PubMed Health⌕ Search

Biomedical subjects

S Kimel

Publications and source records attributed to S Kimel.

At least 19 recordsLinked to original sources
PubMed2003

Cooling efficiency of cryogen spray during laser therapy of skin.

BACKGROUND AND OBJECTIVES: Cryogen spray cooling (CSC) is used extensively for epidermal protection during laser-induced photothermolysis of port wine stains and other vascular skin lesions. The efficacy of CSC depends critically on the heat transfer coefficient (H) at the skin surface for which, however, no reliable values exist. Reported values for H, based on tissue phantoms, vary from 1,600 to 60,000 W/m(2) K. STUDY DESIGN/MATERIALS AND METHODS: A simple experimental model was designed and constructed, consisting of a pure silver-measuring disk (diameter 10 mm, thickness approximately 1 mm), embedded in a thermal insulator. The disk was covered with a 10 microm thick stratum corneum layer, detached from in vivo human skin. The heat transfer coefficient of the stratum corneum/cryogen interface was measured during CSC with short spurts of atomized tetrafluoroethane. RESULTS: H was found to be dependent on the specific design of the cryogen valve and nozzle. With nozzles used in typical clinical settings, H was 11,500 W/m(2) K, when averaged over a 100 ms spurt, and 8,000 W/m(2) K when averaged over a 200 ms spurt. CONCLUSIONS: The presented model enables accurate prediction of H and thus improve control over temperature depth profile and cooling efficiency during laser therapy. Thereby, it may contribute to improvement of therapeutic outcome.

Cryotherapy↗
PubMed2001

Cryogen spray cooling in laser dermatology: effects of ambient humidity and frost formation.

BACKGROUND AND OBJECTIVE: Dynamics of cryogen spray deposition, water condensation and frost formation is studied in relationship to cooling rate and efficiency of cryogen spray cooling (CSC) in combination with laser dermatologic surgery. STUDY DESIGN/MATERIALS AND METHODS: A high-speed video camera was used to image the surface of human skin during and after CSC using a commercial device. The influence of ambient humidity on heat extraction dynamics was measured in an atmosphere-controlled chamber using an epoxy block with embedded thermocouples. RESULTS: A layer of liquid cryogen may remain on the skin after the spurt termination and prolong the cooling time well beyond that selected by the user. A layer of frost starts forming only after the liquid cryogen retracts. Condensation of ambient water vapor and subsequent frost formation deposit latent heat to the target site and may significantly impair the CSC cooling rate. CONCLUSIONS: Frost formation following CSC does not usually affect laser dosage delivered for therapy of subsurface targets. Moreover, frost formation may reduce the risk of cryo-injury associated with prolonged cooling. The epidermal protection during CSC assisted laser dermatologic surgery can be further improved by eliminating the adverse influence of ambient humidity.

Aerosol Propellants↗
PubMed1999

Systemic application of photosensitizers in the chick chorioallantoic membrane (CAM) model: photodynamic response of CAM vessels and 5-aminolevulinic acid uptake kinetics by transplantable tumors.

The aim of this study is to modify the chick chorioallantoic membrane (CAM) model into a whole-animal tumor model for photodynamic therapy (PDT). By using intraperitoneal (i.p.) photosensitizer injection of the chick embryo, use of the CAM for PDT has been extended to include systemic delivery as well as topical application of photosensitizers. The model has been tested for its capability to mimic an animal tumor model and to serve for PDT studies by measuring drug fluorescence and PDT-induced effects. Three second-generation photosensitizers have been tested for their ability to produce photodynamic response in the chick embryo/CAM system when delivered by i.p. injection: 5-aminolevulinic acid (ALA), benzoporphyrin derivative monoacid ring A (BPD-MA), and Lutetium-texaphyrin (Lu-Tex). Exposure of the CAM vasculature to the appropriate laser light results in light-dose-dependent vascular damage with all three compounds. Localization of ALA following i.p. injections in embryos, whose CAMs have been implanted with rat ovarian cancer cells to produce nodules, is determined in real time by fluorescence of the photoactive metabolite protoporphyrin IX (PpIX). Dose-dependent fluorescence in the normal CAM vasculature and the tumor implants confirms the uptake of ALA from the peritoneum, systemic circulation of the drug, and its conversion to PpIX.

