A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans.

We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.

Compensation of motion artifacts in catheter-based optical frequency domain imaging.

A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging.

Preliminary evaluation of noninvasive microscopic imaging techniques for the study of vocal fold development.

Understanding pediatric voice development and laryngeal pathology is predicated on a detailed knowledge of the microanatomy of the layered structure of the vocal fold. Our current knowledge of this microanatomy and its temporal evolution is limited by the lack of pediatric specimen availability. By providing the capability to image pediatric vocal folds in vivo, a noninvasive microscopy technique could greatly expand the existing database of pediatric laryngeal microanatomy and could furthermore make longitudinal studies possible. A variety of natural-contrast optical imaging technologies, including optical frequency domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and spectrally encoded confocal microscopy (SECM) have been recently developed for noninvasive diagnosis in adult patients. In this paper, we demonstrate the potential of these three techniques for laryngeal investigation by obtaining images of excised porcine vocal fold samples. In our study, OFDI allowed visualization of the vocal fold architecture deep within the tissue, from the superficial mucosa to the vocalis muscle. The micron-level resolution of SECM allowed investigation of cells and extracellular matrix fibrils from the superficial mucosa to the intermediate layer of the lamina propria (LP) (350 microm penetration depth). The large field of view (up to 700 microm), penetration depth (up to 500 microm), and resolution (2x2x1microm [XxYxZ]) of FF-OCM enabled comprehensive three-dimensional evaluation of the layered structure of the LP. Our results suggest that these techniques provide important and complementary cellular and structural information, which may be useful for investigating pediatric vocal fold maturation in vivo.

Single-detector polarization-sensitive optical frequency domain imaging using high-speed intra A-line polarization modulation.

We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample.

High-speed polarization sensitive optical frequency domain imaging with frequency multiplexing.

Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm.

Angle-resolved optical coherence tomography with sequential angular selectivity for speckle reduction.

We present a novel method for rapidly acquiring optical coherence tomography (OCT) images at multiple backscattering angles. By angularly compounding these images, high levels of speckle reduction were achieved. Signal-to-noise ratio (SNR) improvements of 3.4 dB were obtained from a homogeneous tissue phantom, which was in good agreement with the predictions of a statistical model of speckle that incorporated the optical parameters of the imaging system. In addition, the fast acquisition rate of the system (10 kHz A-line repetition rate) allowed angular compounding to be performed in vivo without significant motion artifacts. Speckle-reduced OCT images of human dermis show greatly improved delineation of tissue microstructure.

Ultrahigh-resolution full-field optical coherence microscopy using InGaAs camera.

Full-field optical coherence microscopy (FFOCM) is an interferometric technique for obtaining wide-field microscopic images deep within scattering biological samples. FFOCM has primarily been implemented in the 0.8 mum wavelength range with silicon-based cameras, which may limit penetration when imaging human tissue. In this paper, we demonstrate FFOCM at the wavelength range of 0.9 - 1.4 mum, where optical penetration into tissue is presumably greater owing to decreased scattering. Our FFOCM system, comprising a broadband spatially incoherent light source, a Linnik interferometer, and an InGaAs area scan camera, provided a detection sensitivity of 86 dB for a 2 sec imaging time and an axial resolution of 1.9 mum in water. Images of phantoms, tissue samples, and Xenopus Laevis embryos were obtained using InGaAs and silicon camera FFOCM systems, demonstrating enhanced imaging penetration at longer wavelengths.

Spectrally-modulated full-field optical coherence microscopy for ultrahigh-resolution endoscopic imaging.

Full-field optical coherence microscopy (FFOCM) utilizes coherence gating to obtain high-resolution optical sections in thick tissues. FFOCM is an attractive technology for endoscopic microscopy at the cellular level since it does not require a high NA objective lens or beam scanning and is therefore particularly amenable to miniaturization. In this manuscript, we present a novel scheme for conducting FFOCM that utilizes spectrally modulated, spatially incoherent illumination and a static Linnik interferometer. This approach is advantageous for endoscopic microscopy since it allows FFOCM to be conducted through a single multimode fiber optic imaging bundle and does not require moving parts in the endoscope probe. Images acquired from biological samples in free space demonstrate that this new method provides the same detailed microscopic structure as that of conventional FFOCM. High-resolution images were also obtained through a multimode fiber bundle, further supporting the potential of this method for endoscopic microscopy.

