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Although generally ignored in considerations of laser ablation of tissue, reflectance of laser light from tissue during laser-induced ablation is a potentially important factor in determining ablation efficiency because it determines the amount of laser light coupled into the target. To determine the significance of reflectance changes induced by laser irradiation, we examined the reflectance of liver samples during pulsed holmium laser ablation by placing the target at one focus of an ellipsoidal reflector and a detector at the other focus. The temporal behavior, total reflectance, and effect of multiple pulses were examined. Tissue reflectance as large as 50% was observed during holmium laser irradiation but depended upon laser radiant exposure and number of laser pulses. These measurements suggest that changes in the optical properties of the target during ablation are important and should be considered in detailed modeling of the ablation process.

Previous investigators have determined the optical properties of the liver at isolated wavelengths using various models of light propagation. In this study we derived coefficients for absorption, scattering, and anisotropy for rat liver between 350 and 2200 nm using measurements of integrated reflectance, transmittance, and on-axis attenuation and a diffusion approximation algorithm to solve the 1-D transport equation. These results were used to estimate the effective attenuation coefficient, penetration depth, and temperature rise induced by laser irradiation. The data should be of value to investigators in the field of tissue optics and developers of photomedical applications involving the liver.

Primary isolation of bovine rotaviruses was successfully performed on rolling cultures of MA104 cells following trypsin treatment of fecal samples and cells. Fifty-one fecal samples were obtained from 22 herds affected with naturally-occurring acute diarrhea in calves during a period of over two years. Rotavirus particles were demonstrated in only 10 fecal samples by electron microscopy. Fourteen cytopathic bovine rotaviruses were isolated from positive samples and could be serially cultivated on MA104 cells. The presence of virus was identified by specific immunofluorescence in infected cells. These data indicated that approximately 30% of the herds affected with acute diarrhea in their calves were associated with rotavirus infection.

Previous studies have demonstrated that brief pulses of selectively absorbed optical radiation can be used to confine thermal injury to pigmented targets within tissues. We performed studies in rabbits to assess the usefulness of this technique for selectively coagulating the colonic vasculature. By measuring the optical absorbance of rabbit colon with a spectrophotometer, it was determined that hemoglobin exhibits strong absorption relative to the rabbit colon at a wavelength of 577 nm. Because light must be absorbed to affect tissue, it was hypothesized that laser pulses of this wavelength would selectively damage blood vessels. This hypothesis was tested by examining the effect of 300-microseconds-long 577-nm laser pulses on rabbit colon in vivo. For delivered radiant exposures between 4 and 8 J/cm2, selective coagulation of the colonic vasculature could be produced without damage to the surrounding colon. At greater radiant exposures, vessel hemorrhage was occasionally noted but no transmural thermal injury was produced with delivered radiant exposures as high as 22 J/cm2. This technique may form the basis of a safe and simple treatment of vascular lesions of the colon such as angiodysplasia.

Angiodysplasia, a disease for which the optimal treatment is uncertain, is a frequent cause of lower intestinal bleeding among older patients. To study the natural history of angiodysplasia and compare the efficacy of medical therapy, endoscopic electrocoagulation, and surgery, the course of 101 patients evaluated from 1974 through 1983 at the Massachusetts General Hospital was reviewed. Angiodysplasia caused bleeding that ranged from occult blood in stools to massive hemorrhage and was also observed incidentally in nonbleeding patients. Patients were followed for up to 10 years (mean of 22 months). Rebleeding was defined as evidence of hemorrhage requiring hospital admission, transfusion, or surgery. Thirty-one patients were treated surgically, 19 patients were treated endoscopically, and 36 patients were treated medically. Using life table analysis we observed similar rebleeding rates among medically and endoscopically treated groups. The surgically treated group had a frequency of rebleeding less than half that of the other groups (P = 0.15). A multivariate regression analysis failed to identify any factors other than coagulopathy to explain the different incidence of rebleeding in the patients treated by endoscopic electrocoagulation and surgery.

