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Bacterial colonization of airway stents: a promoter of granulation tissue formation following laryngotracheal reconstruction.

OBJECTIVE: To investigate whether airway granulation, a common occurrence during laryngotracheal reconstructive surgery and a common cause of delays in definitive treatment and treatment failure, is associated with a microbial etiology. DESIGN: Prospective case-control study. SETTING: Tertiary referral airway reconstruction unit. PATIENTS: Patients who had an airway stent as part of their treatment for laryngotracheal stenosis. INTERVENTIONS: All airway stents were sent for microbiological analysis. Information about patient demographics, lesion characteristics, and presence of airway granulation tissue at different times during treatment were obtained and correlated against the microbiological findings from airway stents. MAIN OUTCOME MEASURES: A chi2 test was used to correlate airway colonization with specific pathogens and occurrence of airway granulation. Logistic regression analysis was used to identify independent microbiological predictors of airway granulation. RESULTS: Thirty-one airway stents were removed from 26 patients. The mean (SD) age at presentation was 42 (18) years, and postintubation tracheal stenosis was the most common etiology. There were highly significant associations between stent colonization with Staphylococcus aureus and Pseudomonas aeruginosa and the occurrence of airway granulation (P<.02), and these microorganisms were independently associated with the risk of developing airway granulation. Furthermore, S aureus was associated with persistence of airway granulation on average 4 months following removal of the stent. CONCLUSIONS: Airway granulation seems to be associated not with polymicrobial airway colonization but with infection with specific pathogenic microorganisms. All patients undergoing laryngotracheoplasty should receive antibiotic prophylaxis to cover these microorganisms, and the development and use of antibiotic-impregnated airway stents should be explored.

Adult↗

Treatment of oral granulation tissue with the flashlamp pulsed dye laser.

BACKGROUND: Surgical excision and debridement is the standard therapy for cutaneous and intraoral pyogenic granulomas (PGs). Occasionally the mass of granulation tissue proves unresponsive to the usual treatment methods. OBJECTIVE: We report a case in which the flashlamp pulsed dye laser (PDL), previously reported as useful in cutaneous PGs, was used in a patient with persistent granulation tissue around dental implant posts. METHODS: An illustrative case is presented with a brief discussion of the use of lasers in dentistry and in the treatment of PGs. RESULTS: Previously resolute tissue responded well to a series of treatments with the PDL. CONCLUSION: The PDL may have utility in this oral condition, providing a new venue for cooperation between dentists and dermatologists.

Aged↗

Accelerative effect of "nanshikon" and its constituents on the proliferation of granulation tissue in rats.

The present study was carried out to examine the accelerative effect of the ether extract obtained from "Nanshikon" on the proliferation of granulation tissue induced by cotton pellet in rats and to elucidate its active principles. Among naphthoquinone derivatives, the ether extract contained mostly teracrylshikonin. At corresponding doses based on the contents of the naphthoquinone derivatives in the ether extract, the accelerative potencies of teracrylshikonin, beta, beta-dimethylacrylshikonin, and a mixture of alpha-methyl-n-butylshikonin and isovalerylshikonin were about the same. Also, the accelerative potencies of these compounds were somewhat weaker than that of the ether extract. From these results, it is suggested that the accelerative effect of the ether extract on the proliferation of granulation tissue is mainly due to teracrylshikonin, beta, beta-dimethylacrylshikonin and a mixture of alpha-methyl-n-butylshikonin and isovalerylshikonin contained in the ether extract, and the accelerative effect induced by ether extract might be an additive effect of these naphthoquinone derivatives.

Animals↗

Cloning of cDNA for rat pro alpha 1(III) collagen mRNA. Different expression patterns of type I and type III collagen and fibronectin genes in experimental granulation tissue.

