secondary to diseases, diabetes, and radiation therapy, and scattered in internal medicine, radiation therapy or surgery outpatient service and related professional make a diagnosis and give treatment, which produced great difficulty in statistics, so the actual incidence of a disease is higher. The oppressive, diabetic, radioactive and other kinds of proportion of ulcer will increase accordingly.Refractory chronic skin ulcer belongs to chronic diseases. It has no immediate threat to the patient’s life, but due to the course of months or even years and ten years, so the disease seriously affect the rehabilitation of the primary disease and the quality of daily life, and increase the economic burden of patient’s family. In addition, if the wound infections spread, it can lead to complications such as sepsis, not only increasing the primary disease but also endangering the patient lives. Refractory chronic skin ulcer is complex and the type is various, which make it difficult to cure. In addition to the treatment on cause, it is very important to local drug treatments. At present, many local treatment of chronic skin ulcers, such as drug therapy, biological dressing, transgenic therapy, methods of traditional Chinese medicine treatment, but very satisfactory therapy and drug have not been found. Especially for refractory chronic skin ulcer, some protective agents, antibiotics, vitamins, trace elements, is widely used, but the role of these drugs promote wound healing is limited. Laser, light treatment methods, such as operation requirements is very high, excessive exposure to the sun is easy to cause cancer. For refractory chronic skin ulcer, most surgeons preferred surgical clinical surgical treatment to eliminate the wound, but a lot of these patients combined with serious cardiovascular internal medicine diseases, such as surgery contraindications which limits the implementation of surgery, and these methods to make a lot of patients psychologically difficult to accept surgery. With the development of molecular biology, especially the further study of various growth factors makes into a new stage wound repair, how to promote the wound repair for treatment of refractory chronic skin ulcer has been continuously explore problems.Granulocyte and macrophage colony stimulating factor (GM-CSF) as a member of the complex network of cytokines, has extensive role. With the continuous progress of basic research and clinical research on GM-CSF, recombinant human granulocyte macrophage colony stimulating factor has. been widely used in clinical treatment of various fields, such as tumor after radiotherapy and chemotherapy, can be used as the drugs increased leukocyte; Bone marrow transplantation, can be applied to promote the recovery of hematopoietic function;And can be used for the treatment of trauma due to a variety of causes,clinically used to aid in the treatment of hepatitis b and antitumor and so on. At present, the topic of hGM-CSF for all kinds of wounds, especially the treatment of chronic wounds, have been focused on in recent years.Alginate dressings polysaccharide is a kind of similar to cellulose, which cannot dissolve itself. Its raw material is extracted from seaweed algae protein acid, at the time of making dressing, it is converted into a calcium salt. Alginate has strong absorbency. According to research, it can absorb the equivalent of20times its own weight of the liquid, and can effectively control the drainage and extend the use time of dressing. Contacting with the wound, calcium ion replacement can wound drainage of sodium ions, and the alginate form a layer on the surface of the wound after reaction and stable network gel. The gel can keep wounds moist and non-stick wound, cut off from the outside environment, and form a closed around the wound, which can accelerate wound granulation tissue and blood capillary growth, promote wound repair of cell proliferation, and accelerate the epithelium of the wound.Objective:According to characteristics of refractory chronic skin ulcer, for eliminating skin defect ultimately, the alginate dressings and granulocyte-macrophage stimulating factor (hGM-CSF,) are applied in the treatment of refractory chronic skin ulcer, to evaluate the effectiveness of the treatment of wounds and promoting healing, discuss on its mechanism of promoting the healing of the cell biology studies the synergy, make objective evaluation on the patients, and determine the best application methods.Methods:On the principle of voluntary, patients are choosen in October2009-March2012in Jinan Central Hospital of hospitalized patients with painless refractory chronic skin ulcer, mainly including bedsore, varicose veins ulcers, diabetic foot, etc. The standard included in:aged18to60, wound by conventional debridement and anti-inflammatory treatment for more than1month to heal the trauma, and wound area10-100cm2. Exclusion criteria:(1) After strict control, fasting blood glucose>10.0mmol/L(2)Serious cardiac insufficiency (cardiac insufficiency III level and above), severe renal insufficiency(renal insufficiency II and above), serious wasting disease (malignant tumor, tuberculosis, chronic atrophic gastritis, and systemic lupus erythematosus), severe malnutrition, peripheral vascular disease patients, patients with acute infection and acute metabolic disorders.(3) the patients with pregnancy or lactation.(4) poor compliance.