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Purpose To evaluate the effect of age, size, position, and species on the strength of minicapsulorhexes. Setting Surgical Suite and Laser Laboratory, Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. Methods Capsulorhexes 0.7 to 2.3 mm in diameter were made centrally or peripherally in 35 eye-bank eyes and 32 rabbit eyes. A custom-made instrument stretched the capsulorhexes until rupture. Load and stretch at rupture were recorded. Results Maximum load and stretch were 26.3 mN ± 20.3 (SD) and 50% ± 18% for central and 50.8 ± 20.5 mN and 69% ± 17% for peripheral capsulorhexes in eye-bank eyes and 19.8 ± 15.2 mN and 38% ± 13% for central and 13.5 ± 9.5 mN and 30% ± 7% for peripheral capsulorhexes in rabbit eyes. Peripheral capsulorhexes were stronger and more elastic than central capsulorhexes in eye-bank eyes, and maximum load and stretch increased statistically with the capsulorhexis diameter. Conclusions Peripheral minicapsulorhexes were more resistant to rupture than central capsulorhexes in eye-bank eyes, probably because of increased lens capsule thickness at the periphery. An increase in capsulorhexis diameter increased the resistance to rupture.

Toughness in hard biological tissues is associated with fibrous or lamellar structures that deflect or stop growing cracks. In some cases, such as nacreous shell, protein interlayers absorb much of the crack energy. In other tissues, such as tooth enamel, the toughness derives from the mineral microstructure, and the small amount of residual protein apparently has little effect. There have been a number of efforts to make tough synthetic materials using layered structures. In this work, freeform fabrication has been used to make layered structures with a view to introducing similar toughness into brittle materials. Results are presented for epoxy-glass composites with glass fabric interlayers, porous alumina back-filled with aluminium metal, and layered glass-ceramic/silver materials.

Lobar atelectasis is a common complication of cystic fibrosis. The majority of cases respond to intravenous antibiotics and chest physiotherapy. In a subgroup of patients, atelectasis is resistant to medical therapy, and its persistence in the pediatric population is associated with a poor prognosis. Bronchoscopic instillation of human recombinant DNase expanded atelectatic lobes in three children resistant to at least 2 weeks of medical therapy. This method of administration of DNase has been successful in resistant cases of lobar atelectasis in patients with chronic obstructive pulmonary disease, quadriplegia, and status asthmaticus. Purulent cystic fibrosis sputum has a very high DNA content, and DNA has been shown to become more pourable in vitro when treated with rhDNase. Bronchoscopic instillation of rhDNase should be considered in cases of persistent lobar atelectasis unresponsive to medical therapy.

Background and Objective The size (0.5–1.0 cm) of early nonpalpable breast tumors currently detected by mammography and confirmed by stereotactic core biopsy is of the order of the penetration depth of near infrared photons in breast tissue. In principle, stereotactically biopsied tumors, therefore, could be safely and efficiently treated with laser thermotherapy. The aim of the current study is to confirm the controlled heating produced by clinically relevant power levels delivered with an interstitial laser fiber optic probe adapted for use with stereotactic mammography and biopsy procedures. Study Design/Materials and Methods Temperature increases and the resultant thermal field produced by the irradiation of ex vivo (porcine and human) and in vivo (porcine) tissue models appropriate to the treatment of human breast tissue by using cw Nd:YAG laser radiation delivered with a interstitial fiber optic probe with a quartz diffusing tip, were recorded with an array of fifteen 23-gauge needle thermocouple probes connected to a laboratory computer-based data acquisition system. Results By using a stepwise decreasing power cycle to avoid tissue charring, acceptably symmetric thermal fields of repeatable volumetric dimensions were obtained. Reproducible thermal gradients and predictable tissue necrosis without carbonization could be induced in a 3-cm-diameter region around the fiber probe during a single treatment lasting only 3 minutes. The time-dependences of the temperature rise of the thermocouples surrounding the LITT probe were quantitatively modeled with simple linear functions during the applied laser heating cycles. Conclusion Analysis of our experimental results show that reproducible, symmetric and predictable volumetric temperature increases in time can be reliably produced by interstitial laser thermotherapy. Lasers Surg. Med. 26:67–75, 2000. © 2000 Wiley-Liss, Inc.

Background: This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable surficial change, reduced patient trauma, and lowered overall treatment costs. Study Design: Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue. Results: Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin. Conclusions: Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.

Background and Objective: The purpose of this work was to quantify the magnitude of an artifact induced by stainless steel thermocouple probes in temperature measurements made in situ during experimental laser interstitial thermo-therapy (LITT). A procedure for correction of this observational error is outlined. Study Design/Materials and Methods: A CW Nd:YAG laser system emitting 20W for 25–30 s delivered through a fiber-optic probe was used to create localized heating. The temperature field around the fiber-optic probe during laser irradiation was measured every 0.3 s in air, water, 0.4% intralipid solution, and fatty cadaver pig tissue, with a field of up to fifteen needle thermocouple probes. Results Direct absorption of Nd:YAG laser radiation by the thermocouple probes induced an overestimation of the temperature, ranging from 1.8°C to 118.6°C in air, 2.2°C to 9.9°C in water, 0.7°C to 4.7°C in intralipid and 0.3°C to 17.9°C in porcine tissue after irradiation at 20W for 30 s and depending on the thermocouple location. The artifact in porcine tissue was removed by applying exponential and linear fits to the measured temperature curves. Conclusion Light absorption by thermocouple probes can induce a significant artifact in the measurement of laser-induced temperature increases. When the time constant of the thermocouple effect is much smaller than the thermal relaxation time of the surrounding tissue, the artifact can be accurately quantified. During LITT experiments where temperature differences of a few degrees are significant, the thermocouple artifact must be removed in order to be able accurately to predict the treatment outcome. Lasers Surg. Med. 23:94–103, 1998. © 1998 Wiley-Liss, Inc.

