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Terminal plate fracture in vertebrae of the aged.

The terminal plate fracture of human vertebrae was studied morphologically on midsagittal specimens from 92 autopsy cases which included 82 patients over 60 years. 1. Histologically, the terminal plate fracture was classified into three types by its representative histology. (a) Fracture with intervertebral disk (ID) prolapse: a healed fracture characterized by the presence of the prolapsed ID at the fractured site. ID prolapse in the marrow cavity may or may not be present. The group includes the typical case of the Schmorl's nodule. (b) Fracture with the granulation tissue: The fracture site was embedded by the granulation tissue. Callus and ID prolapse, if any, were insignificant. (c) Diffuse replacement of the hyaline cartilage layer by osteoid tissue: The alteration is seen often at a concaved surface of the terminal plate of significantly deformed vertebrae. 2. The fracture may be classified by the depth of the ID prolapse. (a) Grade 1: ID prolapse may be seen within the fracture aperture, but, not in the marrow cavity. (b) Grade 2: ID prolapse is confined to a labyrinth of subcortical trabeculae. (c) Grade 3: ID prolapse extends to a deep marrow space. The typical Schmorl's nodule belongs to this group. 3. In the present study, the terminal plate fracture was noted in 78% of the patients over 60 years. The female group was affected more often (68% in male, 86% in female). Grade 2 was more often seen in atrophic vertebrae than Grade 1. However, in Grade 3, the fracture appeared unrelated to the atrophy of the vertebrae. 4. The terminal plate fracture was more often seen in the lower deck than the upper deck at the site of two-thirds dorsal from the ventral edge of the vertebral body. The site corresponds roughly to the nucleus pulposus. 5. Histologic variations of the terminal plate fracture and of ID prolapse may relate to senescence of both vertebrae and ID.

Aged↗

Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager.

BACKGROUND: To obtain more information about microcirculatory disturbances in venous ulcers, we studied their laser Doppler flux images and capillary densities. MATERIALS AND METHODS: On photographs of venous ulcers and the adjacent skin of 17 patients, four regions of interest were marked: one non-granulation tissue area (NGTA) within the venous ulcer, one granulation tissue area (GTA) within the ulcer, one adjacent skin area (ASA) and one distant skin area (DSA). Within these four regions the average laser Doppler area fluxes and capillary densities were determined for each patient using a laser Doppler imager and capillary microscopy respectively. RESULTS: The laser Doppler area flux (mean +/- SD in AU) was significantly lower in NGTA (1.39 +/- 1.12) than in GTA (4.06 +/- 1. 52) or DSA (3.86 +/- 1.54) (P < 0.00001). In addition, the ASA flux (1.95 +/- 1.39) was significantly lower than the GTA or DSA flux (P < 0.0001). Capillary density (capillaries per mm2) in NGTA (0.82 +/- 1.98) was significantly lower than that in GTA (6.00 +/- 2.55), ASA (13.88 +/- 5.16) or DSA (10.29 +/- 3.41) (P < 0.0001). In addition, the capillary density of ASA was significantly higher than that of GTA or DSA (P < 0.05). CONCLUSION: The four areas showed the following characteristics: NGTA, low laser Doppler area flux and lowest capillary density (possible sign of ulcer area without healing tendency); GTA, high laser Doppler area flux and second lowest capillary density (possible sign of wound healing); ASA, low laser Doppler area flux and highest capillary density (possible sign of healing process nearly completed; scar); DSA, high laser Doppler area flux and second highest number of capillaries (sign of microcirculation of chronic venous disorder).

Aged↗

Acquired lobar emphysema in premature infants with bronchopulmonary dysplasia: an iatrogenic disease?

Five premature infants in whom bronchopulmonary dysplasia developed following prolonged neonatal respiratory support are presented. In all five patients, right middle and/or lower lobe emphysema related to focal obstructing endobronchial masses of granulation tissue subsequently developed. It is speculated that the granulation tissue formed in response to the repeated mechanical trauma of endotracheal tube suctioning.