115 kHz tuning repetition rate ultrahigh-speed wavelength-swept semiconductor laser.

We demonstrate an ultrahigh-speed wavelength-swept semiconductor laser using a polygon-based wavelength scanning filter. With a polygon rotational speed of 900 revolutions per second, a continuous wavelength tuning rate of 9200 nm/ms and a tuning repetition rate of 115 kHz were achieved. The wavelength tuning range of the laser was 80 nm centered at 1325 nm, and the average polarized output power was 23 mW.

Wide Tuning Range Wavelength-Swept Laser With Two Semiconductor Optical Amplifiers.

We demonstrate a wide tuning range high-speed wavelength-swept semiconductor laser based on a polygon scanning filter that is common to two laser cavities. Linear wavelength tuning was achieved over 145 nm around 1310 nm at a tuning repetition rate of 20 kHz. The wavelength tuning filter is expandable to accommodate multiple semiconductor optical amplifiers for further widening of the laser wavelength tuning range.

Radiation treatment in patients with recurrent Kimura's disease.

PURPOSE: To assess the benefits of radiotherapy for patients with recurrent Kimura's disease and to document the role of radiation treatment as a successful mode of therapy. METHODS AND MATERIALS: From 1985 to 1991, a total of 26 patients with Kimura's disease were treated by local excision and/or systemic steroids at Yonsei University, Yonsei Cancer Center Hospital. Seventeen patients among them eventually had local recurrence after surgical excision. The 17 patients with recurrent Kimura's disease were divided into two groups on the basis of those who received radiation treatment and those who did not. Eight patients in the nonradiation group were treated by systemic steroids alone with individualized doses and schedules. The remaining nine patients in the radiation group were treated by external beam irradiation. The prescribed radiation doses varied from 21.6 to 45 Gy. A comparative analysis on treatment results between both groups was undertaken retrospectively. RESULTS: The majority of the recurrent cases in the nonradiation group treated by steroids alone experienced rapid rerecurrence of the disease. In contrast, all of the patients except one case in the radiation group achieved excellent local control with moderate doses of radiation. There was a significant difference in the rerecurrence rate between the patients of the radiation group (11%) and the nonradiation group (75%). No clear dose-response relationship could be derived from the patients of the radiation group. No secondary malignancies in the irradiated areas have been observed. CONCLUSION: Our results suggest that radiation treatment is preferable as an alternative option for patients with recurrent Kimura's disease who have failed to achieve local control by other modalities.

Vascular thermal adaptation in tumors and normal tissue in rats.

PURPOSE: The vascular thermal adaptation in the R3230 adenocarcinoma, skin and muscle in the legs of Fischer rats was studied. METHODS AND MATERIALS: The legs of Fischer rats bearing the R3230 AC adenocarcinoma (subcutaneously) were heated once or twice with a water bath, and the blood flow in the tumor, skin and muscle of the legs was measured with the radioactive microsphere method. RESULTS: The blood flow in control R3230 AC tumors was 23.9 ml/100 g/min. The tumor blood flow increased about 1.5 times in 30 min and then markedly decreased upon heating at 44.5 degrees C for 90 min. In the tumors preheated 16 h earlier at 42.5 degrees C for 60 min, reheating at 44.5 degrees C increased the tumor blood flow by 2.5-fold in 30 min. Contrary to the decline in blood flow following an initial increase during the 44.5 degrees C heating without preheating, the tumor blood flow remained elevated throughout the 90 min reheating at 44.5 degrees C. These results indicated that thermal adaptation or thermotolerance developed in the tumor vasculatures after the preheating at 42.5 degrees C for 60 min. The magnitude of vascular thermal adaptation in the tumors 24 h and 48 h after the preheating, as judged from the changes in blood flow, were smaller than that 16 h after the preheating. Heating at 42.5 degrees C for 60 min induced vascular thermal adaptation also in the skin and muscle, which peaked in 48 h and 24 h, respectively, after the heating. CONCLUSION: Heating at 42.5 degrees C for 1 h induced vascular thermal adaptation in the R3230 AC tumor, skin, and muscle of rats that peaked 16-48 h after the heating. When the tumor blood vessels were thermally adapted, the tumor blood flow increased upon heating at temperatures that would otherwise reduce the tumor blood flow. Such an increase in tumor blood flow may hinder raising the tumor temperature while it may increase tumor oxygenation.