Search

OBJECTIVES Translingual neurostimulation (TLNS) studies indicate improved outcomes in neurodegenerative disease or spinal cord injury patients. This study was designed to assess the safety and efficacy of TLNS plus targeted physical therapy (PT) in people with a chronic balance deficit after mild-to-moderate traumatic brain injury (mmTBI). MATERIALS AND METHODS This international, multicenter, randomized study enrolled 122 participants with a chronic balance deficit who had undergone PT following an mmTBI and had plateaued in recovery. Randomized participants received PT plus either high-frequency pulse (HFP; n = 59) or low-frequency pulse (LFP; n = 63) TLNS. The primary efficacy and safety endpoints were the proportion of sensory organization test (SOT) responders (SOT composite score improvement of ≥15 points) and fall frequency after five weeks of treatment, respectively. RESULTS The proportion of SOT responders was significant in the HFP + PT (71.2%) and LFP + PT (63.5%) groups compared with baseline (p

Early detection of pulmonary complications can improve outcomes for patients with hematological malignancy (HM). For detecting lung injuries, lung ultrasound (LUS) images have been found to be of greater sensitivity than radiographic images. Our group performed a pilot study of LUS imaging to enhance early detection of pulmonary complications in HM patients. This prospective single-center feasibility study evaluated LUS for detecting pulmonary complications in 18 HM patients enrolled while hospitalized for a hematopoietic cell transplant (HCT) (concurrent-HCT group) or re-hospitalized for complications (post-HCT group). Serial LUS exams were performed and assigned a score from 0 to 5 based on pleural line, B-line, consolidation and pleural effusion features. Correlations between patients' clinical characteristics and LUS features were analyzed. Comparisons between the LUS and radiographic images were evaluated. In the concurrent-HCT patients (79 LUS exams), non-significant fluctuating findings were commonly identified, but one-third of the patients presented pathologic findings (LUS scores ≥ 3). In the post-HCT patients (29 LUS exams), LUS images revealed severe pathologic findings (LUS score = 5) in every patient and, compared with radiographic images, were more sensitive for detecting pleural effusions (p0.05). LUS can be routinely performed on hospitalized HM patients, allowing point-of-care early detection of pulmonary complications.

Background Postpartum hemorrhage is a leading cause of maternal mortality globally. A tamponade agent that can be quickly and easily placed in a range of settings could advance the treatment of atonic hemorrhage. Method We adapted a highly effective trauma dressing for use in postpartum hemorrhage. This mini-sponge tamponade device is comprised of two components: compressed mini-sponges contained within a strong mesh pouch and a tubular applicator. Compressed mini-sponges rapidly absorb blood, expand within seconds, and exert sustained pressure uniformly to bleeding sites. The sponges are deployed within a mesh pouch to facilitate simple vaginal removal. Experience We successfully placed the mini-sponge device in nine patients experiencing postpartum hemorrhage after vaginal birth, with resolution of bleeding within 1 minute. The mean time to place the device was 62 seconds. Uterine fill was documented in all cases by ultrasound scan, and device placement was rated as "easy" to "very easy." Mini-sponges were left in place on average for 1 hour (0.5 hours-14 hours). Bleeding did not recur. There were no adverse events; all patients remained afebrile and did not require subsequent surgical intervention. Conclusion This study supports further evaluation of the mini-sponge device for the management of postpartum hemorrhage. Funding This study was funded by OBSTETRX, Inc.

The growing field of regenerative rehabilitation has great potential to improve clinical outcomes for individuals with disabilities. However, the science to elucidate the specific biological underpinnings of regenerative rehabilitation-based approaches is still in its infancy and critical questions regarding clinical translation and implementation still exist. In a recent roundtable discussion from International Consortium for Regenerative Rehabilitation stakeholders, key challenges to progress in the field were identified. The goal of this article is to summarize those discussions and to initiate a broader discussion among clinicians and scientists across the fields of regenerative medicine and rehabilitation science to ultimately progress regenerative rehabilitation from an emerging field to an established interdisciplinary one. Strategies and case studies from consortium institutions-including interdisciplinary research centers, formalized courses, degree programs, international symposia, and collaborative grants-are presented. We propose that these strategic directions have the potential to engage and train clinical practitioners and basic scientists, transform clinical practice, and, ultimately, optimize patient outcomes.