Background and Objective As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration. Study Design/Materials and Methods The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected. Results The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was > 200 mJ/cm2. Conclusions PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery. Lasers Surg. Med. 21:179–185, 1997. © 1997 Wiley-Liss, Inc.

BACKGROUND: Tissue damage in corneal transplantation procedures was previously assessed in comparative pilot studies using vacuum-assisted metal blade trephines and a noncontact hydrogen fluoride laser trephine system. With the laser, endothelial damage was less than 20 × 30 µm at the edge of the posterior corneal perforation. METHODS: In this study, a second generation vacuum-assisted Hessburg-Barron trephine was evaluated in full-thickness penetrating trephination performed in 16 rabbit eyes and eight fresh human donor eyes. RESULTS: We found a relatively large, 150micrometer wide, annular zone of endothelial damage on the recipient cornea located 1 .25 mm away from the trephined opening. Our study demonstrates that endothelial damage is linked to the instrument's vacuum fixation ring. CONCLUSION: With this trephine, endothelial damage may be avoided by using partial -depth trephination, filling the anterior chamber with viscoelastic and completing the procedure using a metal blade or diamond knife. ,Refract Corneal Surg 1993;9:255-258.) RÉSUMÉ INTRODUCTION: Les lésions tissulaires au cours de la trépanation cornéenne ont été préalablement évaluées dans une étude pilote comparative entre un laser hydrogène-fluore et des trépans mécaniques à fixations pneumatiques. Avec le laser, les lésions endotheliales sont de l'ordre de 20. à 30 microns de part et d'autre des berges postérieures de la trépanation. MÉTHODES: Dans cette étude, une seconde génération de trépan de Hessburg-Barron à fixation cornéenne a été évaluée après trépanation transfixiante sur oeil de lapin et globe oculaire de donneur. RÉSULTATS: Nous avons observé une zone de lésions endotheliales d'environ 150 microns de largeur sur le versant receveur de la cornée. Nous démontrons que cette lésion endotheliale est liée à la partie externe de l'anneau de fixation. CONCLUSION: Avec ce trépan, les lésions endotheliales peuvant être évitées en procédant à une trépanation des 3/4 de la profondeur de la cornée, puis en complétant l'ouverture de la chambre antérieure avec une lame métallique ou une lame diamant évitant tout effondrement brutal de la chambre antérieure ainsi que les lésions endotheliales observées. (Translated by Jean Marc Legeais, MD, Paris, France.) SOMMARIO PREMESSA: Il danneggiamento tissutafe nei frapianto di cornea è stato valutato in passato in studi-pilota comparativi, utilizzando trapani a suzione con lama di metallo e un sistema laser non a contatto alimentato con fluoruro di hydrogeno. Con il laser, il danno endoteliale era confinato a 20-30 µm rispetto al bordo della perforazione corneale posteriore. METODI: In questo studio, viene valutata una seconda generazione di trapani a suzione di Hessburg-Barron nella trapanazione a tutto spessore eseguita in 16 occhi di coniglio ed in 8 occhi umani di donatore. RESULTATI: Abbiamo riscontrato una zona ad anello relativamente larga, di 150 µm, dì danno endoteliale delia cornea ricevente, localizzata a 1.25 mm di distanza dalla zona trapanata. Il nostro studio dimostra che il danno endotellale è dovuto all'anello di suzione dello strumento.

Several intraocular lens designs and surgical approaches have been proposed to restore dynamic accommodation in the presbyopic eye.1–5 One of the fundamental hurdles in the development of such approaches is the absence of a definitive explanation for the progressive decrease in the accommodative ability with age, which leads to presbyopia. Most likely, presbyopia results from a combination of factors affecting several of the anatomic structures involved in accommodation.6–9 Most of the current theories of presbyopia attribute the loss of accommodation directly or indirectly to age-related changes in the lens itself.7,10–14 Alternatively, Strenk et al.6 recently suggested that presbyopia may also be due to an inward movement of the ciliary muscle that occurs with age and reduces the tension on the zonules when the ciliary muscle is relaxed. Croft et al.15 proposed that a reduction in the forward movement of the ciliary body could contribute to the decrease in lens accommodation with age. The relation between the changes in zonular tension and the resultant changes in lens shape and dioptric power is a key characteristic of these current theories of presbyopia and of the accommodation mechanism in general. The relation between the lens biometric and optical responses has been relatively well characterized in vivo.16–23 In contrast, the relation between the forces of accommodation and the resultant biometric and optical responses remains to be quantified. Unfortunately, there is currently no suitable technique for direct measurements of the accommodation force in absolute, physical units in an in vivo setting. Direct quantitative measurements of the force–power relation have been obtained on human tissue postmortem by simulating the force exerted on the zonules during disaccommodation. The first studies of this kind appear to be those of Pau,24 who simulated the force of accommodation on the lens by attaching weights to the ciliary body. Fisher25 later designed a device that mimicked the pull on the zonules by spinning isolated lenses to produce a centrifugal force and a second, more sophisticated, system26 that simulated accommodation by radial stretching and recorded the changes in lens focal length, curvature, and thickness. Fisher estimated the stretching force indirectly, by comparing the thickness measured in the stretching device with the thickness produced when the same lens was submitted to a spinning experiment. Around the same time, Sunderland and O’Neill27 developed a system that simulated accommodation by applying circumferential forces to isolated feline lenses, using an approach similar to that of Pau.24 More recently, Van Alphen and Graebel28 relied on uniaxial loading experiments to estimate the relative force required to stretch the lens, zonules, ciliary body, and choroid. Pierscionek29,30 and Glasser and Campbell31 have developed experimental setups that stretch lenses to simulate accommodation. Their studies focused on quantifying biometric changes and did not include force measurements. Several other lens-stretching or -spinning systems have been designed recently32,33 (Michail H et al. IOVS 2004;45:ARVO E-Abstract 1726) to study the optomechanical response of the lens. The purpose of the present study was to quantify the power- and diameter-force characteristics of primate lenses by using a lens-stretching system (EVAS; Ex Vivo Accommodation System, designed and constructed in-house at the Ophthalmic Biophysics Center) that allows direct measurements of the force required to stretch the crystalline lens to its unaccommodated state while simultaneously measuring the associated change in lens power and equatorial diameter. Results obtained with rhesus monkey, cynomolgus monkey, and human crystalline lenses are presented.