Transscleral photocoagulation of the ciliary body was achieved in pigmented rabbits using a sapphire probe delivery system coupled to a commercial surgical continuous-wave Nd:YAG laser. This contact technique was found to be effective in reducing intraocular pressure (IOP); greater treatment energies were associated with a more prolonged reduction in IOP, and also correlated with a greater degree of histologic damage to the ciliary body. Treatment energies of 0.8-1.0 Joules produced substantial disruption of the ciliary body. This technique is easy to learn and offers ease in control and placement of the coagulation spots.

The relationship between the antitumor activity and the inhibition of thymidylate synthase after oral administration of 5-FU, FT-207 or UFT was examined. The inhibition of tumor growth on sarcoma-180 after oral administration of 5-FU (20 mg/kg), FT-207 (120 mg/kg) or UFT (30 mg/kg) was 40%, 50% or 70%, respectively. It was found that the inhibition of thymidylate synthase in sarcoma-180 tumor tissue after single oral administration of 5-FU (20 mg/kg), FT-207 (30 or 120 mg/kg) or UFT (30 mg/kg) were about 45%, 20%, 50% or 65%, respectively, but the activities of other enzymes involved in DNA synthesis were not almost inhibited. Thymidylate synthase was inhibited more severely by oral administration of UFT (30 mg/kg). The activities of other enzymes were not inhibited even by continuous oral administration of these drugs for 6 or 11 days. The extent of inhibition of thymidylate synthase seemed to be parallel to that of inhibition of tumor growth. These results suggest that the inhibition of thymidylate synthase by FdUMP converted from 5-FU, FT-207 or UFT plays a major role in their antitumor actions.

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.

Ablation efficiency and residual thermal damage produced by pulsed holmium laser radiation were investigated in vitro for bovine mitral valves and human calcified and noncalcified cardiac valves. Low-OH quartz fibers (200 and 600 microns core diameter) were used in direct contact perpendicular to the specimen under saline or blood. Etch rate was measured with a linear motion transducer. Radiant exposure was varied from 0 to 3 kJ/cm2. For 200-microns fibers, the energy of ablation was approximately 5 kJ/cm3 in noncalcified and 15 kJ/cm3 in calcified valves. Etch rates were dependent on mechanical tissue properties. Maximum etch rate at 1,000 J/cm2 was 1-2 mm/pulse at 3 Hz repetition rate. Microscopic examination revealed a zone of thermal damage extending 300 microns lateral into adjacent tissue. Thermal damage was independent of radiant exposure beyond twice threshold.

The optical absorption coefficients for biliary calculi are important in understanding the mechanism of laser-induced stone fragmentation. However, the heterogeneous composition of calculi and difficulties in producing optically thin samples prevent conventional spectrophotometric measurement techniques from being used. To overcome these limitations, we used a pulsed photothermal radiometry system to measure the optical absorption coefficients and thermal diffusivities of various biliary calculi. In the wavelength range examined (350-1,060 nm), there was strong optical absorption which was greater for pigment stones than for cholesterol stones. The data support the theory that the initiation of the plasma accompanying laser fragmentation of calculi is a thermal process.

Seven monoclonal antibodies with neutralizing activity to equine herpesvirus-1 were produced. These recognized either an 81 kD or an 88 kD viral glycoprotein. Some of the antibodies were shown to protect hamsters in a passive immunization experiment.

Endoscopic hemostatic therapies have become increasingly popular and appear capable of controlling hemorrhage from peptic ulcers and reducing the need for surgery, but many physicians are unsure that the efficacy justifies the cost. In order to study this clinically and economically important issue, we developed a mathematical model to analyze the economics of endoscopic therapy of bleeding peptic ulcers. Endoscopic therapy appears capable of reducing direct hospital costs only when selectively applied to those patients with the highest risk of requiring surgery. Sensitivity analysis identifies efficacy, treatment cost, and the rebleeding rate in untreated patients as the most critical variables affecting the cost of interventional endoscopy. Using neodymium: YAG laser photocoagulation as an example, interventional endoscopy can be cost-effective for treating selected patients with bleeding peptic ulcers. Should other hemostatic devices such as the heater probe and bipolar electrocoagulator prove to be as effective as the laser, even greater cost savings could be achieved.

