Dynamics of picosecond laser ablation for surgical treatment of colorectal cancer.

Endoluminal surgery for the treatment of colorectal neoplasia is typically carried out using electrocautery tools which imply limited precision and the risk of harm through collateral thermal damage to the adjacent healthy tissue. As a potential alternative, we present the successful colonic epithelial laser ablation by means of picosecond laser pulses. Laser ablation studies performed in ex-vivo colon tissue result in cavities with comparable thickness to early stage colorectal cancers. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue and the depth of the ablation can be controlled precisely by means of the pulse energy. High-speed imaging has been used for the first time to visualize picosecond laser ablation of cancerous tissue in a clinically relevant model. This information was correlated with histopathology and optical surface profilometry revealing the dynamic nature of the laser tissue interaction and the need for temporal or spatial separation of pulses for optimum efficacy with regards to tissue removal. Overall, the application of picosecond laser pulses to ablate endoluminal bowel lesions demonstrates significantly improved precision and reduced thermal damage to the adjacent tissue in comparison to conventional procedures and hence will enable more precise surgical treatment of cancers.

A retrospective cohort study of racing performance in Quarter Horses undergoing prosthetic laryngoplasty for treatment of recurrent laryngeal neuropathy.

OBJECTIVE To determine effects of prosthetic laryngoplasty on return to racing, performance index, and career longevity in racing Quarter Horses with recurrent laryngeal neuropathy (RLN) and to evaluate performance variables for horses with RLN undergoing prosthetic laryngoplasty, compared with a control horse population. DESIGN Multicenter, retrospective cohort study. ANIMALS 162 racing Quarter Horses with RLN treated with prosthetic laryngoplasty (case horses) and 324 racing Quarter Horse without RLN (control horses). PROCEDURES Medical and race records of case and control horses examined at 5 referral centers between January 2000 and December 2015 were reviewed retrospectively. Two control horses were matched with each case horse. Return to racing, earnings, number of racing starts, performance index, and career longevity were evaluated. RESULTS The odds of returning to racing did not differ significantly between case and control horses but decreased with increasing age. Neither racing starts nor career longevity were affected by prosthetic laryngoplasty or by RLN grade. In fact, horses undergoing laryngoplasty for treatment of RLN and horses with the lowest RLN grade before surgery had higher performance indices after the surgery, compared with indices for control horses. CONCLUSIONS AND CLINICAL RELEVANCE The faster speeds and shorter distances raced with Quarter Horses could alter how RLN impacts respiratory variables and performance in Quarter Horses, compared with other racehorse breeds. Further study is needed to understand the impacts of RLN and surgical treatments for RLN in racing Quarter Horses.

Superficial digital flexor tendonitis in cutting horses: 19 cases (2007-2011).

OBJECTIVE: To characterize superficial digital flexor (SDF) tendon lesions in the forelimbs of cutting horses and determine recurrence rate and prognosis for this condition. DESIGN: Retrospective case series. ANIMALS: 19 cutting horses with SDF tendonitis. PROCEDURES: Medical records for horses evaluated for SDF tendonitis in 2007 through 2011 were reviewed. Data regarding age, sex, lameness grade, affected limb, and treatment were collected. Ultrasonographic images were reviewed, and lesion characteristics were recorded. Follow-up telephone interviews with owners or trainers were conducted to determine recurrence of SDF tendonitis, return of horse to its previous level of activity, and duration of the convalescent period. RESULTS: All 19 horses initially evaluated for SDF tendonitis had similar lesions in the lateral aspect of the tendon. The right forelimb was affected in 11 horses, and the left forelimb was affected in 7 horses; 1 horse was affected in both forelimbs. Mean lameness grade was 1.26 (range, 0 to 3). Of 17 horses for which follow-up information was available, 3 had recurrence of tendon lesions and 1 developed a lesion in the contralateral forelimb SDF tendon; 16 horses returned to their previous level of activity. CONCLUSIONS AND CLINICAL RELEVANCE: The location of SDF tendonitis in cutting horses appeared to be unique in that no central core lesions were detected ultrasonographically. Lesions at the periphery of the tendon may have an increased ability to heal, compared with lesions at the central core. Results suggested that cutting horses with SDF tendonitis have a better prognosis than that reported for affected racehorses.

