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Biomedical subjects

E R Owen

Publications and source records attributed to E R Owen.

At least 19 recordsLinked to original sources
PubMed2004

Human hand transplantation: what have we learned?

Hand transplantation may become an important procedure for upper limb functional restoration. To date, 18 patients have been undergone 24 hand operations in the world. Initial results are extremely promising; the functional results are apparently superior to those obtained with prostheses. We report on the combined French and Italian experience of six patients (eight hands), which is based on a jointly devised protocol and represents the largest available clinical series. Six male patients aged 43, 33, 35, 32, 33, and 22 years received either a single right hand-dominant transplantation (four cases) or a simultaneous double hand transplantation (two cases). The time since the amputation ranged from 3 to 22 years. The level of transplantation was at the wrist in five cases (six hands) and at the distal forearm in two cases (two hands). Cold ischemia averaged 11.5 hours. Three patients simultaneously received additional full-thickness skin taken from the donor and transplanted onto their left hip area. This skin served as a source for biopsies and as an additional area to monitor rejection (distant sentinel skin graft). The immunosuppressive protocol included polyclonal antibodies (three patients) or monoclonal anti-CD 25 antibody (three patients), tacrolimus, mycophenolate mofetil, and prednisolone. No surgical complications occurred. Skin rejection occurred at least once in all patients at a mean of 40 days postoperatively. Three patients recovered protective and some discriminative sensation in their palm and fingers. Two patients are recovering sensation, but are still in the early phases of the regenerative process, due to the short time since the transplantation. One patient was not compliant with the immunosuppressive therapy, and underwent uncontrolled rejection and reamputation.

Adolescent↗
PubMed2004

Experimental limb transplantation, part I: identification of an effective tapered triple combination immunosuppressive regime.

Limb transplantation was performed across the Brown Norway to Fischer 344 histocompatibility barrier in rats to evaluate the effects of triple combination immunosuppressive therapeutic regimens. Sixty rats were divided into five groups: group I (F344 to F344) isograft controls group II (BN to F344) allograft controls received no immunosuppressive treatment. Groups III and V (BN to F344) received various exposures to tacrolimus (TRL), mycophenolate mofetil (MMF) and prednisolone (Pred) for two weeks: namely, group III: TRL 0.5 mg/kg/d; MMF 10 mg/kg/d; Pred 0.5 mg/kg/d; group IV: TRL 2 mg/kg/d, MMF 15 mg/kg/d, Pred 0.5 mg/kg/d; and group V: TRL 3 mg/kg/d; MMF 20 mg/kg/d; Pred 0.5 mg/kg/d. After 2 weeks, group III and V animals underwent a simultaneous 20% taper of Pred and MMF each further week such that by week 7 the animals were only on TRL. At this time TRL was tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d. Evidence of rejection was sought by daily visual observation for swelling, redness, erythema, edema, or skin necrosis. Salvage treatment was used only if rejection occurred after the first 7 weeks, namely, reversing to 100% of the initial TRL dose in that group for 2 weeks with a subsequent taper. Skin and muscle biopsies were obtained from grafted limbs on day 3, 13, 24, 35, and at the endpoint (9 months or uncontrollable rejection). There was no rejection in group I, while all animals showed acute rejection as expected in group II. All group III rats displayed a similar though delayed acute rejection, showing that the regimen was not therapeutic. Rats in group IV displayed the best results, namely, 10 of 12 (83%) with no rejection or side effects at 9 months. Rats in group V displayed numerous, unacceptable side effects due to overtreatment with a 1-month mortality rate of 50%. This study shows that low-dose TRL in combination with MMF and Pred may achieve excellent long-term results of composite tissue transplants. TRL can be used alone as maintenance therapy following an initial loading dose and a tapering period. Rejection is easily reversed by only temporarily increasing the TRL dose.

Animals↗
PubMed2004

Experimental limb transplantation, part II: excellent return of function and indefinite survival after withdrawal of immunosuppression.

