Comparison of granulation tissue formed beneath epithelial transplants with high and low bone-inducing potential.
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Animals↗
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Bronchoscopic foreign bodies: overcoming granulation tissue.
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Bronchoscopy↗
Thalidomide reduces vascular density in granulation tissue of subcutaneously implanted polyvinyl alcohol sponges in guinea pigs.
The efficacy of thalidomide in the treatment of erythema nodosum leprosum is a well established fact; there is also accumulating evidence of its therapeutic value in a number of other inflammatory and immune-mediated conditions. In addition, thalidomide has been shown to be an inhibitor of angiogenesis induced by basic fibroblast growth factor (bFGF). Nevertheless, its mechanism of action remains speculative. Using guinea pigs, orally administered thalidomide significantly enhanced the response of multinucleated foreign body giant cells (p<0.05) in subcutaneously implanted polyvinyl alcohol sponges. Furthermore, the drug exerted a dual effect in that it reduced vascular density (p<0.05), which was not abolished by recombinant human bFGF, and at the same time amplified the granulomatous response with and without bFGF (p<0.05 and p<0.01, respectively). The results of our experiments represent a further step toward understanding the mechanism of action of thalidomide, with implications for its potential use in wound healing and scar formation as well as in the control of tumorigenesis.
Animals↗
The effects of beta-aminopropionitrile on colonic anastomosis in rats.
Wound contraction is a clinically important biological process because it frequently results in contractures, strictures, and stenosis. If collagen synthesis could be altered to minimize the contracture, then the outcome could be improved. Lathyrism produces poorly cross-linked collagen in healing anastomosis, keeping a larger portion of the synthesized collagen soluble. Ultimately, the amount of contracting collagen is reduced, lowering the bulk and lessening the contracture. The aim of this study was to observe the effects of a lathyrogen, beta-aminopropionitrile (BAPN), on the healing of colonic anastomosis. Thirty rats were divided into three groups. Colostomy and anastomosis were performed on all rats. Intraperitoneal saline solution (control) and either intraperitoneal (ip) or oral (po) BAPN were administered. The rats were killed 1 week later. Anastomotic healing was assessed by bursting pressure and the hydroxyproline content of the anastomotic tissues. Granulation tissue thickness, number of fibroblasts, inflammatory cells, and growing capillaries in granulation tissue per unit area were determined. Collagen fibril diameters were estimated, and spatial arrangements of fibrils were examined by an electron microscope. All results were evaluated by Mann-Whitney U-test. The analyses of anastomotic tissues from BAPN-treated rats showed a significantly reduced mean bursting pressure (158.9 +/- 12.3, 171.3 +/- 13.9, ip and po, respectively), hydroxyproline content (8.9 +/- 2.6, 10.1 +/- 2.7), granulation tissue thickness (24.3 +/- 2.6, 16.1 +/- 5.2), number of inflammatory cells (37.8 +/- 4.3, 25 +/- 4.3), fibroblasts (3.2 +/- 1.1, 2.8 +/- 0.7), and a significantly reduced collagen fiber diameter (15 +/- 2, 20 +/- 3) compared with those of control group (236.9 +/- 9, 14 +/- 4.4, 26.8 +/- 4.8, 39 +/- 2.6, 6.9 +/- 1.1, and 35 +/- 5, respectively). As a result, collagen fibers were flimsy, and lost their regular parallel alignment in the BAPN groups. On the other hand, a number of growing capillaries were found to be significantly increased in these groups (16.5 +/- 1.1, 18.2 +/- 0.7) compared to the control (6.7 +/- 1.3). Thus, it is suggested that BAPN may be useful in the prevention of gastrointestinal stricture formation.
Aminopropionitrile↗
[Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 2. Changes in the area of Fürstenberg's rosette].