(5) the dying cannot achieve the experimenter. Patients signed informed consent rear accessibility test.A total of60patients Meet the inclusion criteria, including male35cases,25cases of female, aged20to75years old. The cases include25cases of bedsore (11cases of diabetes, cerebral infarction sequela14cases),12cases of varicose ulcer,23cases of diabetic foot. The ulcer area is11-85cm2, an average of17.2±8.0cm2. Course:1-3.5months (1.8±2.1) months on average. Depth of the ulcer were in subcutaneous soft tissue layer, and wound secretion before using this drug inspection were reported positive bacteria.According to the principle of random grouping, the patients were divided into alginate dressings and hGM-CSF combined treatment group (group A), hGM-CSF treatment group (group B)and the conventional treatment group (group C). The age, sex, disease, the course of the disease, ulcer area of comparison of three groups were no statistically significant difference.When dressing, the patients were removed the outer covering, cleaned up the wound with saline rinse, removed of necrotic tissue and wound through standardized clinical pathway, and wiped dry with sterile cotton ball and. Daily dressing for wound exudation larger, when ooze reduced day after treatment. Group A were applied with granulocyte-macrophage stimulating factor (hGM-CSF, changchun Kinsey pharmaceutical industry limited liability company, approval number:S20080003approved by the state and specifications for100ug rhGM-CSF/10g, molecular weight:14KD)in wound, covered with alginate dressings (British&company, the approval number:2005.2640100). Group B were applied with hGM-CSF on wound and covered the wound with petrolatum gauze. Group C were only covered with vaseline gauze on the wound. After the completion of each group were covered with sterile gauze bandaging appropriately. Pay attention to the aseptic operation treatment process. Three groups of patients with drug use and drug use before7th,14th,21th day observation wound exudate, granulation tissue and epithelial growth and the change of infection situation, observe whether the wound around the occurrence of skin irritation, allergic, and so on and so forth; The preparation before and7th,14th,21th day calculated between groups in patients with wound healing area, speed testing, statistical wound healing progress; The preparation before and line7th,14th day wound pain visual analogue scale (VAS) score method, The preparation before and7th,14th day patients to evaluate the curative effect; Drugs and drug use before7th,14th day to return and tissue samples, by HE staining and optical microscope each wound granulation tissue in the number of capillaries and fibroblasts. Data were used by SPSS16.0software for analysis.Results:1. At the14th and21th days, three group of patients with wound also compare the colour and lustre, granulation tissue growth rate, difference was statistically significant, group A bright red color and granulation tissue grew well, better than that of group B and group C; Group B is better than that of group C.2. At the7th,14th,21th days, the healing rate of group A were9.3±5.5%,23.2±7.7%and56.1±7.5%, the healing rate of group B were6.5±4.3%,15.3±4.9%and33.7±7.9%, the healing rate of group C were2.3±4.2%,8.5±6.9%and20.9±8.8%. The difference between three groups was statistically significant.3. At the7th,14th.21th days, the difference of each wound pain in patients with visual analogue scale between three groups was statistically significant.4. At the7th,14th days, evaluation of its effect for the treatment of patients of group A score were3.7±1.5,4.9±1.3; group B were2.4±1.2,3.8±2.0; group C were2.0±.1,2.6±1.5. The difference between three groups was statistically significant.5. At the7th,14th days, wound granulation tissue of the capillary number were compared and the difference was statistically significant. Group A is better than that of group B and group C, group B is better than that of group C.6. At the7th,14th days, wound granulation tissue into fiber cell number comparison were compared and the difference was statistically significant, group A is better than that of group B and group C, group B is better than that of group C.Conclusion:The treatment of refractory chronic skin ulcer disease, due to the complex and the various type, is difficult. At present, the treatment on the refractory chronic skin ulcer, such as medication, transgenic therapy, Chinese medicine treatment methods, is various The drugs and methods on refractory chronic skin ulcer, has always been a research hot spot.Granulocyte-macrophage stimulating factor not only has effect on promoting wound healing, as a systemic application of cytokines, but also can; become an effective and safe treatment on refractory chronic skin ulcer caused by a variety of reasons, such as deep burn wounds, venous ulcers, diabetic ulcer, stress ulcer, burn remnant wounds, etc.Alginate dressings used in refractory chronic skin ulcer, form a relatively closed environment on the wound, which can accelerate the new capillary hyperplasia, keep the moist environment, enhances regeneration ability of skin cells, accelerate the epidermal cells, and promote wound healing. In addition, the alginate dressings during dressing change significantly reduce pain, which is not easy to damage the new organization, so it is easily accepted by patients.That alginate dressings and hGM-CSF joint application in treatment of painless chronic skin ulcer, can decrease the drainage of the wound, promote the growth of granulation tissue, and accelerate again epithelial change; At the same time, the two joint application, can effectively reduce the wound pain and improve patient satisfaction, can become an effective treatment of refractory chronic skin ulcer.Alginate dressings and hGM-CSF joint application in treatment of painless chronic skin ulcer, can obviously promote wound healing. Its mechanism to promote refractory chronic skin ulcer wound has relation to capillary generation and fibroblast proliferation and migration. |
