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PubMed2006

A simple, pain-free treatment for ingrown toenails complicated with granulation tissue.

BACKGROUND: The treatment of ingrown toenail complicated with granulation tissue is usually partial or total nail avulsion with or without matricectomy. It costs loss of occupational power, however, because most patients cannot go to work or school for some time after surgery, and it is a costly and uncomfortable procedure for most patients. OBJECTIVE: This study aimed to find an easy, painless, and inexpensive alternative. MATERIALS AND METHODS: Seven patients with ingrown toenails complicated with granulation tissue are included. A small apparatus was applied on the nails, granulation tissue was chemically cauterized, and a foot bath was recommended twice daily. They were followed on a weekly basis or every other week until recovery. None of the patients received systemic treatment. RESULTS: All seven patients were completely cured without requiring surgery and/or systemic treatment. The procedure did not have any effect on their daily life. The follow-up examination of the patients at 6 months revealed that they were totally cured, and there were no recurrences. CONCLUSION: Patients with ingrown toenails complicated by granulation tissue might have an inexpensive and pain-free treatment alternative, although new studies with more patients are required.

Adolescent↗
PubMed1997

Role of macrophages in the stimulation and regeneration of sensory nerves by transposed granulation tissue and temporal aspects of the response.

Application of granulation tissue, which is rich in macrophages, to a peripheral nerve induces a conditioning effect, in that it enhances the regeneration capability of peripheral nerves after a test crush lesion. The temporal aspects of this response and the role of macrophages and interleukin-1 beta (IL-1 beta) were studied in the sciatic nerves of 71 rats. Granulation tissue was implanted close to the sciatic nerve and test crush lesions were applied after various periods of time (0-21 days). Regeneration was evaluated after an additional two, three, four, or six days. Regeneration distances were longer in granulation-treated nerves than in nerves treated with subcutaneous tissue. Furthermore, in animals in which the test crush lesion was made at the same time as the granulation tissue was implanted (n = 6), regeneration distances were longer, 8.1 (0.8) mm compared with 7.2 (0.6), than those in which the crush was made after conditioning intervals of 3 (n = 6, 7.6 (0.4) compared with 6.9 (0.4), p = 0.03); 7 (n = 6, 7.4 (0.4) compared with 6.6 (0.1), p = 0.03); and 21 days [(n = 8, 7.2 (0.6) compared with 6.4 (0.5)]. Inactivation of the granulation tissue by freezing suppressed the conditioning effect. There were numerous ED1 and ED2 positive macrophages as well as positive staining for IL-1 beta in the granulation tissue on day 0. Positive staining for IL-1 beta was also seen in nerve fibres as well as in non-neuronal cells after a conditioning interval. The results suggest that regeneration is stimulated by factors released from the cells of the granulation tissue, and that the amount of factors released or the responsiveness of the regenerating nerve change during the conditioning interval.

Animals↗
PubMed1982

The effect of D-penicillamine and methylprednisolone on the morphology of experimental granulation tissue in rats.

The effects of D-penicillamine and methylprednisolone on the formation of granulation tissue was studied in rats with Visella-sponge induced granulation tissue after 42 days of treatment. D-penicillamine in doses of 20 mg-, 100 mg-, 500 mg/kg/day caused no morphological differences compared with the control groups as regards ingrowth of granulation tissue and its content of collagen fibres, inflammatory cells, vessels and glycosaminoglycans. Treatment with methylprednisolone, 0.2 mg-, 2.0 mg-, and 5.0 mg/kg/day caused a dose dependent reduction in the ingrowth of granulation tissue. Methylprednisolone caused a reduction in the number of fibroblasts and collagen fibres, but no differences in the content of glycosaminoglycans could be demonstrated between the treated and the control groups. Granulation tissue produced during combination treatment with D-penicillamine 100 mg and methylprednisolone 2.0 mg/kg/day did not differ from that observed after methylprednisolone treatment alone. Thus, only high doses of methylprednisolone gave rise to an antiinflammatory action in this morphological study on granulation tissue, whereas D-penicillamine had no effect within the present dose interval. The quantitative alterations are in agreement with parallel biochemical analyses. However, the inhibitory effect of D-penicillamine on collagen crosslinking was not associated with light microscopic changes in the ultrastructure of the collagen fibres.

Animals↗
PubMed1975

The effects of cyclophosphamide and azathioprine on collagen in skin and granulation tissue in rats, and the effects of cyclophosphamide on collagen in human skin.