Ultrasound shear wave elastography (SWE) has become a clinically accepted tool for tissue characterization, cancer diagnosis, and therapy assessment. However, it is only commercially available on premium ultrasound scanners and high-performance transducers capable of sustaining high-voltage, long-duration acoustic push-pulses. Mechanical vibration is an alternative method for acoustic radiation force (ARF) to induce shear wave propagation inside soft tissue, thus enabling ultrasound SWE on low-cost and portable systems. One potential application is compartment syndrome (CS), with the acute cases commonly seen in traumatic injuries and chronic cases caused by exercise injuries. CS is a condition in which the increased pressure in the muscle compartment inhibits capillary blood flow and subsequently causes muscle ischemia. To avoid permanent muscle injury, CS must be diagnosed and treated rapidly. In this study, a vibration-enabled SWE prototype was implemented on a commercial scanner and evaluated using an in vivo swine CS model as a proof-of-concept for non-invasive CS detection.

Tropoelastin (TE), the soluble precursor of insoluble elastin fibers, is produced in minimal amounts in adults. Burn injuries result in inflexible collagen-rich scars because of lack of elastin fiber formation. We studied the feasibility of using recombinant human tropoelastin to enable elastin fiber production in burn and surgical scars to improve skin flexibility. In a swine hypertrophic burn scar model, normal skin and 3 × 3-cm partial thickness thermal burns underwent dermatome resection at 1 week post burn and randomized to four subcutaneous injections of saline or TE (either 0.5, 5, or 10 mg/ml) spaced 3 days apart. Two burn sites received TE injections after wound closure (0.5 or 10 mg/ml). At 90 days, skin hardness, flexibility, and histology were evaluated. All injury sites developed hypertrophic scars. New elastin fibers were found in burn scars in all injuries injected after skin closure with low (5/5) and high (6/6) TE doses (P < .05). No elastin fibers were observed without TE treatment. No significant differences in skin hardness, flexibility, or inflammation were observed. This is the first report demonstrating that subcutaneous injections of TE into surgical and burn injuries can safely produce new elastin fibers in scars. Despite the development of new elastin fibers, skin flexibility was not improved, possibly because of insufficient elastin fiber maturation or the hypertrophic model used. The ability to restore elastin fiber formation in adult skin after burns, trauma, and surgery may improve skin regeneration and reduce disabling complications of scar formation.

Following spinal cord injury (SCI), inflammation amplifies damage beyond the initial insult, providing an opportunity for targeted treatments. An ideal protective therapy would reduce both edema within the lesion area and the activation/infiltration of detrimental immune cells. Previous investigations demonstrated the efficacy of intravenous injection of multipotent adult progenitor cells (MAPC®) to modulate immune response following SCI, leading to significant improvements in tissue sparing, locomotor and urological functions. Separate studies have demonstrated that tissue inhibitor of matrix metalloproteinase-3 (TIMP3) reduces blood-brain barrier permeability following traumatic brain injury in a mouse model, leading to improved functional recovery. This study examined whether TIMP3, delivered alone or in concert with MAPC cells, improves functional recovery from a contusion SCI in a rat model. The results suggest that intravenous delivery of MAPC cell therapy 1 day following acute SCI significantly improves tissue sparing and impacts functional recovery. TIMP3 treatment provided no significant benefit, and further, when co-administered with MAPC cells, it abrogated the therapeutic effects of MAPC cell therapy. Importantly, this study demonstrated for the first time that acute treatment of SCI with MAPC cells can significantly reduce the incidence of urinary tract infection (UTI) and the use of antibiotics for UTI treatment.

Background Polidocanol foam (PF), used clinically as a venous sclerosant, has recently been studied as a safe and inexpensive means for permanent contraception. Delivering the sclerosant to the fallopian tubes as a foam rather than a liquid increases the surface areas and thus enhances the desired epithelial disrupting activity of the agent. However, the foam is inherently unstable and degrades with time. Therefore, increasing foam stability and thus duration of the agent exposure time could increase epithelial effect while allowing reduction in agent concentration and potential toxicity. Materials and Methods We studied methods to improve foam properties that might improve safety and efficacy of PF for intrauterine application. Several types of microporous filters adapted to a syringe-based foaming device were used to study the effect of pore structures on the formation of PF. The foam drainage time and bubble size were characterized. The addition of benzalkonium chloride (BZK) to polidocanol was also investigated for its effects on foam characteristics. Results A syringe-based foaming device adapted with an inline filter produced smaller bubble PF with a longer foam drainage time. PF generated with a circular pore filter lasts longer than with a noncircular pore filter. The addition of 0.01% of BZK also improved the stability of PF. Conclusion The stability of PF is affected by the pore characteristics of the filter used for foam generation and enhanced by the presence of a small amount of BZK. The improved foam, if shown to be efficacious in animal models of contraception, could lead to a safe, simple and inexpensive method alternative to surgical contraception.

