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2.
Arch Neurol ; 58(10): 1635-7, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11594922

ABSTRACT

BACKGROUND: Carpal tunnel syndrome is a debilitating neuropathy affecting millions of individuals. Although there are published reports of familial associations of carpal tunnel syndrome, the molecular mechanisms are unknown. OBJECTIVE: To determine the prevalence and potential role of the chromosome 17 microdeletion associated with hereditary neuropathy with liability to pressure palsies in patients diagnosed as having carpal tunnel syndrome. DESIGN: Prospective study. PATIENTS AND METHODS: Since hereditary neuropathy with liability to pressure palsies may present as carpal tunnel syndrome, we evaluated 50 patients with idiopathic carpal tunnel syndrome for hereditary neuropathy with liability to pressure palsies. RESULTS: No hereditary neuropathy with liability to pressure palsies deletions were detected. CONCLUSION: Molecular genetic testing for hereditary neuropathy with liability to pressure palsies in patients with idiopathic carpal tunnel syndrome is of limited value.


Subject(s)
Carpal Tunnel Syndrome/genetics , Carpal Tunnel Syndrome/physiopathology , Chromosome Deletion , Tangier Disease/genetics , Adult , Aged , Carpal Tunnel Syndrome/epidemiology , Chromosomes, Human, Pair 17 , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Tangier Disease/epidemiology , Tangier Disease/physiopathology
3.
J Vasc Surg ; 33(4): 821-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11296338

ABSTRACT

PURPOSE: Indirect evidence suggests that tissue plasminogen activator (tPA) either limits or does not alter restenosis. However, tPA enhances tumor invasiveness through matrix remodeling, and several elements of degraded matrix enhance smooth muscle cell mitogenesis. We use either local adenoviral-mediated overexpression of tPA or systemic infusion of recombinant tPA combined with mechanical overdilation of rabbit common femoral arteries to evaluate the impact of tPA on neointima formation. METHODS: Left common femoral arteries of New Zealand white rabbits were transfected in situ either with an adenoviral-construct-expressing tPA or a viral control (adenoviral-construct-expressing beta-galactosidase) or nonviral (buffer) control after balloon angioplasty injury. At 7 and 28 days, left common femoral artery segments were harvested (n = 4 for each group and time point). Vessel segments were examined for intimato-media ratio, smooth muscle cell proliferation, extracellular matrix, and inflammatory response. Thrombus formation was evaluated after 3 days (n = 3 for each group). In a second experiment, New Zealand white rabbits (n = 3 per group, per time point) underwent mechanical dilation followed by buffer treatment or systemic tPA infusion according to a widely clinically used accelerated infusion protocol. Treated artery segments were harvested after 7 or 28 days and processed for intima-to-media ratio determination and class-wide histochemical determination of collagenous extracellular matrix and collagen content. RESULTS: Both rate and degree of neointima formation increase dramatically with overexpression (250%-461% relative to controls at 7 and 28 days). Substantial early matrix degradation is observed in vessels treated with local overexpression of tPA, although no increases in local inflammation or in smooth muscle proliferation occur. Late enhancement of smooth muscle proliferation emerges, consistent with secondary impact of perturbed matrix components. Systemic infusion of tPA according to clinical protocols also results in early and late enhancement of neointima formation in this model (34%-52% relative to controls at at 7 and 28 days), with significant early collagenous matrix degradation. Systemic infusion, although significant, did not attain the degree of neointima formation present with overexpression. CONCLUSION: With some evidence of dose-dependence, tissue plasminogen activator enhances neointima formation after angioplasty in a rabbit model. Early matrix degradation precedes change in rates of proliferation and underlies this effect in spite of several antirestenotic actions including decreased thrombus and decreased macrophage recruitment in this model.


