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PubMed1996

Photoacoustic Fibrinolysis: Pulsed-Wave, Mid-Infrared Laser-Clot Interaction.

Objectives: The purpose of this study was to determine whether a mid-infrared laser can induce selective fibrinolysis and to analyze the effect of altered fibrin structure (thin vs. thick fibers) on laser-clot interaction. Background: Mechanical disruption of thrombus can be achieved with balloon angioplasty, sonication, and thermal energy. Thrombi avidly absorb light in the mid-infrared optical spectrum due to their high water content. This phenomenon provides a potential for mid-infrared lasers as a source for selective thrombolysis. As fibrin is the essential component of clot, a study of mid-infrared laser-fibrin interaction is warranted. Methods: Clots of varying fibrin structure were lased in cuvettes with a solid-state, pulsed-wave, mid-infrared laser (2.1 micron, 500 mJ/pulse, 250 msec pulse length). Total pulse energies of 5 Joules (J), 10 J, 37.5 J, 75 J, and 112.5 J were tested. Protein content of the extruded fluid was measured by optical density absorbance at 280 nm. Th e amount of released material was studied as a function of lasing energy and clot structure. SDS-polyacrylamide gel electrophoresis was applied for analysis of protein bands in order to identify unique protein bands released by the selective effect of laser fibrinolysis. Results: A threshold for mid-infrared laser induced fibrinolysis was found; application of up to 20 J of energy did not result in dissolution. As lasing energy was increased above 37.5 J, the structure of these gels was mechanically destroyed and 12.4 +/- 6.7% (mean +/- SEM) of the original content of protein was released. Electrophoresis revealed that lased gels did not release any unique protein band. Lased, thin fibers released significantly less protein than thick fibers, indicating that they are more resistant to the effect of this wavelength of energy. Conclusions: Mid-infrared laser can induce in-vitro photoacoustic dissolution of fibrin clots. However, this wavelength laser achieves fibrinolysis by me chanical destruction of the target clot rather than by a selective effect, as induced by the pulsed-dye laser. A threshold exists for energy levels required. Thin fibrin fibers, with their high elastic modulus (i.e., gel rigidity) appear more resistant than thick fibers to the effect of lasing at this wavelength.

Journal Article↗

PubMed1997

Posterior capsule polishing with the neodymium:YLF picosecond laser: model eye study.

PURPOSE: To determine the ability and threshold energy of the neodymium:yttrium-lithium-fluoride (Nd:YLF) picosecond laser to achieve micron-level polishing of a latex posterior capsule facsimile (PCF) as an alternative to laser capsulotomy to treat posterior capsule opacification. SETTING: University of Rochester Medical Center, Rochester, New York, USA. METHODS: A solid-state, mode-locked Nd:YLF picosecond laser was used to polish a latex PCF in contact with a poly(methyl methacrylate) intraocular lens (IOL) in an experimental model eye. Eight study groups were treated at different energy levels ranging from 5 to 15 microJ. All treatments were done at least three times in different latex capsules and lenses. An atomic force microscope was used to measure IOL damage and an interferometric surface analysis microscope to assess the polishing effect on the PCF. The IOLs were further subjected to a scatter analysis to assess the optical significance of the damage produced. RESULTS: The latex PCF revealed a polishing effect with all energy settings used. The IOLs were damaged with all energy settings but 5 microJ. Energy settings higher than 5 microJ caused significantly more polishing effect to the latex and damage to the lenses. At the 10 microJ energy level, a single parameter with no depth produced a relative polishing depth of 3.01 microns +/- 0.10 (root mean square +/- SD). At this energy, the damage to the IOLs was 188 +/- 20.52 nm, and it was associated with typical craters over the surface at regular intervals that corresponded to each individual laser pulse. CONCLUSION: This model documented the feasibility of achieving micron-level precision in excising material with the picosecond laser and showed that posterior capsule polishing should be feasible and safe in human eyes.

Humans↗

PubMed1992

Holmium laser coronary thrombolysis--a new treatment modality for revascularization in acute myocardial infarction: review.