In this study the three components of an immunosuppressive combination therapy were gradually withdrawn in a rat limb transplantation model to evaluate the effects on long-term survival of the grafted limbs, rejection rate, and functional recovery. The procedure was performed in 16 rats across a strong Brown Norway to Fischer 344 histocompatibility barrier. Eight animals served as a control group that was not given any antirejection therapy and rejected their limb within a few days. The remaining eight animals were administered a 2-week course of immunosuppressive therapy including tacrolimus (TRL; 2 mg/kg/d), mycophenolate mofetil (MMF; 15 mg/kg/d), and prednisolone (Pred; 0.5 mg/kg/d). At 2 weeks, Pred and MMF were simultaneously tapered by 20% of the dosage every week; by week 7 the animals were on TRL only. TRL was then tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d at week 12. After 6 months the immunosuppression was stopped. Four of 8 animals did not reject throughout the study up, to the 1-year endpoint. At this stage they show excellent functional outcomes, evaluated by clinical tests and walking tract analysis. The remaining four rats developed a rejection at an average of 267 days postoperatively (range 224 to 302 days), corresponding to an average of 87 days (range 44 to 122 days) without any immunosuppression. They were sacrificed as soon as rejection was confirmed for histological examination of the various tissues. This study showed that a triple combination therapy provides excellent long-term functional outcomes of the transplanted limbs, with no rejection episodes, no side effects, or complications, even 6 months after withdrawal of all immunosuppressive components, suggesting the possible emergence of tolerance.

Animals↗
PubMed2000

Optimal parameters for laser tissue soldering: II. Premixed versus separate dye-solder techniques.

BACKGROUND AND OBJECTIVE: Laser tissue soldering by using an indocyanine green (ICG)-doped protein solder applied topically to the tissue surface and denatured with a diode laser was investigated in Part I of this study. The depth of light absorption was predominantly determined by the concentration of the ICG dye added to the solder. This study builds on that work with an in vitro investigation of the effects of limiting the zone of heat generation to the solder-tissue interface to determine whether more stable solder-tissue fusion can be achieved. STUDY DESIGN/MATERIALS AND METHODS: An alternative laser tissue soldering technique was investigated, which increased light absorption at the vital solder-tissue interface. A thin layer of ICG dye was smeared over the surface to be treated, the protein solder was then placed directly on top of the dye, and the solder was denatured with an 808-nm diode laser. Because laser light at approximately 800 nm is absorbed primarily by the ICG dye, this thin layer of ICG solution restricted the heat source to the space between the solder and the tissue surfaces. A tensile strength analysis was conducted to compare the separate dye-solder technique with conventional techniques of laser tissue soldering for which a premixed dye-solder is applied directly to the tissue surface. The effect of hydration on bond stability of repairs formed by using both techniques was also investigated using tensile strength and scanning electron microscopy analysis. RESULTS: Equivalent results in terms of tensile strength were obtained for the premixed dye-solder technique using protein solders containing 0.25 mg/ml ICG (liquid solder, 220 +/- 35 N/cm(2); solid solder, 602 +/- 32 N/cm(2)) and for the separate dye-solder technique (liquid solder, 228 +/- 41 N/cm(2); solid solder, 578 +/- 29 N/cm(2)). The tensile strength of native bovine thoracic aorta was 596 +/- 31 N/cm(2). Repairs created by using the separate dye-solder technique were more stable during hydration than their premixed dye-solder counterparts. The conventional premixed dye-solder was simpler and approximately twice as fast to apply. The separate dye-solder technique, however, increased the shelf-life of the solder, because the dye was mixed at the time of the experiment, thus conserving its spectral absorbency properties. CONCLUSION: Two laser-assisted tissue soldering techniques have been evaluated for repairing aorta incisions in vitro. The advantages and disadvantages of each of these techniques are discussed.

Absorption↗
PubMed2000

Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump.

Animals↗
PubMed1999

Optimal parameters for laser tissue soldering. Part I: tensile strength and scanning electron microscopy analysis.