Purpose: To assess the efficacy of a novel orbital tissue expander (OTE) in treating congenital anophthalmic and microphthalmic infants. Methods: The OTE implant is an inflatable (0.5 to >6cc) silicone rubber globe sliding on a titanium T-shaped bone plate secured to the temporal bone with 1mm titanium screws. In vitro testing was performed to assess injection volume versus diameter measurements to determine consistency between devices, flex fatigue for durability of the implants when compressed, weight change in isotonic saline at 37°C to mimic human body temperature, seal durability by puncturing the globe numerous times while inflating, capacity before rupture to determine the maximum amount of saline it is able to contain, and effective sterilization. Ex-vivo testing was performed for adjustments prior to in vivo study. An OTE was then implanted in five 2-week old kittens (OS only) and inflated in 0.5cc increments. Three control animals received enucleation alone. All 8 animals were followed for 18 weeks and underwent euthanasia for morphological and histopathological analysis. Results: In vitro testing confirmed a

Purpose To determine if an intraocular pressure (IOP)-reducing device containing tungsten powder decreases pressure comparably to the traditional mercury-containing apparatus. Design Prospective randomized, single-blind, controlled, phase I equivalence study. Method At a tertiary care center, both eyes of 24 volunteers with normal IOP were treated with an ocular compression device containing either liquid mercury or tungsten powder. The IOP was measured at baseline and after 10 minutes of ocular compression. Results The mean reduction in IOP was 3.6 mm Hg ± 2.0 with the mercury-containing device and 4.4 mm Hg ± 2.1 with the tungsten-filled apparatus. An equivalence study analysis using a paired t -test and a sequential analysis protocol did not demonstrate a statistically significant difference between the IOP-lowering effects of the two devices. Conclusions The IOP-lowering effect produced by a tungsten powder-filled balloon ocular decompression device compared with a traditional mercury-containing device was not statistically different.

A therapeutic procedure to treat small, surface breast tumours up to 10 mm in radius plus a 5 mm margin of healthy, surrounding tissue using laser interstitial thermotherapy (LITT) is currently being investigated. The purpose of this study is to analyse and model the thermal and coagulative response of ex vivo fibro-fatty tissue, a model for breast tissue, during experimental laser interstitial thermotherapy at 980 nm. Laser radiation at 980 nm was delivered interstitially through a diffusing tip optical fibre inserted into a fibro-fatty tissue model to produce controlled heating at powers ranging from 3.2 to 8.0 W. Tissue temperature was measured with thermocouples placed at 15 positions around the fibre. The induced coagulation zone was measured on gross anatomical sections. Thermal analysis indicates that a finite sum of exponential functions is an approximate solution to the heat conduction equation that more accurately predicts the time-temperature dependence in tissue prior to carbonization (T100 degrees C) during LITT than the traditional model using a single exponential function. Analysis of the ellipsoid coagulation volume induced in tissue indicates that the 980 nm wavelength does not penetrate deep enough in fibro-fatty tissue to produce a desired 30 mm diameter (14.1 x 10(3) mm3) coagulation volume without unwanted tissue liquefaction and carbonization.

Purpose: To develop a technique to assess isotonic solutions for crystalline lens preservation. Methods: BSS, Ringer’s, Dulbecco’s Modified Eagle Medium (DMEM), and TC 199 have been selected for experimentation. Donor human cadaver lenses are extracted by cutting the zonules and vitreous adherences. A custom-made testing cell and modified optical comparator are used for imaging, and the lens diameter and thickness profiles are measured using digital photography and a graphics program. Measurements are taken every 5 minutes for the 1st hour and then every 15 minutes for 4 hrs. The volume of the lens at each interval is approximated, assuming rotational symmetry, by using the equation for the volume of an ellipsoid. The changes in diameter, thickness, and volume versus time are analyzed to compare the effect of each solution. Results: The measurement resolution for the digital technique is 13μm. Lens thickness changed more significantly than diameter and volume. All four solutions produced similar preliminary results with maximum diameter, thickness, and volume changes of approximately -2%, +6%, and +3%, respectively. Conclusion: Shadowphotogrammetry can measure the lens physical dimensions to +/-13um and can be used to determine the effect of preservation media. This technique may be useful for assessing the physical effects of chemical and biological substances on the lens osmotic transport system.

