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Biomedical subjects

J S Nelson

Publications and source records attributed to J S Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cryogen spray cooling and higher fluence pulsed dye laser treatment improve port-wine stain clearance while minimizing epidermal damage.

BACKGROUND: When a cryogen spurt is applied to the skin surface for an appropriately short period of time (on the order of tens of milliseconds), the cooling remains localized in the epidermis, while leaving the temperature of the deeper port-wine stain (PWS) blood vessels unchanged. OBJECTIVE: The objective of this study was to compare the efficacy and safety of noncooled laser treatment (NC-LT), and cryogen spray cooled laser treatment (CSC-LT) of PWS birthmarks in a large series of patients. METHODS: A retrospective review was conducted of 196 patients with head or neck PWS birthmarks treated with the pulsed dye laser (lambda = 585 nm; taup = 450 microseconds) over a 7-year period. Subjects' ages ranged between 2 months and 62 years; there were 109 females and 87 males, all of whom were Asian. Ninety-eight patients received NC-LT using light dosages of 5-7 J/cm2. Subsequently, 98 patients received CSC-LT using light dosages of 8-10 J/cm2. The primary efficacy measure was the quantitative assessment of the blanching response scores of NC-LT PWSs as compared, on a blinded basis, to CSC-LT PWSs. RESULTS: Based on chi-squared analysis, there were clinical, and statistically significant, differences in the blanching response scores favoring PWS receiving CSC-LT as compared to the NC-LT group (P <.001). Permanent scarring was noted in 3.1% (n = 3) of the patients in the NC-LT group. Permanent scarring was not observed in the CSC-LT treatment group. Transient hyperpigmentation was noted in 57% (n = 56) and 48% (n = 47) of the patients in the NC-LT and CSC-LT groups, respectively. In both groups, the transient hyperpigmentation resolved in all patients within 1 year. Two patients in the NC-LT group developed delayed permanent hypopigmentation. Permanent hypopigmentation was not observed in the CSC-LT group. CONCLUSION: CSC permitted the use of higher incident light dosages leading to improved PWS clearance without producing complications such as permanent scarring or dyspigmentation.

Adolescent↗
PubMed1999

Comparison of binding of N3'-->P5' phosphoramidate and phosphorothioate oligonucleotides to cell surface proteins of cultured cells.

The binding of uniformly modified N3'-->P5' phosphoramidate and stereorandom and stereopure phosphorothioate oligonucleotides (ODN) to cell surface proteins was studied, using both a fibroblast and an epithelial cell line, to assess the effect of different analog backbone types and base composition on cell surface protein binding. Marked differences were observed, both quantitative and qualitative, in the proteins to which individual ODN bound. One phosphoramidate, antisense to the insulin-like growth factor-1 (IGF-1) receptor (IGF-1R), bound to different proteins than did either a 6-base mismatch phosphoramidate IGF-1R sequence or a sense N-ras sequence. The latter bound poorly to the fibroblast line and predominantly to a 46 kDa protein in the epithelial line, as did many of the other ODN. This binding was not so marked as that of the isosequential end-capped phosphodiester N-ras sequence, which bound to this protein in both cell lines. Stereopure and stereorandom phosphorothioates containing a G-quartet (shown in other studies to form high-order tetrad structures), antisense to c-myc, exhibited considerable nonspecific binding to many proteins, as did the isosequential phosphoramidate. In particular, this ODN sequence gave notable binding to high molecular weight proteins. In general, binding of the c-myc ODN to proteins of 28-30, 46, 67, and 70-90 kDa was found in this study.

3T3 Cells↗
PubMed1998

An improved synthesis of oligodeoxynucleotide N3'-->P5' phosphoramidates and their chimera using hindered phosphoramidite monomers and a novel handle for reverse phase purification.

Oligodeoxynucleotide N3'-->P5' phosphoramidates are promising candidates for antisense therapeutics, as well as for diagnostic applications. We recently reported a new method for the synthesis of these oligonucleotide analogs which makes use of a phosphoramidite amine-exchange reaction in the key coupling step. We report herein an improved set of monomers that utilize a more reactive, hindered phosphoramidite to produce optimal yields in a single coupling step followed by oxidation, thereby eliminating the need for the previously reported couple-oxidize-couple-oxidize approach. On the 10 micromol scale, the synthesis is performed using only 3.6 equivalents (equiv.) of monomer. An improved oxidation reagent consisting of hydrogen peroxide, water, pyridine and THF is also introduced. Reported here for the first time is the use of a reverse-phase purification methodology employing a ribonucleotide purification handle that is removed under non-acidic conditions, in contrast to the conventional dimethoxytrityl group. The synthesis and purification of uniformly modified N3'-->P5' phosphoramidate oligodeoxy-nucleotides, as well as their chimera containing phosphodiester and/or phosphorothioate linkages at predefined positions, using these new methodologies are included herein. The results of31P NMR studies that led to this improved amine-exchange methodology are also described.