In the present study endoscopically diagnosed changes of the Fürstenberg's rosette were examined histologically. For this purpose the teats of 200 slaughtered cows were inspected. In 19 cases proliferations in the region of the Fürstenberg's rosette were found. Additionally, tissue samples were taken from the Fürstenberg's rosette of 26 cows which showed milk flow disorders due to stenoses of this part of the teat. Teats of slaughtered cows as well as biopsy specimens were fixed in 5% formaldehyde and embedded in paraffin and in plastic. All specimens were stained according to H.E., Giemsa and Turnbull, respectively. Histologically, the proliferations of the Fürstenberg's rosette consisted of fibrovascular tissue (granulation tissue) covered by keratinized squamous epithelium (teat canal epithelium) in eleven cases. In the other cases double-layered cuboid epithelium (cisternal epithelium) was found additionally. The formation of granulation tissue and deposition of blood pigment was observed exclusively in areas covered by stratified epithelium. Therefore a traumatic lesion of the teat canal was supposed to be the cause of the histological findings. In contrast to several reports in the literature, however, no indications of an inversion of the teat canal epithelium were found. On the basis of these findings, the hitherto assumed idea of pathogenesis of proliferations of the Fürstenberg's rosette was modified and a new pathogenesis pattern was developed.
Animals↗
[Endoscopic, pathologic-anatomic and histologic findings in the bovine teat. 1. Changes in the area of the teat cistern in slaughtered cows].
In the present study 795 teats of slaughtered cows were examined endoscopically. Teats which showed lesions were examined histologically. Abnormalities were detected endoscopically in 37 teats. In five cases red discolorations were observed. Histologically these alterations proved to be fresh bleedings within the fibromuscular layer of the teat cistern. Thirteen teats showed yellowish discolorations of the cistern surface. Three of these cases could not be cleared up histologically. In the other cases moderate or severe blood pigment deposition (n = 10) or severe fibrosis (n = 3) of the fibromuscular layer were found. Neither fresh bleeding nor severe blood pigment deposition was found in teats with normal coloured epithelium of the cistern. Cistern surface was smooth in 18 cases, whereas in 19 cases nodules were found. Histologically all nodules consisted of fibrovascular tissue ("granulation tissue") covered with cisternal epithelium. Detailed histological examinations, however, revealed considerable morphological variations regarding the overlying epithelium, the extent and kind of cellular infiltration, the extent of angioplasia and fibroplasia as well as fresh bleedings or deposition of blood pigment in the underlying fibrovascular tissue in some cases. It was concluded, that teat endoscopy enables a differentiation between fresh and old bleedings according to the coloration of the cisternal surface. Nodular proliferations of the cistern surface generally consists of fibrovascular ("granulation") tissue. Further histological details, however, and thus possible information about the pathogenesis of the lesions cannot be assessed endoscopically.
Animals↗
Quantitation in inflammatory pleural disease to distinguish tuberculous and paramalignant from chronic non-specific pleuritis.
AIM: To determine by morphometry if pleural biopsies with the histopathological diagnosis of "non-specific pleuritis", malignant, and tuberculous disease could be distinguished morphologically from those with truly non-specific disease. METHODS: Each pleural biopsy was reviewed taking into account three compartments of reference: the visceral/parietal mesothelial compartment, the submesothelial screen compartment, and the submesothelial adipose tissue compartment. Normal connective tissue, granulation tissue, fibrocellular proliferation, fibrin, polymorphonuclear cells, mononuclear cells, and mesothelial cells were measured using conventional point counting procedures in terms of the fractional area occupied by each parameter within each compartment of reference. Ranking was carried out on 164 patients, based on their diagnosis: chronic non-specific disease (n = 57), tuberculosis (n = 27), malignant disease (n = 58), and conditions associated with transudative effusions (n = 22). RESULTS: Stepwise discriminant analysis of the resulting data showed that biopsies from patients with tuberculosis, malignant disease, and chronic non-specific disease could be distinguished between themselves and normal cases. Statistical differences among the four groups were observed for eight morphometric parameters related to components of inflammation and extension throughout the three pleural anatomical compartments. A robust discriminant function permitted an adequate classification of the three groups of disease in 88.41% of the cases. Pleural biopsies with fibrin incorporated within granulation tissue on the submesothelial screen compartment showed 100% specificity for patients with tuberculosis, while mononuclear cells in a band-like infiltrate on the submesothelial adipose tissue compartment showed 93.1% specificity for patients with malignant disease. The truly non-specific pleuritis was characterised by deposits of fibrin in the subpleural compartment and discrete signs of chronic inflammation and reparatory fibrosis on the submesothelial screen. CONCLUSIONS: Morphometric analysis of pleural biopsies may be a useful supplementary histological procedure to support the diagnosis of pleural tuberculosis and malignant disease.
Biopsy, Needle↗
cAMP levels in reactive tissues around dimethylpolysiloxane solid implants.