The purpose of these preliminary experiments was to calculate the activation energy and the frequency factor constants of the Arrhenius equation for prediction of the denaturation zone produced by laser interstitial thermotherapy in female breast tissue models. In a first step, pairs of parameters consisting of the activation energy (ΔE) and frequency factor (A) were calculated for different half denaturation times at 50°C and 60°C. Pairs of parameters were eliminated if the calculated time of denaturation at 70°C was excessively short (

Laser interstitial thermotherapy (LITT) is a minimally-invasive laser hyperthermia procedure for the treatment of localized tumours. Real-time monitoring of LITT is essential to control the extent of tumour destruction and ensure safe and effective treatments. The feasibility of using high-resolution digital x-ray mammography to monitor LITT of breast cancer was evaluated. Tissue phantoms including polyacrylamide hydrogel and cadaver porcine tissue were heated using a 980 nm diode laser delivered through optical fibres with diffusing tips. Digital images of the tissue phantoms were recorded with a high-resolution digital stereotactic breast biopsy system during heating. The recorded images were processed and analysed to detect heat-induced changes. No changes were detected during heating of the hydrogel. Pixel-by-pixel subtraction of the initial image from images taken during laser heating shows observable thermally-induced changes around the fibre during laser irradiation that correlate with the thermal denaturation zone observed by gross anatomy. These experiments demonstrate that high-resolution digital x-ray mammography can be used to detect heat-induced tissue changes during experimental LITT in fibro-fatty tissue.

Purpose: the purpose of these experiments was to evaluate the temperature and predicted cell kill distribution during LITT of breast tissue phantoms at 940nm and compare with the results of previous experiments ar 830 nm and 980 nm. Material and Methods: A Dornier Medilas D Skinpulse 940 nm diode lase system coupled to a Dornier D-6111-T2 fiber (Dornier Surgical Products, Phoenix, AZ) was used to irradiate the porcine tissue three times at approximately 5 W for 10 minutes. Results: The initial rate of temperature increase at 940 nm for locations 5, 10, and 15 mm from the fiber axis ranged from 0.076 to 0.142 °C/s, 0.027 to 0.041 °C/s, and 0.008 to 0.013 °C/s, respectively, wile the maximum temperature increase ranged from 37.8 to 46.9 °C, 19.3 to 26.1 °C, 8.6 to 13.0 °C, respectively, temperature curves hed lower slopes at 940 nm than at 830 nm and 980 nm. the maximum temperature increase was higher at 940 nm than at 830 nm. Predicted area of 100% cell kill was approximately 2 cm by 2 cm Conclusion: Results of experiments at 940 nm were more comparable to those at 980 nm than at 830 nm.

The purpose of these experiments was to compare the temperature increase in ex-vivo porcine mammary chain tissue as a breast tissue model during interstitial laser irradiation with diode lasers emitting at 980 nm and 830 nm. Both wavelengths were delivered at 4.0 W for 10 minutes through a diffusing fiber inserted into ex-vivo porcine tissue. The temperature was measured with a set of 15 thermocouples placed 5, 10, and 15 mm from the fiber axis. The initial rate of temperature increase 5 mm away from the fiber tip was higher at 980 nm (0.12 to 0.20 degree(s)C/s) than at 830 nm (0.10 to 0.16 degree(s)C/s). At 10 mm and 15 mm (areas with less radiation), the rate was smaller than at 5 mm (less than 0.06 degree(s)C/s at 10 mm and less than 0.02 degree(s)C/s at 15 mm) for both wavelengths with no significant difference between the 980 nm and 830 nm radiation. The temperature increase at 5, 10 and 15 mm away from the fiber tip after 10 minutes of irradiation was higher at 980 nm (36 to 45 degree(s)C at 5 mm, 14 to 30 degree(s)C at 10 mm and 9 to 17 degree(s)C at 15 mm) than at 830 nm (27 to 33 degree(s)C at 5 mm, 11 to 17 degree(s)C at 10 mm and 8 to 9 degree(s)C at 15 mm) after 10 minutes. These results were found to be highly dependent on tissue composition (muscle vs. fatty tissue).

A tissue phantom for experimental studies in Laser Interstitial ThermoTherapy (LITT) for the treatment of small breast tumors was developed and evaluated. The tissue phantom consists of a polyacrylamide/acrylate hydrogel matrix containing various concentrations of an absorber (Nigrosin) and a scatterer (Intralipid 10% solution), allowing the optical properties to be varied in accordance to experimental need. Temperature measurements in the phantom were performed with a thermocouple array placed symmetrically around the fiber axis during laser irradiation for different output powers, treatment duration, and different concentrations of absorber. A 980 nm diode laser system was used in conjunction with an REM LightStic 360 diffusing tip fiber. The polyacrylamide/acrylate matrix tissue phantom remained stable during laser irradiation and produced reproducible results. The behavior of the temperature curves produced by the phantom during laser irradiation was similar to the behavior of the temperature curves in ex-vivo tissue. Therefore, this tissue phantom can be used as a model for the thermal response of tissue during laser interstitial thermotherapy. The phantom will be used as an experimental model to determine a set of optimum laser treatment parameters for laser interstitial thermotherapy of breast cancer.

