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Biomedical subjects

W C Lineaweaver

Publications and source records attributed to W C Lineaweaver.

At least 19 recordsLinked to original sources
PubMed2003

The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds.

The effect of exogenous vascular endothelium growth factor (VEGF) on wound healing in an ischaemic skin flap model was evaluated in this study. Seventy-two Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. The study was divided into two parts. In Part I, VEGF protein levels were determined from the incisional and H-shaped ischaemic wounds at 12 and 24 h, postoperatively. In Part II, tensile strength and immunohistochemical stains were examined to determine the level of microvessel density (MVD) at 1 and 2 weeks, postoperatively in simple incisional wounds, ischaemic wounds, and ischaemic wounds following 1 ml (1 microg/ml) exogenous VEGF injections into the subcutaneous tissue. The results showed a significantly higher level of VEGF protein in the ischaemic wounds than the incisional wounds. Tensile strength was statistically higher in the incisional wound group and in the ischaemic flap wounds with VEGF treatment compared to the ischaemic flaps with no treatment at 1 week, postoperatively (p>0.05). MVD data indicated that ischaemic wound repair with VEGF treatment had significantly higher MVD than the normal incisional wounds and ischaemic wounds without treatment. We conclude that exogenous application of VEGF can increase early angiogenesis and tensile strength in the ischaemic wound.

Animals↗
PubMed2003

Vascular endothelial growth factor (VEGF) expression and the effect of exogenous VEGF on survival of a random flap in the rat.

The induction of endogenous vascular endothelial growth factor (VEGF) production in the skin flap with ischemic injury and the effect of exogenous VEGF on survival of the ischemic skin flap were studied in rats. A dorsal flap model (3x10 cm(2)) was used in this study. In Part I, biopsies were taken from the flap at 2.5, 5.5, and 8.5 cm distances from the distal edge at 0, 6, 12, and 24 h after the flaps were sutured. Malonyldialdehyde (MDA) and VEGF(165) protein level were measured. In Part II, exogenous VEGF (1 microg/ml) was injected subdermally into the flaps in 14 rats before the flaps were replaced. Flaps that received a saline injection were used as the controls. The skin paddle survival was measured on postoperative day five. The results showed that the MDA level in the distal part of the flap significantly increased at 24 h postoperatively when compared to MDA in other parts of the flap. However, VEGF levels in the distal part of the flap significantly decreased when compared to the middle part of the flap. Subdermal injection of exogenous VEGF to the distal area of the flap could significantly improve survival of the distal flap (89% of total skin paddle) when compared to the control, which had a 64% mean percent survival. We conclude that production of endogenous VEGF protein is significantly increased in the skin flap with mild ischemia, but decreased in the flap with severe ischemia. Administration of exogenous VEGF could significantly enhance survival of ischemic flaps.

Animals↗
PubMed2002

Cellular and molecular alterations in spinal cord injury patients with pressure ulcers: a preliminary report.

The study was designed to investigate the changes, both numerically and functionally, of the molecules critical to wound healing in spinal cord injury (SCI) patients. Spinal cord injury patients who demonstrated delayed healing of their pressure ulcers were used as study subjects. Age-matched healthy individuals served as controls. Adhesion molecule expression of the peripheral blood leukocytes, including lymphocytes and granulocytes, was measured by flow cytometric analysis. Binding capacity of the lymphocytes was evaluated using human umbilical cord vein endothelial cells (HUVECs) as the binding matrix. Samples from pressure ulcers of the patients were immunostained to define fibronectin, kalinin, beta4 integrin, alpha2beta1, alpha3beta1, alpha5beta1, and CD138 expression. Compared to healthy controls, there was decreased expression of CD11a, CD11b, CD18, CD49b, CD49c, CD49d, CD54, and CD8 in patients' lymphocyte populations and CD11a, CD18, CD49c, CD49d, and CD8 in patients' granulocyte populations. The binding capacity, expressed as percentage binding of the lymphocytes to the HUVEC matrix, was greatly diminished in the patients. There was markedly diminished immunohistochemical staining of fibronectin in pressure ulcers. These findings showed that delayed healing of pressure ulcers in SCI patients can be attributed to reduced adhesion molecule expression, impaired cell-cell interaction, and lack of extracellular matrix structural and functional protein.

Adult↗
PubMed2002

Accelerating flap maturation by vascular endothelium growth factorin a rat tube flap model.