By the aid of radioimmunologic assay, the authors measured the cAMP content of the reactive capsules around solid dimethylpolysiloxane implants in mice at different times; they also measured the same substance in some human connective tissues (granulation tissue and normal dermis) and compared together all the values they obtained. Different concentrations of cAMP in different tissues seem to reflect correspondent histologic findings, since they vary according to them. These values also seem to indicate a close correspondence between the development of the process of wound healing and of the foreign-body reaction following the implantation of alloplastic materials. On the basis of these data, the authors suggest an experimental therapeutic trial to enhance peripheral cAMP synthesis in order to control the process of reactive capsule constitution.
Animals↗
Gallium-67 citrate uptake in experimental tumors and inflammatory lesions--an histo-autoradiographic correlation.
In a DAB-hepatoma organic tumor, Ga-67 accumulated markedly in the hepatocellular carcinoma with scant stroma but not in the cholangioma that was rich in connective tissue. No granulation tissue was formed around the tumor. In transplanted tumors (Ehrlich's tumor and Sarcoma 180), Ga-67 accumulated in the granulation tissue within the fibroblasts, leukocytes and capillaries surrounding the tumor, rather than in the tumor. In inflammatory lesions, Ga-67 uptake was similar in granulation tissue with large numbers of phagocytes, such as leukocytes and histiocytes, and capillaries. There was a very good correlation between the degree of Ga-67 uptake and of cellular infiltration and the proliferation of capillaries. Ga-67 uptake, both in inflammatory lesions and in transplanted tumors, was observed in the granulation tissue. This result implies that the mechanisms of Ga-67 uptake in tumor and inflammatory tissues are not the same, because Ga-67 accumulated in the DAB-hepatoma that had no inflammatory granulation tissue. This study indicates that a non-transplanted tumor is required to study Ga-67 accumulation in tumors, as different results may occur in tumors with and without inflammatory granulation tissue.
Animals↗
[Successful treatment of benign tracheal stenosis with a silicone stent (Polyflex-Stent) over 5 years].
Inoperable, functional relevant stenoses of the airways can be effectively treated short-termed and medium-termed by means of bronchoscopic stenting occasionally, silicone stents cause problems after long-term periods, such as migration and retention of bronchial secretions. Metallic stents can lead to obstructing granulomas or even bronchial wall perforation. As regards long-term treatment with airway stents over several years, there is little experience and no uniform recommendations are known. We report on a 76-year old female patient with a severe benign subglottic tracheostenosis after tracheostomy who was successfully treated by means of bronchoscopic dilatation and stenting with a silicone stent (POLYFLEX stent). POLYFLEX Stent is a self-expanding silicone stent with an encapsulated monofilament network made of polyester. The network is completely covered by a silicone layer with a smooth inner surface (protecting against incrustation) and a structured outer surface of the stent (protecting against migration). The ends of the monofilaments were provided with a special protection to avoid tissue granulation and to yield x-ray contrast. During a follow-up of almost 5 years the stent is well tolerated and there is no restenosis. Complications such as migration, obstructing secretions and obstructing granulomas did not occur. A slight bronchial hypersecretion presented no problem under regular inhalation therapy with isotonic NaCl solution. 21 and 56 months after stenting there were two episodes of minor haemoptysis. There was no demonstrable source of haemorrhage by bronchoscopy. After 56 months, biopsy at the distal opening of the stent showed a squamous cell metaplasia, but no granulation tissue. Microbiological analysis of bronchial secretions revealed an increasing, but clinically silent colonisation with potentially pathogenic microorganisms.
Aged↗
Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.
An important event during wound healing is the contraction of newly formed connective tissue (granulation tissue) by fibroblasts. The role of polypeptide growth factors in the process of wound contraction was investigated by analyzing the influence of transforming growth factor beta (TGF-beta), platelet-derived growth factor on the ability of fibroblasts to contract a collagen matrix in an in vitro system. TGF-beta, but not the other growth factors tested, markedly enhanced the ability of BHK-21,3T3-L1, and human foreskin fibroblasts to contract collagen gels. These results suggest that TGF-beta released from platelets and inflammatory cells at sites of tissue injury stimulates fibroblasts to contract the provisional wound matrix and that this effect contributes to the ability of TGF-beta to accelerate wound healing.
