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PubMed1987

[Effects of the calcium ion on the wound healing process].

The present study was undertaken to elucidate the effect of calcium ion on the granulation tissue formation during wound healing. Male guinea pigs of Pilbright strain were chosen as the experimental animal. An appropriate open wound was aseptically made on the dorsum of the guinea pigs, which was then equipped with a sterile Teflon-cylinder. The amounts of granulation tissues developed within the cylinder were determined during 10 day period of the observation. In addition, various concentrations of CaCl2 were applied on the wound surface for up to 3 days after the wounding. Calmodulin contents in the granulation tissue were also determined using calmodulin-deficient phosphodiesterase prepared from bovine heart. Purified pig skin epidermal calmodulin was used as the standard. The results obtained were as follows: The amount of the granulation tissue increased in a stepwise manner during 3, 5, 7, and 10 days after the wounding. Calmodulin content in the granulation tissue was maximal on the day 3 after the wounding, waned on the day 5, and remained low on the days 7 and 10. A significant augmentation of the granulation tissue production as well as of calmodulin content was observed when CaCl2 was applied on the wound surface during 3 days after the wounding. These results suggest that calcium ion might have a significant role on granulation tissue development, possibly through the Ca++-calmodulin system, during early stages of wound healing process.

Animals↗
PubMed2006

Granulation encapsulated stent: a new therapeutic approach for vascular implantation.

OBJECTIVES: To determine if stents could be encapsulated with immunocompatible granulation tissue for the treatment of vascular diseases. METHODS: Bare metal stents were implanted in New Zealand white rabbits so they would be encapsulated with immunocompatible granulation tissue. The granulation encapsulated stents (GES) were then treated with either mitomycin C or saline, and implanted into rabbit iliac arteries for 4 weeks. To test whether the effect of mitomycin C was retained, we co-cultured smooth muscle cells for 3 h with subcutaneous tissue (as control) or with granulation tissue from GES treated with mitomycin C and saline. RESULTS: Vessels with GES treated with mitomycin C (MS) and washed with saline had significantly less neointimal area (NA) after 4 weeks (0.27 (SD 0.03) mm(2) than vessels containing bare metal stents (B) (1.15 (SD 0.10) mm(2), n = 5, p<0.05) or GES treated with saline (S) (4.78 (SD 0.72) mm(2), n = 5, p<0.05). The average vessel injury score was not significantly different among these three groups (S: 1.98 (SD 0.51), MS: 1.46 (SD 0.18) and B: 1.51 (SD 0.32)). GES treated with saline had significantly less NA than the other two groups and also blocked blood flow in the contralateral iliac artery in the abdominal aortic bifurcation immediately after implantation and 4 weeks later. Histology also showed neointimal overgrowth in the vessel wall over the contralateral iliac artery. CONCLUSIONS: GES treated with mitomycin C can significantly inhibit neointimal formation in rabbit arteries due to the formation of granulation tissue. GES treated with saline demonstrated significantly increased NA and resisted normal rabbit artery pressures.

Animals↗
PubMed1979

Evaluation of the tissue response to the wear products of the hip joint endo-arthroprosthesis.

The causes of tissue reaction surrounding heterogeneous materials are: cell-mediated hypersensitivity due to an implant material; infection; post-surgery hematoma, following lysis of red cells and deposition of hemosiderin; "True" implant reaction, i.e., tissue modifications produced by wear particles of components of the prosthetic devices used. The stages of inflammation due to wear particles are: phagocytosis of particles by newly formed fibrous capsule cells; lymphatic drainage of particles through the newly formed joint capsule; granulation tissue reaction in the internal surface of the joint capsule which stores non-removed particles from inadequate drainage; necrosis of granulation tissue in contacting the artificial joint surface; formation of free masses of necrotic tissue in the joint cavity; formation of new granulation tissue due to these necrotic masses and by wear particles liberated from them (the beginning of a vicious cycle); insufficient storage by granulation tissue; formation of "auxiliary" granulation tissue in the fibrous layer of the bone-cement interfaces and in the R.E.S. of the bone-marrow; bone resorption and its replacement by granulation tissue; loosening of the prosthesis.