Granulation tissue was produced in rats by subcutaneous implantation of cellulose sponges. The effect of daily intraperitoneal injections of cyclophosphamide or azathioprine on rat skin and granulation tissue was examined after 14 and 42 days. Skin biopsies from patients with glomerulonephritis were analyzed before and after 42 days of treatment with cyclophosphamide or placebo. In the rats, cytostatic treatment caused an increase in the dry weight of the skin, and azathioprine increased the dry weight and the protein content of the granulomas. The increase in the dry weight was accompanied by a decrease in water percentage. The alpha-amino nitrogen/OH-proline ratio in purified acid soluble collagen from skin and granulation tissue increased with the dose and duration of cytostatic treatment. No effect on the aldehyde content was observed. Cyclophosphamide caused a decrease in the alpha/beta ratio in acid soluble collagen from granulation tissue, but not in the collagen from the skin. Salt soluble collagen was increased in the skin after 14 days of cytostatic treatment, but remained unchanged in the granulation tissue. In human skin cyclophosphamide caused no statistically significant changes in the amount of salt soluble or total collagen. It is concluded, that daily treatment of rats with cyclophosphamide or azathioprine from 14 to 42 days seems to inhibit the catabolic processes in the skin and granulation tissue, to decrease the hydroxylation of proline in collagen, and to inhibit the intermolecular cross-linking in collagen.?222

Animals↗
PubMed1978

Reversibility of the effects of cyclophosphamide on collagen: biochemical studies on skin and granulation tissue and determination of thermal stability of tail tendons of rats.

Granulation tissue was produced in rats by subcutaneous implantation of viscose cellulose sponges. Treatment with cyclophosphamide in a dose of 10 mg/kg/day for 14 days caused an increase in acid soluble OH-proline and a decrease in alpha/beta ratio of acid soluble collagen of granulation tissue. Forty-two days of continuous cyclophosphamide treatment caused a decrease in dry weight, in free OH-proline, and in salt soluble OH-proline in granulation tissue. These findings are in accordance with previous observations of a decreased collagen synthesis and an inhibited collagen degradation in granulation tissue after cyclophosphamide treatment. In skin, the only change after cyclophosphamide was a decrease in total content of OH-proline and an increase in alpha/beta ratio of acid soluble collagen after 42 days of treatment. No effect of the subcutaneous sponge implantation was observed on the collagen variables in the skin. In comparison with unstarved controls, a reduction in dry weight and in free OH-proline in granulation tissue, as well as an increase in salt soluble OH-proline in the skin were observed 28 days after a 14-day treatment with cyclophosphamide. These observations indicate a sustained effect of cyclophosphamide on collagen 28 days after cessation of treatment. In addition the thermal stability of rat tail tendons was decreased 28 days after withdrawal of cyclophosphamide to the same extent as after starvation for 42 days and after 42 days of continuous cyclophosphamide treatment. It is concluded that the cyclophosphamide-induced collagen alterations, which may be of importance in the anti-inflammatory action of cyclophosphamide, are only in part reversible, 28 days after cessation of 14 days of cyclophosphamide treatment.

Animals↗
PubMed2003

Wound splinting regulates granulation tissue survival.

PURPOSE: Fibroblast survival within an in vitro collagen matrix is dependent on matrix anchorage to a rigid substratum. The purpose of this study was to determine whether granulation tissue survival in vivo also is dependent on matrix anchorage. We hypothesized that splinting an excisional wound (i.e., anchoring the wound edges) would promote granulation tissue survival and that desplinting a splinted wound would produce granulation tissue apoptosis. METHODS: Eighteen Wistar rats (3 months, 350 g) underwent excisional wounding (2 x 2 cm, dorsal skin) with immediate wound splinting (a metal template affixed with sutures) on day 0. On day 6, rats (n = 6 per group) underwent splint removal (desplinted), splint removal with circumferential incision of the wound edge (desplint/release), or no intervention (splinted); sacrifice of all animals was on day 7. Frozen sections of granulation tissue were stained with TUNEL or H and E; data were analyzed with ANOVA and the unpaired t test. RESULTS: The cross-sectional and surface area of the desplinted and desplint/release granulation tissue both decreased compared to the splinted granulation tissue (*P < 0.05). The nuclear density of the desplint/release granulation tissue was 25% less compared to the splinted granulation tissue (*P < 0.05). The desplinted and desplint/release apoptotic rates were twice and >10x greater than the splinted apoptotic rate, respectively (*P < 0.05). CONCLUSIONS: The rate of cell death in a splinted wound (an in vivo equivalent of an anchored FPCM) is minimal to nil, which is consistent with our hypothesis. Desplinting and releasing the wound edge of a previously splinted wound (the in vivo equivalent of a detached FPCM) results in granulation tissue regression and a large increase in apoptosis. Desplinting a wound alone results in changes somewhat intermediate to the splinted and desplint/release conditions. Loss of wound anchorage acutely promotes granulation tissue apoptosis.