Subject(s)
Fibrinolytic Agents/pharmacology , Tissue Plasminogen Activator/pharmacology , Tunica Intima/drug effects , Adenoviridae , Angioplasty, Balloon/adverse effects , Animals , CD4 Lymphocyte Count , Cell Division/drug effects , Extracellular Matrix/pathology , Femoral Artery/drug effects , Femoral Artery/injuries , Femoral Artery/pathology , Gene Transfer Techniques , Genetic Vectors , Macrophages/pathology , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Neutrophils/pathology , Rabbits , Recombinant Proteins/pharmacology , Thrombosis/etiology , Thrombosis/pathology , Tissue Plasminogen Activator/genetics , Tunica Intima/cytology , Tunica Intima/pathology
4.
Plast Reconstr Surg ; 106(2): 373-82, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10946936

ABSTRACT

The adipofascial flaps currently described in the literature frequently lack the volume requirements for reconstructive goals. In this study, the authors examined the use of long-term local delivery of insulin and insulin-like growth factor-1 (IGF-1) using polylactic-coglycolic acid/polyethylene glycol (PLGA/PEG) microspheres to augment inguinal adipofascial flaps based on the inferior epigastric vessels in the rat. Two flap models, the island flap and the limited dissection flap, were used to demonstrate simultaneous treatment and pretreatment modalities, respectively. Experimental groups received 12.5 mg of insulin microspheres (carrying 1 IU of insulin) plus 12.5 mg of IGF-1 microspheres (carrying 2.5 microg of IGF-1). A group undergoing the operation only (no treatment with microspheres) and a group treated with blank microspheres (no growth factor) served as external controls for the surgical procedure and the drug delivery device, respectively. In all groups (n = 5 animals in each), the contralateral flap served as an internal control. Upon harvest on postoperative day 28, the insulin and IGF-1-treated flaps in both models weighed statistically more than the internal control flaps and the two external control flaps. Likewise, on gross inspection, the adipogenic growth factor-treated flaps had greater volumes than the internal control flap groups and both of the external control flap groups (operation only and blank microspheres). Other intergroup comparisons suggested the absence of a systemic insulin and IGF-1 effect on adiposity. A histomorphometric analysis suggested (1) that insulin and IGF-1 treatment does not alter flap cell composition and (2) that flap augmentation is secondary to the stimulation of cell proliferation and adipocytic differentiation rather than the hypertrophy of mature adipocytes. Further evidence in favor of cell proliferation and differentiation was the discovery of nonanatomic, ectopic fat islands on the pedicle sheath of the treated flaps and the lack of variation in cell size distribution among groups. The authors concluded that the long-term local delivery of insulin and IGF-1 with PLGA/PEG microspheres is an effective method of adipofascial flap augmentation; this method increases the number of mature adipocytes rather than increasing the size of preexisting cells.


Subject(s)
Insulin-Like Growth Factor I/pharmacology , Insulin/pharmacology , Surgical Flaps/pathology , Adipose Tissue/drug effects , Adipose Tissue/pathology , Adipose Tissue/transplantation , Animals , Cell Count , Cell Differentiation/drug effects , Cell Division/drug effects , Drug Implants , Fascia/drug effects , Fascia/pathology , Fascia/transplantation , Male , Microspheres , Rats , Rats, Sprague-Dawley
5.
Circulation ; 102(3): 332-7, 2000 Jul 18.
Article in English | MEDLINE | ID: mdl-10899098

ABSTRACT

BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.


Subject(s)
Thrombomodulin/metabolism , Tunica Intima/physiopathology , Animals , Catheterization/adverse effects , Extracellular Matrix/metabolism , Femoral Artery/injuries , Femoral Artery/metabolism , Femoral Artery/pathology , Gene Transfer Techniques , Rabbits , Thrombomodulin/genetics , Thrombosis/etiology , Tunica Intima/pathology , Tunica Media/pathology , Vasculitis/etiology , Wounds and Injuries/physiopathology
6.
Plast Reconstr Surg ; 105(5): 1712-20, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10809102