Acetabulum↗
PubMed1997

The role of cryotherapy for airway complications after lung and heart-lung transplantation.

OBJECTIVE: Although airway problems after lung and heart-lung transplantation have been greatly reduced due to changes in surgical technique, excessive granulation tissue at the anastomosis may threaten airway patency. Treatment options include electrocautery, dilation, laser coagulation and stent placement however, recurrence remains a problem. Cryotherapy, the controlled application of extreme cold, is effective at causing cell lysis in granulation tissue and may therefore be effective after lung transplantation for airway problems arising from granulation stenosis. Our objective was to review our experience with cryotherapy as a first-line treatment for airways compromised by granulation tissue after lung and heart-lung transplantation. METHODS: A retrospective analysis of patient records after lung and heart-lung transplantation was performed. A total of 696 patients were identified who received lung or heart-lung transplants, 64 of whom were found to have granulation tissue at the site of airway anastomosis (8.9% of 721 airways at risk). When the granulation tissue was found to narrow the lumen by > or = 50% and affect lung function. RESULTS: The trachea was involved in 5 patients and the main stem bronchus in 16. Each patient required a mean of 2.6 +/- 2.0 cryoapplications. Anatomical results of cryotherapy were judged excellent to good in 15 patients and fair in 6 patients. Eight patients required endobronchial stenting as part of a multimodality treatment. Overall, the post-treatment FEV1 and FVC increased by 34 +/- 36% and 25 +/- 27% from pre-treatment values respectively (P < 0.001). In 13 patients in whom cryotherapy and dilation alone were effective, the FEV1 increased by 41 +/- 43% (range -11 +/- 138%) and the FVC by 28 +/- 29% (range -4 +/- 96%). These changes were also significant (P < 0.001). Changes in these two parameters were positively and significantly correlated (P < 0.01). Acturial survival at 3 and at 5 years were 57 and 43%, respectively (NS compared to total cohort), and median survival was 978 days (range 365-1862). Six patients are alive at a median follow-up of 5.75 years (range 0.6-8.3). CONCLUSIONS: We conclude that cryotherapy is a safe, effective treatment for excessive granulation tissue after lung and heart lung transplantation and may reduce the need for endobronchial stenting and limit recurrence.

Adult↗
PubMed1991

Induced expression of syndecan in healing wounds.

We have studied the expression of an integral cell surface proteoglycan, syndecan, during the healing of cutaneous wounds, using immunohistochemical and in situ hybridization methods. In normal mouse skin, both syndecan antigen and mRNA were found to be expressed exclusively by epidermal and hair follicle cells. After incision and subsequent suturing, remarkably increased amounts of syndecan on the cell surfaces of migrating and proliferating epidermal cells and on hair follicle cells adjacent to wound margins were noted. This increased syndecan expression was shown to be a consequence of greater amounts of syndecan mRNA. Induction was observed already 1 d after wounding, was most significant at the time of intense cell proliferation, and was still observable 14 d after incision. The migrating cells of the leading edge of the epithelium also showed enhanced syndecan expression, although clearly less than that seen in the proliferating epithelium. The merging epithelial cells at the site of incision showed little or no syndecan expression; increased syndecan expression, however, was detected during later epithelial stratification. When wounds were left unsutured, in situ hybridization experiments also revealed scattered syndecan-positive signals in the granulation tissue near the migrating epidermal sheet. By immunohistochemical analysis, positive staining in granulation tissue was observed around vascular endothelial cells in a subpopulation of growing capillaries. Induction of syndecan in granulation tissue both at the protein and mRNA levels was temporally and spatially highly restricted. Granulation tissue, which formed in viscose cellulose sponge cylinders placed under the skin of rats, was also found to produce 3.4 and 2.6 kb mRNA species of syndecan similar to that observed in the normal murine mammary epithelial cell line, NMuMG. These results suggest that syndecan may have a unique and important role as a cell adhesion and a growth factor-binding molecule not only during embryogenesis but also during tissue regeneration in mature tissues.

Animals↗
PubMed1999

[Experimental observation of origins of osteoblasts in guided bone regeneration in long bone].

