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Biomedical subjects

J S Nelson

Publications and source records attributed to J S Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Targeted inhibition of transcription elongation in cells mediated by triplex-forming oligonucleotides.

Triple-helix-forming oligonucleotides (TFOs) bind in the major groove of double-stranded DNA at oligopyrimidine small middle dotoligopurine sequences and therefore are candidate molecules for artificial gene regulation, in vitro and in vivo. We recently have described oligonucleotide analogues containing N3'-P5' phosphoramidate (np) linkages that exhibited efficient inhibition of transcription elongation in vitro. In the present work we provide conclusive evidence that np-modified TFOs targeted to the HIV-1 polypurine tract (PPT) sequence can inhibit transcriptional elongation in cells, either in transient or stable expression systems. The same constructs were used in transient expression assays (target sequence on transfected plasmid) and in the generation of stable cell lines (target sequence integrated into cellular chromosomes). In both cases the only distinguishable feature between the cellular systems is the presence of an insert containing the wild-type PPT/HIV-1 sequence, a mutated version with two mismatches, or the absence of the insert altogether. The inhibitory action induced by np-TFOs was restricted to the cellular systems containing the complementary wild-type PPT/HIV-1 target, and consequently can be attributed only to a triple-helix-mediated mechanism. As a part of this study we also have applied an imaging technique to quantitatively investigate the dynamics of TFO-mediated specific gene silencing in single cells.

Animals↗
PubMed2000

Bioheat transfer analysis of cryogen spray cooling during laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: The thermal response of port wine stain (PWS) skin to a combined treatment of pulsed laser irradiation and cryogen spray cooling (CSC) was analyzed through a series of simulations performed with a novel optical-thermal model that incorporates realistic tissue morphology. STUDY DESIGN/MATERIALS AND METHODS: The model consisted of (1) a three-dimensional reconstruction of a PWS biopsy, (2) a Monte Carlo optical model, (3) a finite difference heat transfer model, and (4) an Arrhenius thermal damage calculation. Simulations were performed for laser pulses of 0.5, 2, and 10 ms and a wavelength of 585 nm. Simulated cryogen precooling spurts had durations of 0, 20, or 60 ms and terminated at laser onset. Continuous spray cooling, which commenced 60 ms before laser onset and continued through the heating and relaxation phases, was also investigated. RESULTS: The predicted response to CSC included maximal pre-irradiation temperature reductions of 27 degrees C at the superficial surface and 12 degrees C at the dermoepidermal junction. For shorter laser pulses (0.5, 2 ms), precooling significantly reduced temperatures in superficial regions, yet did not effect superficial vessel coagulation. Continuous cooling was required to reduce significantly thermal effects for the 10-ms laser pulse. CONCLUSIONS: For the PWS morphology and treatment parameters studied, optimal damage distributions were obtained for a 2-ms laser pulse with a 60-ms precooling spurt. Epidermal and vascular morphology as well as laser pulse duration should be taken into account when planning CSC/laser treatment of PWS. Our novel, realistic-morphology modeling technique has significant potential as a tool for optimizing PWS treatment parameters.

Biopsy↗
PubMed2000

Deep coagulation of dermal collagen with repetitive Er:YAG laser irradiation.

BACKGROUND AND OBJECTIVE: Er:YAG lasers are known to effectively ablate human skin with minimal thermal damage to subjacent dermal tissue. We have investigated whether deep coagulation of dermal collagen, similar to that observed with the CO(2) laser, could be achieved with repetitive Er:YAG laser exposures. STUDY DESIGN/MATERIALS AND METHODS: Skin on the back of a Sprague-Dawley rat in vivo was irradiated with sequences of 1-10 Er:YAG laser pulses at a repetition rate of 10 or 33 Hz and single-pulse fluences from 0.8 to 1.4 J/cm(2). The resulting lesions were biopsied within 1 hour after laser exposure, and the histologic sections were examined by using optical microscopy. RESULTS: The depth of dermal collagen denaturation increases dramatically when 3-10 low-fluence Er:YAG laser pulses are stacked at a repetition rate of 10 or 33 Hz. CONCLUSION: Coagulation of dermal collagen deeper than 200 microm below the epidermal-dermal junction is feasible by using the appropriate settings of a repetitive Er:YAG laser.