Animals↗
PubMed1975

[The ultrastructure of the cellular elements of granulation tissue].

Electron-microscopy studies of the granulation tissue cells in an experimental wound in mice during one week after its infliction were carried out. Twenty four hours following the trauma neutrophilic leucocytes were found to be predominant in the wound. Disintegrating, they were utilized by macrophages, the latter being numerous in the granulation tissue on the 2nd-3rd day. Their protoplasm was found to contain multitude of various vacuoles and inclusions, which testified to a high phagocytic activity of these cells, whose main function in the wound process is purification of the wound. Evolution of the ultrastructural changes in fibroblasts of the granulation tissue was followed up. On the 5th-7th day they showed a pronounced hyperplasia of the granulation endoplasmic reticulum and an increased number of ribosomes. These changes in fibroblasts reflect their high synthetic activity and represent a structural base of the intensive collagenformation.

Animals↗
PubMed1983

Retinoid therapy is associated with excess granulation tissue responses.

In our clinical trials of isotretinoin therapy for cystic acne and etretinate treatment of psoriasis, eight patients had growth of excessive granulation tissue. The granulation tissue was found in resolving acne lesions in one patient taking isotretinoin. Among the psoriatic patients taking etretinate, the granulation tissue usually was seen adjacent to nail plates. In two patients, the side effect caused them to stop retinoid therapy. The tissue response did not appear to be related to the daily or cumulative retinoid dose.

Acne Vulgaris↗
PubMed2004

Hexose sugars differentially alter collagen gene expression and synthesis in fibroblasts derived from granulation tissue, hypertrophic scar and keloid.

Clinical observations have suggested that sugar and honey enhance granulation tissue formation and in vitro studies have shown that monosaccharide sugars stimulate mesenchymal and endothelial cells. In this study, the effects of glucose, fructose, galactose and mannose on type I and type III collagen gene expression and synthesis were studied in granulation tissue, hypertrophic scar and keloid fibroblast cultures. Glucose elevated both type I and type III collagen mRNAs in hypertrophic scar fibroblasts. Fructose increased type III collagen mRNA almost sevenfold in granulation tissue fibroblasts. Galactose caused an increase in type I and type III collagen mRNAs in granulation tissue fibroblasts and hypertrophic scar fibroblasts but, in contrast, mannose decreased type I and type III collagen levels in hypertrophic scar and keloid fibroblasts. Analysis of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) revealed that glucose decreased the amount of PINP in granulation tissue and keloid fibroblasts, whilst fructose decreased the amount in all the fibroblast cell lines studied. Galactose caused a decrease in the synthesis of type I collagen in all cell lines but a decrease was seen in type III collagen only in hypertrophic scar fibroblasts. Mannose decreased the amount of PINP in all cell lines but a decrease in the amount of PIIINP was seen only in granulation tissue fibroblasts. The effect of sugars on the ratio type I/type III collagen was negligible or decreasing with the exception of galactose, which increased the ratio in hypertrophic scar fibroblasts. The results suggest that glucose, fructose and galactose have no significant value in the stimulation of collagen synthesis in vitro. Mannose may have value in the prevention or treatment of abnormal scars.

Cells, Cultured↗
PubMed2006

High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue.

BACKGROUND: Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. METHODS AND MATERIALS: Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDR brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with (192)Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. RESULTS: The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. CONCLUSION: High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.

Adult↗
PubMed1986

Granulation tissue proliferation during isotretinoin treatment.

Excessive, pseudotumoral granulation tissue proliferations appeared in three patients receiving isotretinoin for nodulocystic acne. A review of the literature disclosed few reports of this unusual adverse reaction. Two clinical patterns have been reported; one in a periungual location and the other occurring in the sites of acne lesions during isotretinoin therapy. Loose edematous connective tissue with small vessels and chronic inflammatory infiltrate were the histologic findings in all three cases.

Acne Vulgaris↗
PubMed1989

Partial purification of gelatinases and effect of anti-inflammatory drugs on the tumor necrosis factor-stimulated production of active gelatinase by granulation tissue in culture.