OBJECTIVE: To study the origins of osteoblasts in guided bone regeneration (GBR) so as to understand the mechanism of GBR. METHODS: New Zealand rabbits were used. Standard ununited defect models were made in bilateral middle radial shaft of each rabbit. Randomly, one defect enveloped with silicon membrane as test, another without membrane as control. 12 rabbits were selected for X-ray examination weekly after procedure. 30 rabbits were divided into 6 groups, and sacrificed at 3 days, 1, 2, 3, 4, 5 weeks after surgery for histological observation by immunohistochemical staining of BMP, BGP. RESULTS: The sealed spaces were made by silicon membranes in the defects to prevent peripheral tissue ingrowing early. The defect spaces were filled by granulation tissue formed from proliferative endoperiosteal and medullary stromal cells in bone end. Histological characteristics after callus forming showed that there were 2 - 3 layers of osteoblasts in the surface of callus, and granulation tissue in the center of bone defect. The transforming region existed between the extending callus and granulation tissue, which consisted of a few of cells and a lot of stroma. Early proliferative endo-periosteal and medullary stromal cells in the bone end were positive against BMP, BGP. Some cells in the transforming region were positive against BMP, BGP after callus forming. CONCLUSIONS: Osteoblasts derive from endoperiosteum and medullary stroma in the early stage of GBR and from granulation tissue formed by proliferative endo-periosteal and medullary stromal cells in the later stage.

Animals↗
PubMed1998

The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation.

STUDY DESIGN: Surgically obtained herniated lumbar disc specimens were stained with hematoxylin-eosin or toluidine blue (for detection of proteoglycans) or were immunostained with monoclonal antibodies (CD68), antihuman interstitial collagenase (matrix metalloproteinase [MMP]-1) and antihuman stromelysin (MMP-3). OBJECTIVE: To investigate the possible correlation of matrix metalloproteinase activity to granulation tissue formation and lumbar disc herniation, depending on the type of herniation. SUMMARY OF BACKGROUND DATA: Interstitial collagenase and stromelysin have been implicated in the degradation of the matrix of articular cartilage in rheumatoid arthritis, osteoarthritis and degenerated disc tissues. However, their role in the herniation of the intervertebral disc has received little study. METHODS: Twenty-one specimens of lumbar disc herniation (classified as protrusions, subligamentous extrusions, transligamentous extrusions, and sequestrations) and four nonherniated discs were stained with hematoxylin-eosin or toluidine blue or were immunostained with monoclonal antibodies to CD20, CD45RO, and CD68, anti-MMP-1, and anti-MMP-3, using the avidin-biotin-peroxidase complex method. The amount of granulation tissue and results of staining were graded to examine differences in histology among the four herniation types. RESULTS: In sequestration and transligamentous extrusion specimens, granulation tissue containing many CD68-positive macrophages was commonly observed. Most cells in granulation tissue, as well as chondrocytes, stained positively with anti-MMP-1 and anti-MMP-3 antibodies. Granulation tissue was less commonly observed in subligamentous extrusions and was absent from most protrusion specimens and all nonherniated specimens. B and T lymphocytes could not be demonstrated in granulation tissue. CONCLUSIONS: The increased staining of MMP-1 and MMP-3 associated with inflammatory cells of granulation tissue in herniated discs suggests a causal correlation of these proteinases to tissue degradation in herniation.

Adolescent↗
PubMedDate not supplied

Thoracic, abdominal, and vertebral actinomycosis. Diagnosis and long-term therapy in three dogs.