The size (0.5-1.0 cm) of early nonpalpable breast tumors currently detected by mammography and confirmed by stereotactic core biopsy is of the order of the penetration depth of near infrared photons in breast tissue. In principle, stereotactically biopsied tumors, therefore, could be safely and efficiently treated with laser thermotherapy. The aim of the current study is to confirm the controlled heating produced by clinically relevant power levels delivered with an interstitial laser fiber optic probe adapted for use with stereotactic mammography and biopsy procedures.Temperature increases and the resultant thermal field produced by the irradiation of ex vivo (porcine and human) and in vivo (porcine) tissue models appropriate to the treatment of human breast tissue by using cw Nd:YAG laser radiation delivered with a interstitial fiber optic probe with a quartz diffusing tip, were recorded with an array of fifteen 23-gauge needle thermocouple probes connected to a laboratory computer-based data acquisition system.By using a stepwise decreasing power cycle to avoid tissue charring, acceptably symmetric thermal fields of repeatable volumetric dimensions were obtained. Reproducible thermal gradients and predictable tissue necrosis without carbonization could be induced in a 3-cm-diameter region around the fiber probe during a single treatment lasting only 3 minutes. The time-dependences of the temperature rise of the thermocouples surrounding the LITT probe were quantitatively modeled with simple linear functions during the applied laser heating cycles.Analysis of our experimental results show that reproducible, symmetric and predictable volumetric temperature increases in time can be reliably produced by interstitial laser thermotherapy.

This report is a summary of the work completed for an LDRD project. The objective of the project was to develop a solid freeform fabrication technique for ceramics and composites from fine particle slurries. The work was successful and resulted in the demonstration of a manufacturing technique called robocasting. Some ceramic components may pow be fabricated without the use of molds or tooling by dispensing colloidal suspensions through an orifice and stacking two-dimensional layers into three-dimensional shapes. Any conceivable two-dimensional pattern may be ''written'' layer by layer into a three-dimensional shape. Development of the robocasting technique required the materials expertise for fabrication and theological control of very highly concentrated fine particle slurries, and development of robotics for process control and optimization. Several ceramic materials have been manufactured and characterized. Development of techniques for robocasting multiple materials simultaneously have also been developed to build parts with unique structures or graded compositions.

Temperature increases and the resultant thermal field produced by the irradiation of ex vivo (porcine and human) and in vivo (porcine) tissue models appropriate to the treatment of human breast tissue using Nd:YAG (cw:60W) radiation delivered with an interstitial fiber optic probe were recorded with an array of fifteen 23 gauge needle thermocouple probes connected to a laboratory computer based data acquisition system. Using a stepwise decreasing power cycle to avoid tissue charring, acceptably symmetric thermal fields of repeatable volumetric dimensions were obtained. Reproducible thermal gradients and predictable tissue necrosis without carbonization could be induce din a three centimeter diameter region around the fiber probe during a single treatment lasting only 3 minutes. The time-dependence of the temperature rise of the thermocouples surrounding the LITT probe were quantitatively modeled with simple linear functions during the applied laser heating cycles.

Layerwise processing methods allow parts to be built with sensors placed within the structure and fully embedded. Blocks of epoxy resin have been formed with embedded optical fibers. The fiber can be used to monitor curing and water uptake of the epoxy using ambient light which passes through the resin, is collected by the fiber and analyzed in a near-IR spectrometer. Piezoelectric polymer films have also been embedded in epoxy and used to monitor curing by changes in response to an external stress pulse. In the long run, it would be desirable to form parts containing many sensors with sensitivity differing environmental variables. Epoxy parts have been freeformed with lines of conducting carbon-filled polymer written into the structure during forming. Where they are at the surface of the part, these materials respond to solvent exposure by a resistance change. Parts have been made with sensors distributed across the surface and their ability to sense gradients of solvent vapor, and so direction to a source, is being tested.

Direct fabrication of alumina parts by robocasting was completed. This method is based on three-dimensional deposition of binderless aqueous alumina slurries. Parts were made with different deposition paths and mechanical·testing performed·to determine the effects •of bead alignment. Properties were also compared to. alumina processed more traditionally

This investigation describes the preclinical development of a laser fiberoptic interstitial delivery system for the thermal destruction of small breast cancers. We propose adaptation of this technology to stereotactic mammographic instrumentation currently employed for diagnostic core biopsy to thermally ablate a site of disease with maximal treatment efficacy, minimal observable superficial change, reduced patient trauma, and lowered overall treatment costs.Laser hyperthermia is a clinical modality that seeks to achieve tumor destruction through controlled tissue heating. The advantage of laser-induced hyperthermia over traditionally used heat sources such as ultrasound, microwave, or radiowave radiation lies in the ability to focus heat localization to the specific tumor tissue site. Neodymium:yttrium aluminum garnet (Nd:YAG) laser light transmitted through a fiberoptic cable to a diffusing quartz tip can induce such temperature increases leading to localized tissue destruction. Because breast cancer occurs with greatest frequency in the mature woman whose breast tissue has undergone glandular involution with fatty replacement, this study concentrates on determining the resultant laser energy heat distribution within fat and fibrofatty tissue. This investigation studied the time-temperature responses of ex vivo human breast and porcine fibrofatty tissue, which led to an in vivo subcutaneous porcine model for the practical demonstration of a laser hyperthermia treatment of small volumes of porcine mammary chain tissue.Spatial recordings of the resultant temperature fields through time exhibited similar, reproducible thermal profiles in both ex vivo human breast and subcutaneous porcine fat. In vivo laser-produced temperature fields in porcine subcutaneous fat were comparable to those in the ex vivo analyses, and showed a histologically, sharply defined, and controllable volume of necrosis with no injury to adjacent tissues or to overlying skin.Interstitially placed, fiberoptically delivered Nd:YAG laser energy is capable of controlled tissue denaturation to a defined volume for the treatment of small breast cancers. It is hoped that this minimally invasive approach, with further investigation and refinement, may lead to the effective treatment of small, well-defined breast cancers that are commonly diagnosed through stereographic mammography and stereotactic core biopsy. The juxtaposition of such a localized treatment modality with these increasingly used diagnostic tools is of considerable promise.

