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Biomedical subjects

J R Blair

Publications and source records attributed to J R Blair.

18 recordsLinked to original sources

Thermoradiotherapy of intraocular tumors in an animal model: concurrent vs. sequential brachytherapy and ferromagnetic hyperthermia.

PURPOSE: To compare concurrent vs. sequential ferromagnetic thermoradiotherapy in vivo. METHODS AND MATERIALS: Greene melanomas were implanted subretinally in rabbits and observed until they were 3-5 mm in diameter. Episcleral plaques were assembled with 125I seeds for radiation therapy, or with ferromagnetic (FM) thermoseeds and nonradioactive I seeds for hyperthermia. Rabbits were implanted by centering a plaque over the intraocular melanoma. After a given dose of radiation had been delivered, the plaque was removed and a nonradioactive plaque containing FM thermoseeds was inserted into the same extrascleral space. One hour later, hyperthermia (46-47 degrees C at the plaque-scleral interface) was initiated and continued for a period of 1 h by placing the rabbits in a magnetic induction coil powered to 1200 W. Tumor size was determined at 1- to 2-week intervals by indirect ophthalmoscopy and by ultrasound. RESULTS: Dose-response analysis of 27 treated eye melanomas showed 50% local tumor control at 43 Gy for 125I alone and 29.4 Gy for 125I followed by FM hyperthermia. The thermal enhancement ratio was 1.4. CONCLUSION: Comparison with a previously published thermal enhancement ratio of 4.4 (for concurrent 125I and FM hyperthermia) leads us to conclude that thermal enhancement of 125I brachytherapy is more efficient in this tumor model system when hyperthermia is delivered during, rather than after, the irradiation process.

Animals↗

Comparison of scleral tensile strength after transscleral retinal cryopexy, diathermy, and diode laser photocoagulation.

OBJECTIVES: To determine the effect of transscleral diode photocoagulation on the tensile strength of sclera in an experimental rabbit model and to compare it with that of transscleral cryotherapy and diathermy. METHODS: Twenty-four Dutch-belted rabbits received one of the following three treatment modalities in one eye: (1) transscleral cryotherapy, (2) transscleral diathermy, or (3) transscleral diode laser photocoagulation. The opposite eye served as a paired control. Tensile strength measurements of scleral strips excised from areas of treatment were obtained 6 weeks later. RESULTS: No statistically significant difference in mean tensile strength was observed between eyes receiving transscleral cryopexy (n = 7) or transscleral diode photocoagulation (n = 8) and their corresponding, paired, control eyes. In contrast, transscleral diathermy reduced mean scleral tensile strength to 26% of that of the paired control eyes (n = 8, P = .0001). CONCLUSIONS: In this rabbit model, scleral weakening is significant following transscleral diathermy while transscleral cryopexy or transscleral diode photocoagulation produces no significant weakening relative to paired, untreated controls.

Animals↗

Histopathologic study of autosomal dominant vitreoretinochoroidopathy in a 26-year-old woman.

The clinicopathologic findings were obtained from enucleated eyes, obtained post mortem, of a 26-year-old woman with autosomal dominant vitreoretinochoroidopathy. Light microscopy demonstrated atrophic, disorganized peripheral retina with retinal blood vessels obscured by pigmented cells surrounding periodic acid-Schiff-positive deposits. Peripheral retinal pigment epithelial cells showed multilayering and pigmentation, with a thickened basal lamina. By electron microscopy, the peripheral retinal vessel endothelium was replaced by an arrangement of morphologically polarized pigmented cells of presumed retinal pigment epithelial origin oriented with their basal surfaces toward a fibrillar matrix occupying the vessel lumen. The similarity of the findings in this young patient to those of an aged patient described previously suggest that autosomal dominant vitreoretinochoroidopathy is an early-onset dystrophy of the peripheral retina with minimal subsequent progression, characterized by a retinal pigment epithelial response that includes marked intraretinal migration and extracellular matrix deposition.