The effect of exogenous vascular endothelium growth factor (VEGF) on the survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part I, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle was divided after an interval of 3, 4, 5 or 7 days, and the survival area of each distal skin paddle was measured 5 days after the pedicle was divided. The percentages of survival were 0, 24.9%, 89.9% and 100%, respectively. In part II, tube flaps were created in 20 rats. In the experimental group, 2 ml of VEGF (50 microg ml(-1)) was injected into the recipient bed during tube flap creation in each rat. In the control group, 2 ml of saline was given. The tubed pedicle was divided 4 days after creation. The mean survival area of the distal skin paddle in the group treated with VEGF was 7.32 +/- 1.36 cm(2) (80.91%) at 5 days after pedicle division, which was of statistical significance when compared with the survival in the control group of 2.70 +/- 1.89 cm(2) (27.9%). The histology showed angiogenesis at the skin paddle-recipient bed interface following VEGF injection. These results demonstrate that the subcutaneous administration of VEGF into the recipient bed of the tube flap transfer can induce angiogenes is at the junction between the donor and the recipient bed, and improve skin paddle survival with early pedicle division.

Analysis of Variance↗
PubMed2001

Vascular grafts in the rat model: an anatomic study.

Vascular grafts in animal models have been used extensively in the microsurgical laboratory, and the rat offers an excellent source of graft to meet these needs. In this study, we compiled a list of vessels that were previously identified in experimental literature for use as vascular grafts in the rat model. We then dissected and measured both arterial and venous grafts taken from these sites in 12 adult rats. The surgical procedure for approaching each vascular graft was recorded. The diameter and harvestable length, the start and end points, and the number of branches of the graft were tabulated. We believe that these data will provide valuable insight applicable to the use of the rat vascular graft in microsurgical research and training.

Animals↗
PubMed2001

Nerve growth factor inhibition prevents traumatic neuroma formation in the rat.

Nerve growth factor (NGF) is thought to play a role in the pathogenesis of neuroma formation as well as in the development of neuropathic pain. In this study we attempted to antagonize NGF by using trkA-IgG, an inhibitor of NGF, consisting of the NGF receptor linked to an immunoglobulin. It was delivered by an implanted osmotic pump directly to the site of a sciatic nerve transection in 16 rats for 30 days. The animals were monitored daily for the first 2 weeks for evidence of auto-cannibalization (autotomy) of the denervated foot (a sign of neuropathic pain). Four (25%) of the 16 rats receiving trkA-IgG exhibited such cannibalization compared with 9 of 15 control rats (60%) that underwent an identical procedure but were not treated with the trkA-IgG solution. One month after surgery the sciatic nerves and representative dorsal root ganglia (DRG) from these rats were evaluated histologically. Six of the 16 experimental rats (38%) demonstrated histological evidence of neuroma formation compared with 12 of the 15 controls (80%). There were no histological differences between the DRG from the two groups. These results support the notion that inhibiting NGF following peripheral nerve injury in the rat can reduce neuroma formation and neuropathic pain without damaging the cell bodies of the transected neurons.

Animals↗
PubMed2001

Gene expression of transforming growth factor beta isoforms in interposition nerve grafting.

Scar production and neuroma formation at nerve graft coaptation sites may limit axonal regeneration and impair functional outcome. Transforming growth factor beta (TGF-beta) is a family of growth factors that is involved in scar formation, wound healing, and nerve regeneration. Fifteen adult Sprague-Dawley rats underwent autogenous nerve grafting. The nerve grafts were analyzed by in situ hybridization to determine the temporal and spatial expression of TGF-beta1 and TGF-beta3 messenger RNA (mRNA). The grafted nerves showed increased expression of TGF-beta1 and TGF-beta3 mRNA in the nerve and the surrounding connective tissue during the first postoperative week. These data suggest that modulation of TGF-beta levels in the first postoperative week may be effective in helping to control scar formation and improve nerve regeneration.

Animals↗
PubMed2001

Role of medical students in microsurgery research.

Microsurgery is an integral element in many surgical specialties, as well as an important technique for surgical research. Student participation in microsurgery research programs can be a source for both high quality training in skills and for research contributions. In this article, the authors review their experience in developing general principles for setting up medical student microsurgery research programs, and analyze the research output and career choices made by the students who have participated.

Adult↗
PubMed2001

Reconstruction of ureteral defects with microvascular vein grafts in a rat model.

