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[The laser therapy of wound complications with partial dehiscence following gynecologic operations. Clinical studies].

Clinical studies were carried out on 160 women, aged from 26 to 58 years, with partial wounded dehiscence after gynecological operations. The influence of helium neon laser energy with densities of power of 100, 90, 80, 70, 50 m W/cm2 at exposition time of the field of 1.5 min was studied in respect to anesthetic and antiinflammatory effects, initial clearing of devitalized tissues with the appearance of young granulation tissue on the wounded defects till the final healing of the complicated operative wounds. Resorption of inflammatory tissue changes and analgetic effect occurred for the shortest periods of treatment in patients with wounded dehiscences, irradiated with densities of power of laser irradiation of 90 mW/cm2. Initial clearing of devitalized tissues with appearance of young granulation tissue was achieved by the smallest number of irradiations with density of power of laser irradiation within the ranges of 90-70 mW/cm2. The highest alternatively relative part of healed partial wounded dehiscences for a period of 5-10 days of treatment was achieved by the applied density of power of laser irradiation within the ranges of 100-70 mW/cm2. The density of power of the laser irradiation of 50 mW/cm2 was slightly effective in respect to its stimulating possibilities both at the inflammatory phase and at the phases of proliferation and reorganization of the wounded process.

Adult↗

Histological study of periradicular tissue responses to uninfected and infected devitalized pulps in dogs.

Uninfected necrotic tissue, such as that which follows a myocardial or cerebral infarct, is capable of inducing an inflammatory reaction. Eventually, the infarct is organized by granulation tissue. Why then, does uninfected devitalized pulp tissue, such as in traumatized teeth, not cause periradicular inflammation and does not become organized by granulation tissue? Four beagle dogs were used in this experiment. A total of 48 teeth, which included 24 maxillary and 24 mandibular incisors, were aseptically devitalized, leaving residual pulp tissues in the root canals, and equally divided into two groups. Group A (24 uninfected): A sterile cotton pellet was placed deep into the canal orifice before the pulp chamber and access opening were closed with a layer of zinc-oxide eugenol cement followed by glass ionomer cement. Group B (24 infected): The teeth were left open to the oral cavity for 7 days and then closed with a cotton pellet and zinc-oxide eugenol and glass ionomer cement. The animals were sacrificed one year after the experiment and prepared for histological examination of periradicular tissue responses to uninfected and infected devitalized pulp tissues. The results indicate that uninfected devitalized pulp tissues did not continuously release inflammatory mediators and cause persistent periradicular inflammation over a period of one year. However, infected devitalized pulp tissues induced various degrees of periradicular inflammation. Only the apical few millimeters of uninfected devitalized pulp tissue in the root canals were organized by granulation tissue from vital periodontal ligament tissue.

Animals↗

Macrophage aggregates in cytomegalovirus esophagitis.

Cytomegalovirus (CMV) esophagitis may be difficult to identify in small endoscopic biopsy specimens, because diagnostic CMV inclusions may be absent or hard to find. The author has noticed aggregates of macrophages in the granulation tissue and exudates of esophageal ulcers with CMV inclusions and postulated that this may be a characteristic inflammatory response to the virus, similar to that seen in herpes simplex virus (HSV) esophagitis. To test this hypothesis, 14 esophageal biopsy specimens diagnosed with CMV infection at the University of Michigan over the last 10 years were analyzed for the amount and distribution of macrophage aggregates. Twelve of 14 biopsies showed aggregates of macrophages; five had patchy aggregates of macrophages in exudates, four had a perivascular distribution of macrophages present in granulation tissue, and three had macrophages present in both exudates and granulation tissue. The number of macrophages in CMV esophagitis was generally less than in HSV esophagitis, whereas the perivascular distribution of macrophages in granulation tissue was unique to CMV esophagitis. These findings indicate that aggregates of macrophages are a characteristic of CMV esophagitis as well as of HSV esophagitis and their presence in a biopsy specimen that does not show diagnostic viral inclusions warrants further study to identify CMV or HSV.

Biopsy↗

Auricular prostheses and osseointegrated implants: UCLA experience.

