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Biomedical subjects

T E Wright

Publications and source records attributed to T E Wright.

At least 19 recordsLinked to original sources

Transforming growth factor beta(2) lowers the incidence of incisional hernias.

BACKGROUND: Approximately 200,000 incisional hernias are repaired annually in the United States. The high incidence (11-20%) and recurrence rate (24-54%) for incisional hernias have not changed appreciably in 75 years. Mechanical advances in suture material, incision orientation, and closure technique have failed to eliminate this common surgical complication. A biological approach to acute wound failure may offer a new strategy. METHODS: A rodent incisional hernia model was used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in groups 2 and 3 was injected immediately prior to incision with 100 microl of vehicle alone or vehicle containing 1 microg of transforming growth factor beta(2) (TGF-beta(2)). Necropsy was performed on Postoperative Day 28 and the wounds were examined for herniation. RESULTS: Incisional hernias developed in 88% (35/40) and 79% (11/14) of untreated incisions and those treated with vehicle alone. No hernias formed in the TGF-beta(2)-treated incisions (0/16, P < 0.05). Standard histology and immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast chemotaxis and increased collagen I and III production in TGF-beta(2) treated incisions. CONCLUSIONS: Treatment of abdominal wall fascial incisions with TGF-beta(2) prevented the development of incisional hernias in this rat model. TGF-beta(2) stimulated fascial macrophage and fibroblast chemotaxis as well as acute wound collagen production. A biological approach such as this may reduce the incidence of incisional hernia formation in humans.

Abdominal Muscles↗

Abdominal wall repair is delayed during hepatic regeneration.

BACKGROUND: Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor beta levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. MATERIALS AND METHODS: Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 microg of transforming growth factor beta(2) (TGF-beta(2)) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-beta(2)) and hepatocyte growth factor (HGF) levels were measured by ELISA. RESULTS: Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P<0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-beta(2) levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-beta(2) shifted the healing trajectory of deficient wounds back toward a control pattern. CONCLUSION: Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-beta(2) suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.

Abdominal Muscles↗

Fascial incisions heal faster than skin: a new model of abdominal wall repair.

BACKGROUND: Optimal healing of the fascial layer is a necessary component of complete abdominal wall repair. The majority of acute wound healing studies have focused on the dermis. We designed a model of abdominal wall repair that, to our knowledge, for the first time simultaneously characterizes differences in the wound healing trajectories of the fascia and skin. METHODS: Full-thickness dermal flaps were raised on the ventral abdominal walls of rats, and midline fascial celiotomies were completed. The dimensions of the flap were developed so as to have no detrimental effect on skin healing. The dermal flaps were replaced so that the fascial incisions would heal separately from the overlying skin incisions. Animals were killed 7, 14, and 21 days after operation and fascial and dermal wounds were harvested and tested for breaking strength. Fascial and dermal wounds were also compared histologically for inflammatory response, fibroplasia, and collagen staining. RESULTS: Fascial wound breaking strength exceeded dermal wound breaking strength at all time points (9.16 +/- 2.17 vs 3.51 +/- 0.49 N at 7 days, P <.05). Fascial wounds also developed greater fibroblast cellularity and greater collagen staining 7 days after the incision. There was no difference in wound inflammatory response. CONCLUSIONS: Fascial incisions regain breaking strength faster than simultaneous dermal incisions. The mechanism for this appears to involve increased fascial fibroplasia and collagen production after acute injury.

Abdominal Muscles↗

Initiating the inflammatory phase of incisional healing prior to tissue injury.

BACKGROUND: The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS: In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS: Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION: This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.

Animals↗

Effects of intrapartum administration of invert sugar and D5LR on neonatal blood glucose levels.

OBJECTIVE: To compare the effects of D5LR and invert sugar administered intrapartum on neonatal blood glucose concentrations. STUDY DESIGN: This is a prospective, randomized, double-blind study. A total of 32 insulin-requiring diabetic patients were randomized to receive either intravenous 10% invert sugar or lactated Ringer's solution with 5% dextrose (D5LR). Regular insulin was given intravenously with an infusion pump to maintain the plasma glucose concentration between 60 and 90 mg/dl. Neonatal blood glucoses were measured at 30 minutes after birth, four times every hour, and thereafter as indicated. Student's t-test was used for continuous variables and Fisher's exact test was used for categorical data. RESULTS: There were no differences in neonatal blood glucose levels, incidence of neonatal hypoglycemia, or length of neonatal hospital stay between the two groups. CONCLUSION: Intrapartum administration of invert sugar is not associated with better neonatal homeostasis of glucose compared with using D5LR. Thus, given the expense of invert sugar, D5LR appears to be preferable for intrapartum control of maternal blood glucose.