Background Although uterine tamponade is an effective treatment for postpartum hemorrhage (PPH), current methods have key limitations in their use, particularly in low resource settings. The XStat™ Mini Sponge Dressing (MSD) is approved for the management of non-compressible wounds in the battlefield/trauma setting. The MSD applies highly compressed medical sponges capable of stopping high-flow arterial bleeding within seconds. The objective of our study was to adopt the MSD for use in managing PPH. Methods We performed desktop testing using a uterine model with pressure sensors to compare key design elements of the obstetrical prototype MSD (fundal pressure achieved, reduction in fluid loss, time to deploy, and time to remove) with alternativetechniques (uterine packing, balloon tamponade). To evaluate safety, we delivered the fetus of pregnant ewes by cesarean section and used the prototype to deliver the MSD into one uterine horn, and closed the hysterotomy. We followed the clinical recovery of animals (n = 3) over 24 h, and then removed the reproductive tract for histologic evaluation. To evaluate late effects, we surgically removed the MSDs after 24 h, and followed the clinical recovery of animals (n = 6) for an additional seven days before tissue removal. Results The obstetrical prototype has a long tapered delivery system designed to be deployed during vaginal examination, and administers three times the volume of the approved MSD trauma bandage. The MSD are deployed within a mesh bag to facilitate removal by vaginaltraction. On desktop testing, the MSD resulted in the highest average fundal pressure (113 mmHg), followed by the MSD bag device (85.8 mmHg), gauze packing (15.5 mmHg), and the uterine balloon (8.2 mmHg). The MSD bag test group achieved the largest fluid flow reduction of −74%, followed by gauze packing (−55%), MSD (−35%), and uterine balloon (−19%). Animal testing demonstrated good uterine fill with no evidence of adverse clinical recovery, uterine trauma or infection at 24 h, or up to 7 days following device removal. Conclusion We adapted a highly effective trauma dressing and applicator for use in the treatment of severe PPH. Preliminary desktop and animal testing provide a basis for initial clinical trials in women. Electronic supplementary material The online version of this article (doi:10.1186/s12884-017-1373-x) contains supplementary material, which is available to authorized users.

The development of vascular grafts has focused on finding a biomaterial that is non-thrombogenic, minimizes intimal hyperplasia, matches the mechanical properties of native vessels and allows for regeneration of arterial tissue. In this study, the structural and mechanical properties and the vascular cell compatibility of electrospun recombinant human tropoelastin (rTE) were evaluated as a potential vascular graft support matrix. Disuccinimidyl suberate (DSS) was used to cross-link electrospun rTE fibers to produce a polymeric recombinant tropoelastin (prTE) matrix that is stable in aqueous environments. Tubular 1 cm diameter prTE samples were constructed for uniaxial tensile testing and 4 mm small-diameter prTE tubular scaffolds were produced for burst pressure and cell compatibility evaluations from 15 wt% rTE solutions. Uniaxial tensile tests demonstrated an average ultimate tensile strength (UTS) of 0.36±0.05 MPa and elastic moduli of 0.15±0.04 MPa and 0.91±0.16 MPa, which were comparable to extracted native elastin. Burst pressures of 485 ± 25 mmHg were obtained from 4 mm ID scaffolds with 453 ± 74 μm average wall thickness. prTE supported endothelial cell growth with typical endothelial cell cobblestone morphology after 48 hours in culture. Cross-linked electrospun recombinant human tropoelastin has promising properties for utilization as a vascular graft biomaterial with customizable dimensions, a compliant matrix, and vascular cell compatibility.

An off-the-shelf vascular graft biomaterial for vascular bypass surgeries is an unmet clinical need. The vascular biomaterial must support cell growth, be non-thrombogenic, minimize intimal hyperplasia, match the structural properties of native vessels, and allow for regeneration of arterial tissue. Electrospun recombinant human tropoelastin (rTE) as a medial component of a vascular graft scaffold was investigated in this study by evaluating its structural properties, as well as its ability to support primary smooth muscle cell adhesion and growth. rTE solutions of 9, 15, and 20 wt% concentrations were electropun into sheets with average fiber diameters of 167 ± 32, 522 ± 67, and 735 ± 270 nm, and average pore sizes of 0.4 ± 0.1, 5.8 ± 4.3, and 4.9 ± 2.4 μm, respectively. Electrospun rTE fibers were cross-linked with disuccinimidyl suberate (DSS) to produce an insoluble fibrous polymeric recombinant tropoelastin (prTE) biomaterial. The smooth muscle cells attached via integrin binding. The proliferation of the smooth muscle cells on the electrospun prTE biomaterial was comparable to growth on prTE coated glass, glass alone and tissue culture plastic. Electrospun tropoelastin demonstrated the cell compatibility and design flexibility required of a graft biomaterial for vascular applications.