A clinical study of 40 craniofacial implants placed in 13 auricular defects was conducted over a 6-year period. Implant-retained prostheses were fabricated, the implant success rate was determined, and the soft tissue responses were recorded at regular intervals. All of the implants became osseointegrated and none demonstrated failure during the study period. A five-point scale was used to record the health of the peri-implant soft tissues and the patients were followed up for up to 69 months. The results were as follows: 55.1% of the visit/sites demonstrated an absence of inflammation; 32.3% of the visit/sites demonstrated slight redness; 4.7% demonstrated red and moist peri-implant tissues; 5.5% demonstrated granulation tissue associated with the implants; and in 2.4% of the implants, infection of the peri-implant soft tissues was noted. Good patient hygiene compliance combined with thin and immobile peri-implant soft tissues resulted in minimal soft tissue complications.

Adolescent↗

Carcinoma of the neovagina: case report and review of the literature.

BACKGROUND: Carcinoma of the vagina is a rare disease, and it is even more rare in the neovagina. Nevertheless, it has been well described. The aim of this report was to analyze the reported cases and to add observations concerning a risk profile for this rare occurrence of carcinoma. CASE REPORT: The 29-year-old patient's history included congenital absence of vagina as a result of Rokitansky-Kuster syndrome. In 1987, when the patient was 17 years old, a neovagina was constructed by dissection between the bladder and the rectum, according to the Warthon method, and the apex of the neovagina was covered with Dura-mater. In 1990 the patient underwent radiation treatment with brachytherapy three times in combination with surgical treatment, because of granulation tissue in the neovagina. In 1999 several specimens of the granulation tissue were removed and histological examination showed intermediate differentiated squamous cell carcinoma. Total exenteration with pelvic and lower paraaortic lymph node dissection was performed, and the patient received a continent neobladder (Mainz Pouch I), colostoma, and sigma neovagina. Two months later in January 2000 the patient showed local recurrence and after local excision the patient received radiotherapy. The follow-up to June 2001 showed no evidence of disease. CONCLUSION: All patients with vaginoplasty should undergo regular 1-year follow-ups, including smear analysis because of the possibility of the development of carcinoma. Granulation tissue arising in a neovagina should be biopsied and no prosthesis should be used until lesions have healed completely. Patients who have undergone radiation of the neovagina carry an additional risk.

Adult↗

Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds.

In this study, we examined the impact of matrix metalloproteinases (MMP) on epithelialization, granulation tissue development, wound contraction, and alpha-smooth muscle actin (ASMA) expression during cutaneous wound repair through systemic administration of the synthetic broad-spectrum MMP inhibitor GM 6001 (N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide). Four full-thickness excisional wounds (50 mm2) on the back of 22 young female Sprague-Dawley rats, 12 treated with GM 6001 100 mg/kg and 10 with vehicle, were allowed to heal by secondary intention. GM 6001-treated wounds were minimally resurfaced with neoepithelium, despite unaltered keratinocyte proliferation in wound edges, whereas control wounds were completely covered with 3-7 cell layers of parakeratinized epithelium on post-wounding day 7. Hydroxyproline concentration, a marker of collagen, and cell proliferation in granulation tissue did not differ significantly between GM 6001-treated and control groups. Impaired wound contraction (P < 0.01) was associated with a dramatic reduction of ASMA-positive myofibroblasts in granulation tissue of GM 6001 wounds. This was not due to GM6001 blocking transforming growth factor-beta1 (TGF-beta1)-induced myofibroblast differentiation since GM 6001 did not inhibit TGF-beta1-induced ASMA expression and force generation in cultured rat dermal fibroblasts. The profound impairment of skin repair by the nonselective MMP inhibitor GM 6001 suggests that keratinocyte resurfacing, wound contraction, and granulation tissue organization are highly MMP-dependent processes.

Animals↗

[Fibrinoid and fibrinoid necrosis in the morphogenesis of chronic stomach ulcers (electron and light microscopy)].

