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Biomedical subjects

M W Berns

Publications and source records attributed to M W Berns.

At least 163 records · Page 9Linked to original sources
PubMed1987

Photosensitizers in dermatology.

Systemic injection of hematoporphyrin derivative (HpD) in contribution with visible light (red or blue-green) delivered by laser was used to treat a patient with psoriasis. The psoriatic lesions responded vigorously to laser treatments, forming eschars by 1 week post irradiation. In contrast, only minimal erythema was observed in the noninvolved, clinically normal appearing skin. Two approaches for localized HpD administration were investigated in the guinea-pig and minipig models as a means of achieving local photodynamic effects. Intracutaneous injection of HpD produced localized cutaneous photosensitization with either UVA or red light. Azone increased percutaneous penetration of HpD in human skin in vitro. Topical application of HpD and irradiation with UVA produced localized cutaneous photosensitivity and inhibition of epidermal DNA synthesis.

Animals↗
PubMed1987

Comparison of continuous-wave lasers for endarterectomy of experimental atheromas.

The standard surgical lasers, argon ion, neodymium-yttrium aluminum garnet, and carbon dioxide, are often operated as continuous wave lasers with specific uses. Clinical trials of laser therapy for arteriosclerotic cardiovascular disease are underway with all three lasers. Therefore, we compared these three lasers under controlled experimental conditions. A thoracoabdominal exploration was performed in 17 arteriosclerotic rabbits. The aorta was isolated, heparin administered, and multiple endarterectomies were performed in each rabbit with each of the lasers. A line of laser craters was created at the proximal and distal ends of an atheroma. Continuous-wave laser radiation was used to connect the craters and thereby form proximal and distal end points. The plaques were dissected free from the aorta with laser light and the end points were fused by laser. The aortas were removed for light microscopy and the animals were killed. The endarterectomy surfaces and end points were serially sectioned and graded according to light microscopic findings (1 = worst, 4 = best). Argon ion laser endarterectomy (N = 16) required 106 +/- 10 J/cm2. The surface score was 3.5 and end point score 3.4. Neodymium-yttrium aluminum garnet laser endarterectomy (N = 13) required 1,289 +/- 115 J/cm2 with a surface score of 2.4 (p less than 0.001 from argon ion) and an end point score of 1.3 (p less than 0.001 from argon ion). Carbon dioxide laser endarterectomy (N = 9) required 30 +/- 5J/cm2 with a surface score of 2.0 (p less than 0.001 from argon ion) and and end point score of 1.6 (p less than 0.001 from argon ion). Perforation occurred in one of 16 argon ion studies (technical error, not laser), in 11 of 13 neodymium-yttrium aluminum garnet studies, and in six of nine carbon dioxide studies. This study demonstrates that of the currently available clinical continuous-wave lasers, the argon ion laser is superior for endarterectomy of experimental atheromas.

Animals↗
PubMed1987

Delayed retinal effects of the frequency-doubled YAG laser (532 nm).

In order to compare the retinal effects of the frequency-doubled YAG laser (532 nm) with those of argon laser, rabbit eyes were exposed to green YAG laser irradiation and processed for light and electron microscopic study at 24 hr, 2 weeks and 4 weeks. Detailed analysis was conducted on tissue exposed to 7.3 and 7.6 millijoules (mj). Response of the photoreceptors and retinal pigmented epithelium to green YAG was very similar to that described for argon laser over the same time period. By 2 weeks post-exposure, there was histologic evidence of partial recovery with absence of damaged, pycnotic photoreceptor nuclei, increased numbers of typical photoreceptor outer segment lamellae and repair of retinal pigmented epithelium. Four weeks after irradiation, normal-appearing photoreceptor nuclei were present although inner photoreceptor segments still showed mitochondrial damage. Outer segments at 4 weeks showed regular lamellar structures. We conclude that the frequency-doubled YAG laser is equivalent to the argon laser with respect to the production of thermal lesions in the retina. Its additional advantages include increased efficiency, portability, reliability and lack of absorption by macular xanthophyll pigment.

Animals↗
PubMed1986

Study of the in vivo and in vitro photosensitizing capabilities of uroporphyrin I compared to photofrin II.