Allantois↗
PubMed1999

Oxygen depletion during in vitro photodynamic therapy: structure-activity relationships of sulfonated aluminum phthalocyanines.

Photodynamically induced oxygen depletion has been measured in an Ehrlich ascites mouse tumor cell line using a Clark-type electrode. Cells are loaded with aluminum phthalocyanines, sulfonated to different degrees (A1PcS(n), n = 0,2,3,4) and consisting of various isomeric species. Different cell lines and incubation procedures are used in order to investigate the cellular uptake mechanism. Uptake (in units of molecules/cell), post-irradiation redistribution and A1PcS(n) photodegradation are measured using spectroscopic techniques. For a given sensitizer, the oxygen depletion rate per cell increases sublinearly with uptake and superlinearly with cell density. In order to compare oxygen depletion rates of different compounds, we have defined the biological quantum yield (BQY) as the number of oxygen molecules that disappear per absorbed photon. The BQY is independent of uptake and cell density; therefore, it denotes the intrinsic photoactivity of a sensitizer. Sensitizers with high BQY show efficient post-irradiation intracellular redistribution. Photodegradation during irradiation is similar for all sensitizers (20-30%).

Aluminum↗
PubMed1998

Photodynamic damage by liposome-bound porphycenes: comparison between in vitro and in vivo models.

Photodynamic efficacy of four tetrakis (methoxyethyl) porphycene (TMPn) derivatives encapsulated in liposomes, was studied in vitro and in vivo. Fluorescence and absorption measurements were used to determine aggregation in dipalmitoyl phosphatidylcholine (DPPC) liposomes; no spectral changes were found when dissolving in an organic solution or in an aqueous dispersion of DPPC liposomes. This indicates that the porphycenes were located in the lipophilic bilayer of the liposomes. Fluorescence quenching experiments with I- showed, specifically, that porphycenes located in the liposome bilayer at various depths, according to the hydrophilicity of the porphycene side chains. Dose-response relations were established: increasing porphycene concentration or light dose enhanced the damage proportionally. In cultured MDCK cells, photodynamic damage was in accordance with location: a porphycene 'buried' inside the bilayer did not cause damage to the cell culture. PDT efficacy was tested also in vivo by the damage to blood vessels of the chorioallantoic membrane (CAM) of the fertilized chick embryo. Unlike in the in vitro case, the porphycene 'buried' inside the bilayer did cause significant photodynamic damage in vivo. This difference suggests that in vitro photodynamic action follows contact-mediated sensitizer transfer to cell membranes from liposomes, which remain distinct from cells, whereas in vivo the photosensitizer is delivered to tissue via fusion of liposomes with endothelial cell membranes.

Absorption↗
PubMed1997

Photodynamic efficacy of naturally occurring porphyrins in endothelial cells in vitro and microvasculature in vivo.

Photodynamic therapy (PDT) has been described in terms of cellular and vascular effects. The precise mechanisms of cellular and vascular damage are still unknown. In this study, the photodynamic inactivation of endothelial cells in vitro and damage to the microvasculature in vivo by naturally occurring porphyrins (uroporphyrin III (UP), coproporphyrin III (CP) and protoporphyrin IX (PP)) were investigated. The chick chorioallantoic membrane model (CAM model) was used, which is convenient for the study of damage to the microcirculation induced by PDT. The hydrophilic porphyrins UP and CP exhibited low cytotoxicity towards endothelial cells. Only small amounts of UP and CP were taken up, resulting in weak inactivation after irradiation. In contrast, the more lipophilic PP showed a marked cytotoxicity. Considerable amounts of PP were accumulated in the cells, leading to pronounced inactivation after light exposure. For the three porphyrins, damage to the microvasculature was observed. The damage caused by the hydrophilic porphyrins UP and CP was strongly dependent on the drug and light dose. For vascular injury, the efficacy was graded as UP < CP < PP.