A cDNA clone for rat pro alpha 1(III) collagen mRNA was isolated from a cDNA library constructed for poly(A)+ RNA from 15-day experimental granulation tissue. Two clones, pRGR1 and pRGR5, were characterized by restriction mapping and sequencing. Comparison with human type III collagen sequences revealed 92% identity at the level of translated amino acids, and 88% identity at nucleotide level in the coding region. In the 3'-untranslated sequence the identity was even higher (90%). The clones were used together with cDNA clones for type I collagen chains, fibronectin and gamma-actin to study the expression of the corresponding mRNAs during the development of experimental sponge-induced granulation tissue in rats. These studies revealed a marked activation of type I and type III collagen genes during the second week of granuloma development followed by a transient reduction in their levels during the third week. The mRNA levels for both collagen types remained relatively unchanged from day 25. The molar ratio of pro alpha 1(III) and pro alpha 1(I) collagen mRNAs was at a maximum on day 6, and then decreased to reach a plateau by the end of the third week. Fibronectin mRNA levels were found to increase slower; the maximum value was reached during the fifth week of granuloma development. The mRNA levels of gamma-actin increased continuously up to the end of the fourth week, thus following the cellular maturation of the tissue.

Actins↗

On the mechanism of skin wound "contraction": a granulation tissue "knockout" with a normal phenotype.

This report explores the mechanism of spontaneous closure of full-thickness skin wounds. The domestic pig, often used as a human analogue for skin wound repair studies, closes these wounds with kinetics similar to those in the guinea pig (mobile skin), even though the porcine dermis on the back is thick and nearly immobile. In the domestic pig, as in the guinea pig, daily full-thickness excisions of the central granulation tissue up to but not including the wound edges in both back and flank wounds do not alter the rate or completeness of wound closure or the final pattern of the scar. A purse-string mechanism of closure was precluded by showing that surgical interruption of wound edge continuity does not alter closure kinetics or wound shape. We conclude that "tightness" of skin is not a key factor nor is the central granulation tissue required for normal wound closure. These data imply that in vitro models such as contraction of isolated granulation tissue or of the cell-populated collagen lattice may not be relevant for understanding the cell biology of in vivo wound closure. Implications for the mechanism for wound closure are discussed.

Animals↗

[Effects of Shengji Huayu Recipe and its decomposed formulas on synthesis of collagen types I and III in granulation tissue of rats in early wound healing].

OBJECTIVE: To study the effects of Shengji Huayu Recipe (a traditional Chinese medicine compound recipe for resolving stagnation and promoting granulation) and its decomposed formulas (Huayu Recipe for resolving stagnation and Shengji Recipe for promoting granulation) on the synthesis of collagen types I and III in granulation tissue of rats in early wound healing. METHODS: Twenty-four male Sprague-Dawley (SD) rats with full-thickness skin lesion were randomized into 4 groups: Shengji Huayu Recipe-treated group, Shengji Recipe-treated group, Huayu Recipe-treated group and untreated group. Collagen types I and III in granulation tissue of the rats were tested with immunohistochemical methods and image analysis. RESULTS: On the third day of wound healing, collagen I of the rats in both Shengji Huayu Recipe-treated group and Shengji Recipe-treated group was higher than that in the untreated group, and collagen I of the rats in Huayu Recipe-treated group was lower than that in the untreated group (P<0.05). Collagen III of the rats in the three treated groups were lower than that in the untreated group (P<0.05). On the seventh day of wound healing, Collagen I of the rats in both Shengji Huayu Recipe-treated group and Shengji Recipe-treated group was higher than that in the untreated group (P<0.05), and collagen III of the rats in both Shengji Recipe-treated group and Huayu Recipe-treated group was higher than that in the untreated group (P<0.05). CONCLUSION: Resolving stagnation and promoting granulation therapy can promote the wound healing in rats.

Animals↗

Morphological aspects of early and late collagen degradation in granulation tissue.

A sequential histologic, ultrastructural and immuno pathologic study was carried out in the Selye's inflammatory pouch model to observe extracellular matrix and cellular changes during granulation tissue formation. Besides changes involving different components of the connective tissue, it was observed that collagen resorption occurred under a biphasic process. At an early phase (3rd to 15th day), in which exudative inflammatory changes predominated, signs of collagen synthesis and degradation were seen simultaneously. Extracellular breakdown and internalization of collagen fragments within fibroblasts and myofibroblasts were observed. Later on (30th to 60th day), changes affecting collagen had a different ultrastructural appearance. Collagen fragmentation, focal "lytic" and "electron dense" changes occurred in the extracellular space specially at the periphery of fibroblasts, myofibroblasts and smooth muscle cells. Collagen degradation, thus seems to be a continuous process in granulation tissue, occurring with different morphologies at different times.