Thrombolytic therapy has changed the approach to management of acute myocardial infarction (AMI). Although its therapeutic benefit has been well established, only about one-third of AMI patients receive lytics. In AMI patients for whom thrombolytics fail to achieve revascularization or for whom lytics are contraindicated, percutaneous transluminal coronary balloon angioplasty (PTCA) can be utilized. However, in a clinical setting of AMI PTCA is less successful and is associated with a higher complication rate than with PTCA for angina alone. This review details a novel application of laser angioplasty; in patients with AMI complicated by continuous chest pain and ischemia, a mid-infrared (2.1 micron) solid-state, pulsed-wave Holmium:YAG coronary laser (Eclipse, Palo Alto, CA) can be utilized for coronary thrombolysis and plaque ablation. In each patient the laser was applied after failure of a thrombolytic agent or when thrombolytics were contraindicated. We have gained experience with 13 lesions, 12 in a coronary artery and 1 in a vein graft. In each case a multifiber with laser catheter (1.4, 1.5, 1.7 or 2.0 mm) was advanced over a guide wire, emitting 250-600 mj/pulse at 5 Hz, followed by adjunctive PTCA. Clinical success (defined as less than or equal to 50% residual stenosis, adequate thrombolysis, no complications [including death, CVA, CABGs, dissection, perforation]) was achieved in all patients. All patients improved clinically, survived the AMI, and were discharged. This initial clinical experience demonstrates the feasibility and safety of Holmium:YAG coronary laser angioplasty in revascularization during AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗

PubMed1993

Laser facilitated angioplasty and thrombolysis in acute myocardial infarction complicated by prolonged or recurrent chest pain.

To date, application of laser angioplasty in acute myocardial infarction (MI) has not been reported. In nine patients with acute myocardial infarction complicated by continuous or recurrent severe ischemia and chest pain, a mid-infrared, solid-state, pulse-wave holmium/thulium:YAG coronary laser was applied. In six of these patients the laser was specifically utilized for the purpose of coronary thrombolysis. In each case a guidewire was placed across the stenosis and a multifiber laser catheter was utilized, emitting 250-600 mJ/pulse at 5 Hz, followed by adjunctive balloon angioplasty. Laser success (defined as ability to cross the lesion, reduction of > or = 20% in stenosis and thrombolysis when a thrombus is present) was achieved in all patients. Final angiograms revealed residual stenosis < or = 30%, adequate thrombolysis and no major complication (MI, perforation, emergency CABGS, CVA, death) in each patient. Clinically, all nine patients improved, survived the acute infarction and were discharged. This initial clinical experience demonstrates the feasibility and safety of holmium/thulium:YAG laser application in thrombolysis and plaque ablation in selected patients who experience acute myocardial infarction complicated by prolonged or recurrent ischemia and chest pain.

Adult↗

PubMed1991

Lithotripsy with a Q-switched alexandrite laser system. Preliminary in vivo and in vitro results.

An alexandrite laser system which emits a wavelength of 750 nm, has recently been proposed as a substitute for the pulsed-dye laser (504 nm) for laser lithotripsy. We have carried out in vitro lithotripsy trials in order to evaluate the efficiency of a flashlamp pumped Q-switched alexandrite laser. In the first experiment, we compared the Q-switched alexandrite laser to the pulsed-dye laser with respect to their effectiveness in fragmentizing urinary and model stones (HMT target stones). In the second experiment, we evaluated the effect of Q-switched alexandrite radiation on the urinary wall (bladder, ureter, renal pelvis and liver) of animals (Wistar rats and rabbits) under general anesthesia. In conclusion, the alexandrite laser system is comparable to the pulsed dye laser. The 750-nm wavelength involves minimal risk of damage to the urinary tract and constitutes a safe alternative, especially during blind lithotripsy. It is a compact solid-state system, with no toxic chemical agents as laser material.

Animals↗

PubMed1993

THC:YAG nasolacrimal duct recanalization.

In an early exploration of a new technique for creating a patent nasolacrimal duct system, a chromium-sensitized and thulium- and holmium-doped YAG laser was used to canalize the nasolacrimal duct of a fresh-frozen bisected human cadaver head. The laser--long-pulsed (300 milliseconds), compact, self-contained, and solid-state--operates in the near infrared range (2.1 microns). The technique involved passing a 550-micrometer quartz fiberoptic through the dilated superior punctum and canalicular system, down through the nasolacrimal duct. The quartz fiberoptic was then withdrawn into the area of the lacrimal sac. Pulse energies of 500 mJ were used at a repetition rate of five pulses per second to ablate the duct lining. The nasolacrimal duct was then unroofed and the epithelial lining of the duct histopathologically evaluated.