The clinical, laboratory, radiographic, and histologic features and the response to therapy in three dogs with actinomycosis are reported. One dog (dog 1) had a 12-cm nonresectable mass extending from the ventrolateral chest wall into the left ventricular myocardium. Another dog (dog 2) had a diffuse peritonitis with "sulfur granules" and two large masses. One of these masses was nonresectable involving adjacent abdominal structures. A third dog (dog 3) had a subvertebral mass at T1-3 producing quadraplegia. Two dogs had periosteal reactions involving adjacent sternebrae (dog 1) or ribs and vertebral bodies (dog 3) that are characteristic of Actinomyces spp infections. In dogs 1 and 2 the diagnosis was based on the morphologic and tinctorial properties of free sulfur granules and/or tissue granules. Culture results were variable. Tissue from dog 1 yielded no growth, while polymicrobial infections, which included Actinomyces spp, were identified in dogs 2 and 3. Actinomyces odontolyticus was isolated from dog 3. Although the actinomycotic granulomas were either not excised or only partially excised from dogs 1 and 2, both animals were cured by the oral administration of high doses of penicillin G for 19 and 6 months, respectively. Dog 3 responded dramatically to the same antibiotic therapy given for 5 months. However, within 4 months of discontinuing treatment an abscess and draining fistulous tracts developed in the left axillary region. Two surgical fistulectomies and additional penicillin therapy were required to cure this animal. These cases and the current veterinary and human literature on actinomycosis are used to propose a rational approach to the treatment of actinomycosis in the dog.

Actinomyces↗
PubMed1992

[The pH value of granulating wound and skin graft in burn patients].

The relationship between pH of granulation of burn wound and take rate of skin graft was presented. The bacteria in the granulation tissue were also quantified. The results showed: (1) The optimal pH of granulation wound for the take of skin graft is 7.2-7.5; (2) pH of granulation of burn wound is related to quantity and species of bacteria in the granulation tissue. The wound pH is 6.7 or lower when the number of Escherichia coli or Staphylococcus aureus is over 10(7)/gm of granulation tissue. The wound pH is 8.0 when the number of Pseudomonas aeruginosa is 10(8)/gm of granulation tissue. Because the measurement of wound pH is rapid, simple and noninvasive, it might be useful in predicting the take rate of skin graft.

Adolescent↗
PubMed2003

Collagen deposition in the subcutaneous tissue during wound healing in humans: a model evaluation.

Wound healing encompasses coagulation, inflammation, angiogenesis, fibroplasia, contraction, epithelialisation and remodeling. A granulation tissue is produced following incision of tissue such as skin, abdominal wall or the gastrointestinal tract, and the strength of the wound is determined primarily by the collagen content early in the healing course. Few models are available to study wound healing in man. The percutaneous insertion of expanded poly-tetrafluoroethylene tubes (ePTFE) into the subcutaneous tissue has been an established model for 20 years. The procedure is performed using a local anesthesia. The model has a diameter of 2.5 mm, a length of 5-10 cm and a pore size of 90-120 microns which is substantially more than that of vascular grafts. The polymer accumulates granulation tissue, the architecture of which resembles that of a normal surgical wound. Previous studies on the use of the ePTFE model in wound healing research are summarized in detail. Histological and immunohistochemical analyses of the granulation tissue deposited in the model were undertaken. The content of amino acids following hydrolysis of the granulation tissue was determined applying spectrophotometric or HPLC assays. Collagen amounts accumulated in the model are expressed as hydroxyproline per length of ePTFE or per total protein. Following a study in rats we examined 85 healthy volunteers and 158 surgical patients in the studies. Higher contents of hydroxyproline were found 10 days after implantation as compared to 5 days with considerable inter-person variation. Regarding median values there was a 25% difference between two measurements performed on two distinct ePTFE tubes from the same person, and a 12% difference between values obtained from two different pieces of the same ePTFE. Higher accumulation levels of hydroxyproline did not result in higher variability. Deposition of proline in the model correlated closely to total protein content. The ePTFE and a modified PVA model were compared in surgical patients. No reproducible measurements of hydroxyproline deposition were obtained with the PVA model as opposed to the ePTFE model. It is concluded that the modified PVA model is inadequate for determination of collagen deposition in subcutaneous granulation tissue. We found no correlation between collagen deposition levels obtained with placement of the ePTFE model in the subcutaneous tissue of the arm and in an uncomplicated surgical wound of the groin in the same patient, respectively. Significantly higher collagen deposition levels in the model were found in the surgical wound. Conversely, there was a significant correlation between protein deposition levels obtained at the two sites. Patients undergoing minor surgery (groin hernia repair) did not differ from healthy non-traumatized volunteers as regards deposition of collagen in subcutaneous tissue of the arm, whereas patients subjected to major general surgery demonstrated a significant decline during the postoperative phase compared to a preoperative evaluation. This decline was enhanced in patients who had infectious complications. Non-smoking volunteers were found to specifically accumulate more collagen (median value 82%) than smokers matched for age and gender. Irrespective of the smoking status women accumulated significantly more collagen in the model than men. These findings were re-tested in a prospective series leading to the same conclusion. Matrix metalloproteinases (MMP-2 and MMP-9) were determined in wound fluid obtained from the subcutaneous cavities of herniotomy wounds 24 and 48 h after operation. A significant and inverse correlation was demonstrated between MMP-9 after 24 h and accumulation levels of collagen in the ePTFE tube 10 days after implantation in the wound. Finally, it was demonstrated that local application of granulocyte-macrophage colony-stimulating factor into the ePTFE model during implantation specifically and dose-dependently reduced the number of fibroblasts and deposition of collagen. The doses chosen for the experiments resulted in both a local and a systemic effect. It is concluded that the minimally invasive ePTFE model, despite a certain level of variability, presently provides one of the best possibilities of evaluation of the wound healing potential in both volunteers and patients under various conditions. We found the model convenient for the assessment of both matrix deposition during wound healing and the influence of several factors including demographic characteristics, trauma, tobacco smoking, drugs and tissue degrading components of the wound.