Female↗

[Fatal stenosis of trachea and main bronchus due to compression by the spine and sternum in three patients with severe motor and intellectual disabilities].

Three patients with severe motor and intellectual disabilities developed fatal respiratory insufficiencies caused by stenosis of the trachea and main bronchus due to compression by the spine and trachea. The onset of respiratory insufficiency was by 20, 16, and 29 years of age. Chest computed tomography demonstrated deformation and narrowing of the trachea and main bronchus, and shortening of the distance between spine and sternum. Although respiratory insufficiency was temporarily relieved by insertion of a stent into the main bronchus in patient 1, he died at the age of 21 due to proliferation of granulation tissue. Patient 2 died of bleeding from the granulation tissue around the window of tracheotomy at the age of 18 years, and patient 3 died of recurrent pneumonia at the age of 34 years. In conclusion, stenosis of the trachea and bronchus observed in these patients was caused by progressive deformation of the thorax. The stenosis may result in sudden death or recurrent respiratory infections in patients with severe motor and intellectual disabilities.

Adolescent↗

The diabetic rat as an impaired wound healing model: stimulatory effects of transforming growth factor-beta and basic fibroblast growth factor.

Two models of wound repair compared the effect of defined, recombinant growth factors on the rate of wound repair in both normal and streptozotocin-induced diabetic rats: subcutaneous implantation of polyvinyl alcohol sponges and incisional wounding. Transverse incisional wounds were made on the dorsal surface of rats and closed with steel sutures. Three days postwounding the rats received a single injection of either transforming growth factor-beta or vehicle alone directly into the wound site. Animals were sacrificed 7, 14, and 21 days postwounding, and fresh and formalin-fixed wound tensile strength were measured. Diabetic rats had expected defects in wound repair, including decreased granulation tissue and reduced amounts of collagen, protein, and DNA. Fresh tensile strength of the diabetic incisions was 53% of normal on Day 7 (p < or = .01) and 29% of normal on Day 21. Fixed tensile strength was 41% of normal on Day 7 (p < or = .01) and fell to 78% of normal by Day 21 (p < or = .01), suggesting that collagen concentrations of diabetic wounds increased towards normal but did not undergo maturation. TGF beta produced a moderate increase in tensile strength of fresh and fixed wounds of diabetic rats, but not to the levels of wounds in untreated normal rats. Sponges fill with granulation tissue, their reproducible rate of organization being measured by histological and biochemical methods. A single injection into sponges 3 days postimplantation of basic fibroblast growth factor, transforming growth factor-beta, or vehicle only, was evaluated at 7 and 9 days postimplantation. In the sponge model, bFGF and TGF beta were each able to induce significant increases in the accumulation of granulation tissue in both diabetic and normal rats. TGF beta increased the collagen content of sponges by 136% in sponges from diabetic animals (p < or = .001), thereby raising the collagen content to that of normal control wounds, while stimulating a 49% (p < or = .02) increase in sponges from normal animals on Day 9. By contrast, the response to bFGF was predominantly an increase in the protein and DNA content of the sponges. These results emphasize the differential effects of the two cytokines in accelerating healing under conditions of defective wound repair.

Animals↗

Retained ventilation tubes: should they be removed at 2 years?