The in vivo biological activity of uroporphyrin I has been studied by determining the amount of necrosis produced in murine tumors exposed to various total doses of light at 615 nm. Similarly, the in vitro photosensitizing activity of uroporphyrin I was examined by measuring the percentage of cells killed in a cell culture system. Light doses used were 25-400 J/cm2. Mice that received uroporphyrin I at 40 mg/kg had only minimal superficial necrosis upon histological examination at doses of 400 J/cm2 (615 nm). Those tumors that received 300 J/cm2 or less showed no histological evidence of necrosis. Mice that received hematoporphyrin derivative (Photofrin II) at 10 mg/kg were completely necrotic at total doses of 100 J/cm2 (630 nm). PTK2 epithelial cells incubated with uroporphyrin I at either 40 micrograms/ml or 80 mu/ml and 10 J/cm2 (615 nm) showed no apparent damage and had 100% cell survival. By contrast, those cells treated with hematoporphyrin derivative (Photofrin II) at 25 micrograms/ml and 10 J/cm2 (630 nm) exhibited 100% cell kill. It is concluded that uroporphyrin I is a poor photosensitizer in both in vivo and in vitro systems compared to hematoporphyrin derivative (Photofrin II).

Animals↗
PubMed1986

Hematoporphyrin phototherapy of cancer.

Hematoporphyrin phototherapy of cancer is a new modality for cancer diagnosis and treatment that is currently undergoing clinical trials worldwide. A variety of tumors have been studied, e.g., breast (mostly recurrent skin), lung, bladder, eye, head and neck, gynecological and brain. The most success to date has been with lung and the gynecological tract. Cell and animal studies are being conducted to elucidate the basic photobiological mechanisms involved, as well as the histopathological events associated with tumor destruction. Although major questions remain to be resolved, hematoporphyrin phototherapy is an exciting new therapeutic modality for the treatment of cancer, especially in sites where the unique features of lasers and fiber optics are advantageous.

Breast Neoplasms↗
PubMed1986

Characterization of cutaneous phototoxicity induced by topical alpha-terthienyl and ultraviolet A radiation.

Alpha-terthienyl (alpha-T), a phototoxic thiophene compound isolated from marigolds (Tagetes species), affects cell membranes and does not appear to induce cytogenetic damage. This study was undertaken to investigate topical delivery of alpha-T and characterize its cutaneous phototoxicity in combination with long-wave UV radiation (UVA) in comparison with locally (intradermal) administered alpha-T. Percutaneous penetration (PC) of 0.1% and 1% alpha-T in a 3% Azone gel vehicle was studied in guinea pig skin in vitro and quantitated by UV fluorescence microscopy. Dose-dependent PC of epidermis, adnexae, and superficial dermis was demonstrated in vitro. Alpha-terthienyl (0.1% and 1%) in this vehicle was applied topically in vivo and irradiated with 30 J/cm2 UVA at intervals of 10 min-24 h. Maximum sensitization was achieved with irradiation 1 h following drug application. The clinical response was dose-dependent consisting of erythema, edema, crusting, erosion, and inhibition of hair growth and was observed 72 h to 7 days postirradiation. A comparable dose-dependent phototoxic response was observed when 5-500 micrograms alpha-T were injected intradermally and irradiated with UVA. These results indicated that low-dose topical alpha-T in a nonirritating vehicle can rapidly produce cutaneous photosensitization. Topical alpha-T/UVA may provide a selective and safer alternative approach for the photochemotherapy of psoriasis and other cutaneous diseases.

Administration, Oral↗
PubMed1985

Laser endarterectomy.

Laser radiation can be applied directly at a diseased artery to dissect the plaque away from the media and perform an open endarterectomy. The appropriate cleavage plane within the media can be achieved with the laser beam for precise reconstruction of the artery. Laser endarterectomy offers a technique for the study of laser radiation upon arteriosclerosis and may become a new modification of a standard surgical technique.

Animals↗
PubMed1985

Laser applications to arteriosclerosis: angioplasty, angioscopy, and open endarterectomy.