Animals↗
Dynamics and localization of activin A expression in rat gastric ulcers.
BACKGROUND: Activin A, the homodimer of the activin/inhibin betaA subunit, has been shown to participate in cutaneous wound healing. In this study we intended to determine its part in gastric ulceration. METHODS: Activin A expression was studied by immunohistochemistry and in situ hybridization in acetic-acid-induced chronic gastric ulcers in rat. The dynamics of this process were also assessed by quantitative real time RT-PCR and RNase protection assays (RPA). The effects of different doses of this cytokine on epithelial and mesenchymal cell proliferation were quantitated in vitro. RESULTS: Low amounts of activin A and its mRNA were expressed by epithelia, endothelia and fibroblasts in intact gastric tissue. Granulation tissue of gastric ulcers and gastric glands adjacent to the ulcer rim expressed markedly increased amounts of activin protein as well as activin/inhibin betaA mRNA. RPA and RT-PCR studies revealed a more than 3-fold increase in the relative abundance of this mRNA. Activin A did not affect the proliferation rate of fibroblasts and epithelial cells in vitro. CONCLUSIONS: Activin A participates in gastric ulcer healing in a similar fashion as in cutaneous wounding. Its expression on protein and mRNA level is markedly increased in ulcer base and rim.
Activins↗
The reliability of digital imaging in the remote assessment of wounds: defining a standard.
CONTEXT: Telemedicine has been used for remote management of many medical problems. Given the ever-expanding demands to provide increasing service with increasingly limited resources, quality care and practice efficiency can be enhanced by telemedicine. OBJECTIVE: This study was undertaken to explore the reliability of wound assessment using computer-transmitted digital imagery compared with a traditional bedside evaluation and also to assess its potential role in healthcare delivery. DESIGN/SETTING/PATIENTS: In the hospital setting, rounding vascular surgeons and a surgical resident evaluated the wounds on the service. A digital photograph was obtained with a 3.3 megapixel camera, and a wound-assessment tool was completed. A plastic surgery attending then reviewed the images at a later date and completed the same data tool. MAIN OUTCOME MEASURES: Wounds were rated for eschar, exposed bone, cellulitis, purulence, swelling, granulation tissue, granulation color, and depth using a standardized data collection tool. kappa statistics were computed for all variables, between raters. RESULTS: There were 2 phases of the study. In both phases, there was 100% agreement by the rounding physicians that the digital image was representative of the wound. Phase 1 agreement between evaluators was moderate to almost perfect, as demonstrated by kappa values (range, 0.50-0.87). In phase 2, all variable kappa values were rated as almost perfect, except the ability to evaluate depth of the wound to the millimeter, which was rated as substantial. CONCLUSIONS: The ability to accurately evaluate a wound on the basis of a digital image is possible. However, it requires training of participants and is facilitated by use of an assessment tool. With these caveats, evaluation of wounds using digital images is equivalent to bedside examination. This technology can improve practice efficiency, provide needed expertise at remote sites, and is an acceptable alternative method of wound assessment.
Computers↗
Subepidermal calcified nodule in a 7-month-old boy.
A 7-month-old healthy white boy presented for evaluation of a papule on his right ear. His mother reported a small cut-like lesion at this site shortly after birth that had gradually grown over time. The patient was born full term via repeat cesarean section. On physical examination, located on the right superior helix, there was a 5-6 mm, pink, firm papule with a rough scaly surface and peripheral erythema (Figure 1). The lesion was shave excised and sent for histologic analysis. Microscopic examination revealed a defect of the epidermis with underlying fibrin deposits (Figure 2). Subjacent to the ulcer, there was chondroid tissue, granulation tissue with prominent vascularity, and an extensive amount of amorphous calcified material throughout the dermis extending to the base of the specimen (Figure 3). The clinical and pathologic findings were consistent with a subepidermal calcified nodule (SCN), an uncommon idiopathic calcinosis. The lesion was surgically removed with good results.
Calcinosis↗
Influence of chlorhexidine rinsing on the healing of oral mucosa and osseous lesions.