Dacryocystorhinostomy↗

PubMed1994

Chiral detection in high-performance liquid chromatography by vibrational circular dichroism.

A novel chiral detector for high-performance liquid chromatography has been developed. This detector is based on the measurement of circular dichroism of chiral effluents in the infrared region, i.e., vibrational circular dichroism (VCD). In this instrument, a solid-state spectral tunable (from 2.4 to 3.5 microns) F-center laser was used as the light source. The linearly polarized laser beam was converted into left circularly polarized light (LCPL) and right circularly polarized light (RCPL) at 42 kHz by means of a photoelastic modulator. The intensity of the LCPL and RCPL transmitted through the sample was measured by a liquid nitrogen cooled indium antimonide detector. Double modulation was employed to reduce the noise associated with the laser beam. Specifically, the linearly polarized laser beam, prior to being converted to CPL, was modulated at 85 Hz by a mechanical chopper. Demodulation and amplification were accomplished with the use of two lock-in amplifiers. In its present configuration, the instrument can be used to measure the VCD of O-H groups. Its sensitivity is so high that it was able, for the first time, to detect chirally (with limits of detection of micrograms) (R)- and (S)-2,2,2-trifluoro-1-(9- anthryl)ethanol and (R)- and (S)-benzoin when these compounds were chromatographically separated from the corresponding racemic mixtures by a Chiralcel-OD column. The main advantage of this chiral detector is, however, its universality; i.e., it can be used to virtually detect any chiral compounds which has O-H group (e.g, aliphatic alcohols such as 2-octanol).

Chromatography, High Pressure Liquid↗

PubMed2000

Ultrawide band multifrequency high-field EMR technique: A methodology for increasing spectroscopic information.

We report methodology that combines an ultrawide band multifrequency microwave system with technology of high magnetic fields for solving challenging problems in electron magnetic resonance (EMR) spectroscopy. This strategy has been made possible due to a novel EMR facility operating in an exceptionally wide range of microwave frequencies of 24 GHz to 3 THz, at magnetic fields up to 17 T, and in the temperature range of 1.6 to 330 K. The basic configuration of the multifrequency system works in a transmission mode and employs oversized cylindrical waveguides for routing the microwave power. A wide-band, low-noise, liquid helium cooled (4.2 K) InSb bolometer is used for signal detection. This approach results in an extremely wide-band performance, thus making it possible to employ a variety of solid-state millimeter and submillimeter microwave sources in combination with a far infrared laser microwave source for performing multifrequency EMR experiments. A complexity of resonant structures and related technical problems such as microphonics at high magnetic fields is virtually eliminated. The system is simple, yet sensitive, and has been revealed to be extremely advantageous while solving such problems as observation of AFMR transitions in spin-ordered systems, g-factor resolution enhancement in complex organic radicals, and resonance signal detection in EMR-silent spin systems having integer spin and large zero field splitting. A technical description of the multifrequency high-field EMR facility is presented and results of its performance tests are given. The potential utility of using the multifrequency high-field methodology in EMR studies is illustrated with selected examples of its recent applications.

Electron Spin Resonance Spectroscopy↗

PubMed1998

Fiber bundle based scanning detection system for automated DNA sequencing.

High-throughput DNA sequencing techniques are under rapid development currently, mainly triggered by the Human Genome Project. At the present time, slab gel based automated DNA sequencing is the standard procedure, utilizing fluorophore labeling and laser-induced fluorescence detection with scanning technology. In this paper, a novel, fiber-optic bundle based detection system is introduced, where a central illuminating fiber is used for the excitation of the electrophoretically separated fluorophore-labeled DNA sequencing fragments, along with several collecting fibers disposed around the illuminating fiber to collect the emitted fluorescent signal. As a model system, Cy5-labeled DNA sequencing fragments were separated on an ultrathin polyacrylamide slab gel and detected by the fiber bundle based laser-induced fluorescence detection system. A 640-nm diode laser was used to generate the illumination beam, and the emitted light collected by the fiber bundle was detected by a solid-state avalanche photodiode.