Amines↗
PubMed1998

Analysis of an oligonucleotide N3'-->P5' phosphoramidate/phosphorothioate chimera with capillary gel electrophoresis.

N3'-->P5' phosphoramidate/phosphorothioate chimeric oligonucleotides (ODNs) are presently under investigation as potential antisense drugs. Within the field of antisense research, "second generation" chimeric ODNs have exhibited improved characteristics relative to oligonucleotides with uniformly modified backbones. The ODN of interest for this study consisted of a chemically synthesized 18-mer of mixed nucleotide base sequence with a backbone consisting of eight central phosphorothioate linkages flanked by four N3'-->P5' phosphoramidate (amidate) linkages on the 5'-end and five amidate linkages ont he 3'-end. This chimera presents analytical challenges due to the central phosphorothioate region. Here, we present a capillary gel electrophoresis (CGE) method for the analysis of the above N3'-->P5' phosphoramidate/phosphorothioate chimera. CGE was used to analyze the product prior to its purification by reversed phase - high performance liquid chromatography (RP-HPLC), and each fraction collected from the purification was similarly analyzed. An internal standard was utilized to determine the relative mobility of our product, and polyacrylamide gel electrophoresis (PAGE) analysis was used to verify CGE results.

Chromatography, High Pressure Liquid↗
PubMed1998

Signal attenuation and localization in optical coherence tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical coherence tomography (OCT). A geometrical optics implementation of the OCT probe with low-coherence interferometric detection was combined with three-dimensional stochastic Monte Carlo modelling of photon propagation in the homogeneous sample medium. Optical properties of the sample were selected to simulate intralipid and blood, representing moderately (g = 0.7) and highly (g = 0.99) anisotropic scattering respectively. For shallow optical depths in simulated intralipid (<3 scattering mean free path (mfp) units), the number of detected backscattered photons followed the extinction-single-backscatter model, and OCT was found to detect only minimally scattered photons. Within this depth range the backscatter positions of detected photons corresponded well with the nominal focus position of the probe. For propagation to deeper positions in intralipid, localization of backscattering was quickly lost due to detection of stray photons, and the number of detected photons remained constant with increasing depth in the non-absorbing medium. For strongly forward-directed scattering in simulated blood, the number of detected photons approached the extinction-single-backscatter model only for very shallow depths (<2 mfp units). However, backscattering positions for detected photons correlated well with the nominal focus position of the probe even for optical depths greater than 40 mfp units.

Blood↗
PubMed1998

Accuracy and noise in optical Doppler tomography studied by Monte Carlo simulation.

A Monte Carlo model has been developed for optical Doppler tomography (ODT) within the framework of a model for optical coherence tomography (OCT). A phantom situation represented by blood flowing in a horizontal 100 microm diameter vessel placed at 250 microm axial depth in 2% intralipid solution was implemented for the Monte Carlo simulation, and a similar configuration used for experimental ODT measurements in the laboratory. Simulated depth profiles through the centre of the vessel of average Doppler frequency demonstrated an accuracy of 3-4% deviation in frequency values and position localization of flow borders, compared with true values. Stochastic Doppler frequency noise was experimentally observed as a shadowing in regions underneath the vessel and also seen in simulated Doppler frequency depth profiles. By Monte Carlo simulation, this Doppler noise was shown to represent a nearly constant level over an investigated 100 microm interval of depth underneath the vessel. The noise level was essentially independent of the numerical aperture of the detector and angle between the flow velocity and the direction of observation, as long as this angle was larger than 60 degrees. Since this angle determines the magnitude of the Doppler frequency for backscattering from the flow region, this means that the signal-to-noise ratio between Doppler signal from the flow region to Doppler noise from regions underneath the flow is improved by decreasing the angle between the flow direction and direction of observation. Doppler noise values from Monte Carlo simulations were compared with values from statistical analysis.

Diagnostic Imaging↗
PubMed1998

Accuracy of subsurface temperature distributions computed from pulsed photothermal radiometry.

