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Biomedical subjects

William C Lineaweaver

Publications and source records attributed to William C Lineaweaver.

At least 55 records · Page 3Linked to original sources

Regulation of inducible nitric oxide synthase in ischemic preconditioning of muscle flap in a rat model.

PURPOSE: Ischemic preconditioning has been shown to influence flap tolerance to prolonged ischemia. Nitric oxide (NO) synthesis is one of the proposed mechanisms involved in ischemic preconditioning. In this study, the molecular marker of NO is examined in correlation with ischemic preconditioning on improving muscle flap survival. METHODS: Fifty male Sprague-Dawley rats were randomized into experimental and control groups. The gracilis muscle flap with femoral vascular pedicle was used as a flap model. Ischemic preconditioning consisted of 3 sequences of clamping the pedicle for 10 minutes followed by 10 minutes of reperfusion for a total of 1 hour. In part I, the experimental group (n = 10) underwent ischemic preconditioning for 1 hour. In the control group (n = 10), the flaps were dissected without clamping of the pedicle. Both groups were then subjected to 4 hours of global ischemia by continuous pedicle clamping, after which the flaps were sutured to their beds. On postoperative day 3, flap survival was determined by gross and histologic examinations. The evaluators were blinded to the treatment. In part II, the experimental group (n = 12) underwent ischemic preconditioning, while the control group (n = 12) did not. The flaps from each group were harvested for inducible nitric oxide synthase (iNOS) gene expression using reverse transcriptase-polymerase chain reaction at the end of 1 hour after reperfusion and at 4 hours of global ischemia. RESULTS: The results indicated a significantly higher survival rate in the experimental group than in the control group (90 versus 50%, P < 0.05). iNOS gene expression was significantly higher in the experimental group than in the control group at 1 hour after ischemic preconditioning (0.73+/-0.18 versus 0.26+/-0.11, P < 0.01). However, after 4 hours of global ischemia, iNOS expression in the control group was statistically higher than in the experimental group (0.83+/-0.16 versus 0.26+/-0.07, P < 0.01). CONCLUSIONS: We conclude that ischemic preconditioning can enhance flap tolerance to ischemia-reperfusion injury and improve flap viability rate. This study provides evidence that the regulation of NOS may play a role in ischemic preconditioning phenomenon and warrants further investigation.

Analysis of Variance↗

Vascular endothelium growth factor, surgical delay, and skin flap survival.

OBJECTIVE: Cytokines may be a mechanism by which surgical delay can increase flap survival. We previously found that preoperative vascular endothelium growth factor (VEGF) administration in the rat transverse rectus abdominis myocutaneous (TRAM) flap could improve skin paddle survival. In this study, we used partial elevation of the rat TRAM flap as a surgical delay to assess endogenous cytokine expression and tissue survival comparable to undelayed TRAM flaps. METHODS: In Part I, TRAM flaps underwent surgical delay procedures; 7 days later, the flaps were completely elevated and reinset. At the same time, other flaps were raised and reinset without delay. Skin paddle survival in both groups was evaluated at 7 days. In Part II, skin biopsies from TRAM zones I to IV were taken at the time of delay and at intervals of 12, 24, 48, and 72 hours. Specimens were assessed for selected cytokine gene expression by reverse transcription-polymerase chain reaction analysis (TR-PCR). RESULTS: Surgical delay significantly (P < 0.001) increased skin paddle survival in the delayed TRAM flaps (16.14 +/- 1.53 cm, 81.9%) compared with undelayed flaps (7.68 +/- 3.16 cm, 40.9%). TGF-beta and PDGF expressions were not changed by surgical delay, but basic fibroblast growth factor (bFGF) and VEGF expressions increased significantly (P < 0.05 and P < 0.01) after delay. CONCLUSIONS: In the rat TRAM model, surgical delay resulted in increased VEGF expression and increased skin paddle survival. These results correlate with previous studies showing the preoperative injection of VEGF increases skin paddle survival. VEGF may be an important element in the delay phenomenon and may be an agent for pharmacological delay.

Analysis of Variance↗

Revolutionary advances in sun-protective clothing--an essential step in eliminating skin cancer in our world.