BACKGROUND AND OBJECTIVES: The use of liquid and solid albumin protein solders to enhance laser tissue repairs has been shown to significantly improve postoperative results. The published results of laser-solder tissue repair studies have, however, indicated inconsistent success rates. This can be attributed to variations in laser irradiance, exposure time, solder composition, chromophore type, and concentration. An in vitro study was performed using indocyanine green-doped albumin protein solders in conjunction with an 808 nm diode laser to determine optimal laser and solder parameters for tissue repair in terms of tensile strength and stability during hydration. STUDY DESIGN/MATERIALS AND METHODS: Twenty-five different combinations of laser irradiance (6.4, 12.7, 19.1, 25.5, 31.8 W/cm2) and exposure time (20, 30, 40, 50, 100 or 40, 60, 80, 100, 200 seconds) were used. The effect of changing bovine serum albumin (BSA) concentration (25% and 60%) and indocyanine green (ICG) dye concentration (2.5 mg/ml and 0.25 mg/ml) of the protein solder on the tensile strength of the resulting bonds was investigated. The effect of hydration on bond stability was also investigated using both tensile strength and scanning electron microscopy analysis. RESULTS: Tensile strength was observed to decrease significantly with increasing irradiance. An optimum exposure time was found to exist where further irradiation did not improve the tensile strength of the bond. Tensile strength was found to be greatly improved by increasing the BSA concentration. Finally, the lower ICG dye concentration increased the penetration depth of the laser light in the protein solder leading to higher tensile strengths. The strongest repairs were formed by using 6.4 W/cm2 irradiation for 50 seconds with a protein solder composed of 60% BSA and 0.25mg/ml ICG. In addition, the solid protein solder provided more stable adhesion to the tissue than did the liquid protein solder when the tissue was submerged in a hydrated environment. CONCLUSIONS: This study greatly enhances the current understanding of the various factors affecting the soldering process. It provides a strong basis for optimization of the laser light delivery parameters and the solder constituents to achieve strong and reliable laser tissue repairs.

Animals↗
PubMed1999

Assessment of tissue blood flow following small artery welding with an intraluminal dissolvable stent.

Using the technique of radioactive 51Cr-labeled biological microspheres, this study evaluated arterial blood flow following small vessel anastomosis by CO2 laser welding and a dissolvable stent in the lumen. A total of 30 Sprague-Dawley rats were divided into two groups. Group A: 11 rats had their femoral arteries ligated on one side. The contralateral side served as a control, with the artery transected and repaired using conventional microsuturing. Group B: 19 rats had their femoral arteries transected and repaired using CO2 laser welding and an intraluminal dissolvable stent technique. The contralateral side was again used as a control using conventional microsuturing. At 1 hr postoperatively, 51Cr-labeled biological microspheres were injected centripetally into the left common carotid artery and the legs and thighs immediately harvested for measurement of radioactivity. All repaired arteries were patent (30/30 in the microsuturing group and 19/19 in the stented welding group), with no detectable stenosis or dilation at the repaired site. Statistical analysis showed that tissue radioactivity (cpm/g) in the ligated group (3,972 +/- 384 in thighs and 3,142 +/- 742 in legs) was significantly lower than in the microsuturing group (7,132 +/- 1,723 in thighs and 6,557 +/- 1,469 in legs) (P < 0.01). In the ligated group, a significant reduction of blood flow was seen in the legs when compared with the thighs (P < 0.05). There was no significant difference in radioactivity when comparing the microsuturing control with the stented welding group, in both thighs (7,064 +/- 2,599 and 7,006 +/- 2,406, respectively; P > 0.05) and legs (6,386 +/- 1,703 and 6,288 +/- 1,757, respectively; P > 0.05). This study provided evidence that the dissolvable stent placed intraluminally does not impair blood circulation and that when coupled with CO2 laser welding offers a high-quality alternative to conventional small vessel anastomosis.

Absorbable Implants↗
PubMed1999

Free-flap transfer with a synthetic arterial pedicle.