The influence of chlorhexidine rinsing on wound healing was studied using standardized, open mucosal-osseous wounds in the left side of the palate in Wistar rats. In five test groups, each containing 10 rats, rinsing was performed twice daily for 30 sec with 0.1, 0.2 and 0.5% chlorhexidine solution, chlorhexidine solution vehicle, and Ringer solution. A sixth test group (control) was not rinsed at all. Seven days postoperatively, wound healing was evaluated clinically (size of the defect) and histomorphometrically (percent composition of mature connective tissue, immature connective tissue, granulation tissue, fibrin with granulocytic infiltrate). Clinically it was clear that wound healing was best in those animals that rinsed with Ringer solution, and worst in those that rinsed with 0.5% chlorhexidine solution. Increasing concentration of chlorhexidine caused a delay in wound healing, which in the following cases resulted in significant differences: rinsing with Ringer solution and vehicle versus all concentrations of chlorhexidine, no rinsing versus 0.5% chlorhexidine. Intensive rinsing with high concentrations of chlorhexidine may, after oral surgical operations, especially surgery in which bone is exposed, result in delay and disturbance of wound healing in humans.
Animals↗
Effect of cerebrospinal fluid leakage on wound healing in flap surgery: histological evaluation.
The aim of this study was to find out the effect of CSF leakage on wound healing after flap surgery. Sixteen male Wistar rats were used. The superiorly based rectangular dorsal skin flap 3 x 3 cm was elevated at the interscapular region. Through this opening, paraspinal muscle dissection and three-level bilateral laminectomy were done. Finally, a dura defect with a diameter of 3-4 mm was created. In the control group, laminectomy was performed as in the study group but the dura was left intact. Persistent CSF leakage was confirmed using isotope cisternography. At the end of 2-week study period, there was no necrosis, infection, or dehiscence of the flap in either group. On necroscopy, cyst formation over the dura defect was detected in 4 animals of the study group. Another gross finding in this group was intensive vascularization of the undersurface of the flap and wound bed. With HE staining, the tissue sections from the study group revealed new vessel formation with small diameter, increase in the reactional mesenchymal tissue, granulation tissue, degeneration of the striated muscle fibers, dystrophic calcifications, fat necrosis, and coagulation necrosis (ischemic necrosis). In the control group, there was only minimal lymphocytic invasion of the subdermal plane. In this study, we have shown that CSF leakage itself has effects on wound healing in the absence of known causative factors.
Animals↗
Auditory tube and middle ear mucosa in nonpurulent otitis media.
Most functional disturbances within the auditory tube can be shown and documented morphologically. In the case of a blocked tube we demonstrated changes on the tubal lining as well as in the adjacent salivary glands. Complete obliteration of the lumen is a very rare instance. A lack of ventilation already produces a vacuum within the tympanic cleft, followed by a typical effusion out of the altered mucosa. Anaerobic conditions favor hypertransformation and metaplastic transformation of the epithelium. The missing clearance makes the middle ear discharge a great challenge to the mucosa. Granulation tissue proliferates, an enzyme production starts, phagocytes help to eliminate the tympanic content. If the auditory tube is blocked long enough, the result is the atelectatic tympanum, filled by scar tissue, granulations with fatty degeneration or dystrophic calcification. The ossicular chain is fixed, if not destroyed or interrupted. A retraction pocket within the eardrum membrane, often a reason for secondary acquired cholesteatoma, is very dangerous.
Ear, Middle↗
Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer as a drug delivery system for 5-fluorouracil: a histopathological evaluation.
Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer (PGLA) is a potentially useful depot drug delivery system for 5-fluorouracil (5-FU). The purpose of this study was to evaluate the fibroinflammatory reaction induced by this polymer. Polymer discs without 5-FU were inserted subconjunctivally in one eye of each of two guinea pigs and four pigmented rabbits (control group), and discs containing 20% 5-FU were inserted subconjunctivally in both eyes of nine pigmented rabbits (study group). The tissue reaction to the copolymer did not differ between rabbits and guinea pigs, with a mild mixed inflammatory reaction 1 week after implantation. At 2 weeks a thin fibrous capsule surrounded the discs, with no change in the amount of inflammation. At 4 weeks the disc had disintegrated, but residual polymer was seen within multinucleated giant cells in the episcleral tissue. Granulation tissue and inflammatory responses were mild. Less inflammation and fibrosis occurred in the study eyes, although the pattern of response was similar in the two groups. The inflammatory response to PGLA was markedly less than that to implanted collagen shields, and our findings suggest that PGLA implant is a promising ocular drug delivery system for 5-FU after filtration surgery.
Animals↗