Bleeding from the liver surface is common after hepatic resection. Animal studies have demonstrated superiority of argon beam coagulation (ABC) and 38% human serum albumin when applied together after partial liver resection when compared to ABC alone. There are no data addressing the combination of albumin and argon beam coagulation (ABCA) applied to the bleeding liver after resection in humans. The aim of this study was to evaluate the safety and efficacy of ABCA on hemostasis when applied to the surface of the liver remnant post-hepatic resection.Ten patients underwent liver resection and were treated with ABCA immediately after the liver was divided. The liver surface was coated with albumin and ABC applied simultaneously, the liver was covered with gauze for 3 min, and ABCA was repeated if necessary. Number of rebleeding episodes requiring re-application of ABCA, time of ABCA application, overall blood loss, and liver functions were monitored. Patients were followed for at least 6 months.Nine of 10 patients required a single application of ABCA, and one patient required two treatments. Average time of ABC use was 5 ± 3 min. Median blood loss was 230 ml. Liver functions returned to near normal within 4 days of resection.ABCA performed well with respect to hemostatic properties, much like previous observations in animal studies. Further clinical trials are justified using this technique.

Drs.Bachtell,Grunkemeier,andJinarewithProvidenceHealthSystem;T.GoodelliswithOregonHealthS and Dr. Gregory is with Oregon Medical Laser Center, Portland, Oregon. Background.Bleedingfromcoagulopathichemodialysispuncturesitescancontributetoanemiaindialysispatients,andcurrent compressive dressings may contribute to graft thrombosis. We studied the safety and efficacy of a new chitosan-based bandage with an active clotting surface and compared its time to hemostasis and compression strap usage in dialysis access puncture wounds with that of conventional gauze dressings. Methods. Fifty patients received both the chitosan-based and conventional gauze dressings in random order on 2 successive visits. Time to hemostasis and compression strap usage were compared between the visits. Time to hemostasis was analyzed using the binary response variable at 2 and 4 minutes. A compression strap wasused if dressing application was unsuccessful at 4 minutes. Covariates included coagulation state as measured by laboratory analysis and anticoagulation therapy. Results.Hemostasiswasachievedby2minutesin30%ofthechitosan-basedand38%oftheconventionaldressings(p ¼0.608) andby4minutesin86%ofthechitosan-basedand72%oftheconventionaldressings(p ¼0.040).Compressionstrapusagewas reducedby50%inthechitosan-basedgroupcomparedtotheconventionalgroup(7vs.14patients;p ¼0.052).Noadverseevents were reported with either dressing. Conclusions. The chitosan-based bandage from HemCon is a safe and effective hemostatic agent to reduce prolonged posthemodialysis puncture site bleeding and may reduce the use of occlusive compression straps.

Topically applied concentrated albumin with argon beam coagulation (ABCA) has been shown to be more effective at achieving hemostasis than using argon beam coagulation alone (ABC) in a liver injury model. This study investigated the host response to the concentrated albumin after argon beam coagulation. Complete hemostasis was achieved using ABCA (N = 10) or ABC (N = 10) on a nonanatomic liver resection in a heparinized porcine model. The repairs were evaluated grossly and microscopically at postoperative periods of 30 and 90 days. We found no evidence of biliary leakage, rebleeding, or intraabdominal infection. Blood analysis indicated liver chemistry indices were within normal range after ABC and ABCA treatments. The histopathology showed that the postoperative healing response was similar in both groups: a moderate chronic inflammatory response as part of an on-going normal healing process. All repairs were encapsulated by fibrous tissue. There was no difference in the postsurgical adhesion scores for the ABCA (mean 3.4) and ABC (mean 3.8). It was concluded that use of the concentrated albumin as biological glue in conjunction with argon beam coagulation is a safe and efficient procedure for controlling hepatic hemorrhage in surgery. Further studies are warranted to investigate the clinical significance of this technique.