In this study, a unilateral epigastric free flap was raised in 12 rabbits. After the arterial portion of the flap (the superficial femoral artery) was replaced by a 1-cm-long polytetrafluoroethylene graft with an internal diameter of 1 mm, the flap was revascularized by two conventional microvascular end-to-end anastomoses (graft to artery and vein to vein). At 3 weeks, all flaps were raised again and the patency of the polytetrafluoroethylene grafts was checked. All grafts, including the proximal and distal anastomoses, were harvested and processed for light and electron microscopy. All grafts remained patient, and all flaps survived the period of 3 weeks. At reexploration, the graft was completely covered with connective tissue. Light and scanning electron microscopy evaluation showed that the internal surface of the graft was covered by a fibrin layer, and that the ingrowth of neoendothelium had just started from both anastomotic sites. The use of small-diameter polytetrafluoroethylene grafts in a rabbit free-flap model was demonstrated to be a reliable alternative for pedicle elongation.

Animals↗
PubMed1999

Photothermal effects of laser tissue soldering.

Low-strength anastomoses and thermal damage of tissue are major concerns in laser tissue welding techniques where laser energy is used to induce thermal changes in the molecular structure of the tissues being joined, hence allowing them to bond together. Laser tissue soldering, on the other hand, is a bonding technique in which a protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. The addition of protein solders to augment tissue repair procedures significantly reduces the problems of low strength and thermal damage associated with laser tissue welding techniques. Investigations were conducted to determine optimal solder and laser parameters for tissue repair in terms of tensile strength, temperature rise and damage and the microscopic nature of the bonds formed. An in vitro study was performed using an 808 nm diode laser in conjunction with indocyanine green (ICG)-doped albumin protein solders to repair bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The efficacy of temperature feedback control in enhancing the soldering process was also investigated. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the repairs. A reduction in dye concentration from 2.5 mg ml(-1) to 0.25 mg ml(-1) was also found to result in an increase in tensile strength. Increasing the laser irradiance and thus surface temperature resulted in an increased severity of histological injury. Thermal denaturation of tissue collagen and necrosis of the intimal layer smooth muscle cells increased laterally and in depth with higher temperatures. The strongest repairs were produced with an irradiance of 6.4 W cm(-2) using a solid protein solder composed of 60% BSA and 0.25 mg ml(-1) ICG. Using this combination of laser and solder parameters, surface temperatures were observed to reach 85+/-5 degrees C with a maximum temperature difference through the 150 microm thick solder strips of about 15 degrees C. Histological examination of the repairs formed using these parameters showed negligible evidence of collateral thermal damage to the underlying tissue. Scanning electron microscopy suggested albumin intertwining within the tissue collagen matrix and subsequent fusion with the collagen as the mechanism for laser tissue soldering. The laser tissue soldering technique is shown to be an effective method for producing repairs with improved tensile strength and minimal collateral thermal damage over conventional laser tissue welding techniques.

Animals↗
PubMed1999

Sutureless microvascular anastomoses by a biodegradable laser-activated solid protein solder.

A new sutureless technique to successfully anastomose the abdominal aorta of rats (1.3 mm in diameter) by using a fully biodegradable, laser-activated protein solder is presented. A total of 90 rats were divided into two groups randomly. In group one, the anastomoses were performed by using conventional microsuturing technique, whereas in group two, the anastomoses were performed by using a new laser welding technique. In addition, each of the two groups were divided into five subgroups and evaluated at different follow-up periods (10 minutes, 1 hour, 1 day, 1 week, and 6 weeks). At these intervals, the anastomoses were evaluated for patency and tensile strength. Three anastomoses in each subgroup were processed for light and electron microscopy. All anastomoses were found to be patent. The mean clamp time of the anastomoses performed with conventional suturing was 20.6 minutes compared with 7.2 minutes for the laser-activated welded anastomoses (p < 0.001). The strain measurements showed a stronger mechanical bond of the sutured anastomoses in the initial phase. However, at 6 weeks the tensile strength of the laser-welded anastomoses was higher compared with the conventional suture technique. Histologic evaluations revealed a near complete resorption of the solder after 6 weeks. The junction site of the vessel ends cannot be determined on the luminal side of the artery. In conclusion, a resorbable protein used as a solder, activated by a diode laser, can provide a reliable, safe, and rapid arterial anastomosis, which could be performed by any microsurgeon faster than conventional suturing after a short learning curve.