Animals↗
PubMed1992

Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.

Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.

Animals↗
PubMed1990

Expression of different glycosaminoglycan synthetic phenotypes by lapine dermal and dermal wound fibroblasts.

Synthesis of extracellular matrix by dermal fibroblasts is an important component of cutaneous wound repair. Scar remodeling and maturation is generally seen as the result of a fibroblast-regulated equilibrium between production and degradation of specific matrix constituents. Fibroblasts from normal dermis, reparative granulation tissue and mature scars were compared in vitro in terms of their ability to produce extracellular glycosaminoglycans (GAGs). All cell lines secreted dermatan sulfate (DS) and chondroitin sulfate (CS) into the culture medium. Hyaluronate (HA) was detected in medium from mature granulation tissue and scar cells, but little or none was found in medium from early granulation tissue or skin cells. In medium from normal skin fibroblasts, an unusual GAG was identified as a potential variant of DS on the basis of co-migration with HA but susceptibility to digestion with chondroitinase ABC. Heparan sulfate (HS) was the major pericellular GAG of all cultures except the mature scar cells, which contained a predominance of DS. A second pericellular GAG was identified as CS in mature granulation tissue cells, scar cells and skin cells; while HA was identified in the pericellular matrix of early granulation tissue cells. In addition, fibroblasts from both skin and early granulation tissue contained a GAG believed to be a variant of CS. These differences in GAG synthesis/secretion between cells maintained under identical culturing conditions could indicate either that distinct fibroblastic substrains exist during different stages of healing or that influences present during the healing process induce stable phenotypic alterations that are maintained through explant culturing and subsequent subcultivation.

Animals↗
PubMed1984

A comparative study of fibroblasts in healing freeze and burn injuries in rats.

In rats, the healing process of a full-thickness dermal freeze injury differs from that of a burn wound. Whereas burn wounds heal by wound contraction, the movement of surrounding normal skin over the defect, freeze wounds heal without wound contraction. That absence of contraction may be due to the freeze wound's lack of myofibroblasts, the cells reportedly associated with wound contraction. Myofibroblasts can be demonstrated histologically by staining the F-actin filaments of the stress fibers with NBD-phallacidin, a fluorescent reagent specific to F-actin filaments. Fibroblasts in normal dermis have no staining stress fibers. However, staining myofibroblasts are uniformly distributed in the granulation tissue of the healing burn and in the islands of granulation tissue between residual connective tissue fibers in the healing freeze wound. These residual dermal fibers were identified by their patterns of birefringence. Residual connective tissue matrix persists following cold trauma and acts like an internal splint. Burn trauma destroys cells and the connective tissue matrix, which is completely replaced with granulation tissue which undergoes wound contraction. Freeze trauma kills the cellular components of dermis, while some residual connective tissue fibers endure. This study shows that the connective tissue matrix can play an important role in the control of wound contraction.

Animals↗
PubMed1989

Differential stimulation of collagenase and chemotactic activity in fibroblasts derived from rat wound repair tissue and human skin by growth factors.