We have investigated the long-term effect of aluminum chloride (AlCl(3)) treatment on the calcification and inflammatory reaction of a porcine elastin-derived biomaterial (PEB) in a novel subdermal adult mouse model. Untreated PEB disks and PEB treated with AlCl(3) were implanted subdermally in BALB/c mice for 30, 60, and 180 days. The calcification of the elastin disks was examined with histological analysis and atomic absorption analysis of calcium content. The inflammatory reaction was evaluated both with histological analysis of explants and by an enzyme-linked immunosorbent assay of the serum in each mouse to determine the production of antielastin antibodies. Robust calcification was evident in all untreated PEBs with calcium levels of 107.1 +/- 11.8, 151.4 +/- 14.4, and 227.2 +/- 23.8 microg/mg for 30, 60, and 180 days, respectively. AlCl(3) treatment only temporarily prevented the calcification of the elastin disks for 30 days. By 60 and 180 days, the AlCl(3)-treated materials had significant calcification with 88.7 +/- 17.4 and 105.3 +/- 27.0 microg/mg calcium, respectively. The inflammatory reaction was moderate for both types of implants. The AlCl(3)-treated implants displayed significantly more macrophage and lymphocyte infiltration at 180 days after implantation, and a trend to higher humoral responses at 30 and 60 days when compared with untreated PEBs. We conclude that PEBs extensively calcify in the adult mice model. AlCl(3) treatment of elastin enhances the long-term immunological response to xenogenic elastin implants and merely delays the onset of calcification.

Background and Objectives: The success of laser tissue welding or soldering depends on optimal laser settings, solder material, and tissue type and geometry. To develop a practical laser welding technique for ureteral repair, an intraluminal albumin stent was designed to enhance the welding effects on ureteral end to end anastomosis. Study Design/Materials and Methods: In vitro porcine ureters were anastomosed using an albumin stent alone, the albumin stent plus a solder, and the solder alone. All welding was performed with an 810-nm diode laser with either a continuous wave (1 W, CW) or two pulse modes (2 W, 3.3 Hz; 1 W, 5 Hz). Laser parameters, tensile strength (TS) and burst pressure (BP) of the ureteral anastomosis, and tissue thermal injury were measured. Results: In the 2-W pulse mode, BP in the albumin stent plus solder group (mean 185 mmHg) and the stent only group (mean 133 mmHg) were significantly higher than the solder only group (mean 77 mmHg, P < 0.05). Laser ureteral anastomosis with the stent plus solder group at 1-W CW and 2-W pulse laser modes yielded the highest TS (mean 97, 82 g) and BP (mean 183, 185 mmHg). Among the three modes, the 1 W pulse delivered the lowest energy and yielded the lowest TS and BP in ureteral anastomosis. There was no significant difference in the thermal damage to the tissue among the modes and groups. Conclusions: Using the albumin stent increased the reliability of ureter end-to-end laser anastomosis. Further studies will be warranted in vivo and other tubular organs as well. Lasers Surg. Med. 31:225–229, 2002. 2002 Wiley-Liss, Inc.

Background/Objective: Laser thrombolysis is the selective removal of thrombus from occluded blood vessels using laser energy. A reconstituted clot model with reproducible optical absorption properties was de- veloped to evaluate the effect of various laser parame- ters on thrombus removal rate. Study Design/Materials and Methods: Reconstituted clots were made with known fibrinogen concentra- tions and hematocrits. Ex vivo clots were collected from ten swine. Four red gelatin phantoms were prepared. Mass removal rates and ablation efficiencies were de- termined using a 577 nm, 1 µsec pulsed dye laser. The ablation efficiencies of the three clot models were com- pared at an energy of 25 mJ and a repetition rate of 4 Hz. In addition, the reconstituted clot model was ablated as pulse energy and repetition rate were varied with aver- age power held constant at 100 mW. Results: The mean ablation efficiency for ex vivo clots ranged from 0.4 ± 0.1 to 3.4 ± 0.7 µg/mJ/pulse, with sig- nificant differences between groups (ANOVA p < 0.05). Reconstituted clots of varied fibrinogen content had ab- lation efficiencies of 1.5 ± 0.2 to 1.6 ± 0.3 µg/mJ/pulse at this energy and repetition rate. Gelatin ablation efficiency was inversely proportional to protein con- tent and ranged from 0.5 ± 0.3 to 2.0 ± 0.7 µg/mJ/pulse. Reconstituted clot mass removal rates (in µg/s) were clinically similar for settings ranging from 13 mJ at 8 Hz to 33 mJ at 3 Hz. Conclusions: The reconstituted model clot is a repro- ducible and biologically relevant thrombolysis target. Ex vivo clot lacks reproducibility between individu- als and gelatin phantoms lack clinical relevance. At a constant average power, varying laser parameters did not affect mass removal rates to a clinically significant degree.