The use of pulsed laser radiation to recanalize occluded biliary endoprostheses was examined. In vitro measurements demonstrated that a repetitively pulsed organic dye laser transmitted through a small diameter quartz fiber can recanalize an occluded stent in less than 10 sec without causing visible damage to the stent. The laser parameters required for recanalization do not result in significant damage to the common bile duct of a pig even when the laser energy is delivered directly into the tissue, indicating that biliary endoprostheses can be cleared with a large margin of safety. Although the duration of this effect is unknown, pulsed laser radiation is a simple, safe, and effective means of recanalizing occluded biliary endoprostheses and may be an alternative to stent replacement.

The pulsed dye laser (wavelength 504 nm, pulse duration 1 microsecond) is widely used for fragmenting urinary and biliary calculi. In this study, the performance of this laser was compared with pulsed dye lasers producing pulse durations of 8 and 20 microseconds. Fragmentation thresholds and fragmentation rates were measured using a variety of urinary and biliary calculi. Effective fragmentation of urinary and biliary calculi was obtained with 1-microsecond and 8-microseconds pulse durations, but satisfactory fragmentation could not be achieved at 20 microseconds.

A pulsed holmium laser (wavelength 2.1 microns, pulse duration 250 microseconds) was used to ablate rabbit liver, stomach, and colon in vivo. Microscopic examination of the tissues revealed zones of thermal damage extending 0.5-1.0 mm from ablation sites. In addition, ablation rates were measured using a mass loss technique and found to increase linearly with delivered radiant exposure. The threshold radiant exposure for ablation was calculated to be 50 J/cm2 with a heat of ablation of 7000 J/cm3. Because the holmium laser produces less thermal necrosis than current endoscopic laser systems, such as the continuous-wave neodymium:YAG laser, and because the ablation rate can be precisely controlled, the holmium laser shows promise as an alternative method for endoscopic removal of tissue.

Fourteen cytopathic bovine rotaviruses isolated from naturally affected calves were characterized serologically by serum neutralization. Antisera were prepared in guinea pigs against the three isolates and the Lincoln strain of bovine rotavirus. These four rotaviruses were segregated into at least two distinct serotypes (designated types 1 and 2) by serum neutralization. The remaining 11 isolates were also placed into two groups according to neutralization specificity by using the antisera against types 1 and 2 bovine rotavirus. When colostrum-deprived calves were experimentally inoculated with type 1 or 2 bovine rotavirus, respectively, the calves produced neutralizing antibodies against the inoculated serotype but not against the other serotype. Calf sera obtained from six herds with naturally occurring rotavirus infections possessed neutralizing antibodies against type 1 or 2 or both. Thus, distinct serotypes of bovine rotavirus were demonstrated by serum neutralization. The possible role of serotypes in the epidemiology of rotavirus infection among bovine species is discussed.

The feasibility of using lasers to fragment biliary calculi was examined in vitro. Flashlamp-pumped tunable dye lasers were coupled to small-diameter flexible quartz fibers that were placed in direct contact with biliary calculi. The minimum laser energy necessary to damage a calculus was measured for wavelengths between 450 and 700 nm and for pulse durations between 0.8 and 360 microseconds. This threshold energy increased with increasing wavelength but was not significantly affected by pulse duration. Cholesterol stones had uniformly higher thresholds than pigmented ones. When a repetitively pulsed laser was used, complete fragmentation required fewer than 500 pulses and fragments were predominantly less than 2 mm. The pulsed dye laser can effectively fragment biliary calculi when transmitted through a small-diameter quartz fiber and may be useful as a tool for fragmenting retained common duct stones.