OBJECTIVES: To assess the complications of ventilation tubes that were retained in children for 2 years or longer and the necessity of removal. DESIGN: A retrospective chart review of all patients who underwent ventilation tube removal from 1997 to 2000, with the exclusion of patients with craniofacial anomalies. SETTING: A tertiary children's hospital. PATIENTS: One hundred twenty-six children with ventilation tubes that were retained for 2 years or longer. INTERVENTIONS: Ventilation tube removal and tympanic membrane (TM) patching. MAIN OUTCOME MEASURES: Otorrhea, formation of granulation tissue, TM perforation, development of cholesteatomas, and tube reinsertion. RESULTS: A total of 126 patients aged 2(1/2) to 14 years (59 girls and 67 boys) underwent removal of their ventilation tubes after 2 years or more. The patients were divided into 2 groups. Group 1 included 67 patients (29 girls and 38 boys) who were younger than 7 years at the time of tube removal. The tubes were retained for 2 to 5(1/2) years (mean retention time, 3.3 years). Group 2 included 59 patients (30 girls and 29 boys) aged 7 years and older at the time of tube removal. The tubes were retained for 2 to 10(1/2) years (mean retention time, 4.2 years). Complications such as otorrhea, formation of granulation tissue, and TM perforation were seen in 10.3%, 13.8%, and 5.2% of the patients with tube retention of 2 to 3 years, compared with 40.0%, 40.0%, and 46.7% of patients with tube retention of more than 5 years. In group 1, transient otorrhea, formation of granulation tissue, and TM perforation occurred in 13.4%, 7.4%, and 6.0% of the patients, respectively, after 2 years of tube retention. In group 2, similar complications occurred in 23.7%, 25.4%, and 27.1% of the patients, respectively. Forty-six patients in group 1 underwent TM patching (31 with paper and 15 with absorbable gelatin film, with a success rate of 91.3%; however, 8 patients (11.9%) required tube reinsertion. In group 2, patching of the TM was done in 40 patients (13 with paper, 24 with absorbable gelatin film, and 3 with fat), with a success rate of 67.5%. Tube reinsertion was necessary in 1.7% of the patients in group 2. No cholesteatoma was encountered. CONCLUSIONS: Higher complication rates are seen in children when ventilation tubes are retained longer than 2 years. Children 7 years and older have a higher incidence of complications from the tube retention than children younger than 7 years. Early removal of ventilation tubes in children younger than 7 years of age, when the risk for otitis media is still present, may result in the need for tube reinsertion.

Adolescent↗

Tracheal surgery in children.

BACKGROUND: The aim of this study is to show that five distinct types of tracheal anomalies should be differentiated with respect to therapy and prognosis. METHODS: The records of 12 infants and children seen over a period of 20 years for different tracheal anomalies such as laryngotracheal stenosis (n = 3), long or short-segment stenosis of the upper (n = 2), middle (n = 6), and lower (n = 1) trachea were reviewed. In addition to these 12 patients with congenital stenosis, 3 other patients needed tracheal resections because of oncologic or traumatic disease: in 2, the trachea was infiltrated by a papillary carcinoma of the thyroid gland and in one, the upper part of the trachea was injured by an oral explosion accident. 25 patients presenting during the same period for other tracheal pathologies including esophagotracheal cleft syndrome (n = 7), tracheomalacia (n = 4), total tracheal agenesis (n = 3), or for placement of a tracheostomy (n = 11) due to other diseases were excluded from this study. RESULTS: There was 1 early death after repair of a laryngotracheal stenosis by cricoid-split and cricoid-splint due to both cerebral hemorrhage and cardiac insufficiency secondary to Fallot's tetralogy. Another child died four weeks after slide tracheoplasty as a result of hypoxic cerebral lesions induced by severe central catheter-related septicemia. One child with therapy-resistant obstructing granulation tissue which developed after a slide tracheoplasty required a tracheostomy. The patient with the tracheal injury died after another accident one year after discharge. All other patients (n = 11) are doing well. CONCLUSIONS: With respect to therapy of congenital and post-intubation tracheal stenosis, four types should be distinguished. Each of these types requires an adequate surgical procedure. The most important postoperative problem in tracheal surgery is the development of granulation tissue. However, the pathogenesis of granulation is still unknown.

Bronchoscopy↗

Follow up of patients with ocular scarring secondary to LOC syndrome treated by amniotic membrane transplantation.