Animals↗
PubMed2000

Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling (CSC) is a means to protect the epidermis while leaving dermal structures susceptible to thermal damage. The purpose of this study was to determine optimal spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute temperature distributions in human skin in response to CSC. Optimal tau(s) and tau(d) are determined by maximizing the temperature difference between a modeled basal layer and an imaginary target chromophore. RESULTS: The model predicts an optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150 microm) and deeper (400 microm) targets, respectively. Spraying for longer than the optimal tau(s) does not critically impair cooling selectivity. For a spurt duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good compromise. A delay is justified only when basal layer and target chromophore are relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid frostbite.

Cryotherapy↗
PubMed2000

Epidermal protection with cryogen spray cooling during high fluence pulsed dye laser irradiation: an ex vivo study.

BACKGROUND AND OBJECTIVE: Higher laser fluences than currently used in therapy (5-10 J/cm(2)) are expected to result in more effective treatment of port wine stain (PWS) birthmarks. However, higher incident fluences increase the risk of epidermal damage caused by absorption of light by melanin. Cryogen spray cooling offers an effective method to reduce epidermal injury during laser irradiation. The objective of this study was to determine whether high laser incident fluences (15-30 J/cm(2)) could be used while still protecting the epidermis in ex vivo human skin samples. STUDY DESIGN/MATERIALS AND METHODS: Non-PWS skin from a human cadaver was irradiated with a Candela ScleroPlus Laser (lambda = 585 nm; pulse duration = 1.5 msec) by using various incident fluences (8-30 J/cm(2)) without and with cryogen spray cooling (refrigerant R-134a; spurt durations: 40-250 msec). Assessment of epidermal damage was based on histologic analysis. RESULTS: Relatively short spurt durations (40-100 msec) protected the epidermis for laser incident fluences comparable to current therapeutic levels (8-10 J/cm(2)). However, longer spurt durations (100-250 msec) increased the fluence threshold for epidermal damage by a factor of three (up to 30 J/cm(2)) in these ex vivo samples. CONCLUSION: Results of this ex vivo study show that epidermal protection from high laser incident fluences can be achieved by increasing the cryogen spurt duration immediately before pulsed laser exposure.

Aerosol Propellants↗
PubMed2000

Active skin cooling in conjunction with laser dermatologic surgery.

The clinical objective in the laser treatment of patients with specific dermatoses is to maximize thermal damage to the target chromophore while minimizing injury to the normal skin. Unfortunately, for some lesions, the threshold incident light dosage for epidermal injury can be very close to the threshold for permanent removal of the target chromophore, thus precluding the use of higher light dosages. An important method of overcoming the aforementioned problem is to selectively cool the most superficial layers of the skin. Although melanin absorption will result in heat production during laser exposure, cooling the epidermis can prevent its temperature elevation from exceeding the threshold for thermal injury. Spatially selective cooling can be achieved by active cooling using a cryogen spray or cold sapphire contact handpieces. These devices promote rapid and spatially selective epidermal cooling to low temperatures without affecting the target chromophore temperature before the laser pulse is delivered. Cooling has become an Integral part in the emerging discipline of laser dermatologic surgery. Attend almost any academic dermatology conference and you are likely to find many lectures that relate to cooling during dermatologic laser surgery. Although cooling in conjunction with laser therapy has become the clinical standard for many laser procedures, considerable controversy surrounds this methodology. We present herewith an overview of currently used techniques for active cooling of human skin and explore their advantages and disadvantages in relationship to specific dermatoses amenable to laser therapy.