The effect of increased intraocular pressure (IOP) in human cadaver eyes implanted with posterior fixation keratoprosthesis was evaluated. Experiments were carried out with six fresh pairs of human cadaver eyes. One eye of each pair was implanted with a PCL-5 keratoprosthesis (8.60 mm diameter with an optic of 5.60 nm diameter) and the contralateral eye was used as a control. The keratoprosthesis was inserted through a 6 mm diameter opening trephined in the cornea. The resistance of the implanted eye to pressure on `aqueous humor' leak and/or keratoprosthesis extrusion was tested by infusing water at a constant flow of 60 mmHg/second into the anterior chamber. IOP variations were recorded with a transducer connected to a computer. IOP could be increased up to 1520 to 2324 mmHg before aqueous humor leaks occurred. Leaks were always located at the keratoprosthesis-cornea interface. No prosthesis extrusion was observed. Implanted eyes that did not leak aqueous and control eyes tore at the sclera. All posterior fixation keratoprostheses implanted eyes resisted more than 100 times the normal physiological intraocular pressure and on this standpoint is safe. Additional experiments were needed to assess the influence of suture fixation and wound healing in an animal model.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The treatment of primary breast cancer in the last half century has progressively decreased in its disfiguring consequences while maintaining the same level of cure. Extending this philosophy beyond lumpectomy, we propose to treat small primary breast cancers by laser interstitial therapy with minimal possible cosmetic distortion. Our program to achieve that goal has made considerable progress in the preclinical instrument modification and development of physical, tissue, and live animal models. In anticipation of a clinical trial this report updates information presented in 1996.

Piezoelectric polyvinylidenefluoride films have been embedded between layers of composite laminates and cured at temperatures up to 200 degree(s)C. The films retain much of their piezoelectric response upon cooling even though the cure temperature exceeds the melting point of the film. The response of these embedded sensors to impact loading is discussed. We have also used embedded sensors to monitor curing of reinforced low temperature curing epoxy films sandwiched between polycarbonate sheets and subjected to an intermittent external load perpendicular to the surface. The sensor response drops as cure continues since the stiffer resin transfers less load to the film.

A mammographic stereotactic core biopsy instrument can be adapted for laser hyperthermic ablation of breast cancer. The object of this study is to characterize laser endohyperthermia ex-vivo and in-vivo to develop a reliable approach leading to human trials. Light of a Nd:YAG laser passed through a fiberoptic cable to a diffusing quartz tip upon entering surrounding tissues can bring about very high temperatures. This approach concentrating on the heat distribution to fat and fibrofatty tissue, first analyzed a physical model into which both the quartz tip and thermocouple needles were placed. Temperature recordings in volume through a time course demonstrated a progressive thermal increase around the tip. Additional light distribution studies in several media demonstrated the tip's output. The technique transferred to ex-vivo human breast and porcine fibrofatty tissue showed similar findings leading to an in-vivo analysis of subcutaneous porcine fibrofatty tissue. A step-down energy program beginning at 20 watts and decreasing to 15 watts, 10 watts, and to 7 watts, at 30 second intervals was held at the latter power for the remainder of 6 minutes. Three such cycles appear to be the optimal treatment program to develop temperatures between 60 degrees Celsius and 80 degrees Celsius (approximately equals 9700 joules). In-vivo experiments conducted on 5 occasions revealed no skin change. At necropsy the treated tissues demonstrated a circular sharply defined 3 cm volume of necrosis with no change in adjacent tissue. Time-temperature correlations between ex-vivo and in-vivo tissues showed great similarity. Nd:YAG laser energy distributed to a quartz tip through a fiberoptic cable is capable of uniform, complete tissue destruction to a 1 1/2 cm radius with no change beyond that field. This technique with further refinement will be appropriate to the treatment of small breast cancers that have been stereotactically biopsied.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Thermokeratoplasty is a procedure utilizing heat to reshape the surface of the cornea through shrinkage of collagen within the stroma. We have constructed an apparatus for measurements of thermally induced corneal shrinkage. Using this apparatus, we have defined the cornea shrinkage rate and examined the relationships between age, shock temperature, and shock temperature duration to the amount of shrinkage on fifteen corneal strips from Eye-Bank eyes. The results show that less heat energy was required to induce shrinkage in older corneas, that acute shrinkage increases with increasing shock temperature and that shrinkage increases with increasing shock temperature duration.

Choroidal melanoma is the most common primary malignant ocular tumor, yet none of the several available treatments is wholly successful. One therapy recently tried in humans was transpupillary thermotherapy. In this procedure, an 810 nm wavelength laser beam passes through the cornea, aqueous, lens, and vitreous to be absorbed by the tumor in the back of the eye. The results of transpupillary thermotherapy were encouraging, but in some patients only the anterior portion of the tumor was necrosed while the center and posterior portions remained viable. The new treatment modality proposed in this study is similar in concept to transpupillary thermotherapy, but we propose to apply the laser energy through the sclera onto the posterior portion of the tumor, known as the tumor bed. At infrared wavelengths, sclera has excellent transmission characteristics, while most ocular tumors are mildly absorbing. Some of the laser energy is absorbed in the posterior portion of the tumor, but some transmission of the energy through the tumor allows the anterior portion of the tumor to be heated as well. In qualitative terms, this scheme sounds appealing, but it is not yet known whether it will fulfill the quantitative requirements required to achieve the appropriate biological response -- that is, raising the temperature of the tumor to the level which causes cell necrosis (greater than or equal to 43 degrees Celsius) for the appropriate amount of time, without causing photocoagulation of the tumor (approximately equal to 60 degrees Celsius) or damage to the sclera (approximately equal to 55 degrees Celsius). The calculation of temperature distribution is a complicated matter, however, because the actual result of a rise in temperature happens only after the applied laser light has undergone several physical processes.