We have studied laser radiation of arteriosclerotic cardiovascular disease to determine the best technique for evaluation. Rabbits with arteriosclerosis were treated by intraluminal laser angioplasty (N = 8), laser angioscopy (N = 2), and open laser endarterectomy (N = 5). All studies were performed with an argon ion laser delivering energy through a 400-microns quartz fiber. Power delivered was varied in order to determine the best value for this animal model. Following angioplasty, perforation was seen in three rabbits (in one case, it was due to mechanical trauma from the fiber optic), and early thrombosis occurred in two rabbits. Plaques were vaporized by angioscopy, but the depth of laser beam penetration or angle of incidence could not be controlled. Open laser endarterectomy gave consistently good results with removal of an arteriosclerotic plaque within the media. The optimum power was found to be 1.0-2.0 W. Endarterectomy required an energy density of 100-140 J/cm2. We conclude that open laser endarterectomy can be a standardized technique for the in vivo evaluation of laser radiation upon arteriosclerotic lesions.

Animals↗
PubMed1985

Corneal incisions produced with the fourth harmonic (266 nm) of the YAG laser.

The fourth harmonic wavelength (266 nm) of a neodymium YAG laser was used to cut precise grooves on the surface of the human cornea. Well-controlled cuts were made using the laser operating at 1.3 kHz. The width of the grooves was 2-3 micron. The depth could be controlled by varying the amount of laser exposure.

Cornea↗
PubMed1985

Retinal effects of the frequency-doubled (532 nm) YAG laser: histopathological comparison with argon laser.

Retinal lesions produced in Dutch Cross rabbits with a frequency-doubled (532 nm) YAG laser in single pulse mode (30-100 microJ) and in train of uniform pulses (2.6 and 7.5 mJ) underwent histopathological examination by light and electron microscopy. The results were compared to argon laser lesions (11 and 15 mJ) in the same animals. Low-energy single-pulse YAG lesions produced separation of the neural retina from the retinal pigmented epithelium (RPE), while higher energies caused severe disruption of retinal structures with moderate damage to the RPE. A striking and consistent finding of all the single-pulse lesions was the presence of red blood cells between the RPE and neural layers. The findings appear to support a process of mechanical disruption. In contrast, the lesions produced by a uniform train of pulses showed well-defined damage to RPE and photoreceptors with no red blood cells between these two layers, no choroidal damage, and relatively little disruption of the inner retina. The typical argon lesion evidenced cellular damage from the RPE through all retinal layers. Leukocytes in the choroid contained "holes" or vacuoles not seen in YAG lesions. Both the uniformly pulsed YAG laser burst and argon laser produced effects consistent with a thermal process. Some differences between argon and YAG burst were observed. The results suggest that there may be a clinical potential for the 532-nm burst YAG in treating retinopathies.

Animals↗
PubMed1985

Experimental arteriosclerosis treated by conventional and laser endarterectomy.

Open laser endarterectomy was compared to standard surgical endarterectomy in the rabbit arteriosclerosis model. The aorta was exposed by a thoracoabdominal exploration in 16 rabbits. In Group I (8 rabbits), a conventional endarterectomy (CE) was performed with standard vascular instruments. In Group II (8 rabbits), laser endarterectomy (LE) was performed with an argon ion laser (488 nm and 514.5 nm) at a power of 1.0 W. Aortas were fixed, serially sectioned (6 micron) and stained (H +/- E) following each procedure. Gross and light microscopic examination revealed identical results for the endarterectomy surfaces of CE and LE. The proper cleavage plane within the media was developed with both techniques and the remaining arterial wall was not damaged with either procedure. The end points of LE were consistently superior to those of CE because of phototherapy fusion. The LE end points were tapered and the intima was fused. Intimal flaps were seen in 2/8 CE experiments and the remaining end points exhibited an uneven transition. LE required an average energy density of 124 +/- 9 J/cm2. We conclude that LE provides a satisfactory method for the in vivo evaluation of laser radiation upon arteriosclerotic arteries. LE may be the way to begin clinical laser trials.

Animals↗
PubMed1985

The use of lipid emulsion as an intravesical medium to disperse light in the potential treatment of bladder tumors.