Adult↗
PubMed2000

Modelling multiple laser pulses for port wine stain treatment.

Many port wine stains (PWS) are still resistant to pulsed dye laser treatment. However, anecdotal information suggests that multiple-pulse laser irradiation improves patient outcome. Our aims in this note are to explain the underlying mechanism and estimate the possible thermal effects of multiple pulses in vascular structures typical of PWS. Based on linear response theory, the linear combination of two thermal contributions is responsible for the total increase in temperature in laser irradiated blood vessels: direct light absorption by blood and direct bilateral thermal heat conduction from adjacent blood vessels. The latter contribution to the increase in temperature in the targeted vessel can be significant, particularly if some adjacent vessels are in close proximity, such as in cases of optical shielding of the targeted vessel, or if the vessels are relatively distant but many in number. We present evidence that multiple-pulse laser irradiation targets blood vessels that are optically shielded by other vessels. Therefore, it may be a means of enhancing PWS therapy for lesions that fail to respond to single-pulse dye laser treatment.

Blood Vessels↗
PubMed2000

Combining two excitation wavelengths for pulsed photothermal profiling of hypervascular lesions in human skin.

When pulsed photothermal radiometry (PPTR) is used for depth profiling of hypervascular lesions in human skin, melanin absorption also heats the most superficial skin layer (epidermis). Determination of lesion depth may be difficult when it lies close to the epidermal dermal junction, due to PPTR's limited spatial resolution. To overcome this problem, we have developed an approximation technique, which uses two excitation wavelengths (585 and 600 nm) to separate the vascular and epidermal components of the PPTR signal. This technique permits a noninvasive determination of lesion depth and epidermal thickness in vivo, even when the two layers are in close physical proximity to each other. Such information provides the physician with guidance in selecting the optimal parameters for laser therapy on an individual patient basis.

Blood↗
PubMed2000

Update on selected viral exanthems.

Viral exanthems are common in childhood and account for a large number of patient visits to pediatric or family medicine clinics. Most exanthems are virtually harmless to the healthy child, but others can be signs of more significant systemic disease. Some exanthems that are benign or self-limited in the healthy child may propose significant risk to pregnant or immunocompromised individuals. Therefore, recognition of exanthems, which may be associated with certain viral illnesses, is important for the primary care provider. For example, prompt recognition of a viral exanthem caused by parvovirus may allow a pregnant female from exposing her fetus to a potentially fatal infection, or, if the exposure has already occurred, may indicate the need for appropriate fetal monitoring. In this manuscript, we review the recent literature pertaining to four characteristic exanthems that are thought to be viral in nature: papular purpuric gloves and socks syndrome; pityriasis rosea; unilateral lateral thoracic exanthem; and Gianotti-Crosti syndrome.

Acrodermatitis↗
PubMed2000

Optical coherence tomography of the rat cochlea.

Optical coherence tomography (OCT) was used to image the internal structure of a rat cochlea (ex vivo). Immediately following sacrifice, the temporal bone of a Sprague-Dawley rat was harvested. Axial OCT cross sectional images (over regions of interest, 1x1 mm-2x8 mm) were obtained with a spatial resolution of 10-15 microm. The osseous borders of the lateral membranous labyrinth overlying the cochlea and the scala vestibuli, media, and tympani, which were well demarcated by the modiolus, Reissner's and the basilar membranes, were clearly identified. OCT can be used to image internal structures in the cochlea without violating the osseous labyrinth using simple surgical exposure of the promontory, and may potentially be used to diagnose inner ear pathology in vivo in both animal and human subjects labyrinth.

Animals↗
PubMed2000

Proteoglycan synthesis in porcine nasal cartilage grafts following Nd:YAG (lambda = 1.32 microns) laser-mediated reshaping.