For many years, individuals around the world have relied on sunscreen alone as their primary form of protection against ultraviolet rays (UV-R). Australia has shown that a multitactic approach to skin cancer prevention, combining sun-protective clothing with sunscreen, can be both highly effective and widely accepted by the general public. In the US, the aging baby boomer generation and rising skin cancer epidemic call for a fundamental behavioral shift toward this combination approach to sun protection. Sun-protective clothing, such as that manufactured by Coolibar and awarded the Seal of Recommendation by The Skin Cancer Foundation, offers millions of Americans the opportunity to significantly improve the quality of their lives and is an essential step in eliminating skin cancer in our world. All Coolibar clothing products carry a minimum ultraviolet protection factor (UPF) rating of 30, blocking 97% UV-R or greater. Each product in the Coolibar clothing line is individually tested and rated for its UV protection level; this process is explained in a thorough hangtag attached to the product. This tag specifies what UPF the product has received, how the UPF is figured, which testing procedures the individual product was submitted to, and if that product has received the Seal of Recommendation from The Skin Cancer Foundation. In addition to photoprotective clothing, The Skin Cancer Foundation recommends Rit Sun Guard, a photoprotective laundry additive. Rit Sun Guard washes into the clothing fibers and absorbs broadband UV-R. A single treatment of Rit Sun Guard sustains a UPF of 30 for approximately 20 launderings. The active ingredient in Rit Sun Guard is TINOSORB FD. In order to be certified by The Skin Cancer Foundation, the Coolibar clothing product must undergo extensive UPF testing to confirm the accuracy of the product labeling. Laundry additives evaluated by The Skin Cancer Foundation undergo similar tests to that of photoprotective clothing after a uniform laundering method is used to apply the product to the clothing fibers. Both of these certification processes confirm the UPF, UV-A and UV-B transmittance, and percentage blocking UV-A and UV-B. The certification process is reviewed on an annual basis.

Health Promotion↗

Mandibular reconstruction with microsurgical bone flap and dental implants.

Functional reconstruction of the mandible following resection or traumatic injury depends on the bony reconstruction and support dental implants. Microsurgical bone flaps allow the transfer of bone and soft tissue with a rich vascular supply and provide a firm basis for placement of dental implants in mandible reconstruction. Endosseous dental implants may improve functional restoration by ensuring the stable dentition essential for normal mastication and speech. In this review article, donor sites of microsurgical bone flaps, criteria for placement of dental implants, timing for dental implantation, bone resorption, role of radiotherapy and hyperbaric oxygen, and success rate of dental implants are discussed.

Animals↗

Distally based radial forearm flap with preservation of the radial artery: anatomic, experimental, and clinical studies.

In this article we report on the anatomical, experimental, and clinical investigations of the distally adipofascial pedicled radial forearm flap based on the small perforators around the radial styloid process. There are about 10 small perforators (0.3-0.5 mm in diameter) from the distal radial artery around the radial styloid process. The longitudinal chain-linked vascular plexuses (suprafascial, paraneural, and perivenous) formed by the forearm ascending and descending branches of septofasciocutaneous perforators meet and cross over with the transverse carpal vascular plexuses around the radial styloid region. Based on these directional-oriented plexuses, distally based adipofascial pedicled radial forearm fasciocutaneous and adipofascial flaps were designed and successfully applied in 34 clinical cases. The pivot point was located at 1-2 cm above the radial styloid. The skin island plus adipofascial pedicle measured between 9-18 cm in length, with the adipofascial pedicle 3-4 cm in width. The length-to-width ratio is 3-5:1. The venous drainage of this distally based flap was investigated anatomically and experimentally. The cephalic vein has no positive role for venous drainage in distally based flaps. The difference between distally based flaps and reverse-flow flaps, clinical selection of fasciocutaneous and adipofascial flaps, advantages and disadvantages, and technical tips for operative success are discussed.

Adult↗

Fracture fixation in the mutilated hand.

Early anatomic (or near anatomic; lingers do not impinge or overlap during flexion or extension) stable fracture fixation provides the foundation for successful wound management and for the repair, reconstruction, and healing of all damaged tissues in a mutilating hand injury. It also plays an instrumental role in pain control and affords an optimal opportunity for timely and favorable rehabilitation of and recovery from mutilating injuries of the hand. Kirschner or other wiring systems or mini external fixators may be used for simple fractures, in children, when rapid fracture fixation is necessary, and for provisional fracture fixation. Mini plates should be considered for fractures with comminution or loss and in instances of multiple fractures. Fingers with segmental injury of three or more tissues should be considered for early amputation to avoid prolonged and impaired recovery of the hand. Every effort should be made to preserve the thumb and its function by repair or reconstruction.