Pulsed photothermal radiometry (PPTR) is a non-contact method for determining the temperature increase in subsurface chromophore layers immediately following pulsed laser irradiation. In this paper the inherent limitations of PPTR are identified. A time record of infrared emission from a test material due to laser heating of a subsurface chromophore layer is calculated and used as input data for a non-negatively constrained conjugate gradient algorithm. Position and magnitude of temperature increase in a model chromophore layer immediately following pulsed laser irradiation are computed. Differences between simulated and computed temperature increase are reported as a function of thickness, depth and signal-to-noise ratio (SNR). The average depth of the chromophore layer and integral of temperature increase in the test material are accurately predicted by the algorithm. When the thickness/depth ratio is less than 25%, the computed peak temperature increase is always significantly less than the true value. Moreover, the computed thickness of the chromophore layer is much larger than the true value. The accuracy of the computed subsurface temperature distribution is investigated with the singular value decomposition of the kernel matrix. The relatively small number of right singular vectors that may be used (8% of the rank of the kernel matrix) to represent the simulated temperature increase in the test material limits the accuracy of PPTR. We show that relative error between simulated and computed temperature increase is essentially constant for a particular thickness/depth ratio.

Algorithms↗
PubMed1998

Assessment of high-affinity hybridization, RNase H cleavage, and covalent linkage in translation arrest by antisense oligonucleotides.

Antisense oligonucleotides (ONs) are designed to hybridize target mRNA in a sequence-specific manner and inhibit gene expression by preventing translation, either by activation of RNase H or steric blockage of the ribosome complex. Second-generation ONs, which possess greater binding affinity for target RNA relative to the isosequential phosphodiester (PO) ONs, have been developed and include, among others, peptide nucleic acids (PNA) and N3' P5' phosphoramidate oligonucleotides (npONs). In the present study, PNA and npON derivatives were targeted to the coding portion of the complementary mRNA of the N protein of the vesicular stomatitis virus (VSV) in order to evaluate their ability to arrest translation in an in vitro rabbit reticulocyte lysate system. High-affinity hybridization of ONs lacking RNase H activity was not sufficient to block translation in this test system. Only antisense ONs acting via an RNase H mechanism or by steric hindrance through covalent attachment (via transplatin modification) to the target mRNA were found to definitively arrest translation in this study.

Animals↗
PubMed1998

Cryogen spray cooling for spatially selective photocoagulation of hemangiomas: a new methodology with preliminary clinical reports.

Spatially selective photocoagulation of subsurface-targeted blood vessels by repetitive application of a short cryogen spurt during continuous Nd:YAG laser irradiation has been demonstrated in two human cases. This procedure may be effective for the treatment of thick hemangiomas that require photocoagulation of subsurface blood vessels while protecting the epidermis.

Child, Preschool↗
PubMed1998

A comparative study of human skin thermal response to sapphire contact and cryogen spray cooling.

Surface cooling, in conjunction with various thermally mediated therapeutic procedures, can provide a means to protect superficial tissues from injury while achieving destruction of deeper targeted structures. We have investigated the thermal response of in-vivo human skin to: 1) contact cooling with a sapphire window (6-12 degrees C); and 2) spray cooling with a freon substitute cryogen [tetrafluoroethane; boiling point approximately -26 degrees C at 1 atmospheric pressure (atm)]. Measurements utilizing infrared radiometry show surface temperature reductions from 30 degrees C to 14-19 degrees C are obtained within approximately 1 s in response to sapphire contact cooling. Surface temperature reductions to values between 5 degrees C and -9 degrees C are obtained in response to 20-100-ms cryogen spurts. Computational results, based on fitting the measured radiometric surface temperature to estimate heat transfer parameters, show: 1) temperature reductions remain localized to approximately 200 microns of superficial tissue; and 2) values of heat flux and total energy removed per unit skin surface area at least doubled when using cryogen spray cooling.

Aerosol Propellants↗
PubMed1998

Optical Doppler tomography: imaging in vivo blood flow dynamics following pharmacological intervention and photodynamic therapy.

A noninvasive optical technique has been developed for imaging in vivo blood flow dynamics and vessel structure with high spatial resolution. The technique is based on optical Doppler tomography, which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations in turbid biological tissue. Applications of this technique for monitoring changes in blood flow dynamics and vessel structure following pharmacological intervention and photodynamic therapy are demonstrated.

Allantois↗
PubMed1997

Direct PCR amplification and sequence analysis of extrachromosomal Plasmodium DNA from dried blood spots.