The stomach surgically removed from 38 patients because of chronic ulcers are studied. The fibrinoid necrosis zone observed at the bottom of 30 ulcers is formed of two layers out of which the superficial layer only is necrotic while the deep one represent a fibrinoid swelling. The latter consists of the network of collagen fibers and fibrin elements with surviving connective tissue cells. Two processes going into the opposite directions take place on the border between the fibrinoid zone and granulation tissue: the spread of the fibrinoid to the granulation tissue and its organization by the granulation tissue elements. Interrelationship between these processes as well as the intensity of the fibrinoid necrosis rejection from the surface determines the thickness of the zone. Fibrinoid prevents the stomach wall digestion but at the same time inhibits the ulcer healing.

Adult↗

Experimental grafting of the round window membrane: Part I.

The histology and permeability of cats' round window membranes were described following surgical grafting with gelatin foam or fascia. An increase in the thickness of the round window membrane due to fibrosis, neovascularization, and epithelial metaplasia was observed 2 months following grafting with gelatin foam. Grafting with fascia did not increase the thickness of the round window membrane, but did form a thick layer of granulation tissue adjacent to and overlying the window membrane, with occasional adhesions between. The layer of granulation tissue consisted of cuboidal or columnar ciliated epithelial cells, fibrous tissue, lipid, and undigested grafted material. The granulation tissue did not always completely cover the round window membranes.

Animals↗

Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol.

To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, 1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, 2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, 3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and 4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats. These observations indicate that diabetes-induced increases in regional blood flow, 131I-BSA permeation, GFR, and urinary protein excretion can be markedly reduced or normalized by consumption of myo-inositol-supplemented diets that raise plasma myo-inositol levels approximately fivefold. The failure of the 2% myo-inositol diet to normalize GFR and blood flow and albumin permeation in several tissues despite markedly elevated plasma myo-inositol levels and normal or elevated tissue myo-inositol levels indicates that if vascular functional changes in these tissues are linked to altered myo-inositol levels, they are resistant to normalization by elevation of plasma myo-inositol levels. These results suggest that other factors independent of changes in relative or absolute tissue myo-inositol levels may play an important role in the pathogenesis of diabetes-induced vascular functional changes in these tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunofluorescent identification of fibronectin and fibrinogen/fibrin in experimental myocardial infarction.

Distribution of fibrinogen/fibrin and fibronectin in regions of experimental myocardial infarction were studied by the immunofluorescence technique. Distinct from normal myocardium 3 and 12 to 24 h after coronary artery ligation infiltration of necrotized cardiomyocytes by fibrinogen/fibrin and plasma fibronectin was detected. Fibrinogen/fibrin and plasma fibronectin constitute "primary matrix" of granulation tissue. On the third day after experimental infarction, synthesis of cellular fibronectin begins. Its content in the extracellular matrix (ECM of granulation tissue significantly increases on days 7 to 15. The amount of fibronectin in the ECM of developing scar tissue dramatically decreases 30 days after infarction, Fibrinogen/fibrin was continually identified in granulation tissue in zones of myocardial infarction. However, its amount in the ECM of developing scar tissue gradually decreased.

Animals↗

Granuloma pouch assay. I. Induction of ouabain resistance by MNNG in vivo.

Growth of granulation tissue was induced in rats inside a subcutaneous air pouch by injection of croton oil. Granulation tissue, isolated and cultured in vitro, gave satisfactory and reproducible cloning efficiency of fibroblast-like cells. This experimental model system was used to study the induction of autosomal point mutations in vivo leading to ouabain resistance. For this purpose the mutagen MNNG was administered in the granuloma pouch, and the formation of ouabain-resistant clones was determined in vitro. Various application schedules, expression times in vivo and selective conditions in vitro were evaluated. The highest frequencies of ouabain-resistant clones were found when MNNG was injected into the pouch 24--48 h after induction of granulation tissue, followed by an expression time in vivo of 24--48 h. No ouabain-resistant clones were formed by cells isolated from untreated rats or from animals receiving the highest tolerated doses of MNNG per os or by intraperitoneal injection. The potential usefulness of the granuloma pouch assay for the evaluation of mutagenic and carcinogenic substances in vivo is discussed.