An obstacle to satisfactory treatment of early bladder cancer with hematoporphyrin derivative-photoradiation therapy is nonuniform illumination of the bladder mucosa. This study was done to determine the characteristics and attenuation of laser light passing through the dispersion medium. Bladder simulation was achieved with the use of 5 different sizes of round-bottom flasks. Intralipid was the dispersion medium. For each flask, 6 different concentrations of the dispersion medium were used. An Argon ion laser was used to stimulate a dye laser at 630 nm. The laser was directed toward the center of the flasks via a fiberoptic cable and energy concentration at 7 different angles was measured. We concluded that the optimal medium was a 1:100 dilution of Intralipid with water, which produced an almost uniform dispersion of light on the walls of the flask. There is a linear correlation between power as measured at the fiber tip and the amount of radiation detected on the walls of the flasks. After determining optimal concentration of medium, we calculated the amount of time needed for a desired energy (Joules/cm.2) to treat a tumor. This calculation was based on the size of the bladder and the power as measured at the fiber tip. The results indicate it is possible to treat the entire mucosa of the bladder with a uniform dose of photoradiation energy.

Fat Emulsions, Intravenous↗
PubMed1985

Comparison of fluorescence and photodynamic activities of whole hematoporphyrin derivative and its enriched active components.

The in vivo biologic activities of the hematoporphyrin derivative (Photofrin) and the enriched, so-called "active fraction" (Photofrin II) were determined by measuring the necrosis produced in implanted tumors in DBA/2Ha mice exposed to various total doses of light (20-100 J/cm2) after ip administration of 10 mg/kg standard doses of either Photofrin or Photofrin II. Total relative percentage increase in fluorescence in tumor tissue, as compared to fluorescence in control tissue, also was measured for both Photofrin and Photofrin II. In response to total light doses (630 nm) of 40-100 J/cm2, mice that received Photofrin had comparable amounts of tumor necrosis to those mice that received Photofrin II. At doses of 40-60 J/cm2, 80% tumor destruction resulted, and at 80-100 J/cm2, tumor destruction was 100%. However, at a total light dose of 20 J/cm2, the tumors that received Photofrin II exhibited 60-80% tumor necrosis, whereas those animals that received Photofrin had only small areas of patchy necrosis associated with signs of vascular thrombosis and hemorrhage into the surrounding perivascular stroma. A 25.2% total increase in maximal tissue fluorescence over that in controls was observed for animals that received Photofrin II, as compared to 13.9% for those animals that received Photofrin. It is concluded that the greater demonstrable efficacy of treatment with Photofrin II, as compared to treatment with Photofrin, is due to enrichment of those nonpolar hydrophobic components of the hematoporphyrin derivative mixture that are thought to be primarily responsible for the in vivo biologic activities.

Animals↗
PubMed1985

Experimental arteriosclerosis treated by argon ion and neodymium-YAG laser endarterectomy.

The argon ion laser (488 and 514.5 nm) and the Nd-YAG laser (1.06 micron) have been used in most studies of laser radiation for treatment of arteriosclerotic cardiovascular disease because their beams can be directed through a delivery fiber. We compared the effects of argon ion and Nd-YAG lasers in vivo on arteriosclerotic rabbit aortas with open laser endarterectomy. A thoracoabdominal exploration was performed in 16 rabbits to isolate the aorta. Laser beams were directed through delivery fibers to produce a line of laser craters at the proximal and distal ends of an atheroma. The lines of laser craters were connected by continuous-wave laser radiation to loosen the plaque and the cleavage plane was developed within the media by continuous-wave laser radiation. End points were fused by continuous-wave laser radiation and the aortas were harvested for light and scanning electron microscopy. Argon ion laser endarterectomy (eight rabbits) required an energy density of 98 +/- 19 J/cm2. Nd-YAG laser endarterectomy (eight rabbits) required an energy density of 1147 +/- 129 J/cm2. Perforation did not occur with the argon ion laser but occurred in six of eight Nd-YAG experiments. Even depths of plaque removal resulted from argon ion laser endarterectomy but not from Nd-YAG laser endarterectomy. Gross and microscopic grading of the aortas showed that argon ion endarterectomy surfaces were significantly better than Nd-YAG surfaces (p less than .05). Similarly, argon ion end points were significantly better than Nd-YAG end points (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation.

A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia-associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not.

Animals↗