Freeform fabrication is a family of techniques for preparing solid objects from a 3D computer- based design. The best known method is stereolithography. To date, freedom fabrication has been mainly applied to making prototypes and molds. Similar techniques can be applied to make functional parts of a range materials, including metals and ceramics as well as polymers. In collaboration with Advanced Ceramics Research Corp. of Tucson, Arizona, we have been developing a reactive extrusion method where a part is built up by extrusion of a material stream through a fine needle. A curing reaction at the deposition site allows solid components to be formed. This approach can be readily modified to deposit several materials in the same part and hence to fabricate intelligent materials containing embedded sensors and actuators. This paper describes the application of this method to an epoxy part containing an optical fiber sensor and the response of embedded polyvinylidenefluoride piezoelectric films.

Light of a Nd:YAG laser presented through a fiberoptic cable to a diffusing tip can be adapted to mammographic stereotactic instruments now used for core biopsy in the hyperthermic endoablation of breast cancer. This approach to cancer destruction extends breast preservation to the point of no observable surface skin change. The initial analysis characterizes the effects of laser endohyperthermia in a physical model as well as in tissue, both ex vivo and in vivo, to create a reliable technique that will lead to human trials. A fiberoptic cable with a diffusing quartz tip placed deep within soft tissue can pass light of a neodymium laser and consequent thermal energy for the destruction of surrounding soft tissues. Because breast cancer occurs with greatest frequency in the involuted breasts of women more than 50 years of age and because this tissue is predominantly fibro-fatty in nature, our work has concentrated on model development and the determination of heat distribution and destruction of fat and fibro-fatty tissue. Following the development of a physical model, time-temperature courses were found to be similar in ex vivo human breast tissue and subcutaneous porcine fat. This led to in vivo porcine studies that confirmed similar time-temperature courses. For tissues brought to a range of 60 degrees C to 80 degrees C and sustained for the better part of 20 minutes, gross and histological analyses reveal complete destruction over a 1 1/2 cm radial region around the laser tip. This approach offers great promise for the treatment of stereotactically biopsied small T1 breast carcinomas.

We have found records of 1014 Irish cystic fibrosis patients alive by December 1994, belonging to 883 families. Prevalence in the population is 1/3475 and incidence at birth 1/1461, with a gene frequency of 2.6%. Twenty percent of the patients are aged over 20 years, but at present survival rate falls rapidly after that age. We have identified 85% of the mutations on the CFTR gene in a sample of 29% of the families (506 CF chromosomes). Mutation delta F508 is found in 72% of Irish CF chromosomes, G551D in 6.9%, and R117H in 2%. These are the highest frequencies reported for the latter two mutations world wide. Another seven mutations are found in an additional 4% of CF families. We present new microsatellite haplotype data that could be useful for genetic counselling of CF families bearing some of the 15% of CF mutations still unidentified, and comment on possible uses of our database.

It was found that ablation at radiant exposures below 1 kJ/m2 both for polymethylmetacrylate (PMMA) and for the human cornea is minimal. Above 1 kJ/m2 the ablation rate increased approximately linearly with radiant exposure, the increase being twice as quick for cornea [0.26 (micrometers /pulse)/(kJ/m2)] as for PMMA [0.13 (micrometers /pulse)/(kJ/m2)]. Laminae of PMMA and human cornea of known thickness were ablated with nano second pulses at 213 nm. It is anticipated that the current data will serve as a basis for design of ablation procedures in the cornea.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Twenty children were treated for infective endocarditis (IE) at Our Lady's Hospital for Sick Children during an eleven year period from January 1980 to December 1990. One child had I.E. on two occasions due to different microorganisms. Two had Down syndrome. Congenital heart disease (CHD) was the single most common underlying condition and there was none with rheumatic heart disease. Two had no clinically recognised cardiac anomaly. 13/20 (65%) had acyanotic heart disease and 5/20 (25%) had cyanotic CHD. Among the acyanotic group, ventricular septal defect was most common (6/13); followed by aortic lesions (4/13). There was one case each of coarctation of aorta, patent ductus arteriosus and interrupted aortic arch. Transposition of the great arteries was most common among the cyanotic group (3/5). Four children in the cyanotic group had systemic to pulmonary artery shunts; Blalock Taussig (2), Waterston (1), and aortopulmonary (1). Infection was caused by Streptococcus viridans in 10/20 (50%) and Staphylococcus aureus in 7/20 (35%). Kingella Kingae, Neisseria meningitidis and Streptococcus faecalis were the pathogens in the remainder (15%). Vegetations were detected by echocardiography in 12/19 (63%). The mean duration of antibiotic treatment was 5 weeks (1 day-18 weeks). Surgical intervention was necessary in 4 children (20%). Fifteen children (75%) survived and the mean follow up period was 22.6 months (15 days-6 1/2 years). The overall mortality was 25%.

A robust, low mass carbon‐carbon composite fin structure was developed for application to both low and high temperature radiator designs. The fabrication and test results of three layer structures with unidirectional cores based on vapor grown carbon fibers and on pitch fibers are presented. The development of attachment techniques for this low thermal expansion fin material to titanium heat transport tubing is also described. Results of a three‐dimensional, finite element model which includes three material layers and anisotropic properties are presented and compared with the experimental development work. Promising approaches for fin attachment by brazing are described.