ABSTRACT

The present investigation evaluates the effects of long-term, local delivery of insulin, insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF) on fat-graft survival using a poly (lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microsphere delivery system. Twelve-micrometer PLGA/PEG microspheres incorporated separately with insulin, IGF-1, and bFGF were manufactured using a double-emulsion solvent-extraction technique. Inguinal fat from Sprague Dawley rats was harvested, diced, washed, and mixed with (1) insulin microspheres, (2) insulin-like growth factor-1 microspheres, (3) basic fibroblast growth factor microspheres, (4) a combination of the insulin and IGF-1 microspheres, and (5) a combination of insulin, IGF-1, and bFGF microspheres. The treated fat grafts were implanted autologously into subdermal pockets in six animals for each group. Animals receiving untreated fat grafts and fat grafts treated with blank microspheres constituted two external control groups (six animals per external control group). At 12 weeks, all fat-graft groups were compared on the basis of weight maintenance and a histomorphometric analysis of adipocyte area percentage, indices of volume retention and cell composition, respectively. Weight maintenance was defined as the final graft weight as a percent of the implanted graft weight. All growth factor treatments significantly increased fat-graft weight maintenance objectively, and volume maintenance grossly, in comparison with the untreated and blank microsphere-treated controls. Treatment with insulin and IGF-1, alone or in combination, was found to increase the adipocyte area percentage in comparison with fat grafts treated with bFGF alone or in combination with other growth factors. In conclusion, the findings of this study indicate that long-term, local delivery of growth factors with PLGA/PEG microspheres has the potential to increase fat-graft survival rates. Further, the type of growth factor delivered may influence the cellular/stromal composition of the grafted tissue.


Subject(s)
Adipose Tissue/transplantation , Fibroblast Growth Factor 2/pharmacology , Graft Survival/drug effects , Insulin-Like Growth Factor I/pharmacology , Insulin/pharmacology , Adipose Tissue/pathology , Animals , Cell Count , Female , Male , Microspheres , Rats , Rats, Sprague-Dawley
7.
Plast Reconstr Surg ; 105(5): 1721-9, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10809103

ABSTRACT

This study was undertaken to characterize the duration of long-term growth factor delivery by poly(lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long-term delivery of insulin and insulin-like growth factor-1 (IGF-1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF-1, separately, were produced by a double-emulsion solvent-extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin-containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF-1, insulin + IGF-1, and blank microspheres) (n = 4). Insulin and IGF-1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4-week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF-1, and insulin + IGF-1 microspheres. Such islands were not seen in the blank microsphere group. Hematoxylin and eosin-stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil-Red-O stained sections demonstrated that these cells contained lipid. Computer-aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of "ectopic" adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long-term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long-term local insulin and IGF-1 to induce adipogenic differentiation to mature lipid-containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks.


Subject(s)
Adipose Tissue/drug effects , Cell Division/drug effects , Insulin-Like Growth Factor I/pharmacology , Insulin/pharmacology , Abdominal Muscles/drug effects , Abdominal Muscles/pathology , Adipose Tissue/pathology , Animals , Female , Microspheres , Rats , Rats, Sprague-Dawley
8.
Plast Reconstr Surg ; 105(2): 660-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10697174

ABSTRACT

A new type of a biodegradable nerve graft conduit material, the amnion tube, has been developed in our laboratory. To test the tube in the peripheral nerve regeneration process, it was initially applied across a 1-cm sciatic nerve gap in rats and was compared with other nerve conduit materials. We used male Sprague-Dawley rats as our animal model. The experiment included 66 rats that were randomly assigned into five groups: autograft (n = 17), amnion tube (n = 19), silicone tube (n = 20), no repair (n = 7), and sham group (n = 3). The process of peripheral nerve regeneration was evaluated at 2, 4, 10, and 17 weeks following injury and repair by using morphologic and functional assessments of the outcome of nerve regeneration in each animal. Nerve regeneration across the amnion tube nerve conduit was comparable with that seen in autograft and superior to that of the silicone group. A uniform nerve tissue was seen filling and crossing the amnion conduit, and the regenerated nerve from the proximal stump reached the distal end and was undifferentiated from the normal nerve tissues. At 4 months, the amnion tube biodegraded and no longer could be identified and differentiated from the nerve tissues. The amnion tube animal group showed a number of axons very close to that in the nerve autograft group (37,157 versus 33,054). Functional recovery at a 2- to 4-week interval was significantly statistically higher only in the amnion tube animal group (p = 0.01). However, the improvement disappeared between 10 and 17 weeks. In conclusion, the amnion tube is a potential ideal nerve conduit material secondary to its unique characteristics: it contains important neurotropic factors, is biodegradable, provokes a very weak immune response, is semiflexible, is readily available, and is easily manufactured into different sizes and diameters.