Adult↗

Clinical case experience using microsurgical venous flaps for soft-tissue coverage of the lower extremity.

Numerous venous flap models have been experimentally introduced and clinically attempted in reconstruction of soft-tissue defects. The authors report experience in soft-tissue coverage with microsurgical saphenous venous flap transfers in five patients with lower-extremity wounds. Four of these flaps failed postoperatively. Unhealthy recipient beds and inflamed veins were potential causes for these flap failures. Easy dissection without sacrifice of the artery would seem to provide an ideal situation for venous flap utilization, but this rate of failure prohibits recommendation of this flap in large, traumatic wounds.

Adolescent↗

Enhancement of rat sciatic nerve regeneration by fibronectin and laminin through a silicone chamber.

In this study, the authors examined the effects of fibronectin and laminin on sciatic nerve regeneration in rats. Sixty-eight Sprague-Dawley rats underwent bilateral sciatic nerve transections and silicone tubulizations, with a 10-mm gap between the proximal and distal nerve stumps. Thirty rats (n=30) received 10 microg of fibronectin injection into the right sciatic nerve chamber, while saline was injected into the left nerve chamber, serving as the control. Another 30 rats (n=30) were given 6 microg of laminin injection into the right nerve chambers and saline into the left chambers. At 1, 3, and 4 months postoperatively, electrophysiologic and histologic examinations, including nerve morphometry, were performed. Eight additional rats, receiving fibronectin (n=4) and laminin (n=4) injections, were used for horseradish peroxidase (HRP) tracing at 3 months postoperatively. Results from the study showed that fibronectin- and laminin-treated groups had significantly higher motor nerve conduction velocity and evoked muscle action potential amplitude of the anterior tibial muscle than the control group (p<0.01). Nerve diameter and the number of myelinated axons from the groups receiving fibronectin and laminin applications were greater than the controls (p<0.01). Also, a greater number of HRP-labeled motor neurons were found in the ventral horns and dorsal root ganglia of the fibronectin- and laminin-treatment groups compared to the controls. The authors conclude that local applications of fibronectin and laminin into the nerve chambers can significantly improve axonal regeneration and maturation of injured rat sciatic nerves.

Action Potentials↗

Effect of hyperbaric oxygen therapy on the tubed pedicle flap survival in a rat model.

The effect of hyperbaric oxygen therapy (HBO) on survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part 1, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle of each skin flap was divided at intervals of 3, 4, 5, and 7 days, and the survival area of each distal skin paddle was measured 5 days after each pedicle was divided. The results showed that the percentages of survival were 0%, 29.9%, 89.9%, and 100% at 3, 4, 5, and 7 days, respectively. In part 2, the tube flaps were created on the backs of 28 rats. The tubed pedicles were divided 4 days after creation. In the experimental group 1 (n = 9), the rats received HBO treatment at 2 atm of pressure twice daily for 3 consecutive days before pedicle division. In the experimental group 2 (n = 9), the rats received HBO treatment after pedicle division twice daily for 3 consecutive days. In the control group (n = 10), the rats received no HBO treatment. The results showed that the mean survival area of the distal skin paddle at 5 days after pedicle division for the groups treated with HBO before and after pedicle division was 6.31 +/- 2.69 cm2 (69.19%) and 6.12 +/- 1.52 cm2 (71.22%), respectively. These survival rates were of statistical significance as compared with the survival rates in the control group of 2.70 +/- 1.89 cm2 (27.9%). These results demonstrate that the administration of HBO therapy to the animal with a tubed pedicle flap can increase flap survival with early division of the tubed pedicle.

Animals↗

Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats.

This study evaluated the effects of exogenous vascular endothelial growth factor (VEGF) on the regulation of cytokines in a rat dorsal ischemic skin flap model. Exogenous VEGF (1 microg/ml) was injected subdermally into the flaps of 12 rats before the flaps were sutured back in place. Another 12 rats with flaps received saline injections, as a control group. Biopsy specimens were obtained from the flaps treated with VEGF or saline solution, at positions 2.5, 5.5, and 8.5 cm from the distal edge of the flaps, at 12 hours (n = 6 for each group) and 24 hours (n = 6 for each group) after suturing of the flaps. Expression of cytokine, growth factor, and inducible nitric oxide synthase was measured. The results demonstrated that expression of tumor necrosis factor-alpha and nitric oxide synthase in the distal part of the VEGF-treated flaps was significantly decreased, compared with the control values, at 12 and 24 hours postoperatively. It was concluded that administration of exogenous VEGF could protect flaps from ischemia-reperfusion injury through the regulation of proinflammatory cytokines and the inhibition of cytotoxic nitric oxide production.