This study was undertaken to test the performance of an autologous vein graft as a ureteral replacement in the rat model. Twenty-six rats were divided into three groups. In Group 1 (n = 10), the animals had a 3-mm segment of the ipsilateral ureter excised and the ureteral defect repaired, using a superficial epigastric vein graft. In Group 2 (n = 10), the same ureteral defect was created and again repaired, using a superficial epigastric vein graft, with the addition of a Silastic stent. The control, Group 3 (n = 6), had the ureter transected and repaired solely by means of primary anastomosis. Animals from each group underwent urography and were sacrificed for histology at three different postoperative intervals: 1, 4, and 12 weeks. Postoperative urography results showed normal renal function in the animals with ureteral reconstruction using vein grafting aided by a stent, as well as in those with primary ureteral anastomosis. No renal function return was seen in the animals with ureteral reconstruction by vein grafting alone, without stent support. Histologically, a progressive loss of the vascular endothelium, and replacement with the urothelium typical of the ureter, was seen in the stented vein grafts. Severe ureteral obstruction at the proximal site of the graft and hydronephrosis were seen in the vein-graft group without stenting. This study demonstrates that autologous vein grafts can be used successfully to correct a ureteral deficit, contingent on accurate microsurgical technique and immediate stenting.

Anastomosis, Surgical↗
PubMed2001

Microsurgical flap models in the rat.

Microsurgical flaps have been widely used in clinical reconstructive surgery. Although these procedures have achieved great clinical success, utilization of microsurgical flap techniques have also led to a number of basic questions that researchers must now attempt to answer. The rat has been the source of many flap models in these investigations. This article provides a condensed description of the procedures, anatomic data, and research applications for skin, muscle, myocutaneous, bone, osteomuscular, and osteomyocutaneous microsurgical flap models in the rat.

Anastomosis, Surgical↗
PubMed2001

Quantification of nerve tension after nerve repair: correlations with nerve defects and nerve regeneration.

This study tested the validity of a quantitative in vitro nerve-tension-measuring technique, by correlating the tension measurements with functional and morphologic assessments of nerve regeneration. Initially, harvested nerves were used in vitro to determine a K value for lateral displacement in this tissue. Next, this value was used to calculate the tension of nerve repair, following 0-, 3-, 6-, and 9-mm resections of nerves in groups of rats. After quantifying the nerve tensions following excision and repair, the authors determined a sciatic function index to evaluate functional recovery and axon diameter in the animals. Functional recovery was significantly impaired in animals with elevated measurable tension (9.04 +/- 0.74 g in a 6-mm defect, 27.76 +/- 8.86 g in a 9-mm defect), compared to animals with no or 3-mm excision and measured tension of 3.3 +/- 1.09 g or less. Increased tension was also associated with a significant decrease in axon diameter. This study succeeded, therefore, in quantitatively relating the elements of measured nerve tension, nerve gaps, functional nerve recovery, and morphologic regeneration. Quantification of nerve tension by lateral displacement in vivo offers a possible solution to clinical management of nerve gaps, when the choice between primary repair and nerve grafting is not a clear one.

Anastomosis, Surgical↗
PubMed2001

Influence of recipient-bed isolation on survival rates of skin-flap transfer in rats.

The effect of recipient-bed isolation with artificial barriers on skin-flap survival, compared to flap transfer without bed isolation, was evaluated in a modified rat epigastric skin-flap model. The pattern of blood flow in the raised flap with a proximal axial portion and distal random portion was confirmed by laser Doppler flowmetry. Forty rats were divided into four groups. Three of the groups had one of three different artificial barriers-silicone, polypropylene, or gelatin sponge. In each of these three groups, one of the artificial barriers was placed between the flap and its recipient bed after flap replacement. The flaps without bed isolation (Group 4) were used as controls. The survival area was measured 7 days postoperatively. Results demonstrated that necrosis in the groups with silicone and polypropylene barriers was significantly higher than in the controls. Histologically, neovascularization was shown in the flaps without artificial barriers. Foreign-body reactions were observed in the flaps with bed isolation and among these, severe inflammation and congestion were seen in the flaps with polypropylene isolation. In this study, the authors demonstrated that the random portion of a rat skin flap could survive partially through imbibition of plasma and the ingrowth of new vessels from the recipient bed. This neovascularization can be prevented by recipient-bed isolation with an artificial barrier. Bed isolation with a silicone sheet is suggested for use in the study of rat skin-flap survival.

Animals↗
PubMed2001

Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model.