Adult↗

The effect of TGF-beta2 in various vehicles on incisional wound healing.

BACKGROUND: The isoforms of transforming growth factor beta (TGF-beta) have been shown to be deficient in models of impaired wound healing. Exogenous application of the growth factor to enhance healing as been investigated. TGF-beta1 has been shown to enhance incisional wound strength, but to be dependent on the vehicle used to carry the cytokine. Because TGF-beta2 has shown safety in human trials of chronic wound healing, this study evaluates TGF-beta2 in acute incisional healing using a variety of vehicles. METHODS: Using an acute incisional wound model in healthy rats, rhTGF-beta2 was suspended in various vehicles including fibrin sealant (normal commercial concentration), fibrin sealant (dilute concentration), phosphate buffered saline/serum albumin, and a carboxymethycellulose gel. A single dose of the agent was instilled into the incisions at the time of wound closure and breaking strength analyses and histology performed periodically from days 3-14. RESULTS: TGF-beta2 enhanced the gain of incisional strength in all vehicles during the first two weeks of healing. This was most noticeable by day three with the carboxymethycellulose gel, but by day 7 with the other vehicles. Like reports with TGF-beta1, TGF-beta2 accelerated the gain of wound strength by about three days by day 11. Normal density fibrin sealant delayed incisional healing; whereas, the other vehicles without TGF-beta2 had no significant effect. CONCLUSIONS: The use of TGF-beta2 appears to be of value in increasing incisional wound strength in the first 14 days post-wounding in healthy rats and this effect is demonstrated in a variety of vehicles. These data support the hypothesis that the "normal" incisional wound healing curve can he shifted to the left. Shortening the time for gain of incisional wound strength may have potential clinical use.

Animals↗

Minoxidil and wound contraction.

Minoxidil has been proposed as a potential topical inhibitor of wound contraction and proliferative scarring. Suggestions for this application are derived from in vitro investigations demonstrating inhibition of various fibroblastic functions. The purpose of this study was to attempt to establish in vivo support of these effects using an established animal model of wound contraction. Standardized cutaneous wounds were created on the dorsum of Sprague-Dawley rats, which were divided equally into six treatment groups. Wounds were treated daily after tracing their unhealed areas. On complete closure of the wounds, analyses of the contraction rates and tensile strength were performed for comparison among groups. Minoxidil did not demonstrate significant inhibition of wound contraction rates relative to either an inert vehicle, an active vehicle, or no treatment. Contrarily, as previously demonstrated in this animal model, silver sulfadiazine did demonstrate significant inhibition of wound contraction rates relative to both vehicles. No significant difference in tensile strength was demonstrated among groups. These observations do not support the proposed use of minoxidil as an "antifibrotic" agent.

Animals↗

Performance of the polypropylene fiber tailstring on the Copper 7 intrauterine device.

New and used polypropylene tailstrings from the Copper 7 (Cu-7) intrauterine device were examined by a combination of analytical techniques. Optical microscopy, scanning acoustic and electron microscopy, x-ray diffraction, energy dispersive x-ray analysis, and chemical etching were employed to elucidate both the surface and interior morphology of new Cu-7 tailstrings. Tailstrings removed from women following varying periods of use were investigated with optical microscopy, scanning and transmission electron microscopy. In addition, a subset of the used tailstrings were cultured to identify the types of microorganisms associated with them. Our findings show that unused Cu-7 tailstrings are in various stages of degradation owing to a combination of factors which include the high-draw ratio employed during manufacturing, the method of packaging, and the use of a particulate colourant. Furthermore, it is evident that used Cu-7 tailstrings undergo major deterioration while in situ because of the unfavorable interactions between the highly drawn polypropylene and the physiological environment. These results indicate that the polypropylene tailstrings as manufactured for use with the Cu-7 IUD fail to meet accepted design criteria for biomedical implants.