Flexible delivery of Er:YAG radiation at 2.94 µm with negative curvature silica glass fibers: a new solution for minimally invasive surgical procedures.

We present the delivery of high energy microsecond pulses through a hollow-core negative-curvature fiber at 2.94 µm. The energy densities delivered far exceed those required for biological tissue manipulation and are of the order of 2300 J/cm(2). Tissue ablation was demonstrated on hard and soft tissue in dry and aqueous conditions with no detrimental effects to the fiber or catastrophic damage to the end facets. The energy is guided in a well confined single mode allowing for a small and controllable focused spot delivered flexibly to the point of operation. Hence, a mechanically and chemically robust alternative to the existing Er:YAG delivery systems is proposed which paves the way for new routes for minimally invasive surgical laser procedures.

Delivery of high energy Er:YAG pulsed laser light at 2.94 µm through a silica hollow core photonic crystal fibre.

In this paper the delivery of high power Er:YAG laser pulses through a silica hollow core photonic crystal fibre is demonstrated. The Er:YAG wavelength of 2.94 µm is well beyond the normal transmittance of bulk silica but the unique hollow core guidance allows silica to guide in this regime. We have demonstrated for the first time the ability to deliver high energy pulses through an all-silica fibre at 2.94 µm. These silica fibres are mechanically and chemically robust, biocompatible and have low sensitivity to bending. A maximum pulse energy of 14 mJ at 2.94 µm was delivered through the fibre. This, to our knowledge, is the first time a silica hollow core photonic crystal fibre has been shown to transmit 2.94 µm laser light at a fluence exceeding the thresholds required for modification (e.g. cutting and drilling) of hard biological tissue. Consequently, laser delivery systems based on these fibres have the potential for the realization of novel, minimally-invasive surgical procedures.

Mid-infrared methane detection in a photonic bandgap fiber using a broadband optical parametric oscillator.

We demonstrate methane sensing using a photonic bandgap fiber-based gas cell and broadband idler pulses from a periodically-poled lithium niobate femtosecond optical parametric oscillator. The hollow core of the fiber was filled with a methane:nitrogen mixture, and Fourier transform spectroscopy was used to measure transmission spectra in the 3.15-3.35 mum methane absorption region. The method has applications in gas sensing for remote or hazardous environments and potentially at very low concentrations.

Frequency-doubling in femtosecond laser inscribed periodically-poled potassium titanyl phosphate waveguides.

Frequency doubling has been achieved in femtosecond-laser-inscribed single-mode waveguides written in two periodically-poled potassium titanyl phosphate crystals. A conversion efficiency of 0.22 %W(1) was obtained for first-order quasi-phase matching at 980 nm and an efficiency of 0.02 %W(-1) for third-order quasi-phase matching at 800 nm.

Analysis of optical damage mechanisms in hollow-core waveguides delivering nanosecond pulses from a Q-switched Nd:YAG laser.

Hollow-core waveguides consisting of a glass capillary tube with an internal reflective coating are capable of delivering pulse energies of tens of millijoules with improved focusability compared to step index fibers of similar core diameter. We demonstrate the capability of these fibers to deliver high-power Q-switched pulses at the fundamental (1064 nm), second (532 nm), and third (355 nm) harmonics of a Nd:YAG laser, both in terms of peak power and beam quality delivered. In terms of peak power delivery, the primary limitation is the occurrence of bend-induced optical damage to the reflective coating. The damage mechanism and the influential factors are analyzed, in particular, the dependence upon the number of guided modes, core diameter, coating thicknesses, and input polarization alignment.

Single-mode mid-IR guidance in a hollow-core photonic crystal fiber.