Animals↗

Effects of granulation-tissue-conditioned medium on the growth of human keratinocytes in-vitro.

Human keratinocyte cultures were seeded and grown for 24 hours in the presence of medium conditioned by exposure to granulation tissue and to normal tissue. The effects on cell proliferation were investigated by measurement of [3H]thymidine incorporation into cellular DNA. Keratinocyte growth was found to be markedly inhibited in the presence of granulation-tissue-conditioned medium (p much less than 0.05). Possible factors responsible for the inhibition have been investigated and the observations suggest that fibrin, or products derived from fibrin/fibrinogen may play a role in the suppression of cell growth.

Bacterial Toxins↗

Accelerative effect of shikonin, alkannin and acetylshikonin on the proliferation of granulation tissue in rats.

The present study was carried out to compare the accelerative effect of shikonin (R-type), alkannin (S-type), and acetylshikonin on the proliferation of granulation tissue in rats, and to elucidate the correlation between the potency of the effect and their optical activity. Koushikon mainly contained the R-type of acetylshikonin, and Nanshikon mainly contained the S-type of acetylshikonin. Each compound produced a dose-dependent acceleration of the cotton pellet-induced granuloma formation. In comparing identical doses of shikonin, alkannin and acetylshikonin, the potency of their accelerative effects on the proliferation of granulation tissue was about the same. This result suggests that their absolute configurations (R-type or S-type) and their acetylation on the hydroxy group of the sidechain of shikonin or alkannin may not be important in producing the effect.

Animals↗

Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA.

Sox18 encodes a member of the Sry-related high mobility group box (SOX) family of developmental transcription factors. Examination of Sox18 expression during embryogenesis has shown that Sox18 is expressed transiently in endothelial cells of developing blood vessels, and mutations in Sox18 have been found to underlie the mouse vascular and hair follicle mutant ragged. In this study we have examined the expression of Sox18 in angiogenesis during wound healing. Full-thickness skin wounds were created in mice, and subsequent expression of vascular endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in situ hybridization. As has been previously reported, VEGF was expressed predominantly in the keratinocytes at the wound margins. Sox18 expression was found five days after wounding during capillary sprouting in granulation tissue and persisted through the proliferative phase of healing, but was not detected in fully epithelialized wounds 21 days after wounding. Sox18 mRNA expression was detected in capillaries within the granulation tissue and showed an identical pattern of distribution to Flk-1 and Col4a1 mRNA expression in endothelial cells. Immunostaining with a polyclonal anti-Sox18 antibody showed SOX18 protein localized in capillary endothelial cells within the granulation tissue. Capillaries in the subcutaneous tissue of unwounded skin showed no Sox18 expression. Sox18 may therefore represent a transcription factor involved in the induction of angiogenesis during wound healing and tissue repair, but not in the maintenance of endothelial cells in undamaged tissue.

Animals↗

Influence of fibrin clots on development of granulation tissue in preformed cavities.

To examine the influence of fibrin clots, perforated Teflon cylinders have been implanted subcutaneously in rats. Fibrin clots made from both species specific fibrinogen and from an non-species specific preparation, together with ingrowing granulation tissue, kept the implanted cylinder filled during the four week study period. This was valid for both concentrations investigated. Interaction between granulation tissue and fibrin clot differed between the two fibrin types.

Animals↗

Granulation tissue formation in zinc-treated rats.

Chronic zinc deficiency impairs would healing. It is not known if acute decrease of werum zinc ocdurring after trauma has the same negative effect. We have studied the effect of extra zinc supply in connection with trauma on granulation tissue formation in subcutaneously implanted polyvinyl sponges. Zinc given postoperatively had no effect on granulation tissue formation. Zinc administered also preoperatively resulted in higher amount of collagen by the fourth postoperative day but not later. This effect of zinc on the collagen content can be explained either by an increased collagen synthesis or by decreased collagen break down. The fact that zinc had no effect when given only postoperatively indicates that collagen synthesis is not affected. The demonstrated effect of zinc thus seems to be due to decreased collagen break down.