AIMS: To document and discuss the long term outcome of a new ophthalmic treatment for laryngo-onycho-cutaneous (LOC) syndrome. METHODS: Two children were treated by excision of ocular granulation tissue and ocular surface rehabilitation with frozen amniotic membrane (AM). The clinical course of both patients was followed and documented at 2 years and 4 years following the surgery. RESULTS: Patient 1 demonstrated limited recurrence of granulation tissue at 10 months. After 36 months, re-growth of granulation and scar tissue required a further three subsequent operations to the right eye in an attempt to keep the optical axis clear. 4 years postoperatively, neither eye has a clear visual axis. In contrast similar surgery for the right eye of patient 2 has been highly successful, with only very limited non-progressive recurrence after 2 years of follow up. The operation to the left eye has been similarly effective although the follow up is only 6 months. CONCLUSIONS: Ocular surface rehabilitation with AM is the first partially effective treatment for the eye complications of LOC syndrome. The surprising benefit from AM may stem from the primary pathology of the condition. LOC syndrome is caused by a genetic defect resulting in an unusual N-terminal deletion of the alpha3a chain of the basement membrane protein laminin 5. One mechanism through which AM transplantation may act to reduce ocular scarring in this disease is to supplement the abnormal secreted laminin 5 with healthy transplanted laminin. Despite its initial efficacy one episode of AM treatment does not guarantee long term control of the scarring process and variations in AM graft efficacy may be related to other complicating factors such as limbal stem cell deficiency or severity of the initial scarring process.

Amnion↗

Effect of defibrinogenation on wound strength and collagen formation. A study in the rabbit.

Wound healing was studied in Arvin-defibrinogenated rabbits by determinations of skin wound strength and by analysis of collagen content in sponge induced granulation tissue. Strength development was found to be delayed in skin wounds as was the accumulation of collagen in granulation tissue. These results indicate that the initial fibrin formation in a wound is of significance for repair.

Ancrod↗

Effect of topical rh-TGF-beta 1 on second intention wound healing in horses.

OBJECTIVE: To investigate the effects on wound healing of transforming growth factor-beta 1 as a topical treatment to full-thickness, excisional wounds of the distal limb of horses. DESIGN: A randomised block study using four horses, each with wounds assigned to four treatment groups. ANIMALS: Four adult Standardbred geldings. PROCEDURE: Four, 4 cm2, full-thickness wounds were created on the dorsomedial and dorsolateral aspect of the metacarpus or metatarsus of each limb of four horses, giving a total of 64 wounds. For each limb, wounds were randomly assigned to four treatment groups: no treatment (control), carrier (Methyl Cellulose gel), 50 ng/wound rhTGF-beta 1 in carrier, and 500 ng/wound rhTGF-beta 1 in carrier. Wounds were treated on day 0 and day 8. Effects of treatment were evaluated on the basis of the presence of exuberant granulation tissue requiring excision, number of times excision was required, total wound area, area of epithelialisation, area of granulation, and histological evaluation of biopsy samples of wounds on day 8 and excised wounds on day 21. RESULTS: Topical application of TGF-beta 1 at the two concentrations studied had no significant effect on the total area of wounds (P = 0.7), the area of granulation tissue (P = 0.78), the area of epithelialisation (P = 0.92), histological assessment or subjective clinical assessment of wounds. CONCLUSION: TGF-beta 1 had no beneficial effects on wound healing. Additional trials are needed to test if it has value for wound treatment in horses.

Administration, Cutaneous↗

Human fibroblasts in idiopathic retroperitoneal fibrosis express HLA-DR antigens.

Idiopathic retroperitoneal fibrosis (IRF) is a rare human disease characterized by non-neoplastic fibroblastic proliferation associated with chronic inflammatory cells; its pathogenesis is obscure. We undertook an immunohistochemical study for the expression of HLA-DR antigens and other immune-related markers by retroperitoneal proliferating fibroblasts and inflammatory cells from 2 IRF patients. Patterns of immunoreactivity were compared with those expressed by human nodular fasciitis (NF) and granulation tissue. In IRF, most fibroblasts immunostained strongly for HLA-DR antigens, whereas fibroblasts in NF and granulation tissue did, not immunostain at all. The fibroblasts did not immunostain for interleukin 2 receptor, C3b receptor, CD-4, CD-8, or Leu-M1 in any of the tissue studied. Most macrophages and lymphocytes in IRF and NF immunostained Strangly for HLA-DR antigens. In IRF, the CD-4 and CD-8 immunostained T-lymphocytes appeared equally distributed. The expression of HLA-DR antigens by fibroblasts in IRF indicates that this rare disease may indeed be an immune-associated hypersensitivity disorder.