Subject(s)
Amnion , Nerve Regeneration , Peripheral Nervous System/physiology , Animals , Biomedical Engineering , Male , Peripheral Nervous System/anatomy & histology , Rats , Rats, Sprague-Dawley
9.
Ann Plast Surg ; 44(1): 59-64, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10651367

ABSTRACT

The authors emphasize the possible pharmacological enhancement of axonal regeneration using a specific growth factor/ extracellular media incorporated in a biodegradable nonneural nerve conduit material. They investigated the early effects on nerve regeneration of continuous local delivery of nerve growth factor (NGF) and the local incorporation of hyaluronic acid (HA) inside a newly manufactured nerve conduit material from fresh human amnionic membrane. Human amnionic membrane contains important biochemical factors that play a major neurotrophic role in the nerve regeneration process. The process of manufacturing a nerve conduit from fresh human amnionic membrane is described. This nerve conduit system was used in rabbits to bridge a 25-mm nerve gap over 3 months. NGF was released locally, over 28 days, at the distal end of the tube via a system of slow release, and HA was incorporated inside the lumen of the tube at the time of surgery. NGF/HA treatment promoted axonal regeneration across the amnionic tube nerve conduit (8,962 +/- 383 myelinated axons) 45% better than the nontreated amnionic tube group (6,180 +/- 353 myelinated axons). The authors demonstrate that NGF/HA media enhances additional axonal regeneration in the amnionic tube nerve conduit. This result is secondary to the effect of the amnion promoting biochemical factors, in combination with the NGF/HA effect on facilitating early events in the nerve regeneration process.


Subject(s)
Amnion , Hyaluronic Acid/pharmacology , Nerve Growth Factor/pharmacology , Nerve Regeneration , Sciatic Nerve/surgery , Animals , Axons/drug effects , Biodegradation, Environmental , Female , Humans , Male , Prostheses and Implants , Rabbits , Random Allocation , Statistics, Nonparametric
10.
J Reconstr Microsurg ; 15(6): 415-20, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10480560

ABSTRACT

In this paper the authors describe and illustrate a rare anatomic variation of the ulnar artery, a superficial ulnar artery. The possible embryologic events responsible for this variation are discussed. In addition, they describe the surgical considerations that should be kept in mind when this abnormality is encountered in the clinical setting of free-tissue transfer and vascularized nerve grafting.


Subject(s)
Microsurgery/methods , Plastic Surgery Procedures/methods , Ulnar Artery/abnormalities , Ulnar Artery/embryology , Cadaver , Dissection , Humans , Male , Middle Aged , Sensitivity and Specificity
11.
J Reconstr Microsurg ; 15(1): 31-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10025528

ABSTRACT

The problem of vessel-size discrepancy is still unsolved in microvascular-free tissue transfers. In an effort to develop a technique perioperatively to dilate smaller vessel diameters, the authors utilized a catheter customarily used in coronary angioplasties, the percutaneous transluminal coronary angioplasty (PTCA) catheter. Twenty New Zealand rabbits were divided into two groups: Group 1 consisted of 14 experimental animals; Group 2 of six control animals. In both groups, a segmental defect of 2 cm was created in the proximal portion of the femoral artery just below the inguinal ligament, where the vessel diameter is 2.0+/-0.1 mm. In Group 1 animals, an arterial graft was harvested from the superficial femoral artery in the contralateral lower extremity, where the vessel diameter is 1.0+/-0.1 mm. The arterial graft along its entire length was dilated, using a PTCA catheter up to 2 mm in diameter. The duration of dilation was 3 min with pressure applied at 2.5 atm. Before and following dilation, sections were obtained from both ends of the graft for histologic comparison. The grafts were then interposed within the defect and microvascular anastomoses were performed. In the control group, an arterial graft of the same length as in the experimental group was harvested from the contralateral upper femoral region, where the vessel diameter is 2.0+/-0.1 mm. These grafts were then interposed within the defect and microsurgically anastomosed. Seven days later, the patency of the anastomoses was evaluated in both groups. In 13 of 14 rabbits in the experimental group, the anastomoses were patent and the arterial grafts maintained their dilated diameters (2 mm). In all six control animals, the anastomoses were patent. A statistical comparison of vessel patency using Fischer's exact chi-square test showed no significant differences between the experimental and control groups (p = 0.7). Histologically, the dilated arteries demonstrated intact endothelial layers.