OBJECTIVE--To review the commonest types of cardiac tumours in childhood, their different presentations, and management. DESIGN--A retrospective study of patients with cardiac tumours. SETTING--Cardiac department of a teaching hospital. PATIENTS--Six patients with an age range between one day to three years presented over a period of 10 years. MAIN OUTCOME MEASURES--To determine different presentations, management, and prognosis of cardiac tumours. RESULTS--Three patients presented with an arrhythmia, two with an asymptomatic heart murmur, and the sixth was discovered accidentally. Surgical resection of the tumours was performed in five cases, one patient died during the operation, one developed new tumours after surgery, and the remaining three have had an excellent result. Histology of those operated on showed benign rhabdomyomas in three and fibromas in the other two. The sixth patient was managed conservatively and the multiple tumours he had showed gradual resolution over a period of 10 months follow up. One baby with rhabdomyoma had signs of tuberous sclerosis whereas the others were normal at follow up five months to three years after diagnosis. None of them had a positive family history. CONCLUSION--Cardiac tumours in childhood are extremely rare. The commonest types are rhabdomyomas, then fibromas. Most cases are diagnosed by echocardiography. The prognosis for most patients is excellent.

The effect of novel intraocular implants and refractive surgical techniques on visual acuity and contrast sensitivity is normally determined by the outcome of human clinical trials. Even if intraocular lenses (IOL) are optically `bench tested' prior to implantation, and their contribution to the patient's vision modeled by computer simulation, the clinical outcome is often poorer than mathematically predicted. This is due in large part to the approximations made in the schematic eye used for computation and the biological variables, such as iris geometry, the implant centration, and location with respect to the three-dimensional position of the visual axis and foveal plane. In vitro laboratory optical testing of novel IOLs and lens refractive procedures, such as capsular bag refilling and inflatable balloons, are non-existent. As animal experiments cannot resolve this dilemma, we took a new in vitro approach at assessing the vision of surgically modified and/or implanted human eyes. Using stock parts, a new optical instrument was built to measure the in situ optical resolution and OMTF of fresh cadaver eyes and to comparatively assess novel surgical techniques and implants by pre- and postoperative optical measurements of the retinal image.

Laser surgery on the eye and cornea requires a very high degree of spatial accuracy and reproducibility if refractive outcomes are to be reliable. We have identified and analysed the components of accuracy that need to be addressed, and with the results of this analysis designed and built a computer-controlled laser delivery system for anterior chamber ophthalmic surgery. Design parameters, achievable operating parameters and clinical results are shown and demonstrated.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Photorefractive keratomileusis procedures are currently being evaluated for both direct ablation of the human cornea and for the shaping of synthetic lenticules, with the ArF excimer laser offering the promise of reduced photochemical damage of underlying tissues due to the non-penetrative nature of 193 nm radiation. In order to better consider the possible effects of any secondary luminescence produced by the interaction of 193 nm radiation with these materials, an optical system based on a gated diode array spectrometer was constructed and used to record their fluorescence spectra at known laser fluences. A broadband fluorescence peak centered around 290-330 nm was observed upon irradiation of corneal buttons and collagen-based biopolymers. The optical efficiency of the fluorescence cell was calibrated by the use of a scattering material of known reflectivity allowing estimates of the fluorescence quantum yield of this process to be made.

Between January 1976 and December 1987 42 children with Down syndrome and congenital heart disease underwent cardiac surgery. Four children had two operations. Age at the time of surgery ranged from 11 days to 14 years. The commonest operative procedure was repair of a patent ductus arteriosus. Four patients died post-operatively, two following repair of a complete atrio-ventricular canal defect (CAVD), one following correction of tetralogy of Fallot in association with a CAVD, and a fourth following closure of ventricular septal defect and atrial septal defect. The mortality for those who had open heart surgery was 13.3% and for the series as a whole the mortality was 6.6% over a period of follow-up ranging from two months to four years. A relatively conservative approach has been adopted with regard to surgery, based on the shorter natural expectation of life in Down syndrome, the complexity of many of the cardiac lesions involved and the recognition of the frequency of early intellectual deterioration in Down patients.

Two cases of acute intussusception in older children with cystic fibrosis are reported. Both cases presented with symptoms and signs consistent with meconium ileus equivalent, which delayed the final diagnosis. Both cases required abdominal surgery but made full and uneventful recoveries.

• We used a high-magnification shadow photogrammetric system to evaluate corneal buttons trephined from human donor globes. Whole eyes were trephined with one of five instruments: nonguarded blades held by hand or placed on a handle, Barraquer-Mateus motorized trephine, Hessberg-Barron suction trephine, or Hanna microkeratotrephine. Corneoscleral buttons were punched with one of three punches: Cottingham, Katena Lieberman guillotine, or a modified Lieberman guillotine with an increased impact force (BPEI 2). The precision (how closely buttons approximated the trephine diameter), accuracy (repeatability), acircularity (deviation from roundness), and straightness (verticality of edges) of cut were calculated from the diameter and edge profile angle measurements of buttons cut by the different instruments. These results were statistically compared. The Hanna microkeratotrephine instrument had the greatest precision and accuracy, least acircularity, and straightest edges. Of the corneal punches evaluated, the Cottingham instrument had the greatest precision; however, the BPEI 2 punch cut with the greatest accuracy and the straightest edges.