Animals↗

Elastin powder produced for cosmetic purposes does not affect formation of granulation tissue.

A suspension of elastin powder that is produced for cosmetic purposes has been applied on open skin wounds made in rats. Elastin particles (diameter smaller than 0.1 mm) prepared by extraction of bovine nuchal ligament with alkali had no effect on wet weight and dry weight of granulation tissue formed in the wound within 6 days. Hydroxyproline content which indicates collagen content of the granulation tissue was not also changed.

Animals↗

Collagen synthesis in granulation tissue formed in rats treated with female sex hormones.

In previous studies, we have shown that female sex hormones given in dosages corresponding to plasma levels in the last trimester of pregnancy retard collagen accumulation in early phases of experimental granulation tissue formation. Results of incorporation experiments using radioactive proline reported in this article indicate that this hormone treatment reduces general protein synthesis in granulation tissue and, even more markedly, the synthesis of collagen. Since collagen accumulation into granulomas is normal in the later phases of healing, it is suggested that hormone treatment not only decreases synthesis of collagen but also decreases breakdown of collagen. Hormone treatment did not affect the solubility of labeled collagen. No differences were observed in the synthesis of different collagen types. Under conditions when active collagen and protein synthesis occurs in the uterus and fetus, corresponding synthesis in other tissues is, thus, decreased. This may serve as an energy and protein saving function during pregnancy. The results may have applications for treatment of extensive scar formation.

Animals↗

Effect of carbanilate local anesthetics on granulation tissue formation.

The effect of local anesthetics pentacaine ((+/-)-trans N-/2-(3-pentyloxy-phenylcarbamoyloxy)-cyclohexyl/- pyrrolidinium chloride), heptacaine (N-/2-(2-heptyloxy-phenyl-carbamoyloxy)-ethyl/-piperidini um chloride) and trimecaine (2, 4, 6-trimethylphenylcarbamoyl)-methyldiethylammonium chloride) on granulation tissue formation in open skin wounds was examined in rats. The anesthetics applied on the wounds 3 times a day for 5 days caused increase in granulation tissue weight, in DNA and hydroxyproline contents. Pentacaine had the most pronounced effects (190% dry weight, 253% DNA and 148% hydroxyproline content when compared to saline-treated controls). The smallest changes were observed after heptacaine treatment.

Anesthetics, Local↗

Acute airway obstruction associated with granulation tissue of tracheostoma--a case report.

We report an 85-year-old tracheostomized male patient who underwent ventriculoperitoneal shunt because of hydrocephalus. Postoperative acute airway obstruction and tension pneumothorax developed due to the granulation tissue of tracheostoma which scraped off from the tracheostoma in the act of endotracheal intubation for operation and it lay dormant around until it was drawn into the endotracheal tube (ETT) by negative pressure during suction of trachea in intensive care unit. Persistent hypoxemia in consequence of airway obstruction resulted in cardiac arrest and expiratory seal of trachea eventuated in tension pneumothorax. Flexible fiberoptic bronchoscopy performed during resuscitation disclosed that the obstruction was due to granulation tissue which blocked the ETT lumen. Immediate exchange of endotracheal tube and placement of chest tube made the patient tide over this crisis. No sequela resulted from this crisis and the patient was discharged one week later.

Acute Disease↗

The use of the KTP laser in the management of hypertrophic tracheal mucosa and granulation tissue around Provox valve protheses.

The development of hypertrophic mucosa and granulation tissue around a tracheo-oesophageal fistula voice prosthesis is a commonly encountered problem occurring in 15-20 per cent of patients. Upsizing of the voice prosthesis as well as cautery (silver nitrate and electocautery) are used to counteract this problem to a varying degree of success. The use of the CO2 laser has been mentioned by some authors but details of the method and results have not been published. We report the successful use of the KTP laser for removing such granulations whilst retaining the valve and discuss the reasons why this method should be considered.

Granulation Tissue↗