Autoanalysis↗

PubMed1998

Surface selective 1H/29Si CP NMR by NOE enhancement from laser polarized xenon

The surface proton spin polarization created by the spin-polarization-induced nuclear Overhauser effect from optically polarized xenon can be transferred in a subsequent step by solid-state cross polarization to another nuclear spin species such as 29Si. The technique exploits the dipolar interactions of xenon nuclear spins with high gamma nuclei such as 1H, and is experimentally simpler than direct polarization transfer from 129Xe to heteronuclei such as 13C and 29Si. Copyright 1998 Academic Press.

Journal Article↗

PubMed1996

Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats: a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study.

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200-400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3 warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N'-nitro-L-arginine had no significant effect on the perfusion response or the tissue PO2 during CSD. During most CSD episodes, a brief decrease in MABP by 4-8 mm Hg was noted that might be caused by functional decortication during CSD.

Animals↗

PubMed2006

Diffusion-induced Ramsey narrowing.

Diffusion-induced Ramsey narrowing is characterized and identified as a general phenomenon, in which diffusion of coherence in and out of an interaction region such as a laser beam induces spectral narrowing of the associated resonance line shape. Illustrative experiments and an intuitive analytical model are presented for this spectral narrowing effect, which occurs commonly in optically interrogated atomic systems and may also be relevant to quantum dots and other solid-state spin systems.

Journal Article↗

PubMed1999

Detection of nonthermal melting by ultrafast X-ray diffraction.

Using ultrafast, time-resolved, 1.54 angstrom x-ray diffraction, thermal and ultrafast nonthermal melting of germanium, involving passage through nonequilibrium extreme states of matter, was observed. Such ultrafast, optical-pump, x-ray diffraction probe measurements provide a way to study many other transient processes in physics, chemistry, and biology, including direct observation of the atomic motion by which many solid-state processes and chemical and biochemical reactions take place.

Biochemistry↗

PubMed1997

Protein stability and conformational rearrangements in lipid bilayers: linear gramicidin, a model system.

The replacement of four tryptophans in gramicidin A by four phenylalanines (gramicidin M) causes no change in the molecular fold of this dimeric peptide in a low dielectric isotropic organic solvent, but the molecular folds are dramatically different in a lipid bilayer environment. The indoles of gramicidin A interact with the anisotropic bilayer environment to induce a change in the molecular fold. The double-helical fold of gramicidin M, as opposed to the single-stranded structure of gramicidin A, is not compatible with ion conductance. Gramicidin A/gramicidin M hybrid structures have also been prepared, and like gramicidin M homodimers, these dimeric hybrids appear to have a double-helical fold, suggesting that a couple of indoles are being buried in the bilayer interstices. To achieve this equilibrium structure (i.e., minimum energy conformation), incubation at 68 degrees C for 2 days is required. Kinetically trapped metastable structures may be more common in lipid bilayers than in an aqueous isotropic environment. Structural characterizations in the bilayers were achieved with solid-state NMR-derived orientational constraints from uniformly aligned lipid bilayer samples, and characterizations in organic solvents were accomplished by solution NMR.

Dimerization↗

PubMed1998

Consideration of conformational transitions and racemization during process development of recombinant glucagon-like peptide-1.

Physicochemical characterization of dry, excipient-free recombinant glucagon-like peptide-1 (rGLP-1) indicates the conformation and purity of the bulk peptide is dependent on the purification scheme and the in-process storage and handling. The recombinant peptide preparations were highly pure and consistent with the expected primary structure and bioactivity. However, variations in solubility were observed for preparations processed by different methods. The differences in solubility were shown to be due to conformational differences induced during purification. A processing scheme was identified to produce rGLP-1 in its native, soluble form, which exhibits FT-IR spectra, consistent with glucagon-like peptide-1 synthesized by solid-state peptide synthesis. rGLP-1 was also found to undergo base-catalyzed amino acid racemization. Racemization can impact the yield and impurity profile of bulk rGLP-1, since the peptide is exposed to alkali during its purification. A combination of enzymatic digestion using leucine aminopeptidase (which cleaves N-terminal L-amino acids >> D-amino acids) and matrix-assisted laser desorption ionization mass spectrometry was used to identify racemization as a degradation pathway. The racemization rate increased with increasing temperature and base concentration, but decreased with increasing peptide concentration. The racemized peptides were shown to be less bioactive than rGLP-1.