An esophageal injury with significant tissue loss is very difficult to repair. We conducted an in vivo study to test our elastin based acellular biomaterial patch to repair such defect. The patch was made from porcine aorta, by decellularization and sterilization. Collagen fibers were preserved to retain mechanical strength and enhance cellular in-growth. Ten domestic pigs underwent right thoracotomy. A 2 cm circular defect was made on the distal esophagus, excising half its circumference, and was repaired using the biomaterial patch and sutures. Soon after the procedure, the animals resumed oral feeding. They were followed for clinical status, weight gain, barium studies, and endoscopic studies, and were killed after 6 weeks to 4 months. All ten animals survived long term, with a procedure success rate of 100% (10 of 10). With the exception of one pneumothorax, no complications occurred, and all animals resumed oral feeding and gained weight. Endoscopic studies showed mucosal coverage by 6 weeks, with minimal stricture at the repair site. Excised specimens showed complete mucosal coverage with regeneration of all three layers. Our biomaterial patch can be used safely and reliably for repair of esophageal injury with significant tissue loss when repaired immediately as in our experiment.

Laser tissue welding is a sutureless method of wound closure that has been used successfully in nerve, skin and arterial anastomoses. An elastin-based biomaterial patch was welded to the intimai surface of porcine aorta in the present study. The aorta was stained with indocyanine green dye to efficiently absorb the 808 nm diode laser light. Laser welding with a pulsed diode laser thermally confines heating to the stained portion of tissue, minimizing adjacent tissue damage. Laser welds of stained aorta to biomaterial were attempted by sandwiching the samples between glass slides and applying pressures ranging from 4 to 20 N cm-2 for 5 ms pulse durations and 83 mJ mm-2 radiant exposure. Bleaching of the indocyanine green by as much as 85% was observed after exposure laser irradiation. Finally, successful welds required 5 N cm-2 of pressure between the elastin biomaterial and aorta.

Background and Objective Radiographic contrast media containing iodine-labeled organic compounds can be present in the irradiated field during laser angioplasty using 308 nm excimer laser radiation. These compounds absorb light at 308 nm and may undergo photochemical reactions that produce products that damage cells. Study Design/Materials and Methods This study was undertaken to determine whether photoproducts that damage human lymphocytes in vitro are formed when Angiovist 370 (AV), a contrast medium containing triiodinated aromatic compounds, is exposed to 308 nm radiation. Results The absorption spectrum of AV developed a new peak at 360 nm that extended to wavelengths greater than 500 nm when dilute AV solutions were exposed to 308 nm radiation indicating that photoproducts were formed. Irradiating dilute AV solutions above a layer of human lymphocytes caused a dose-dependent decrease in thymidine incorporation using fluence rates between 5.2 × 106 and 1.0 × 108 W/cm2. Decreased DNA synthesis was independent of the pulse length (10 ns vs. 230 ns) but was lower, at a given dose, when the highest fluence rate was used. Incubation of lymphocytes with preirradiated AV solutions also decreased incorporation of thymidine in a radiation dose-dependent manner. The cell damaging photoproducts in preirradiated AV solutions were unstable; within 15 min, the effectiveness had decreased by ∼85%. Conclusions These results indicate that exposure of AV to 308 nm excimer laser radiation produces photochemical products that damage human cells in vitro. Lasers Surg. Med. 20:111–118, 1997. © 1997 Wiley-Liss, Inc.

