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Biomedical subjects

J A Parrish

Publications and source records attributed to J A Parrish.

At least 19 recordsLinked to original sources

Current and future trends in laser medicine.

In this overview, a number of the major current, and possible future developments in laser medicine are explored. In therapeutic applications, particular emphasis is given to obtaining selectivity in tissue targets and interaction mechanisms in order to achieve specific biological effects. This includes spatial confinement of thermal damage by pulsed laser irradiation and targetting by exogenous photothermal or photochemical chromophores. The potential for diagnostic applications of lasers in medicine is illustrated primarily by various in vivo spectroscopic techniques. Both therapeutic and diagnostic applications will rely increasingly on the development of total systems in which lasers will form only one, albeit an essential, part. Numerous scientific and technical problems need to be solved in order to realize the full clinical potential of the many new concepts in laser medicine. The impetus for such progress will come from integrated, multidisciplinary collaborations between medical, scientific and industrial groups.

Cornea

Application of the 1-microsecond pulsed-dye laser to the treatment of experimental cerebral vasospasm.

Laser energy of 480 nm was applied in 1-microsecond pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-microns fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood. 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-microsecond pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.

Animals

Treatment of vasospasm with a 480-nm pulsed-dye laser.

Laser energy at a wavelength of 480 nm was applied in 1-microseconds pulses of 3 to 10 mJ to two models of vasospasm. Rabbit common carotid arteries (CCA's) were constricted chronically by the application of human blood within a silicone sheath. Peak vasospasm developed 24 to 48 hours later, and persisted for up to 6 days. Endovascular laser treatment was delivered to 40 CCA's via a 200-microns diameter silica quartz fiber introduced through the femoral artery. The CCA caliber increased from 60% of the pre-vasospasm control diameter to a minimum post-laser diameter of 83% of control. No instances of laser-induced perforation or of arterial thrombosis were observed for up to 60 days after treatment. Prophylactic laser application to nine normal vessels was able to attenuate the development of vasospasm if blood was applied immediately thereafter (88% vs. 59% of control diameter, p less than 0.02), but not if blood was applied 7 days later. Studies in 16 normal CCA's established that there was a considerable margin between the laser energy required to induce dilatation and that which caused perforation, providing that the fiber remained relatively central within the artery. Morphological examination demonstrated focal loss of endothelial cells immediately after laser application, followed approximately 7 days later by the development of areas of intimal hyperplasia. Only minimal changes were observed in the medial or adventitial layers. In a second study, the basilar artery of seven dogs was constricted chronically by two intracisternal injections of autologous blood 3 days apart. Five dogs received endovascular laser treatment 7 or 10 days after the first injection, when basilar artery diameter was reduced to a mean of 61% and 77% of control, respectively. Immediately following treatment, basilar artery diameter increased to 104% and 102% of resting diameter, respectively. Both untreated and laser-treated arteries were smaller than the control diameter at 30 days (80% and 82%, respectively), but in each group the vasodilatory response to hypercapnia was preserved. These findings indicate that 1-microsecond laser pulses are well tolerated by systemic and cerebral arteries in two different animal models, and suggest that the 480-nm pulsed-dye laser may have an application for the treatment or prophylaxis of cerebral vasospasm.

Animals

Dohi memorial lecture. Laser medicine and laser dermatology.

As laser devices become smaller, more reliable, and less expensive, dermatology will benefit from new laser-based therapeutic and diagnostic methods. Already there are simple, non-scarring, and relatively painless techniques for removal of pigmented lesions, tattoos, and vascular lesions. Because much of the basic and applied research in photobiology is grounded in dermatology research, dermatology will continue to be a major contributor to advances in laser medicine and photomedicine. An increase in understanding and ability to manipulate laser-tissue interactions will add greatly to the future of medicine and surgery, especially in applications utilizing pulsed lasers. We are learning how to: 1) vary wavelength, pulse duration, and energy to influence the nature of microscopic injury and host response in order to achieve a net therapeutic benefit; 2) utilize exogenous chromophores to increase the selection of targets for laser radiation; and 3) capture optical technology developed for industrial and military use, in order to benefit mankind with new medical and surgical techniques.

Animals

Visible action spectrum for melanin-specific selective photothermolysis.