We report, for the first time, bandgap guidance above 3 mum in a silica based air-core photonic crystal fiber. The peak of the bandgap is at 3.14mum with a typical attenuation of ~ 2.6 dB m-1. By further optimization of the structure, modeling suggests that a loss below 1 dB m-1 should be achievable, greatly extending the useful operating range of silica-based single-mode fibers. Such fibers have many potential applications in the mid-IR, offering an alternative to fluoride, tellurite or chalcogenide glass based optical fibers for chemical and biological sensing applications.

High energy nanosecond laser pulses delivered single-mode through hollow-core PBG fibers.

We report on the development of hollow-core photonic bandgap fibers for the delivery of high energy pulses for precision micromachining applications. Short pulses of (65ns pulse width) and energies of the order of 0.37mJ have been delivered in a single spatial mode through hollow-core photonic bandgap fibers at 1064nm using a high repetition rate (15kHz) Nd:YAG laser. The ultimate laser-induced damage threshold and practical limitations of current hollow-core fibers for the delivery of short optical pulses are discussed.

Catalytic wet oxidation: mathematical modeling of multicompound destruction.

A mathematical model of a three-phase catalytic reactor, CatReac, was developed for analysis and optimization of a catalytic oxidation reactor that is used in the International Space Station potable water processor. The packed-bed catalytic reactor, known as the volatile reactor assembly (VRA), is operated as a three-phase reactor and contains a proprietary catalyst, a pure-oxygen gas phase, and the contaminated water. The contaminated water being fed to the VRA primarily consists of acetic acid, acetone, ethanol, 1-propanol, 2-propanol, and propionic acid ranging in concentration from 1 to 10 mg/L. The Langmuir-Hinshelwood Hougen-Watson (L-H) (Hougen, 1943) expression was used to describe the surface reaction rate for these compounds. Single and multicompound short-column experiments were used to determine the L-H rate parameters and calibrate the model. The model was able to predict steady-state multicomponent effluent profiles for short and full-scale reactor experiments.

[Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes]. / Mekhanizmy nakopleniia i vybrosa azitromitsina v polimorfnoiadernykh leikotsitakh cheloveka.

Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be effective at tissue sites of infection. These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E). Azithromycin was massively accumulated by human PMN (C/E = 387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN. After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux. Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.

Characteristics and mechanisms of azithromycin accumulation and efflux in human polymorphonuclear leukocytes.

Azithromycin achieves prolonged, high tissue concentrations in spite of low serum levels and obviously must be active at tissue sites of infection to be effective. These unique features prompted us to evaluate the interactions of azithromycin and human polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was determined by a velocity-gradient centrifugation technique and expressed as the ratio of cellular to extracellular drug concentration (C/E). Azithromycin was massively accumulated by human PMN (C/E=387.2 at 2 h). Uptake was not influenced by inhibitors of cellular metabolism, but phagocytosis slightly inhibited the entry of azithromycin into PMN. After removal of extracellular drug, the release (efflux) of azithromycin from PMN was extremely slow. Agents which neutralize lysosomal pH, preventing protonation and trapping of azithromycin, markedly increased antibiotic efflux. Active concentration and prolonged retention of azithromycin by phagocytic cells should allow delivery and subsequent release of accumulated drug at sites of infection.

Osteomyelitis of the sustentaculum tali in horses: 10 cases (1992-1998).