Subject(s)
Angioplasty, Balloon, Coronary , Femoral Artery/surgery , Vascular Surgical Procedures/instrumentation , Anastomosis, Surgical/instrumentation , Anastomosis, Surgical/methods , Animals , Disease Models, Animal , Femoral Artery/pathology , Graft Occlusion, Vascular/prevention & control , Graft Survival , Rabbits , Reference Values , Time Factors , Tissue Transplantation/methods , Vascular Patency , Vascular Surgical Procedures/methods
12.
J Reconstr Microsurg ; 15(1): 73-9, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10025534

ABSTRACT

The authors describe a rabbit arterial thrombosis model that employs vessel division followed by microsurgical anastomosis and transluminal sutures, to reliably induce thrombus formation in the common femoral artery (CFA). Using two objective measures, "evacuation/refill" evaluation of patency and computer-aided histomorphometric analysis of the thrombus area, thrombus formation was confirmed and characterized in the model at both short- and long-term observation time-points. In addition, a gene delivery method was developed in the CFA that employs an adenoviral vector solution injected through the inferior epigastric artery (IEA). Using this method, a marker transgene (beta-galactosidase) was delivered to endothelial cells locally and without trauma. By subsequently performing beta-galactosidase staining, effective endothelial transfection was demonstrated simultaneously with endothelial viability, with preserved endothelial synthetic function in the immediate environment of the occluding thrombus. The results suggest that these two techniques can be used together in one model, to effectively introduce a foreign therapeutic transgene into endothelial cells and to evaluate the effect of the expressed protein product in a consistent in vivo thrombosis system. This combined model may be used as one of several assays of efficacy in future endothelial cell-targeted thrombolytic/antithrombotic vascular gene therapy research.


Subject(s)
Gene Targeting/methods , Genetic Vectors/administration & dosage , Thrombolytic Therapy/methods , Thrombosis/therapy , Adenoviridae/genetics , Animals , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Femoral Artery , Genetic Therapy/methods , Image Processing, Computer-Assisted , Male , Microscopy, Electron, Scanning , Rabbits , Transfection , Vascular Patency
13.
Proc Natl Acad Sci U S A ; 96(3): 1065-70, 1999 Feb 02.
Article in English | MEDLINE | ID: mdl-9927694

ABSTRACT

Tissue-type plasminogen activator (tPA) catalyzes the rate-limiting initial step in the fibrinolytic cascade. Systemic infusion of tPA has become the standard of care for acute myocardial infarction. However, even the relatively short-duration protocols currently employed have encountered significant hemorrhagic complications, as well as complications from rebound thrombosis. Gene therapy offers a method of local high-level tPA expression over a prolonged time period to avoid both systemic hemorrhage and local rebound thrombosis. To examine the impact of local tPA overexpression, an adenoviral vector expressing tPA was created. The construct was characterized functionally in vitro, and the function of the vector was confirmed in vivo by delivery to the rabbit common femoral artery. Systemic coagulation parameters were not perturbed at any of the doses examined. The impact of local overexpression of tPA on in vivo thrombus formation was examined subsequently in a stasis/injury model of arterial thrombosis. The construct effectively prevented arterial thrombosis in treated animals, whereas viral and nonviral controls typically developed occluding thrombi. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery.


Subject(s)
Genetic Therapy , Thrombosis/prevention & control , Tissue Plasminogen Activator/metabolism , Adenoviridae , Animals , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/physiology , Femoral Artery , Genetic Vectors , Humans , Rabbits , Recombinant Proteins/biosynthesis , Thrombosis/pathology , Tissue Plasminogen Activator/biosynthesis , Tissue Plasminogen Activator/genetics , Umbilical Veins
14.
Circ Res ; 84(1): 84-92, 1999.
Article in English | MEDLINE | ID: mdl-9915777

ABSTRACT

-Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form, a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi. By histological analysis, nonviral controls exhibited intravascular thrombus occluding a mean of 70.52+/-3.72% of available lumen, while viral controls reached 86. 85+/-2.82% thrombotic occlusion; in contrast, Adv/RSV-THM reduced thrombosis to 28.61+/-3.31% of lumen in cross section. No significant intima-to-media ratio was observed in the thrombomodulin group relative to controls. Local infiltration of granulocytes and macrophages significantly decreased in the Adv/RSV-THM group relative to controls, while neutrophilic infiltration increased in viral controls relative to nonviral controls. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery, without the inflammatory damage that has limited many other adenoviral applications.