Animals↗

Small intestinal submucosa in abdominal wall repair after TRAM flap harvesting in a rat model.

The strength of porcine small intestinal submucosa in abdominal wall repair after transverse rectus abdominis myocutaneous flap harvesting was examined in a rat model. Changes in the levels of selected molecular markers of inflammation after small intestinal submucosa implantation were also studied. Eighty-three rats were divided into three groups. In experimental group I, an abdominal wall defect created by removal of the rectus abdominis muscle was repaired with placement of a 1.5 x 5-cm2 patch of small intestinal submucosa. In experimental group II, the muscle defect was repaired with a combination of small intestinal submucosa patch placement and fascial closure. In the control group, the defect was repaired with direct fascial closure. At postoperative times of 3 days, 2 weeks, 1 month, and 2 months, the muscle tissues adjacent to the abdominal wall repair site were subjected to biopsies for assessment of inflammation markers. Full-thickness sections of the abdominal wall from the repair site in each animal were removed for tensile strength testing and histological examinations. The results demonstrated that interleukin-6 and interferon-gamma levels were increased in the two experimental, small intestinal submucosa-treated groups at 3 days and 2 weeks postoperatively. The results of mechanical testing demonstrated that the average tensile strength of the repaired abdominal wall in the repair model with combined small intestinal submucosa placement and fascial repair was significantly greater than the values for repairs with fascial closure or small intestinal submucosa placement alone. The use of small intestinal submucosa placement in combination with fascial repair can significantly improve the strength of the repaired abdominal wall after transverse rectus abdominis myocutaneous flap harvesting.

Animals↗

Effect of vascular endothelial growth factor on rat Achilles tendon healing.

This study evaluated the effect of exogenous vascular endothelial growth factor (VEGF) on tendon healing and regulation of other growth factors in a rat Achilles tendon model. Fifty Sprague-Dawley rats were used. In the experimental group, the left Achilles tendon was transected and repaired with the modified Kessler suture technique, and the right Achilles tendon was transected and repaired with resection of plantaris tendon. VEGF, 100 mul (50 mug/ml), was injected into each tendon at the repair site. The same surgical procedures were performed in the control group, with the same volume of saline injected into the repair sites. At intervals of 1, 2, and 4 weeks, the animals were killed and the tendons were harvested and evaluated for tensile strength (1, 2, and 4 weeks) and gene expression (postoperative day 4). At 1 week postoperatively, when plantaris tendon was preserved, the tensile strength of the repaired tendons with VEGF treatment (3.63 +/- 0.62 MPa) was significantly higher than the tensile strength of the repaired tendons with saline treatment (2.20 +/- 0.36 MPa). There was no difference in tensile strength between the two groups without the plantaris tendon support. At 2 weeks postoperatively, the tensile strength was 11.34 +/- 3.89 MPa in the group with VEGF treatment and plantaris tendon preservation, which was significantly higher than the tensile strength in the other groups. There was no significant difference in tensile strength among the groups at 4 weeks postoperatively. The gene expression showed that transforming growth factor-beta in the VEGF-treated tendon was up-regulated in the early stage of tendon healing, whereas expression of platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 was not significantly different among the groups. In conclusion, administration of exogenous VEGF can significantly improve tensile strength early in the course of the rat Achilles tendon healing and was associated with increased expression of transforming growth factor-beta.

Achilles Tendon↗

Effect of sodium diphenylhydantoin on skin wound healing in rats.