Animals↗
PubMed1996

Dynamic epidermal cooling in conjunction with laser-induced photothermolysis of port wine stain blood vessels.

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 spatial distribution of cooling remains localized in the normal overlying epidermis, while leaving the temperature of the deeper port wine stain (PWS) blood vessels unchanged. Furthermore, cooling continues after pulsed laser exposure as cryogen remaining on the surface evaporates and removes heat deposited by light absorption in epidermal melanin. An additional advantage of dynamic cooling is a reduction in the level of pain and discomfort associated with flashlamp-pumped pulsed dye laser therapy of PWS. Preliminary clinical studies and supporting theoretical calculations demonstrate the feasibility of selective epidermal cooling while achieving photothermolysis of blood vessels during pulsed laser treatment of PWS.

Laser Therapy↗
PubMed1996

Photodynamic effects on human and chicken erythrocytes studied with microirradiation and confocal laser scanning microscopy.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) of cancers is associated with the destruction of the microvasculature supplying the tumor. The study elucidates the role of red blood cells in PDT-induced vascular injury. STUDY DESIGN/MATERIALS AND METHODS: Intracellular accumulation of several photosensitizers in human (non-nucleated) and chicken (nucleated) erythrocytes, as well as photodynamic induced hemolysis were studied using 488 nm laser microirradiation (15 microW) and confocal laser scanning fluorescence microscopy. RESULTS: Cells incubated with anionic hydrophilic compounds TPPS4 and Pd-TPPS4 exhibited no fluorescence before irradiation, but developed strong and sustained fluorescence in the cellular and nuclear membranes following photoinduced membrane damage. In contrast, microirradiation of Photofrin-incubated erythrocytes showed instantaneous fluorescence which decreased due to photodegradation. For the cationic hydrophilic dye methylene blue, significant fluorescence was detected only in the nucleus. Following ALA incubation, large intercellular differences were observed in fluorescence in the red spectral region. Photofrin induced the most efficient hemolysis. Higher radiant exposures were required for lysis of nucleated rather than of non-nucleated red blood cells, except in the case of methylene blue. CONCLUSION: Laser microbeams were used, for the first time, to study photodynamic cell damage. Erythrocytes were shown to be primary targets in PDT. Damage to red blood cells could be responsible for hemostasis in the vascular bed of a tumor, which was reported by many groups.

Animals↗
PubMed1996

Wavelength dependence of cell cloning efficiency after optical trapping.

A study on clonal growth in Chinese hamster ovary (CHO) cells was conducted after exposure to optical trapping wavelengths using Nd:YAG (1064 nm) and tunable titanium-sapphire (700-990 nm) laser microbeam optical traps. The nuclei of cells were exposed to optical trapping forces at various wavelengths, power densities, and durations of exposure. Clonal growth generally decreased as the power density and the duration of laser exposure increased. A wavelength dependence of clonal growth was observed, with maximum clonability at 950-990 nm and least clonability at 740-760 nm and 900 nm. Moreover, the most commonly used trapping wavelength, 1064 nm from the Nd:YAG laser, strongly reduced clonability, depending upon the power density and exposure time. The present study demonstrates that a variety of optical parameters must be considered when applying optical traps to the study of biological problems, especially when survival and viability are important factors. The ability of the optical trap to alter either the structure or biochemistry of the process being probed with the trapping beam must be seriously considered when interpreting experimental results.

Animals↗
PubMed1995

In vivo damage to chorioallantoic membrane blood vessels by porphycene-induced photodynamic therapy.