Subject(s)
Arterial Occlusive Diseases/prevention & control , Genetic Therapy/methods , Thrombomodulin/physiology , Thrombosis/prevention & control , Adenoviridae , Animals , Arterial Occlusive Diseases/pathology , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/physiology , Femoral Artery/pathology , Humans , Protein C/metabolism , Rabbits , Recombinant Proteins/metabolism , Thrombomodulin/genetics , Thrombosis/pathology , Transfection , Tumor Cells, Cultured , Umbilical Veins
15.
Plast Reconstr Surg ; 103(1): 96-100, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9915168

ABSTRACT

Endoscopic surgical procedures in plastic surgery have been applied in numerous aesthetic and reconstructive surgical techniques. The use of the endoscopic video-assisted technique in peripheral nerve surgery is one of the most recent advances in reconstructive surgery. In this preliminary report, the seventh intercostal nerve, in fresh human cadavers, was harvested with the aid of endoscopy through a single 2-cm transverse incision. The anatomy of the intercostal nerve and the endoscopic surgical technique are described in this report. Multiple intercostal nerve grafts of adequate size, number, and length could be harvested, with less donor site morbidity, and used for future reconstruction of the injured peripheral nerve. The advantages of using an endoscopic technique to harvest the intercostal nerve include a magnified, clear, and illuminated visualization; a better remote access incision site; and an atraumatic technique, which may be proven particularly applicable in clinical procedures in patients who are prone to hypertrophic scars such as in women and children.


Subject(s)
Endoscopy , Intercostal Nerves/transplantation , Cadaver , Female , Humans , Intercostal Nerves/anatomy & histology , Male
16.
Ann Plast Surg ; 41(6): 600-5, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9869132

ABSTRACT

Endoscopic procedures in plastic surgery have been applied in various aesthetic and reconstructive surgical techniques. The authors describe, in this preliminary report, a new surgical technique of endoscopic dissection of the temporoparietal fascial flap. A series of 6 fresh human cadavers (12 flaps) were dissected endoscopically. The surgical incisions, flap anatomy applicable to endoscopy, endoscopic surgical technique, and type of endoscopic setup is standardized for all flaps, allowing direct identification of the temporoparietal fascial layers and the major vascular pedicle. This endoscopic manipulation of the flap, without the traditional large scalp incision, permits local and free transfer of the temporoparietal fascial flap. Exposure of the flap by means of the conventional T or Y temporal incisions has several possible disadvantages, including an increased risk of blood loss, alopecia, and facial nerve injury. Endoscopic dissection and mobilization of the temporoparietal fascial flap can obviate the direct flap incision and yield a flap accessible to dissection and mobilization for additional clinical applications. This new, innovative, and minimally invasive endoscopic procedure may prove particularly applicable to future clinical applications of this type of fascial flap.


Subject(s)
Endoscopy , Surgical Flaps , Cadaver , Dissection/methods , Face , Feasibility Studies , Female , Humans , Male
17.
Radiographics ; 18(6): 1373-94, 1998.
Article in English | MEDLINE | ID: mdl-9821188

ABSTRACT

Gene therapy is an exciting frontier in medicine today. Radiologists will be involved in tracking the effects of these new therapies through imaging. Vascular and interventional radiology techniques also are ideally suited for minimally invasive, readily monitored gene delivery. Gene therapy is accomplished through gene augmentation or gene blocking. The latter is accomplished through antisense oligonucleotides or transcription factor decoys. Vectors are agents that facilitate gene delivery and expression and can be viral or nonviral. The vascular wall is an ideal target for gene therapy because of its central role in many biologic processes and its ready accessibility. Recombinant genes can be delivered ex vivo and in vivo, with the latter approaches involving open surgical, percutaneous injection, and endovascular catheter-based methods. Perforated, hydrogel-coated, and double balloon catheters have been used with varying success. Optimal catheter systems for gene transfer will enable delivery of the vector to the precise anatomic location with transfection limited to the cells of interest and will minimize shedding of the vector to distal sites, systemic effects of the therapeutic agent, and morbidity from the delivery method. Radiologists must become familiar with the basic rationale, strategies, and mechanisms of gene therapy and involved in its clinical trials to ensure an active role in this field.