The Plasmodium parasite possesses two extrachromosomal genomes; the mitochondrial genetic element and the extrachromosomal plastid-like DNA. The latter has only been fully described for one culture strain of P. falciparum. In this study, a rapid procedure for amplifying plastid DNA from dried blood spots of blood infected with different malaria species was developed. PCR amplification of a 595 bp fragment within the plastid-like large subunit ribosomal-RNA (LSU-rRNA) gene was achieved using primers derived from the P. falciparum sequence. The PCR product was observed in all Plasmodium species examined. Sequence analysis of amplified products homologous to an LSU-rRNA fragment of the plastid-like extrachromosomal circle revealed extensive conservation between Plasmodium species including P. falciparum, P. vivax, P. malariae and P. berghei.

Animals↗
PubMed1997

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Antineoplastic Agents, Alkylating↗
PubMed1997

Ablation of human nail by pulsed lasers.

BACKGROUND AND OBJECTIVE: The hard and resistant structure of the nail plate forms a natural barrier that limits the penetration of topical drugs. To overcome this barrier, the use of pulsed laser systems has been suggested. The purpose of this study was to evaluate the effect of four laser systems on nail plate ablation rates, ablation efficiencies, and subsequent craters morphology. STUDY DESIGN/MATERIAL AND METHODS: Solid state Er:YAG (2.94 microns, 250 microseconds), a Ho:YSGG (2.08 microns, 250 microseconds), a XeC1 Excimer (308 nm, 15 ns), and a novel solid-state ultrashort pulse laser (1.05 microns, 350 fs) were used. Ablation rates, surface morphology, and extent of collateral damage were evaluated using light and electron microscopy. RESULTS: Best ablation efficiencies were demonstrated with the ultrashort pulsed laser (1 micron/mJ), whereas maximum material removal per pulse was obtained with the Er:YAG laser (80 microns/ pulse). Scanning electron microscopy showed cracking damage with both Ho:YSGG and Er:YAG. XeC1 and the ultrashort pulse system left tissue surfaces free of cracks or thermal damage. CONCLUSION: With its minimal acoustical and mechanical impact, high efficiency, and negligible collateral damage, the ultrashort pulse laser at 3 J/cm2 was found to be the optimal laser system for nail ablation.

Humans↗
PubMed1997

Wavelengths for port wine stain laser treatment: influence of vessel radius and skin anatomy.

Recent Monte Carlo computations in realistic port wine stain (PWS) models containing numerous uniformly distributed vessels suggest equal depth of vascular injury at wavelengths of 577 and 585 nm. This finding contradicts clinical experience and previous theory. From a skin model containing normal and PWS vessels in separate dermal layers, we estimate analytically the average volumetric heat production in the deepest targeted PWS vessel. The fluence rate distribution is approximated by Beer's law, which depends upon the tissue's effective attenuation coefficient, and includes a homogeneous fractional volumetric blood concentration corrected for finite-size blood vessels. The model predicts 585-587 nm wavelengths are optimal in adult PWSs containing at least one layer of small-radius blood vessels. In superficial PWSs, typically in young children with small-radius vessels, 577-580 nm wavelengths are optimal. Wavelength-independent results similar to those from Monte Carlo models are valid in single-layered PWSs of large-radius vessels. In conclusion, the volumetric heat production in the deepest targeted PWS blood vessel can be maximized on an individual patient basis. However, absorption of 585-587 nm wavelengths is sufficiently high in superficial lesions, so we hypothesize that these wavelengths may be considered adequate for the treatment of any PWS.

Adult↗
PubMed1997

Modelling light distributions of homogeneous versus discrete absorbers in light irradiated turbid media.

Laser treatment of port wine stains has often been modelled assuming that blood is distributed homogeneously over the dermal volume, instead of enclosed within discrete vessels. The purpose of this paper is to analyse the consequences of this assumption. Due to strong light absorption by blood, fluence rate near the centre of the vessel is much lower than at the periphery. Red blood cells near the centre of the vessel therefore absorb less light than those at the periphery. Effectively, when distributed homogeneously over the dermis, fewer red blood cells would produce the same absorption as the actual number of red blood cells distributed in discrete vessels. We quantified this effect by defining a correction factor for the effective absorbing blood volume of a single vessel. For a dermis with multiple vessels, we used this factor to define an effective homogeneous blood concentration. This was used in Monte Carlo computations of the fluence rate in a homogeneous skin model, and compared with fluence rate distributions using discrete blood vessels with equal dermal blood concentration. For realistic values of skin parameters the homogeneous model with corrected blood concentration accurately represents fluence rates in the model with discrete blood vessels. In conclusion, the correction procedure simplifies the calculation of fluence rate distributions in turbid media with discrete absorbers. This will allow future Monte Carlo computations of, for example, colour perception and optimization of vascular damage by laser treatment of port wine stain models with realistic vessel anatomy.

Erythrocytes↗