Photodynamic therapy (PDT) was performed in the chick embryo chorioallantoic membrane (CAM) for the purpose of quantitative evaluation of several porphycenes as potential photosensitizers. Porphycenes are structural isomers of porphine possessing lower symmetry of the macrocycle and are characterized by 10-fold higher absorption at the therapeutic wavelengths for PDT (lambda > 630 nm). PDT-induced damage to CAM blood vessels included vasoconstriction and blanching as was monitored during irradiation and videotaped. Image analysis techniques enabled us to follow PDT-induced constriction of vessel diameter (to 50%), reduction of blood perfusion (to 40% lower optical density) and shrinkage of implanted tumours (to 10% of their original area). The observed PDT efficacy of functionalized porphycenes is positively correlated with the number of polar substituents.

3T3 Cells↗
PubMed1995

Selective cooling of biological tissues: application for thermally mediated therapeutic procedures.

The ability to control the degree and spatial distribution of cooling in biological tissues during a thermally mediated therapeutic procedure would be useful for several biomedical applications of lasers. We present a theory based on the solution of the heat conduction equation that demonstrates the feasibility of selectively cooling biological tissues. Model predictions are compared with infrared thermal measurements of in vivo human skin in response to cooling by a cryogen spurt. The presence of a boundary layer, undergoing a liquid-vapour phase transition, is associated with a relatively large thermal convection coefficient (approximately 40 kW m-2 K-1), which gives rise to the observed surface temperature reductions (30-40 degrees C). The degree and the spatial-temporal distribution of cooling are shown to be directly related to the cryogen spurt duration.

Body Temperature↗
PubMed1995

A theoretical study of the thermal response of skin to cryogen spray cooling and pulsed laser irradiation: implications for treatment of port wine stain birthmarks.

The successful treatment of port wine stain (PWS) patients undergoing laser therapy is based on selective thermal coagulation of blood vessels without damaging the normal overlying epidermis. Cryogen spray cooling of skin may offer an effective method for minimizing epidermal thermal injury. Inasmuch as the density of melanosomes and depth of PWS blood vessels can vary considerably, an optimum cooling strategy is required on an individual patient basis. We present a theoretical study of the thermal response of various pigmented PWS lesions to spray cooling in conjunction with flashlamp-pumped pulsed dye laser irradiation (585 nm). Results of our model indicate that precooling of skin using tetrafluoroethane as the cryogen spray is sufficient to eliminate epidermal thermal injury when using incident fluences less than 10 J cm-2 and 8 J cm-2 on patients with intermediate and high epidermal melanin content, respectively. Cryogens that have lower boiling points than tetrafluoroethane may allow successful treatment when using fluences equal to or greater than those indicated.

Anesthetics↗
PubMed1995

Structure-activity relationship of porphines for photoinactivation of bacteria.

The antibacterial photodynamic effects of uncharged (o-tetrahydroxyphenyl porphine [THPP], m-THPP and p-THPP), cationic (5,10,15,20-tetra[4-N-methylpyridyl]porphine [TMPyP]) and anionic (5,10,15,20-tetra[4-sulfonatophenyl porphine] [TPPS4]) porphines on Staphylococcus aureus and Escherichia coli bacteria inactivation were examined. The results show that uncharged porphines provoked antibacterial photodynamic activity on S. aureus, and also on E. coli in the presence of the membrane-disorganizing peptide polymixin B nonapeptide (PMNP). The TMPyP compound was highly photoactive toward gram-positive bacteria but only marginally effective on gram-negative cells, whereas TPPS4 showed no activity on either gram-positive or gram-negative bacteria. The photoactivity of TMPyP is due to the electrostatic attraction between the positively charged sensitizer molecule and the negatively charged membrane of the gram-positive target cells. For TPPS4, the inactivity toward gram-positive bacteria is due to electrostatic repulsion between the charged sensitizer molecule and the cell membrane. For gram-negative bacteria, the inactivity is conceivably due to preferential (electrostatic) binding to the positively charged PMNP, which is an adjuvant for membrane disorganization, but has no effect on cell viability. For hydrophobic sensitizers, the photoactivity depends on the state of aggregation. The extent of deaggregation of the different THPP isomers was determined by fluorescence measurements of bound sensitizers and could be positively correlated with their photoinactivation capacity. We conclude that the structure-activity relationships of these porphines are affected by their net charge and by aggregation.