Gelatinases produced by granulation tissue in culture were separated into two fractions when the conditioned medium was chromatographed on diethylaminoethyl-Sephacel; one contained latent and active gelatinases with molecular weight of about 74 kDa (low-Mr gelatinase), and the other contained an active gelatinase with molecular weight of about 112 kDa (high-Mr gelatinase) as estimated by gel filtration on Sephadex G-150. The former was unbound and the latter was bound to Zn-chelating Sepharose. Both low- and high-Mr gelatinases, however, occurred in mainly two bands corresponding to molecular weights of 64 and 57 kDa on sodium dodecyl sulfate-substrate polyacrylamide gel electrophoresis. Recombinant human tumor necrosis factor-alpha (TNF) markedly enhanced the production of gelatinases, especially high-Mr active gelatinase. Dexamethasone and hydrocortisone strongly suppressed TNF-mediated production of high-Mr active gelatinase, whereas indomethacin, piroxicam and mepacrine had no effect. The results suggest that steroidal anti-inflammatory drugs suppress a rapid collagen breakdown in granulation tissue through their inhibitory actions--one of which is the suppression of active gelatinase production enhanced by cytokines including TNF.

Animals↗
PubMed1984

Effects of tranexamic acid and local fibrin deposition of fibrinolysis and granulation tissue formation in preformed cavities.

The effects of locally deposited fibrin and of tranexamic acid-induced antifibrinolysis on forming granulation tissue were studied in the light of a recently developed method for treatment of postoperative fistulas by occlusion with a fibrin clot. Perforated teflon cylinders, either empty or fibrin-filled, were implanted subcutaneously in rats and extracted after 2 weeks. Fibrin deposition was found to stimulate granulation tissue ingrowth into the cylinders but it did not change the fibrinolytic activity in the granulation tissue. A significantly higher fibrinolytic activity was, however, found in the tissue fluid collected from the space between the granulation tissue and the implanted fibrin clot compared to tissue fluid from cylinders implanted empty. Tranexamic acid significantly reduced the fibrinolytic activity on the granulation tissue and delayed lysis of the implanted fibrin clot. It also reduced granulation tissue ingrowth but it did not abolish the positive effects of the clot on granulation tissue formation.

Animals↗
PubMed2000

The effect of environmental cues on the differentiation of myofibroblasts in peritoneal granulation tissue.

This study investigated the effect of haemodynamic stress, active stretch, and neuronal input on the differentiation of myofibroblasts in peritoneal granulation tissue. Lengths of silastic tubing (10 mm long x 3 mm diameter) were placed in the peritoneal cavity of the rat. By 2 weeks, a capsule of granulation tissue had formed around the tubing. This capsule consisted of several layers of myofibroblasts and the matrix that they had produced, overlaid by a single layer of mesothelial cells. The silastic tubing was removed and at the same time, the living tube of tissue was everted so that the mesothelium now lined its inner surface. To examine the effect of haemodynamic factors on myofibroblast differentiation, the 10 mm long tubes of mesothelial-lined granulation tissue were transplanted into the severed abdominal aorta of the same rat in which the granulation tissue was grown. End-to-end anastomoses were performed to extend the existing aorta. At 1, 2, and 3 months post-transplantation, the grafts were removed and a progressive increase in the percent volume fraction of myofilaments (% V(v)myo) was observed (from 35.7+/-1.6% to 58.7 3+/-1.4%; p<0.05). To determine whether the active stretching that occurs in vivo could account for differentiation of the constituent myofibroblasts, tubes of granulation tissue were placed into a mechanical device in which they underwent continuous stretching of 5-10% elongation from the resting position at 50 cycles per minute for 3, 24 or 72 h. This caused a significant (p<0. 05) increase in %V(v)myo after 72 h. Granulation tissue was also transplanted into the rat anterior eye chamber, where it became surrounded by adrenergic nerves supplying the host iris. Two months after implantation, there was no significant change in the %V(v)myo of the myofibroblasts (35.7+/-1.6% to 33.3+/-2.7%). These studies show that myofibroblasts of the granulation tissue encapsulating free-floating foreign bodies in the peritoneal cavity further differentiate towards a smooth muscle phenotype when transplanted into a smooth muscle environment, namely the abdominal aorta. Similar changes are seen when the granulation tissue is subjected to active, intermittent stretch in vitro, while the presence of nerves has no effect.

Animals↗
PubMed1988

Prostaglandins in human cholesteatoma and granulation tissue.