Mechanically deformed morphologic cartilage grafts undergo temperature-dependent stress relaxation during sustained laser irradiation resulting in stable shape changes. In this study, porcine nasal septal cartilage specimens were evaluated for viability by measuring the incorporation of Na2(35)SO4 into proteoglycan (PTG) macromolecules in whole tissue culture following laser-mediated reshaping. Synthesis rates of PTG were determined by scintillation counting lyophilized specimens and normalizing these values by total protein content. Positive controls were established by inducing chondrocyte apoptosis using prolonged exposure to nitric oxide (NO). In chondrocytes, apoptosis induced using NO resulted in significantly lower PTG synthesis rates compared to untreated native specimens. Cartilage specimens were irradiated with light emitted from a Nd:YAG laser (25 W/cm2, lambda = 1.32 microns) while recording simultaneously radiometric surface temperature, internal stress and back-scattered light intensity from a probe laser. Each specimen received one, two or three sequential laser exposures. The duration of each exposure was determined from real-time measurements of characteristic changes in back-scattered light intensity that correlate with accelerated stress relaxation. A 5 min time interval between each laser exposures allowed the cartilage specimen to return to thermal equilibrium. Average PTG synthesis rates decreased with successive laser exposures, though these were always higher than baseline rates established for NO-treated tissues, suggesting that laser-mediated cartilage reshaping acutely does not eliminate the entire population of viable chondrocytes. The reduction in PTG synthesis is correlated with the time-temperature-dependent heating profile created during laser irradiation, supporting our hypothesis that careful monitoring of laser dosimetry is required to ensure chondrocyte viability.

Animals↗
PubMed1999

Cryogen spray cooling in combination with nonablative laser treatment of facial rhytides.

BACKGROUND: Cryogen spray cooling can be used to provide epidermal protection while still achieving spatially selective photocoagulation in the upper dermis. The objective of this study is to determine the efficacy and safety of cryogen spray cooling in combination with a nonablative Nd:YAG (lambda = 1320 nm) laser treatment of facial rhytides in human volunteers. OBSERVATIONS: Thirty-five adults with bilateral periorbital rhytides were treated with cryogen spray cooling in combination with 3 nonablative laser treatments performed sequentially at intervals of 2 weeks. Small but statistically significant improvements were noted in the mild, moderate, and severe rhytid groups 12 weeks after the final laser treatment. A final assessment performed 24 weeks after the last treatment showed statistically significant improvement only in the severe rhytid group. The procedure was found to be safe; 4 sites (5.6%) developed transient hyperpigmentation. Two sites (2.8%) subsequently developed barely perceptible pinpoint pitted scars. CONCLUSIONS: Cryogen spray cooling is a safe and effective method for protecting the epidermis during nonablative laser treatment of facial rhytides thereby avoiding much of the morbidity associated with other resurfacing procedures. Minor improvements in rhytides can be achieved with the current technology. Optimization of treatment parameters may further improve these results.

Adult↗
PubMed1999

Modeling laser treatment of port wine stains with a computer-reconstructed biopsy.

BACKGROUND AND OBJECTIVE: The efficacy of laser treatment of port wine stains (PWS) has been shown to be highly dependent on patient-specific vasculature. The effect of tissue structure on optical and thermal mechanisms was investigated for different pulse durations by using a novel theoretical model that incorporates tissue morphology reconstructed tomographically from a PWS biopsy. STUDY DESIGN/MATERIALS AND METHODS: An optical-thermal numerical model capable of simulating arbitrarily complex, three-dimensional tissue geometries was developed. The model is comprised of (1) a voxel-based Monte Carlo optical model, (2) a finite difference thermal model, and (3) an Arrhenius rate process calculation to predict the distribution of thermal damage. Simulations based on previous computer-based reconstruction of a series of 6 microm sections from a PWS biopsy were performed for laser pulse durations (taup) of 0.5, 5.0, and 10.0 ms at a wavelength of 585 nm. RESULTS: Energy deposition rate in the blood vessels was primarily a function of vessel depth in skin, although shading effects were evident. Thermal confinement and selectivity of damage were seen to be inversely proportional to pulse duration. The model predicted blood-specific damage for taup = 0.5 ms, vascular and perivascular damage for taup = 5 ms, and widespread damage in superficial regions for taup = 10 ms. The effect of energy deposition in the epidermis was most pronounced for longer pulse durations, resulting in increased temperature and extent of damage. CONCLUSION: Pulse durations between 0.5 and 5 ms are likely optimal for the PWS analyzed. The incorporation of a tomographically reconstructed PWS biopsy into an optical-thermal model represents a significant advance in numerical modeling of laser-tissue interaction.