Bacterial Infections↗

Residual right-to-left atrial shunt following surgical relief of pulmonary valvar stenosis.

Of 264 patients undergoing pulmonary valvotomy for pulmonary stenosis or atresia at the University of Minnesota, 23 had a right-to-left shunt preoperatively. In none was the atrial communication closed at the time of pulmonary valvotomy. At postoperative cardiac catheterization, no atrial level shunt was found in 19, indicating that effective closure of the communication had occurred. In the remaining 4, a right-to-left shunt persisted despite adequate relief of the stenosis. Each of the 4 has undergone subsequent closure of the atrial septal communication without difficulty.

Adolescent↗

Periodontal status of patients with abnormalities of the immune system. II. Observations over a 2-year period.

Patients with IgA deficiency and agammaglobulinemia were pair-matched to immunocompetent subjects by age and Plaque Index. Clinical examinations performed initially and after 2 years included the Plaque Index, Gingival Index, Periodontal Disease Index, caries experience (DMF-T) and full mouth radiographic surveys. Therapy during the 2-year period included oral hygiene instructions, prophylaxis and indicated restorative treatment. Immunodeficient patients manifested consistently lower levels of gingival inflammation than matched immunocompetent patients at both examination periods. Caries experience of immunodeficient patients was also less during the study interval, and five of these patients demonstrated DMF-T scores of zero. No developmental abnormalities, acute gingival or mucosal lesions, or attachment loss associated with periodontitis was observed in either group.

Adolescent↗

Comparison of the plaque microflora in immunodeficient and immunocompetent dental patients.

The nature and extent of the immune dysfunctions in 20 immunodeficient patients, as well as the immunocompetence of 22 control subjects, were verified by cell-mediated responsiveness and immunoglobulin quantitations. Comparisons of the microbial composition of supragingival plaque between the two populations showed that a greater number of immunodeficient than control subjects harbored Candida sp. and Staphylococcus sp. Conversely, a lower number of immunodeficient than control subjects harbored Streptococcus mutans. Also, patients with immune dysfunctions had a lower dental caries experience than their immunocompetent counterparts.

Antibody Formation↗

IgG subclasses in human periodontal disease. II. Cytophilic and membrane IgG subclass immunoglobulins.

Lymphocyte membrane-associated IgG subclass antibodies in human periodontal disease were studied to ascertain the relative presence of cytophilic IgG antibodies and the membrane Fc receptors which bind them. The experimental approach correlated the effect of incubating gingiva in tissue culture medium to remove cytophilic antibodies with the changes in the number of Fc receptors detectable after washing. The evidence indicated that the majority of lymphocytes in mild gingivitis lesions lacked cytophilic IgG antibodies as well as Fc recetors. In severe gingivitis, the number of IgG subclass bearing lymphocytes increased to about half of the total lymphoid population, while the percentage of Fc receptor bearing cells remained quite low (12.3 % +/- 3.2, S.E.). The majority of IgG subclass bearing lymphocytes had membrane IgG which serve as receptors for antigen; such cells are classically defined as bone marrow (B) derived lymphocytes and serve as the progenitor for plasma cells. Gingival specimens for patients with periodontitis were found to contain the highest percentage of Fc receptor bearing lymphocytes (38.3% +/- 12.6 S.E.) and cytophilic IgG antibodies. The findings indicate that the clinical stages of human periodontal disease are characterized by different populations of infiltrating lymphocytes.

Gingiva↗

Lysosomal enzyme secretion and volume contraction induced in neutrophils by cytochalasin B, chemotactic factor and A23187.

The secretion of lysosomal enzymes from rabbit peritoneal polymorphonuclear leukocytes caused by either cytochalasin B, or cytochalasin B plus chemotactic factors, or by the divalent ionophore, A23187, is associated with a decrease in the volume of these same cells. No quantitative correlation could be found between the extent of lysosomal enzyme secretion and volume decrease for any of the three stimuli. This suggests that the volume decrease is neither the direct cause nor the result of the secretion.

Animals↗

In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent.

Human keratinocyte growth factor-2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor-2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic "nude" rats, surgical incisions in Sprague-Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor-2 were compared to a vehicle control and keratinocyte growth factor-1. Keratinocyte growth factor-2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor-1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor-2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.

Animals↗