Animals↗

Oxygen and carbon dioxide tensions in healing tissue.

Oxygen and carbon dioxide tensions were studied in experimental granulation tissue growing into a thin sheet of cellulose sponge. Both the base-line PO2 and the response in oxygen tension to pure O2-breathing were highest in 7-day-old implants, displaying a slight decrease as the healing progressed. Lower tissue carbon dioxide tensions and oxygen consumption rates were noticed also in older implants. The oxygen tension gradient between the wound fluid and the edge of the granulation tissue in cylindrical cellulose sponge implants decreased as the healing progressed.

Animals↗

Covered, retrievable, expandable urethral nitinol stent: feasibility study in dogs.

PURPOSE: To evaluate the feasibility of using a retrievable urethral stent and to evaluate whether granulation tissue resolves after stent removal in a canine urethra. MATERIALS AND METHODS: Polyurethane-covered retrievable 0.10-mm-thick (n = 11) or 0.15-mm-thick (n = 10) nitinol wire stents were placed in the urethras of 20 dogs. In one dog, a second stent was placed in the urethra because of complete migration of the first stent into the urinary bladder. The stents were removed with retrieval hook wires 4 weeks (n = 10) and 8 weeks (n = 10) after placement. Fourteen dogs were sacrificed just after stent removal, and the other six dogs were sacrificed 2 weeks after stent removal. Information concerning procedure success, stent migration, and tissue response was obtained. RESULTS: Stent placement was technically successful in all dogs. Follow-up urethrograms showed partial (n = 4) or complete (n = 1) stent migration. Stent removal failed in two dogs due to partial or complete migration. Granulation tissue was observed at both ends of the stent in 17 dogs. Urethrograms and urethral specimens obtained 2 weeks after stent removal showed diminished granulation tissue and decreased thickness of the papillary projections of the epithelium compared with results obtained immediately after stent removal. CONCLUSION: Although some design modifications are necessary to reduce current complications, the polyurethane-covered retrievable nitinol stent seems feasible for use in the urethra. Stent-induced granulation tissue formation improved after stent removal.

Alloys↗

[Current methods of morphological and hemostasiological analysis of reparative process in wounds making use of information programs].

Objective rapid morphological and hemostasiological methods for evaluating the reparative process in the wound making use of PC software have been developed for identification of stages of reparative process in the wound under conditions of modern surgical service. Cytran consultative software has been developed for evaluation of phases of reparative reaction in the wound. Coagulogram consultative software was used for identification of reparative reaction phases in the wound from hemostasiological changes in tissue factors of granulation tissue in the wound. Cytran and Coagulogram software were used under clinical conditions in 105 patients with open, suppurative, and burn wounds for characterization of the reparative reaction phases.

Blood Coagulation↗

Development of new wound dressing composed of spongy collagen sheet containing dibutyryl cyclic AMP.

Although cyclic AMP has been considered to regulate cell proliferation, the mechanism of this function is largely unknown. Recent studies suggest that cyclic AMP promotes the proliferation of skin cells in a dose-dependent manner. An ointment containing dibutyryl cyclic AMP has been used in the treatment of skin ulcers and found to be effective in promoting tissue repair. To search more efficacious wound management, the authors developed a new wound dressing composed of a spongy atelo-collagen sheet containing dibutyryl cyclic AMP. This wound dressing was evaluated in two types of animal tests. One is the application of the wound dressing to a full-thickness skin defect in order to evaluate the granulation tissue formation and the wound size reduction. The wound dressing was found to promote the granulation tissue formation and naturally reduce the wound size. The other test was the application of the wound dressing to the full-thickness skin defect, leaving behind a skin island in a central portion, in order to evaluate the epithelialization. This skin island left in a full-thickness skin defect was extremely enlarged. The enlargement of the skin island seems to be related to the epithelialization from the margin of the skin island as well as by the expansion of a skin island induced by contraction of the developed granulation tissue in the surrounding wound area. These results suggest that an atelo-collagen spongy sheet containing dibutyryl cyclic AMP is effective in promoting the granulation tissue formation and epithelialization.