Epidermal growth factor and cartilage-derived basic fibroblast growth factor (EGF and CD-bFGF) are mitogens shown to increase the rate of wound repair in animal models. In addition to being a mitogen for granulation tissue, CD-bFGF stimulates the recruitment of cells to the wound site. CD-bFGF and a closely-related chondrosarcoma-derived fibroblast growth factor stimulated chemotaxis of granulation tissue cells in vitro, each factor having a maximum activity at a concentration of 55 pM. Epidermal growth factor was also a potent chemoattractant for rat granulation tissue fibroblasts; however, maximum activity was obtained at 1.7 nM. Cells from all stages of wound repair were chemotactically responsive to these factors, but there was some attenuation of the response to bFGF in cells derived from fully-organized day 28 granulation tissue. Collagenase-catalyzed restructuring of collagen, an additional significant feature of wound repair, is probably critical to cell movement in an extracellular matrix. Cells derived from organizing (6-day old) sponge granulation tissue secreted latent collagenase constitutively in vitro. In the presence of serum, the production of collagenase was stimulated three-four fold by 1.8 nM bFGF derived either from cartilage or chondrosarcoma. When serum was present, as at a wound site, collagenase production was not enhanced by the addition of EGF. Cells from fully organized, day 21 sponge granulation tissue did not secrete latent collagenase constitutively and could not be stimulated to do so by the addition of EGF, bFGF, or phorbol ester. Human skin fibroblast collagenase production was also stimulated by bFGF and was refractory to EGF. While both classes of growth factor have the ability to promote wound healing, the varying responses they elicit in cell populations from the wound site emphasize the different pathways of cellular activation.

Cartilage↗
PubMed1990

Inhibition of connective tissue formation in dermal wounds covered with synthetic, moisture vapor-permeable dressings and its reversal by transforming growth factor-beta.

An investigation of synthetic, adherent, moisture vapor-permeable dressings (SAM) on dermal wounds healing by secondary intent has yielded the novel observation that SAM dressings severely inhibited the deposition of granulation tissue and subsequent collagenous tissue when compared with air-exposed wounds in mouse and guinea pig systems. Repair tissue was quantitated histomorphometrically in full-thickness wounds covered with SAM or left air-exposed for periods up to 3 weeks. Early in healing, mouse wounds left open to the atmosphere formed a scab which overlay a large volume of granulation tissue derived from two sources, one lateral, and the other deep and centrally located. In contrast, SAM-covered wounds contained only a small amount of granulation tissue which was derived solely from lateral sources. Granulation tissue was replaced by fibrous connective tissue over time, and this was always less in SAM-covered wounds. Deposition of large amounts of connective tissue in air-exposed wounds was associated with significant polymorphonuclear and mononuclear cell infiltrates, while the lack of granulation tissue formation in SAM-covered sites was associated with reduced inflammation. Dressing-induced inhibition of connective tissue could be partially reversed by treatment with transforming growth factor-beta form 1 or 2. Deposition of granulation tissue in large lenticular wounds in guinea pig skin, but not in 6-mm punch wounds, was also inhibited when the wounds were covered with SAM, and the morphology of air-exposed and SAM-covered wounds was similar to that in mice. SAM-covered wounds in mice and guinea pigs may be useful as models of chronic non-healing wounds.

Animals↗
PubMed2001

Foreign body neonatal otitis media in infants.