Adult↗

In vitro studies of bone resorption by the root-resorbing tissue from the bovine deciduous tooth.

Granulation tissue which is responsible for root resorption of deciduous tooth lies between root of the deciduous tooth and its permanent tooth germ. This tissue is called "root-resorbing tissue". Its bone-resorbing activity was investigated in vitro. Bovine root-resorbing tissue was cultured in close contact with 45Ca-labeled dead calvaria of rats. Bone-resorbing activity was determined by measuring 45Ca released from labeled calvaria during culture. It was found that only the root-resorbing tissue which was rich in odontoclasts and had a good blood supply in its surface layer had bone-resorbing ability, and that bone resorption occurred only when it was placed in close contact with calvarium. The root-resorbing tissue which was poor in odontoclasts and blood vessels failed to stimulate by 25-hydroxy-vitaim D3 or heparin, but not by larger amounts of parathyroid hormone, vitamin D3, and dihydrotachysterol when added to the culture.

Alveolar Process↗

Nerve and blood vessel growth in response to grafted dermis and cultured keratinocytes.

The aim of this study was to study innervation and angiogenesis in response to grafts of dermis and cultured keratinocytes using immunohistochemical techniques. In a porcine model, fresh autologous de-epidermalized dermis and cultured autologous keratinocytes were combined using a two-stage technique, to produce keratodermal grafts. Wounds were encased within skin graft chambers that prevented the influence of the surrounding skin. As grafts contracted, a peripheral rim of granulation tissue became exposed, allowing us to compare the wound bed beneath grafts with that beneath the raw granulating surface. Grafts were studied for 6 weeks. Angiogenesis was studied using antisera to von Willebrand factor to detect endothelial cells. Nerve growth was studied using antisera to S-100, a Schwann cell marker, and to four axonal markers: protein gene product 9.5, C-flanking peptide of neuropeptide Y, calcitonin gene-related peptide, and vasoactive intestinal peptide. In kerato-dermal grafts (n = 28), organization of blood vessels and nerve growth occurred only beneath areas with epidermal cover as compared with the surrounding granulation tissue. Initially, the immunoreactivity to von Willebrand factor was high, but in areas with epidermal cover it assumed a more orderly pattern with fewer blood vessels. Innervation was first detected by S-100 immunoreactivity seen at 1 to 2 weeks, closely followed by that to protein gene product 9.5 and much later to calcitonin gene-related peptide. C-flanking peptide of neuropeptide Y and vasoactive intestinal peptide immunoreactivity were detected in the wound depth surrounding large blood vessels at 4 to 6 weeks. In control wounds that had been either grafted with de-epidermalized dermis alone (n = 10) or allowed to granulate (n = 10), persistently there was high immunoreactivity to von Willebrand factor but minimal immunoreactivity to the neural markers. In conclusion, kerato-dermal grafts become innervated, and beneath their surface there is also vascular organization to resemble normal skin. Keratinocytes themselves may influence angiogenesis and innervation, as both processes failed to occur beneath granulating areas.

Animals↗

Inflammatory obstruction of oesophageal tubes.

Two patients, intubated for inoperable carcinoma of the oesophagus, recently presented with their tubes blocked by granulation tissue. This complication has not been previously reported. The tissue macroscopically resembled normal mucosa in one and recurrent tumour in the other. The presentation, aetiology, and significance of this granulation tissue is discussed.

Deglutition Disorders↗

Biology of dermal wound repair.