Escherichia coli↗
PubMed1995

Dynamic epidermal cooling during pulsed laser treatment of port-wine stain. A new methodology with preliminary clinical evaluation.

BACKGROUND AND DESIGN: The clinical objective in the treatment of a patient with port-wine stain (PWS) undergoing laser therapy is to maximize thermal damage to the PWS, while at the same time minimizing nonspecific injury to the normal overlying epidermis. With dynamic cooling, the epidermis can be cooled selectively. 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 PWS vessels unchanged. RESULTS: Comparative measurements obtained by a fast infrared imaging detector demonstrated that the surface temperature prior to laser exposure could be reduced by as much as 40 degrees C using the dynamic cooling technique. No skin surface textural changes were noted on PWS test sites cooled with a 20- to 80-millisecond cryogen spurt after flashlamp-pumped pulsed dye laser (FLPPDL) exposure (lambda = 585 nm; tau p = 450 microseconds) at the maximum light dosage possible (10 J/cm2). In contrast, epidermal necrosis occurred on the uncooled sites after such exposure. Six months after laser exposure, clinically significant blanching on the cooled sites indicates laser photothermolysis of PWS blood vessels did occur. CONCLUSIONS: Our preliminary experiments demonstrate the feasibility of selectively cooling the normal overlying epidermis without affecting the temperature of the deeper PWS vessels. Furthermore, protection of the epidermis from thermal injury, produced by melanin light absorption at clinically relevant wavelengths, can be achieved effectively. An additional advantage of dynamic epidermal cooling is reduction of patient discomfort associated with FLPPDL therapy. Further studies are under way to determine an optimum strategy for applying this dynamic cooling technique during pulsed laser treatment of patients with PWS and others with selected dermatoses (dermal melanocytic lesions and tattoos).

Absorption↗
PubMed1994

Differential vascular response to laser photothermolysis.

Individual blood vessels in the chick choriallantoic membrane were selectively coagulated through photothermolysis, using pulsed laser irradiation at 585 nm. Pulse durations were chosen to be 0.45 ms and 10 ms, which correspond to the thermal relaxation times in blood vessels of 30 microns and 150 microns diameter, respectively. The short pulses, at a light fluence F = 3 Jcm-2, caused permanent occlusion of vessels of 40 microns diameter or less, whereas larger caliber vessels (60-120 microns) required F = 4-5 Jcm-2. The long-duration pulses, at F = 7 Jcm-2, caused coagulation of the larger diameter vessels; the small-caliber vessels and capillaries showed resistance to photothermolysis and required multiple exposures to achieve coagulation. The fluence versus diameter (F versus d) relationship for coagulation was calculated for the two pulse durations. The energy deposited in a cylindrical absorber of diameter d by an optical field, incident perpendicular to the vessel, was expressed analytically and compared with the energy required to coagulate a blood vessel of the same lumen dimeter. When thermal diffusion is incorporated into the model, our findings can be accounted for quantitatively. This information will be of use for improving the laser treatment of port wine stains and other vasculopathies. A surprising observation was that arterioles were damaged at lower incident energy densities than venules having the same lumen diameter, despite the fact that absorbance in oxygen-rich and oxygen-poor blood is the same at 585 nm.

Allantois↗
PubMed1993

Stereochemical factors in the transport and binding of photosensitizers in biological systems and in photodynamic therapy.

The uptake and biological activity of porphyrins and phthalocyanines in tumours were correlated with the geometrical features of the photosensitizer molecules. The data suggest that a critical distance of approximately 1.2 nm between oxygen atoms (originating in SO3-, COO- or OH substituents) characterizes a biologically active photosensitizer for photodynamic therapy. We propose that tubulin, which is available in large amounts during mitosis, is the main receptor molecule which binds these photosensitizers. Basic amino acid residues or tightly bound cations in tubulin or homologous proteins may act as binding sites on the receptor molecule.

Animals↗