Adult↗
PubMed1999

In vitro and in vivo photosensitizing capabilities of 5-ALA versus photofrin in vascular endothelial cells.

BACKGROUND AND OBJECTIVE: The objective of the present study was to evaluate the feasibility of photodynamic therapy (PDT) for complicated hemangiomas. The photosensitizing activities of 5-aminolevulinic acid (5-ALA) and Photofrin were evaluated in vitro with human dermal microvascular endothelial cells (MEC) and in vivo with the chicken cox comb. STUDY DESIGN/MATERIALS AND METHODS: The in vitro absorption and photosensitizing activities of 5-ALA and Photofrin were examined in a MEC culture system. The percentages of MEC killed by different drug concentrations at a wavelength of 630 nm were measured by either live/dead or lactate dehydrogenase-released assays. Similarly, the in vivo biological activities of 5-ALA and Photofrin exposed to different total light dosages at 630 nm were studied by determining the amount of necrosis produced in chicken combs. RESULTS: MEC incubated with 5-ALA at a concentration of 35 microg/ml and exposed to laser light at 630 nm at a power density of 100 mW/cm2 showed a 50% cell kill. MEC incubated with Photofrin at a concentration of 3.5 microg/ml and exposed to laser light at 630 nm at a power density of 100 mW/cm2 showed a 50% cell kill. Chicken combs that received 200 mg/kg of 5-ALA exposed to laser light at 630 nm at a power density of 100 mW/cm2 had an injury depth of 362.5+/-27.6 microm at histologic examination. Combs exposed to a power density of 100 or 120 mW/cm2 showed injury depths of 732.5+/-29.1 and 792.5+/-36.0 microm, respectively. Chicken combs that received 2.5 mg/kg of Photofrin exposed to laser light at 630 nm at a power density of 80 mW/cm2 had an injury depth of 535.6+/-22.3 microm at histologic examination. Combs exposed to a power density of 100 or 120 mW/cm2 showed injury depths of 795.8+/-32.5 and 805.2+/-49.1 microm, respectively. CONCLUSION: Both 5-ALA and Photofrin have the capability to destroy MEC in vitro and vasculature in vivo. However, Photofrin achieved a higher degree of cell kill and tissue destruction at lower drug concentrations and at lower power densities.

Aminolevulinic Acid↗
PubMed1999

Q-switched ruby laser treatment of a congenital melanocytic nevus.

BACKGROUND: The treatment of medium-sized (1.5-20 cm diameter) congenital melanocytic nevi (CMN) has been the concern of dermatologists for decades. Although many techniques have been described and utilized, no single treatment has emerged as applicable under all circumstances. METHODS: The Q-switched ruby laser (QSRL) at 694 nm, a wavelength well absorbed by melanin relative to other optically absorbing structures in skin, causes highly selective destruction of pigment-laden cells. In addition, the 20-nanosecond pulse duration produced by this laser approximates the thermal relaxation time for melanosomes, thereby confining the energy to the targeted cells. RESULTS: In the present report, treatment using the QSRL resulted in complete clinical removal of a biopsy-documented medium-sized compound CMN with no recurrence after 5 years. In contrast to other therapeutic modalities, complications such has hypertrophic scarring, dyspigmentation, or atrophy were not observed.

Facial Neoplasms↗