Dermal wound repair events can be temporally, albeit arbitrarily, grouped into inflammation, granulation tissue formation, and tissue remodeling. These phases are not mutually exclusive but rather overlap in time. This review follows the chronology of dermal wound repair, that is, inflammation, granulation tissue formation, and tissue remodeling.

Biology↗

BPC 157's effect on healing.

The 15 amino acid agent BPC 157, showing a wide range of organoprotective action in different experimental models, was used in our experiments in order to establish its influence on different elements connected with the healing process. Elements thought to be of greatest importance in the process of healing are formation of granulation tissue, angiogenesis and production of collagen. In our work we tested the influence of BPC 157 on: granulation tissue and collagen formation, on angiogenesis as well as on tensile strength development, using three experimental rat models: 1) skin incisional wounds; 2) colon-colon anastomoses; and 3) angiogenesis model with synthetic sponge implantation. The specimens were histologically assessed for collagen, reticulin and blood vessels using scoring and morphometry. In all experiments significant differences between BPC 157-treated animals and controls were found, showing a strong, promoting involvement of BPC in the healing process. It is worth noting that these effects were achieved by different routes of application, including intragastric and local, making BPC 157 a potentially useful therapeutic agent.

Animals↗

Histological change in permanently clipped or ligated cerebral arterial wall. Part I. An experimental study in dogs.

In this paper, we discuss the results of a study by light microscope of the effect of permanent clipping or ligation on the intracranial arteries of 38 operation dogs and 7 control dogs. The findings obtained are: 1. In the cerebral arterial circle, necrosis could easily result from ordinary clipping or ligation because of scarce vasa vasorum. 2. As for the incidence of necrosis, the greatest was found in the case of the Yaşargil clip after electric coagulation, next came the Yaşargil clip alone, next ligation, and last the silver clip. The degree of necrosis correlated with the duration of clipping in the cases treated with a spring type clip, and was influenced more by the closing strength at the time of application in the cases with non-spring type clips or ligation. 3. In some of the cases ligated for long duration, recanalization was caused by the passage of the ligature through the vessel wall, suggesting that ligation is not a certain procedure if it is applied alone. 4. The granulation tissue round the clip and ligature began to grow after one month. As for its degree, the most marked granulation was that caused by the silver clip, next the ligature, than the Yaşargil clip after electric coagulation, and finally the Yaşargil clip used normally; in all of them the correlation with the passage of time was noted. 5. In the group of duration three months or more, concentric intimal proliferation was noted peripheral to the clip, and intimal proliferation was also noted exclusively localized to the side of a branch on the central or truncal side of a clip. This correlated in degree with the passage of time. 6. Clipping and ligation are liable to cause necrosis and fragmentation, but on the other hand it was considered that rupture of the vessel wall did not result because of the reinforcing and reparative effect of the reactive granulation tissue and the intimal proliferation which developed in such a manner as to strengthen the area involved.

Animals↗

Delayed pacemaker erosion due to electrode seal defects.

Over a 7-year period, follow-up data were available on 163 patients who underwent 209 pacemaker-related operations for initial insertion or revision of previously implanted units. During the follow-up period, 16 pacemaker generator units were remoaved from 16 pacemaker generator units were removed from 12 patients solely because of the development of local skin erosion. This represents a 7.7% incidence of pacemaker generator erosion. Tree units were removed within a 3-month interval following pacemaker implantation and were associated with positive bacterial cultures, theraby indicating an infectious cause. Findings at removal of the remaining 13 pacemaker generators included extensive fibrosis with chronic inflammation, fibroblastic proliferation, and granulation tissue, which was most prominent at the site of insertion of the pacemaker lead into the pacemaker generator unit. Granulation tissue frequently led from this area to the area of skin attenuation and erythema. Inspection of the pacemaker generator units and electrodes demonstrated fluid ingress and tissue ingrowth toward the electrode due to inadequate seal mechanisms. Inadequate seal design of the pacemaker generator and electrode junction leads to tissue ingrowth with fibroblastic proliferatiog chronic inflammation, and eventual pacemaker erosion.

Aged↗