Background Noncompressible hemorrhage is the leading cause of preventable death caused by hemorrhage on the battlefield. Currently, there are no hemostatic agents with the ability to control noncompressible hemorrhage. A wound stasis dressing based upon rapidly expanding cellulose minisponges (MS) was developed and tested in a lethal noncompressible model in swine, by fully transecting subclavian artery and vein. MS were compared with conventional hemostasis dressings, Combat Gauze (CG), in a randomized comparison. Methods Sixteen 40-kg swine underwent transection of the subclavian artery and vein through a 4.5-cm aperture. After 30-second free bleeding, randomly selected MS or CG (n = 8 per group) were administered by an independent medical officer. The wound cavity was filled with either MS + no external pressure or one CG + one KERLIX gauze with 3 minutes of external pressure. One reapplication was allowed for CG. Mean arterial pressure was maintained at 60 mm Hg with 500-mL Hextend and lactated Ringer's solution intravenously administered up to a maximum of 10-L until study termination at 1 hour. Results Mean pretreatment blood loss was similar for MS (719 mL) and CG (702 mL). Primary end points, namely, hemostasis at 4 minutes (MS, 75%; CG, 25%; p = 0.13), hemostasis at 60 minutes (MS, 100%; CG, 25%; p = 0.007), and survival at 60 minutes (MS, 100%; CG, 37.5%; p = 0.026), were improved with MS as were secondary end points, namely, total blood loss (MS, 118 mL; CG 1,242 mL; p = 0.021) and length of application time (MS, 25 seconds; CG, 420 seconds; p = 0.004). Conclusion The use of MS is a novel approach for the rapid, simple treatment of severe noncompressible hemorrhage, which provided statistically significant improvement in hemostasis and survival 60 minutes after injury and a large reduction in blood loss, resuscitation fluid requirement, and medic treatment time compared with conventional hemorrhage control dressings in a swine model.

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.

Photo acoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 µm when the gelatin structure was not fractured.

Background The complex data sets generated by higher-order polychromatic flow cytometry experiments are a challenge to analyze. Here we describe Exhaustive Expansion, a data analysis approach for deriving hundreds to thousands of cell phenotypes from raw data, and for interrogating these phenotypes to identify populations of biological interest given the experimental context. Methods We apply this approach to two studies, illustrating its broad applicability. The first examines the longitudinal changes in circulating human memory T cell populations within individual patients in response to a melanoma peptide (gp100209-2M) cancer vaccine, using 5 monoclonal antibodies (mAbs) to delineate subpopulations of viable, gp100-specific, CD8+ T cells. The second study measures the mobilization of stem cells in porcine bone marrow that may be associated with wound healing, and uses 5 different staining panels consisting of 8 mAbs each. Results In the first study, our analysis suggests that the cell surface markers CD45RA, CD27 and CD28, commonly used in historical lower order (2-4 color) flow cytometry analysis to distinguish memory from naïve and effector T cells, may not be obligate parameters in defining central memory T cells (TCM). In the second study, we identify novel phenotypes such as CD29+CD31+CD56+CXCR4+CD90+Sca1-CD44+, which may characterize progenitor cells that are significantly increased in wounded animals as compared to controls. Conclusions Taken together, these results demonstrate that Exhaustive Expansion supports thorough interrogation of complex higher-order flow cytometry data sets and aids in the identification of potentially clinically relevant findings.

Intravascular ultrasound imaging catheters and forward firing laser atherectomy systems are both being used in the coronary vascular tree of man. When used in conjunction, ultrasound imaging may reduce the probability of perforation and dissection related to laser atherectomy. A novel system is presented which combines ultrasound imaging and laser atherectomy capabilities on the same catheter. The system incorporates a holmium YAG laser directed perpendicular to the long axis of the catheter along with a co-directional ultrasound sensor. Ultrasound images are assembled by computer using the angle of the catheter tip and its linear advance associated with each ultrasound echo signal. In vivo experimental results are presented.

This PDF file contains the front matter associated with SPIE Proceedings Volume 6842, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Laser angioplasty systems with laser energy preferentially absorbed by atherosclerotic plaque may offer a safe method of plaque removal. This study evaluated the effect of blood upon selective energy absorption using a pulsed dye laser at 480 nm. Intra-arterial laser irradiation of normal rabbit femoral arteries demonstrated a perforation threshold energy with blood perfusion of 13.1 mJ per pulse compared to 87.9 mJ with saline (P less than .0001), indicating a deleterious effect in the presence of blood. An adverse effect upon arterial healing at 3 days was noted in sheep following intra-arterial irradiation during blood but not saline perfusion. Normal and atherosclerotic human aorta ablation thresholds differed significantly (P less than .0002) under saline (plaque: 20 mJ and normal: 120 mJ) but the difference under blood (plaque: 5 mJ and normal: 20 mJ) was not significant. We conclude that absorption of laser energy by blood can reduce the effect of differential absorption by endogenous chromophores in normal and pathologic vascular tissues and, therefore, removal of blood may be a prerequisite for selective ablation of atherosclerotic plaques.