OBJECTIVE: To determine outcome of horses with osteomyelitis of the sustentaculum tali (ST), with or without associated tarsal sheath tenosynovitis, following surgical debridement and lavage. DESIGN: Retrospective study. ANIMALS: 10 horses in which a diagnosis of osteomyelitis of the ST had been made on the basis of history, physical examination findings, and results of radiography. PROCEDURE: Information on results of diagnostic testing, surgical findings, postoperative treatment, and short-term outcome was obtained from the medical records. Long-term follow-up information was obtained through reevaluation of horses at the teaching hospital and telephone conversations with referring veterinarians, owners, and trainers. RESULTS: Treatment consisted of surgical debridement, intra- and postoperative lavage, and long-term antimicrobial and anti-inflammatory treatment. Eight horses had evidence of involvement of the tarsal sheath. One horse was euthanatized after surgery because of a lack of response to treatment; the other 9 were discharged from the hospital. Severity of lameness had improved, but all still had grade-1 or -2 lameness at the time of discharge. One horse was euthanatized after discharge because of contralateral hind limb laminitis, and another horse was lost to follow-up. Of the remaining 7 horses, 6 returned to their previous use, and 1 was sound but retired for breeding for unrelated reasons. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that horses with osteomyelitis of the ST, with or without concomitant tarsal sheath tenosynovitis, can have an excellent to good outcome and may return to their previous use after surgical debridement of affected tissues and lavage of the tarsal sheath.

Real-time, nonintrusive oxidation detection system for the welding of reactive aerospace materials.

We describe the development of a real-time nonintrusive monitor to detect degradation of a gas shield condition during laser welding by use of on-axis spectrally resolved detection of light emitted from the workpiece. Failure of gas shielding to the point at which there is a risk of contamination from the air is revealed by the marked increase in the intensity of a spectral feature around 426 nm. To avoid unwanted sensitivity to the overall intensity of the radiation, the intensity at 426 nm is normalized by that at 835 nm, where the spectrum is insensitive to gas shielding. We collected the radiation by using the same optics as are used to deliver the processing beam, and thus the detection process is entirely nonintrusive. We demonstrate successful operation for welding stainless steel and titanium under both helium and argon gas shielding.

Stabilization of collagen-tailed acetylcholinesterase in muscle cells through extracellular anchorage by transglutaminase-catalyzed cross-linking.

A component of collagen-tailed acetylcholinesterase (asymmetric; A-AChE) in muscle forms a metabolically-stable pool which can be released from the cell surface only by collagenase, suggesting that part of the enzyme is covalently bound by its tail (COLQ) subunits. We have investigated whether this insoluble pool forms through covalent cross-linking of A-AChE to extracellular matrix glycoproteins by tissue transglutaminase (Tg; type 2 transglutaminase). Tg catalyzed the incorporation of the polyamine substrate 3[H]-putrescine into the collagen tail of affinity-purified avian A12-AChE. Complexes between A12-AChE and cellular fibronectin were also formed in vitro by Tg. In quail myotubes, retinoic acid, which stimulates the formation of epsilon(gamma-glutamyl)lysine isodipeptide bonds by Tg in myotubes, increased the proportion of extraction-resistant (er) A-AChE. Following irreversible inactivation of AChE by diisopropylfluorophosphate, entry of newly-synthesized A-AChE into the extraction-resistant pool was inhibited by a competitive Tg inactivator RS48373-007. The quantity of exogenously-added A 12 AChE incorporated into the extraction-resistant pool in living myotubes was increased by Tg in the presence of calcium. The inhibition of cross-bridge formation in fibrillar collagen by beta-aminopropionitrile, and pre-exposure of myotubes to a monoclonal antibody to fibronectin, resulted in a reduction in the size of the erA-AChE pool present on the cell-surface. The evidence supports the hypothesis that a component of insoluble collagen-tailed AChE, once subject to clustering influences mediated via reversible docking to proteoglycans and their receptors, is anchored at the cell surface through covalent cross-linking by Tg. The high stability of the epsilon(gamma-glutamyl)lysine isopeptide bond is likely to contribute to the observed low turnover of the erA-AChE fraction.

An improved measure for comparing diagnostic tests.

We present a loss based method for comparing the predictive performance of diagnostic tests. Unlike standard assessment mechanisms, like the area under the receiver-operating characteristic curve and the misclassification rate, our method takes specific advantage of any information that can be obtained about misclassification costs. We argue that not taking costs into account can lead to incorrect conclusions, and illustrate with two examples.