Animals↗

[Mechanism of action of pronase on chronic proliferative inflammation including granuloma angiogenesis in mice].

Effects of pronase on granuloma angiogenesis and granulation tissue formation were investigated using granuloma pouches induced by Freund's complete adjuvant containing 0.1% croton oil in normal and alloxan diabetic mice. Granuloma angiogenesis was measured by the carmine dye infusion method. Pronase (2 mg/kg/day) was daily injected into the pouch for 3 to 7 days, and its effects were compared with those of hydrocortisone (1 mg/kg/day) and indomethacin (2 mg/kg/day). Pronase significantly inhibited the wet weight of pouch granuloma, mainly in the later stage of inflammation in normal mice. But it failed to decrease both the content of hydroxyproline in granuloma and the amount of carmine dye infused into the newly developed capillaries, whereas hydrocortisone and indomethacin significantly decreased them. In pathohistological findings, pronase increased angiogenesis and subsequently enhanced the repair rate by a dense arrangement of mature connective tissue, although hydrocortisone and indomethacin markedly decreased angiogenesis. In alloxan diabetic mice, granulation tissue was significantly produced less than that in normal mice. Hydrocortisone potentiated the decrease in granulation tissue formation of diabetic mice, whereas pronase did not markedly affect on it. The ratios of the amount of capillaries to the wet weight of granuloma tissue in pronase-treated mice were higher than those of control mice. Pronase was concluded to enhance angiogenesis in granuloma tissue in addition to the activation of collagenolysis and proteolysis.

Animals↗

Cytotoxicity and immunogenicity of SACCHACHITIN and its mechanism of action on skin wound healing.

SACCHACHITIN membrane, a weavable skin substitute made from the residual fruiting body of Ganoderma tsugae, has been demonstrated to promote skin wound healing. Prior to its clinical application, it is critical to learn more about any possible cytotoxicity, immunogenicity, or allergy response, and at least some of its mechanism(s) of action(s). In the present studies, it has been found that SACCHACHITIN suspension at less than 0.05% shows no cytotoxicity to the primary culture of rat fibroblasts. However, at higher concentrations (> or = 0.1%), it does reduce the growth of fibroblasts, based on MTT assays. This might be caused by positive charges on chitin molecules that are too strong, and may be harmful to the cell membrane. SACCHACHITIN showed no immunogenicity after it was inoculated into rats three times; however, the unmodified, purified rabbit type I and type II collagens did. Subcutaneous injection of SACCHACHITIN suspension into rats showed no gross allergic responses on skin. Nevertheless, it did cause local acute inflammation, as observed by histological investigation. This is similar to what occurred in the wound site covered with SACCHACHITIN membrane. The chemotactic effect of SACCHACHITIN was exhibited in both intact and wounded skin tissues. This may be one of the initial beneficial effects of SACCHACHITIN membrane to wound healing. The rapid acute inflammatory process was followed by the appearance of angiogenesis and granulation tissue formation, which occurred earlier than it normally would. Coverage of the wound area with SACCHACHITIN membrane also induced an earlier formation of scar tissue to replace the granulation tissue. A 1.5 x 1.5 cm(2) wound area covered by SACCHACHITIN completely healed by 21 days, while that covered with cotton gauze did not. Therefore, SACCHACHITIN is a safe biomaterial for use as a wound dressing for skin healing. Its promoting action for wound healing might be due to its chemotactic effect for inflammatory cells. This, in turn, may facilitate subsequent angiogenesis, granulation tissue formation, and faster new tissue formation, leading to faster wound healing.

Animals↗

The effect of methylprednisolone and vitamin A on wound healing. II.

The effect of 100 IU and 1000 IU vitamin A on sponge-induced granulation tissue formation was studied in methylprednisolone-treated and non-treated rats. Collagen accumulation in the new granulation tissue and plasma vitamin A were determined in the animals. Vitamin A severely affected the weight gain of the rats. Methylprednisolone reduced the content of collagen in granulation tissue. This effect of methylprednisolone was not reversed by simultaneous administration of 100 iU or 1000 IU vitamin A.

Animals↗