Bone resorption is a common finding in chronic otitis media with or without cholesteatoma. The etiology of bone resorption in chronic otitis media is still not clear. Bone-resorbing activity of prostaglandins (PGs) has been well known. PGE-like material has been detected in granulation tissue. However, there have been no reports on the comprehensive study of PGs in cholesteatomas or granulation tissue. The purpose of this study is to show that PGs are synthesized in the middle ear tissue and to report concentrations of PGs in cholesteatomas and granulation tissue. Samples of cholesteatoma and granulation tissues were obtained at the time of tympanomastoidectomies. Prostaglandin synthesizing activity was determined by incubating tissue with labeled arachidonic acid (precursor of PGs) and radiochromatography. Levels of PGs were determined by radioimmunoassay. Arachidonic acid metabolites produced in cholesteatoma and granulation tissue included PGE2; 6-keto-PGF1 alpha; PGF2 alpha; PGD2; and 5-, 12-, and 15-hydroxy-eicosatetraenoic acid (HETE). Levels of PGE2 were 2.6 times higher in cholesteatoma (106.8 +/- 46 ng/g) than in granulation tissue (41.0 +/- 14.3 ng/g). Levels of 6-keto-PGF1 alpha were two times higher in granulation tissue (89.0 +/- 27.0 ng/g) than in cholesteatoma. Levels of thromboxane B2 were two times higher in cholesteatoma than in granulation tissue. The results of this study demonstrate that cholesteatoma and granulation tissues actively synthesize PGs and contain high concentrations of them. Since PGs are locally active hormones, the presence of PGs indicates an active role for PGs in the pathogenesis of chronic otitis media with bone resorption.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Laser ablation of granulation tissue at the tracheoesophageal puncture site.

BACKGROUND: Tracheoesophageal fistula speech may be complicated by granulation tissue around the puncture site. Treatment includes antibiotics, antifungals, chemical or electrocautery, and surgical excision of the granulation tissue. Chemical cautery generally requires repeated treatment sessions. METHODS: We report our technique and results of CO(2) laser ablation of granulation tissue at the tracheoesophageal puncture site performed as an outpatient office procedure. RESULTS: Seven of 9 patients (78%) were cured with a single treatment. The prosthesis was replaced immediately after laser ablation of granulation tissue. Of the remaining 2 patients, 1 had a recurrence a year later, requiring repeated laser. The second patient had a large mass requiring 4 laser ablations. There were no complications. CONCLUSIONS: CO(2) laser has the following advantages compared with other methods of treating stomal granulation tissue: office procedure; 78% cured with single treatment; and the extent of tissue necrosis is predictable.

Aged↗
PubMed2001

Antibody neutralization of vascular endothelial growth factor inhibits wound granulation tissue formation.

OBJECTIVE: The goal of this work was to test the functional role of vascular endothelial growth factor (VEGF) in promoting the vigorous granulation tissue formation, wound fluid accumulation, and angiogenic responses characteristic of this wound model. BACKGROUND: Formation of vessel-rich granulation tissue is central to wound repair and is thought to be regulated by locally liberated angiogenic factors. Despite the clinical importance of granulation tissue formation in the early stage of wound healing, surprisingly little is known about the molecular identity of signals leading to granulation tissue invasion of a wound space. Methods. A ventral hernia, surgically created in the abdominal wall of 15 swine, was repaired using silicone sheeting and skin closure. An osmotic minipump, inserted in a remote subcutaneous pocket, delivered saline (n = 5), an irrelevant control antibody (n = 5), or neutralizing anti-VEGF antibody (n = 5) into the wound environment. Serial ultrasonography on Days 2, 4, 7, 9, 11, and 14 was used to determine the dimensions of the subcutaneous granulation tissue and wound fluid compartment. VEGF and transforming growth factor beta1 (TGF-beta1) levels in serial wound fluid samples were quantitated by ELISA. On Day 14, animals were sacrificed and the abdominal wall was harvested for histologic, biochemical, and molecular analyses. RESULTS: In animals receiving saline or an irrelevant antibody, a nearly linear 4-fold increase in granulation tissue thickness and 7-fold increase in wound fluid volume were measured over the 14-day study interval. In contrast, in animals receiving anti-VEGF neutralizing antibody, Day 14 granulation tissue thickness and wound fluid volume measurements were essentially unchanged from Day 2 values. Moreover, in the anti-VEGF animals, ultrasonography was unable to resolve the "angiogenic zone" typical of both controls, and correspondingly, wound vessel count and vascular surface area estimates derived from image analysis of histological sections were 3-fold lower in the anti-VEGF animals compared with the saline and antibody controls. Finally, VEGF levels in wound fluid detectable by ELISA analysis were strikingly (10-fold) reduced in anti-VEGF animals on Postsurgery Days 7-14. In contrast, TGF-beta1 levels were unaffected by the anti-VEGF treatment. CONCLUSION: Functional VEGF is a key mediator in wound angiogenesis, fluid accumulation, and granulation tissue formation.

Abdominal Muscles↗