The effect of vascular endothelial growth factor (VEGF) on skin flap survival and its ability to induce a pharmacological delay by promoting angiogenesis in a flap was studied in a rat transverse rectus abdominis musculocutaneous flap, using a 3 x 8-cm skin paddle with the inferior epigastric vessels as its main vascular supply. Forty-three Sprague-Dawley rats were divided into four groups. In group 1, VEGF was injected into the femoral vein after the flap was elevated. In group 2, VEGF was injected intra-arterially into the flap through the superior epigastric artery after the flap was elevated. In group 3, VEGF was injected into the subcutaneous fascial layer in the area where the flap would be dissected, and the flap was then raised 7 days after injection. In group 4, the flap was dissected and replaced, using saline injection as the control. On postoperative day 5, the survival area of each skin paddle was measured and the flap was harvested for histological analysis. The results showed that the mean survival area +/- standard deviation for the skin paddle was 6.82 +/- 4.89 cm2 (28.4 +/- 20.4% of the whole skin paddle) in the control group, and 4.2 +/- 3.0 cm2 (17.5 +/- 12.5%) and 6.02 +/- 5.97 cm2 (25.1 +/- 24.9%) in the groups with VEGF systemic and intra-arterial administration respectively. The skin survival area in the group with preoperative subcutaneous administration of VEGF was 17.85 +/- 2.88 cm2 (74.4 +/- 12%), which was significantly higher than the other three groups (p < 0.01). Histological semiquantitative analysis showed increased neovascularization in the flap treated with VEGF preoperatively. The data demonstrate that preoperative treatment with VEGF can induce angiogenesis and enhance skin paddle survival in a musculocutaneous flap.

Analysis of Variance↗
PubMed2001

Treatment of facial angiofibromas of tuberous sclerosis by shave excision and dermabrasion in a dark-skinned patient.

Tuberous sclerosis is an inherited disease expressed clinically by the triad of mental retardation, seizures, and tuberous lesions. Facial angiofibromas, a common manifestation of tuberous sclerosis, can cause considerable cosmetic disfigurement, emotional distress, obstruction of vision, and hemorrhage. Treatment by shave excision, as the first step to remove the larger nodules, followed by dermabrasion, to smooth and sculpt the final surface, has been recommended as the most effective form of therapy. However, this method of treatment raises the question of risk for development of hypopigmentation in susceptible patients. The authors present their treatment of angiofibromas with shave excision and dermabrasion in a dark-skinned patient.

Adult↗
PubMed2001

Injuries associated with mandible fractures sustained in motor vehicle collisions.

Motor vehicle collisions are second only to altercations as the most common cause of mandible fractures. This article details in a retrospectively studied group the incidence of isolated mandible fractures and associated injuries in patients who were involved in motor vehicle collisions. This group consisted of 148 patients with mandible fractures listed in the University of Mississippi's trauma registry during the past 5 years. In almost all patients, associated injuries occurred with mandible fractures that were caused by motor vehicle collisions, with an incidence of 99.3 percent. Facial and head lacerations and facial fractures were the leading associated injuries, occurring in more than half of the patients who had a mandible fracture. Closed head injury is the major life-threatening associated injury and cause of mortality. The life-threatening injuries occurred in 64.8 percent of patients in this study. The mortality rate in this group of patients was 8.1 percent. These data suggest that mandible fractures from motor vehicle collisions should never be viewed as an isolated injury but rather as part of a spectrum of significant and sometimes life-threatening injuries that require thorough trauma evaluation at the time of presentation.

Accidents, Traffic↗
PubMed2000

Free vascularized fibular bone flap in the rat.

Free vascularized fibula bone flap has been widely used in reconstruction of the mandible, long segment defect, congenital pseudarthroses, and osteomyelitis. Such applications stirred an interest in basic studies of bone biology, bone healing process, and incorporation of recipient bone defect. An experimental free vascularized fibula rat model is presented here for such investigations. We performed 16 angiograms and anatomic dissections in eight rats for collecting data on fibular length, blood supply, and the caliber of significant vessels. The fibula was harvested with part of the flexor hallucis longus muscle with an average length of 28 mm. The pedicle can be taken in continuity with the popliteal vessels (average diameter of 0.8 mm and 0.9 mm of artery and vein, respectively, with an average pedicle length of 14 mm). This vascularized fibula bone was harvested and transferred to the groin area of the same rat and anastomosed to the saphenous vessels. Twelve transplantations were performed, with a 7-day flap survival rate of 100%. The free fibula vascularized bone flap in the rat is a reliable model for further investigations.

Animals↗
PubMed2000

Learning curve of microvascular venous anastomosis: a never ending struggle?

In this study, a simple protocol based on the rat femoral venous anastomosis was established to provide a quantitative representation of the progress. The learning curve is based on the patency rate in each consecutive group of five anastomoses. Two groups of surgeons were observed. The inexperienced group encountered a tough time in the first 25 anastomoses. However, the progress was fast and is represented by the steep slope of the curve. A plateau was reached whereby the avearge patency rate matches that of the experienced group. As expected, there was no learning curve for the experienced group. Despite every effort to attempt to maintain a perfect 100% patency on this model, the best achievable patency was only 88%. The results and its implication are discussed.

Anastomosis, Surgical↗