Anastomosis, Surgical↗
PubMed1998

Laser nerve repair by solid protein band technique. I: identification of optimal laser dose, power, and solder surface area.

Thirty-four tibial nerves in 17 adult male wistar rats were repaired by applying protein bands longitudinally across the nerve join. The bands were then irradiated with a fibre-coupled diode laser (lambda = 810 nm). The relations among the laser weld breaking force, the power, and the solder surface area were investigated, while maintaining a consistent ratio between the total mass of protein solder in a band and total laser energy delivered (the laser energy dose). When this laser energy dose was held constant, the average breaking force of the laser welds irradiated by 72 mW laser output power was weaker than that reached after 90 mW laser radiation. There is a linear relation between the solder breaking force and the solder surface area when band thickness, laser power, and laser dose are unvaried.

Animals↗
PubMed1998

Laser nerve repair by solid protein band technique. II: assessment of long-term nerve regeneration.

A total of 18 adult male Wistar rats had left tibial nerve repaired by either the laser-solder technique or a more conventional microsuture technique. The diode laser power was 90 mW and the radiation dose 16 J/mg. Three months postoperatively electrophysiology showed that the average compound muscle action potential (CMAP) of the laser repair group was not significantly different from the CMAP of the sutured nerves. Light microscopy confirmed regeneration of myelinated axons in both groups of animals. The laser-solder technique, when used with such parameters, proved to be a reliable method to achieve satisfactory peripheral nerve anastomosis and nerve regeneration.

Action Potentials↗
PubMed1998

Laser welding of vas deferens in rodents: initial experience with fluid solders.

This study evaluates the use of sutureless laser welding for vasovasostomy. In 14 rodents, the left vas deferens underwent vasovasostomy using an albumin-based solder applied to the adventitia of the vas deferens. The solder contained the dye, indocyanine green, to allow selective absorption and denaturation by a fiber-coupled 800-nm diode laser. The right vas deferens served as a control, receiving conventional layered microsurgical repair. We used a removable 4/0 nylon stent and microclamps to appose the vas deferens during repair, with no need for stay sutures. The mean time to perform laser solder repair (23.5 min) and conventional repair (23.3 min) were not significantly different (P=0.91). However, examination after 8 weeks showed that granuloma formation (G) and patency (P) rates for the conventional suture technique (G, 14%; P, 93%) were significantly better than observed for the laser solder technique (G, 57%; P, 50%).

Albumins↗
PubMed1997

Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

BACKGROUND AND OBJECTIVE: Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. STUDY DESIGN/MATERIALS AND METHODS: An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. RESULTS: Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. CONCLUSION: The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

Action Potentials↗
PubMed1996

Assessment of nerve ultrastructure by fibre-optic confocal microscopy.

Fibre-optic technology combined with confocality produces a microscope capable of optical thin sectioning. In this original study, tibial nerves have been stained in a rat model with a vital dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide, and analysed by fibre-optic confocal microscopy to produce detailed images of nerve ultrastructure. Schwann cells, nodes of Ranvier and longitudinal myelinated sheaths enclosing axons were clearly visible. Single axons appeared as brightly staining longitudinal structures. This allowed easy tracing of multiple signal axons within the nerve tissue. An accurate measurement of internodal lengths was easily accomplished. This technique is comparable to current histological techniques, but does not require biopsy, thin sectioning or tissue fixing. This study offers a standard for further in vivo microscopy, including the possibility of monitoring the progression of nerve regeneration following microsurgical neurorraphy.

Animals↗
PubMed1996

Scanning electron microscopy evaluation of endothelial regeneration in 1-mm PTFE prostheses.

This study documents the developmental stages of neoendothelium regeneration in 1-mm polytetrafluoroethylene (PTFE) prostheses. Scanning electron microscopy was used to follow the progression of platelet deposition, fibrin layering, and endothelial cell migration along the graft. The endothelial healing process was divided into six stages: platelet aggregation (stage I); fibrin network (stage II); bridging (stage III); progression (stage IVA); transmural migration (stage IVB); intimal closure (stage V); and endothelial thromboresistance (stage VI).

Animals↗