HYPOTHESIS: An influx of amniotic fluid cellular content (AFCC) into the middle ears during birth may lead to the development of a chronic inflammatory process in the form of varying amounts of granulation tissue even if signs of otitis media are absent. This foreign body neonatal otitis media may predispose the child to recurrent otitis media. BACKGROUND: Foreign body neonatal otitis media caused by AFCC was described by Aschoff and elaborated by Wittmaack 100 years ago. Recent studies have shown how AFCC spreads to various middle ear compartments and causes histologic changes, the severity of which is related to the amount of AFCC. Specific elements become phagocytized after the first months of life but have caused the formation of inflammatory polyps and granulation tissue with round cell secretions in the meantime. METHODS: Ten temporal bones from the Temporal Bone Foundation, derived from infants aged 5 months to 1 year 11 months, were serially sectioned at 20 microm, saved at 0.2-mm intervals, numbered, and stained with hematoxylin and eosin. Every slide was studied for the presence, nature, and stage of pathologic tissue changes of the middle ear and the mastoid antrum. RESULTS: Pseudocystic granulation tissue was massive in the temporal bone of the 8-month-old child born through thick meconium. Severe changes were present in the temporal bones of two infants aged 5 months, one of which showed traces of AFCC. In the temporal bones of two older children, long-standing changes were minor, one of them still showed traces of AFCC. Fresh acute changes and long-standing histologic changes occurred side by side. CONCLUSIONS: Neonatal otitis media caused by AFCC can give rise to extensive granulation tissue and round cell secretion, which is likely to make the ear susceptible to infectious otitis media. Cumulative development of granulation tissue as a result of infection may lead to blockage of attic aeration and drainage pathways, causing irreversible adhesive otitis media. A data base should be formed of all neonates born through meconium-stained amniotic fluid to allow a comparison with those born through clear fluids. Surgery with the creation of auxiliary aeration pathways becomes advisable in the treatment of ears with massive development of granulation tissue.

Amniotic Fluid↗
PubMed2004

Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure.

In myocardial infarction (MI), granulation tissue cells disappear via apoptosis to complete a final scarring with scanty cells. Blockade of this apoptosis was reported to improve post-MI ventricular remodeling and heart failure. However, the molecular biological mechanisms for the apoptosis are unknown. Fas and Fas ligand were overexpressed in the granulation tissue at the subacute stage of MI (1 week after MI) in mice, where apoptosis frequently occurred. In mice lacking functioning Fas (lpr strain) and in those lacking Fas ligand (gld strain), apoptotic rate of granulation tissue cells was significantly fewer compared with that of genetically controlled mice, and post-MI ventricular remodeling and dysfunction were greatly attenuated. Mice were transfected with adenovirus encoding soluble Fas (sFas), a competitive inhibitor of Fas ligand, on the third day of MI. The treatment resulted in suppression of granulation tissue cell apoptosis and produced a thick, cell-rich infarct scar containing rich vessels and bundles of smooth muscle cells with a contractile phenotype at the chronic stage (4 weeks after MI). This accompanied not only alleviation of heart failure but also survival improvement. However, the sFas gene delivery during scar tissue phase was ineffective, suggesting that beneficial effects of the sFas gene therapy owes to inhibition of granulation tissue cell apoptosis. The Fas/Fas ligand interaction plays a critical role for granulation tissue cell apoptosis after MI. Blockade of this apoptosis by interfering with the Fas/Fas ligand interaction may become one of the therapeutic strategies against chronic heart failure after large MI.

Adenoviridae↗
PubMed2004

[The pathogenesis of discogenic low back pain].

OBJECTIVE: To study the pathogenesis of the pain of discography and the discogenic low back pain. METHODS: 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, and 12 physiologically aging discs and 10 normal control discs were collected to investigate the morphologic features and innervation containing neuropeptides substance P (SP), neural filament (NF), and vasoactive-intestinal peptide (VIP). RESULTS: The distinct morphologic characteristic of the disc from the patient with discogenic low back pain was the formation of the strip zone of vascularized granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus in which there was one or several fissures. The structure of annulus fibrosus beyond the strip zone of granulation tissue was basically normal. The structures of the aging discs and the control discs showed the age-related changes. The innervation of SP, NF and VIP immunoreactive nerve fibers in the painful discs was more extensive compared with the aging discs and the control discs. The nerve in growth deep into annulus fibrosus and nucleus pulposus was observed mainly along the strip zone of granulation tissue in the painful discs. CONCLUSIONS: Findings indicate that the strip zone of granulation tissue with extensive innervation in the posterior part of the painful disc is the original site of the pain of discography and the discogenic low back pain. The strip zone of granulation tissue might originate from the injury and subsequent reparation of the margin of annulus fibrosus. The difference of the aging disc and painful disc which can not be differed each other on MRI is the formation of the strip zone of granulation tissue along tear histologically in posterior part of the painful disc.

Adult↗