This study evaluated the effect of phenytoin (sodium diphenylhydantoin) on skin wound healing in a rat model. The study was divided into two parts. In part I, 20 mul of phenytoin (10 mg/ml) was subcutaneously injected into the 3-cm dorsal full-thickness incisional wounds of 14 rats on postoperative days 0, 3, and 6. Twelve rats that received saline injections were used as the controls. The skin samples were harvested and tested for tensile strength and histology. An additional 12 rats with the same incisional wounds were tested for chemokine gene expressions. In part II, 20 mul of phenytoin (10 mg/ml) was applied topically once a day on a 4 x 4 cm area of the open dorsal wounds of 10 rats. Saline was applied to the wounds of the 10 control group rats. The wounds were measured weekly. The results showed that the average tensile strength of the phenytoin-treated wound was 0.49 +/- 0.08 MPa compared with the control group at 0.02 +/- 0.01 MPa (p < 0.05). The density ratio of chemokine monocyte chemotactic protein (MCP-1) to beta-actin in the phenytoin-treated group was also significantly higher than in the control group (p < 0.05). Histologic analysis of the phenytoin group showed a large amount of fibroblast proliferation, collagen synthesis, and neovascularization. Phenytoin-treated wounds were also smaller at 1 to 6 weeks postoperatively than the control group wounds. The authors conclude that the administration of phenytoin can promote wound healing and significantly increase MCP-1 expression. Phenytoin-treated wounds showed significant increase in collagen deposition and neovascularization, which resulted in an increased wound tensile strength and accelerated healing of both open and closed wounds.

Actins↗

Porcine small intestinal submucosa as a carrier for skin flap prefabrication.

The feasibility of porcine small intestinal submucosa (SIS) as a carrier in skin flap prefabrication was examined in this study. Thirty-eight rats were randomly divided into five groups. The saphenous vascular bundle was used as the vascular carrier. In group 1 (n = 8), an arteriovenous fistula was made by anastomosis of distal saphenous artery and vein. A SIS patch (1.5 x 2 cm2) was placed underneath the vascular bundle. In group 2 (n = 8), the vascular bundle was isolated and laid over the SIS patch. The distal saphenous vessels were ligated when the flap was raised. In group 3 (n = 8), an arteriovenous fistula was made without SIS implant. In group 4 (n = 8), the flap was raised with only the vascular bundle with the distal end ligated. After 2 weeks of maturation, the flap was raised with only the vascular bundle. In group 5 (n = 6), SIS was implanted and the flap including the SIS patch was raised and replaced without the vascular pedicles. The survival of the flaps and histology were evaluated at 5 days after flap replacement. The results showed that the average survival area in group 1 was 99% +/- 3% and the survival area in group 2 was 86% +/- 16%. The mean survival areas in group 3 and 4 were 60% +/- 9% and 25% +/- 10%, respectively. No flap survival was observed in the group 5. These were significantly lower than in groups 1 and 2 (p < 0.05, p < 0.01). Histology showed that SIS patch was incorporated into the adjacent connective tissue and increased amounts of neovascularization were seen between the collagenous sheets and dermis. In conclusion, this study demonstrated that porcine SIS can incorporate into the adjacent tissue and induce angiogenesis in flap prefabrication. This biomaterial can provide a scaffold for supporting and enhancing the survival of vascular prefabricated skin flap.

Animals↗

Modification of the vertical rectus abdominis musculocutaneous (VRAM) flap for functional reconstruction of complex vulvoperineal defects.

Radical vulvoperineal ablations present challenging reconstructive dilemmas, especially when local metastatic spread requires distal vaginal and anal resection. Despite advances in vaginal salvage and sphincteroplasty, surface recontouring remains elusive because of the necessity to resurface a large, complex area that includes the mons, vulva, and fourchette. We describe a modification of the inferior-based vertical rectus abdominis musculocutaneous (VRAM) flap where the superior portion is split longitudinally to produce "tongue" flaps, which can resurface complex vulvoperineal wounds. By splitting the flap, one can resurface the vulva, provide an edge to reattach the vaginal cuff, and recreate the fourchette and line the anoderm after anoplasty. This musculocutaneous flap provides adequate contour and protection against radiation injury. Splitting of the flap is based on the vascular territory of the superior epigastric branches and their perforators and can be carried down to the level of their anastomosis, with the inferior system at the level of the umbilicus. The split VRAM flap has been used successfully in 3 patients with complex perineal wounds with excellent results and maintenance of vaginal patency.

Aged↗

Microsurgical anterolateral thigh fasciocutaneous flap for facial contour correction in patients with hemifacial microsomia.

The correction of facial asymmetry in complex hemifacial microsomia presents a challenging problem for reconstructive surgeons. Numerous microsurgical flaps have been introduced for reconstruction of facial asymmetry. This article reports our experience in facial soft tissue reconstruction with microsurgical anterolateral thigh fasciocutaneous flap transfer in six patients with hemifacial microsomia. This flap, which has a reliable vascular pedicle and relatively thin pliable soft tissue, can provide an ideal treatment for facial asymmetry in hemifacial microsomia.

Adult↗