Chemical Precipitation↗

PubMed1997

Long-lifetime metal-ligand pH probe.

We describe the synthesis and fluorescence spectral characterization of a pH-sensitive metal-ligand complex, [Ru(deabpy)(bpy)2]2., where deabpy is 4,4'-diethylaminomethyl-2,2'-bipyridine. This metal-ligand complex (MLC) was found to display pH-dependent intensities, emission spectra, and decay times, with the changes centered near the physiological useful pH value of 7.5. The apparent pKa values were not found to be dependent on ionic strength. The compound was found to be useful for lifetime-based sensing by phase-modulation fluorometry. Global analysis of the intensity decays over a range of pH values revealed two decay times of 235 and 380 ns, associated with the protonated and unprotonated forms, respectively. Because of its long decay time, optical pH measurements could be accomplished by phase-modulation fluorometry with a conveniently low modulation frequency of 700 kHz. The lifetime data were obtained with either a amplitude-modulated laser or with an amplitude-modulated blue-light-emitting diode. This pH-sensitive complex also displays a modest spectral shift with change in pH, allowing its use as a wavelength-ratiometric MLC probe. One can imagine lifetime sensors for a variety of blood cations and point-of-care assays based on long-lifetime metal-ligand complexes and simple solid-state light sources and detectors.

2,2'-Dipyridyl↗

PubMedDate not supplied

A new method for characterizing beta-ray ophthalmic applicator sources.

A technique is described which enables one to obtain detailed dose characteristics of 90Sr beta-ray ophthalmic applicators. A radiochromic radiation detector which is a solid-state solution of hexahydroxyethyl pararosaniline cyanide in a nylon polymer (i.e., thin foil), has been used to determine the surface dose rate and dose distribution of these sources. The detectors are rugged, easily handled, have an equivalent response (optical density per unit absorbed dose) to photons and electrons, and produce high-resolution images. They have been found useful for this application due to the high surface dose rates [0.10-1.0 Gy (H2O)/s] and their low sensitivity (approximately 10(4) Gy for an optical density of 1.0). The foils have been evaluated on a He-Ne scanning laser densitometer with a resolution of 0.3 mum. Comparison with NIST (formerly NBS) extrapolation ionization chamber measurements indicates surface dose-rate agreement within 6%. Spectral dosimetric characteristics are presented and discussed.

Beta Particles↗

PubMed1989

Transition dipole orientations in the early photolysis intermediates of rhodopsin.

The linear dichroism spectrum of rhodopsin in sonicated bovine disk membranes was measured 30, 60, 170, and 600 ns after room temperature photolysis with a linearly polarized, 7-ns laser pulse (lambda = 355 or 477 nm). A global exponential fitting procedure based on singular value decomposition was used to fit the linear dichroism data to two exponential processes which differed spectrally from one another and whose lifetimes were 42 +/- 7 ns and 225 +/- 40 ns. These results are interpreted in terms of a sequential model where bathorhodopsin (BATHO, lambda max = 543 nm) decays toward equilibrium with a blue shifted intermediate (BSI, lambda max = 478 nm). BSI then decays to lumirhodopsin (LUMI, lambda max = 492 nm). It has been suggested that two bathorhodopsins decay in parallel to their products. However, a Monte Carlo simulation of partial photolysis of solid-state visual pigment samples shows that one mechanism which creates populations of BATHO having different photolysis rates at 77 K may not be responsible for the two decay rates reported here at room temperature. The angle between the cis band and 498-nm band transition dipoles of rhodopsin is determined to be 38 degrees. The angles between both these transition dipoles and those of the long-wave-length bands of BATHO, BSI, and LUMI are also determined. It is shown that when BATHO is formed its transition dipole moves away from the original cis band transition dipole direction. The transition dipole then moves roughly twice as much towards the original cis band direction when BSI appears. Production of LUMI is associated with return of the transition dipole almost to the original orientation relative to the cis band, but with some displacement normal to the plane which contains the previous motions. The correlation between the lambda max of an intermediate and its transition dipole direction is discussed.

Animals↗