Subject(s)
Coronary Disease/therapy , Genetic Therapy , Graft Occlusion, Vascular/therapy , Peripheral Vascular Diseases/therapy , Thrombosis/prevention & control , Endothelium, Vascular , Genetic Therapy/methods , Genetic Vectors , Humans , Radiology, Interventional
18.
Plast Reconstr Surg ; 102(4): 1030-3, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9734420

ABSTRACT

The anatomy of the inframammary fold has been a subject of controversy. This report describes the anatomic location and the histologic structure of the inframammary fold on the basis of caderveric dissections and microscopic examination. Ten breast cadaver dissections were performed on female cadavers (ages 35 to 72). Twenty specimens after en bloc resections of the inframammary fold and subcutaneous tissue, including the pectoralis muscle, were harvested. Specimens were examined for gross collagen stricture by using India ink to highlight the collagenous aspects of the subcutaneous soft-tissue networks. The inframammary fold skin and dermis from the contralateral breast and control samples of skin and dermis from the upper chest and the abdomen were collected for microscopic studies. These samples were stained with Sirius red and examined microscopically by polarized light. On histologic examination, regular arrays of collagen were found running parallel with the inframammary fold, and the control sections showed random patterns of collagen deposition. On gross examination, a condensation of the superficial fascial system was observed. This formed a zone of adherence between the skin and the underlying pectoralis fascia. The conclusion of this study is that the inframammary fold is an intrinsic dermal structure consisting of regular arrays of collagen held in place by a zone of adherence that is a specialized area of the superficial fascial system. The clinical significance of this study is that the intradermal structure of the inframammary fold should be preserved in any breast procedure for natural aesthetic results.


Subject(s)
Breast/anatomy & histology , Skin/anatomy & histology , Adult , Aged , Collagen/ultrastructure , Esthetics , Fascia/anatomy & histology , Female , Humans , Mammaplasty , Middle Aged , Reference Values
19.
Clin Plast Surg ; 25(4): 527-36, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9917972

ABSTRACT

OBPP is a condition that, for the majority of patients, resolves spontaneously with appropriate nonoperative treatment. However, those patients who do not improve spontaneously now have a better chance for recovery owing to recent advances in microsurgery and nerve-transfer techniques. The most important aspect of therapy is timely recognition and referral.


Subject(s)
Birth Injuries/therapy , Brachial Plexus/injuries , Paralysis/etiology , Birth Injuries/diagnosis , Birth Injuries/surgery , Brachial Plexus/physiopathology , Humans , Incidence , Infant , Infant, Newborn , Microsurgery , Nerve Transfer , Paralysis/diagnosis , Paralysis/surgery , Paralysis/therapy , Recovery of Function , Referral and Consultation , Remission, Spontaneous , Reoperation , Risk Factors , Time Factors
20.
J Craniomaxillofac Trauma ; 4(2): 16-9; discussion 15, 1998.
Article in English | MEDLINE | ID: mdl-11951428

ABSTRACT

A cadaveric study was conducted with a twofold purpose--to perform diagnostic transantral endoscopy in pure blowout fractures of the orbital floor and to attempt restoration of bony defects in the orbital floor using the endoscope. Endoscopic visual access of the orbital floor allows precise determination of the fracture size and the presence and extent of entrapped periorbital fasciae. A bony defect was created surgically in the orbital floor of 6 fresh cadaver heads, and a split-thickness calvarial bone graft and an alloplast were used to repair the orbital floor. Grafting of the orbital floor with endoscopic visual access was successful, and the potential risks associated with the traditional eyelid incisions were minimized. The anatomic course of the infraorbital nerve was observed and protected. The study confirmed that endoscopy could be used successfully in obtaining visual access to the orbital floor.


Subject(s)
Bone Transplantation/methods , Endoscopy , Orbit/surgery , Orbital Fractures/surgery , Biocompatible Materials , Cadaver , Endoscopes , Endoscopy/methods , Eyelids/surgery , Fascia/pathology , Humans , Orbit/innervation , Orbit/pathology , Orbital Fractures/classification , Orbital Fractures/pathology , Polyethylenes , Prostheses and Implants , Risk Factors , Treatment Outcome
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