The skin of black and albino guinea pigs was irradiated with single, 750 nsec-long laser pulses at 435, 488, 530, and 560 nm in order to determine an action spectrum for the gross threshold response of immediate epidermal whitening. In addition, the immediate and delayed gross and histologic changes induced at, above, and below the threshold radiant exposures at all four wavelengths were studied. The action spectrum in the black guinea pigs was consistent with the reported absorption spectrum of DOPA-melanin. Histologically, there was epidermal damage immediately after radiant exposures at and above threshold at all four wavelengths. In addition, radiant exposures greater than threshold caused an immediate decrease in stainable epidermal pigment that was most marked at 435 and 488 nm. The healing response was also wavelength- and dose-dependent. Seven days after above-threshold exposures, there was little epidermal pigment in the 435 nm specimens. As wavelength increased, there was progressively more pigment, and in the 560 nm specimens, the epidermal pigment was equivalent to that seen in nonirradiated black guinea pig control specimens. Seven days after subthreshold radiant exposures, there was increased epidermal pigmentation and melanocytes at all four wavelengths. This was the most pronounced in the 435 nm specimens. There was no observable epidermal damage in albino guinea pig skin.

Animals

Oral methoxsalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. 1977.

Extensive psoriasis in 1,308 patients has been treated two or three times a week with oral 8-methoxypsoralen followed by high intensity, long-wave ultraviolet light (PUVA). Excluding 169 patients still under early treatment, psoriasis cleared in 88% and failed to clear in 3%. One percent dropped out due to complications of treatment, and 8% for other reasons. The twice-a-week schedule was superior for patients with lighter skin types. Once a remission was induced, there was no difference in its maintenance when patients were treated once a week, once every other week, or once every third week. Each of these schedules was superior to no maintenance treatment. Immediate side effects of the 45,000 treatments administered in the first 18 months of this study were uncommon, temporary, and generally mild. No clinically significant changes in laboratory screening or eye examinations attributable to PUVA have been uncovered.

Administration, Oral

Enhancing the carotenoid content of atherosclerotic plaque: implications for laser therapy.

Selective laser ablation of human atherosclerotic plaque is possible because endogenous carotenoid pigments found in atherosclerotic plaque confer a twofold preferential absorption of laser radiation at 450 to 500 nm. In this study, patients with carotid endarterectomy were pretreated with oral beta carotene to determine if the carotenoid content and therefore laser selectivity of plaque could be increased in vivo. Beta carotene-treated patients had a significant, nearly twofold increase in their plaque carotenoid concentration, which increased from 0.22 to 0.40 microgram beta carotene/mg cholesterol. These results suggest that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with doses of oral beta carotene for short periods of time.

Aged

Longwave ultraviolet radiation (UVA, 320-400 nm)-induced tan protects human skin against further UVA injury.

The protective effect of a UVA (320-400 nm) induced tan against cutaneous injury by further UVA-irradiation was studied by evaluating the histopathologic changes in tanned and untanned normal human buttock skin 24 h after exposure to 2 and 4 minimal erythema doses of UVA. In each subject there were fewer polymorphonuclear leukocytes and less endothelial cell prominence and vessel wall necrosis in the UVA tanned skin than in the untanned UVA-irradiated skin. In the tanned control and tanned UVA-irradiated skin there was a prominent mononuclear cell inflammatory infiltrate that was much greater than in untanned skin. In immunoperoxidase stained tissue sections, the mononuclear cells were predominantly T cells, and in all of the specimens the number of phenotypic helper/inducer cells exceeded the phenotypic cytotoxic/suppressor cells. This demonstrates that a UVA tan provides photoprotection against acute UVA exposure. In addition, tanning, with or without further UVA-irradiation, was associated with a mononuclear cell inflammatory infiltrate.

Adult

Pigmented guinea pig skin irradiated with Q-switched ruby laser pulses. Morphologic and histologic findings.

Q-switched ruby laser pulses cause selective damage to cutaneous pigmented cells. Repair of this selective damage has not been well described. Therefore, using epilated pigmented and albino guinea pig skin, we studied the acute injury and tissue repair caused by 40-ns, Q-switched ruby laser pulses. Gross observation and light and electron microscopy were performed. No specific changes were evident in the albino guinea pigs. In pigmented animals, with radiant exposures of 0.4 J/cm2 or greater, white spots confined to the 2.5-mm exposure sites developed immediately and faded over 20 minutes. Delayed depigmentation occurred at seven to ten days, followed by full repigmentation by four to eight weeks. Regrowing hairs in sites irradiated at and above 0.4 J/cm2 remained white for at least four months. Histologically, vacuolation of pigment-laden cells was seen immediately in the epidermis and the follicular epithelium at exposures of 0.3 J/cm2 and greater. Melanosomal disruption was seen immediately by electron microscopy at and above 0.3 J/cm2. Over the next seven days, epidermal necrosis was followed by regeneration of a depigmented epidermis. By four months, melanosomes and melanin pigmentation had returned; however, hair follicles remained depigmented and devoid of melanocytes. This study demonstrates that selective melanosomal disruption caused by Q-switched ruby laser pulses leads to transient cutaneous depigmentation and persistent follicular depigmentation. Potential exists for selective treatment of pigmented epidermal and dermal lesions with this modality.