It is shown that delivery of laser energy to intravascular targets through a flowing fluid-core laser angioplasty catheter offers new design possibilities and solutions to current practical problems facing laser angioplasty. Fluid-core catheters using iodinated radiographic contrast material as the core fluid can transmit high-peak-power visible laser pulses at high efficiencies while offering improved imaging of the target and distal vasculature. These catheters are simple to produce, are optically and mechanically stable, and are compatible with conventional angioplasty equipment and techniques. In canine coronary arteries in vivo, the catheters proved to be flexible, atraumatic, and able to deliver ablative high-peak-power laser pulses. >

Objectives: To study the feasibility of urethral reconstruction with two urethroplasty techniques using an elastin and collagen heterograft in rabbits. Materials and Methods: Fifty-two male rabbits were studied. Two types of injury, (1) a 1.5 ×× 0.6 cm2 semicircumferential defect; (2) a 1.5 cm segmental defect of the penile urethra, were created and repaired using size-matched elastin and collagen patches or tubed conduits. Urethral repair by primary closure for the type 1 injury and a tubularized autologous bladder mucosal graft for the type 2 injury served as controls. At 3 months, urethral diameter was measured with retrograde urethrography. The animals were then euthanized for histological examination. Results: The postoperative complication rate was significantly higher in the urethral reconstructions using tubed collagen (83%) and elastin (50%) grafts compared to the patch onlay grafts (p = 0.001 for collagen and p = 0.01 for elastin) and tubularized ABM (10%, p = 0.003 and 0.05, respectively). At the type 2 injury site, a dense circumferential fibrosis developed after all repairs. Only minimal ventral fibrosis presented in the type 1 injury repair. The intensity of chronic inflammation and fibrosis was greatest when collagen was used for the urethral repair. In the elastin urethral repairs the urethral diameter decreased significantly for the tubed repair compared to the patch onlay (p = 0.02). Conclusion: Urethral injury repair using elastin and collagen biomaterials is feasible in the rabbit model. The results of onlay urethroplasty using the elastin and collagen patches are significantly superior to those using the elastin and collagen tubed conduits. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006

Elastin, a principal structural component of na- tive arteries, has distinct biological and mechanical advan- tages when used as a biomaterial; however, its low ultimate tensile strength has limited its use as an arterial conduit. We have developed a scaffold, consisting of a purified elastin tubular conduit strengthened with fibrin bonded layers of acellular small intestinal submucosa (aSIS) for potential use as a small diameter vascular graft. The addition of aSIS increased the ultimate tensile strength of the elastin conduits nine-fold. Burst pressures for the elastin composite vascular scaffold (1396 309 mmHg) were significantly higher than pure elastin conduits (162 36 mmHg) and comparable to native saphenous veins. The average suture pullout strength of the elastin composite vascular scaffolds was 14.612 3.677 N, significantly higher than the pure elastin conduit (0.402 0.098 N), but comparable to native porcine carotid arteries (13.994 4.344 N). Cyclic circumferential strain testing indicated that the composite scaffolds were capable of withstanding physiological loading conditions for at least 83 h. Implantation of the elastin composites as carotid inter- position grafts in swine demonstrated its superiority to clin- ically acceptable ePTFE with significantly longer average patency times of 5.23 h compared to 4.15 h. We have devel- oped a biologically based elastin scaffold with suitable me- chanical properties and low thrombogenicity for in vivo implantation, and with the potential for cellular repopula- tion and host integration reestablishing an appropriate elas- tic artery. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 77A: 458 - 469, 2006

Background and Objectives: Laser-assisted end to end vascular anastomosis of an elastin heterograft to native artery may prevent problems associated with currently available vascular synthetic grafts and conventional suture anastomosis. Study Design/Materials and Methods: A total of 21 anastomoses in the carotid arteries of 7 domestic swine were performed with an 800 nm laser and an albumin stent plus solder. There were 5 artery to artery and 16 elastin heterograft to native artery anastomoses. Operative parameters, vascular patency, and histology of the anastomoses were evaluated. Results: Out of 21 anastomoses, 16 were patent for 3 hours. One artery to artery anastomosis was thrombosed and four elastin heterograft to artery anastomoses were excluded from the study due to heterograft burst. The average amount of applied energy was 212 J for artery to artery anastomosis and 273 J for elastin heterograft to native artery. Histology shows coagulative necrosis of the adventitia, hypereosinophilic contraction band in the media of native arteries and no changes in elastin heterografts. Conclusions: Laser-assisted vascular anastomosis (LAVA) of elastin heterograft to medium size vessel using an albumin stent is feasible. Chronic studies are warranted to determine long-term patency and histology of the LAVA. Lasers Surg. Med. 35:201–205, 2004. 2004 Wiley-Liss, Inc.