Animals

Laser lithotripsy: animal studies of safety and efficacy.

The safety and efficacy of pulsed tunable dye laser fragmentation of common bile duct stones was assessed in pigs. Laser pulses were conducted through a flexible quartz fiber that was in direct contact with stones that had been surgically implanted into the common bile duct. All calculi were rapidly fragmented into small pieces without significant damage to the common bile duct. The immediate and delayed effects of pulsed lasers on the common bile duct were also evaluated. The common bile duct demonstrated a high tolerance to laser-induced damage even when the laser was discharged directly into the bile duct wall. These results suggest that laser lithotripsy can be performed in humans with a high degree of safety and efficacy.

Animals

The pulsed dye laser for fragmenting urinary calculi.

The properties of a laser which effect stone fragmentation have been studied. The pulsed dye laser emitting at 504 nm. in one microsecond duration pulses appears to be the optimum out of a wide range of parameters tested. The laser is coupled to a 200 micron core fiber; this complete with its cladding has a total diameter of only 0.25 mm. Most calculi are fragmented by a series of pulses of up to 30 mJ. The system is used by firing bursts of pulses with the fiber actually in contact with the stone. The result is a very controlled fragmentation which is particularly suited to use in the confines of the ureter. This modality of treatment utilises less energy than ultrasound or electrohydraulic probes to fragment a stone and the very fine, flexible fiber represents a considerable miniaturization.

Calcium Oxalate

An assessment of the pulsed dye laser for fragmenting calculi in the pig ureter.

The pulsed dye laser was used to fragment ureteric calculi in 10 pig ureters, compared to electrohydraulic disintegration in six pig ureters. The stones were impacted in the proximal ureter and approached by rigid ureteroscopy. Four ureters did not have stones impacted but had ureteroscopes passed. The stones were fragmented and the particles left to pass spontaneously. The degree of inflammatory reaction was graded at the site of fragmentation as well as in the middle and lower ureter. The degree of inflammation seen at the site of fragmentation was significantly less in the laser group than in the electrohydraulic group (p = 0.0027). It was noted that the degree of inflammation seen in the lower ureter was significantly greater than that seen at the site of fragmentation (p = 0.01), and that this grade of inflammation correlated well with the size of ureteroscope used (p = 0.0026). Further, the degree of dilatation of the ureter and pelvicalyceal system was significantly greater when the larger calibre ureteroscope had been used (p = 0.0056) ranging up to hydronephrosis with flattening of the papillae. If there is any parallel which can be drawn between the pig ureter and the human ureter then it suggests that ureteroscopy is more significant than the modality of fragmentation used. The contribution of the laser may therefore be more by the miniaturization of instrumentation which will be made possible than by any advantage it may have as a fragmenter.

Animals

Tunable pulsed dye laser for the treatment of benign cutaneous vascular ectasia.

A tunable pulsed dye laser emitting at 577 nm and 360 microseconds pulse width was used to treat benign cutaneous vascular ectasias other than port wine stain in 77 patients. Except for leg telangiectasias (34 patients), the overall response was excellent. Forty-two of forty-five patients with hemangiomas, spider nevi, angioma serpiginosum, venous lakes or facial telangiectasias showed excellent results after 1-4 consecutive treatments. Scarring was observed in none of the patients. These results confirm previous data on the use of the tunable dye laser in the treatment of port wine stain, and suggest that 577 nm wavelength and 360 microseconds pulse width allow the selective photothermolysis of vascular cutaneous ectasias with better clinical results than previously reported.

Adult

Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis.

A 2.1-year prospective study of 1373 patients given oral 8-methoxypsoralen photochemotherapy for psoriasis revealed 30 patients with a total of 48 basal-cell and squamous-cell carcinomas. The observed incidence of cutaneous carcinoma was 2.63 (95 per cent confidence limits = 1.91 to 3.90) times that expected for an age, sex and geographically matched population. Relative risk to patients with history of ionizing radiation was 3.68 (99 per cent confidence limits, 2.42 to 8.69). Patients with a previous cutaneous carcinoma had a relative risk of 10.22 (99 per cent confidence limits, 4.78 to 37.08). A higher than expected proportion of squamous-cell carcinomas and an excess of squamous-cell carcinomas in areas not exposed to sun were seen. New patients with known histories of ionizing-radiation exposure or of skin tumors should be given 8-methyoxypsoralen photochemotherapy only if they understand the risks and have disabling psoriasis untreatable by other means.

Administration, Oral

Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen.

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.

Animals