Adult↗

Cardiac electrophysiologic effects of fentanyl and sufentanil in canine cardiac Purkinje fibers.

The electrophysiologic effects of high concentrations of the opioid agonists, fentanyl and sufentanil, on isolated canine cardiac Purkinje fibers were studied. Changes in action potential parameters were examined at the following concentrations: fentanyl 94.6 nM, 0.19 microM, and 0.95 microM; sufentanil 8.6 nM, 86.4 nM, 0.17 microM, and 0.26 microM. Naloxone 5.5 microM was administered after maximal changes were induced by fentanyl in order to explore the possibility of an opioid receptor interaction. Action potential parameters measured were Vmax of phase 0, amplitude, overshoot, maximum diastolic potential, action potential duration at 50%, and 90% repolarization and membrane responsiveness. Fentanyl 0.19 microM and sufentanil-0.17 microM caused a significant lengthening of action potential duration at 50 and 90% repolarization, 6.4% and 7.3%, and 10.2% and 12.4%, respectively, P less than 0.05. Other action potential parameters were not significantly affected by the opioids. Naloxone 5.5 microM alone did not alter action potential characteristics and failed to reverse action potential prolongation produced by fentanyl. The authors suggest that fentanyl and sufentanil prolong action potential duration in canine cardiac Purkinje fibers via direct membrane actions.

Action Potentials↗

Retinal transplants and optic nerve bridges: possible strategies for visual recovery as a result of trauma or disease.

From the review of the current literature it is quite evident that some exciting prospects are on the horizon which will help to better explain the development and functioning of the visual system. In addition, the new technology of CNS tissue grafting coupled to other newly emerging technologies (i.e., microsurgical, microinjection, and micromanipulative techniques coupled with our knowledge of immunosuppressive methods) will allow for a realistic approach in exploring possible strategies for visual recovery as a result of trauma or disease within the near future. One specific area of research that hopefully will emerge from this new body of knowledge comes from the realization that at the present time there is no effective therapy for practically all types of hereditary retinal degenerative disorders in man. It would seem most appropriate to take advantage of the new neuronal transplantation technology mentioned in this article and the availability of hereditary retinal degeneration models in the hope of developing new methods for a therapeutic approach to this problem. Such an approach could involve replacing the abnormal, absent, and/or lost host retinal cells with tissue from healthy donors by means of a grafting technique with the goal of arresting and/or reversing the disease process. Of course, this is but one example of the many challenges in this area of research which increasingly appear to be within our grasp.

Animals↗

Optimum conditions for successful transplantation of immature rat retina to the lesioned adult retina.

We have previously reported the successful transplantation of neonatal rat retina to the lesioned retinas of adult host rats. The current studies provide a much more in-depth evaluation of the optimal conditions under which successful grafting can be achieved. Utilizing the same surgical approach and techniques as in our earlier studies, the variables of host lesion conditioning and donor age were investigated. The grafts were evaluated for survival, location, and degree of achievement of selected histological characteristics. The latter category was organized into an evaluation index (E.I.) which provided a consistent system of scoring for purposes of inter-group comparisons. In order to study the effects of lesion conditioning, neonatal grafts were delivered into fresh (0), 1, 2, 4, and 8 week conditioned lesions. Excellent survival and placement were observed at all conditioning times examined. Even the E.I. failed to reveal any statistically significant differences among the lesion conditioning groups. However, there was the suggestion of reduced scarring in the older, more stable lesion groups. The second portion of the study, dealing with donor age, involved the transplantation of E14, E16, E20, PN1, and PN10 retina into freshly lesioned sites in the host retina. Again the result was excellent overall graft survival and placement in all groups. The E.I. score, however, revealed highly significant differences between PN10 grafts and those from all other groups tested. These differences were revealed for all histological criteria with the exception of non-neuronal barrier formation. These studies show the utility of the current model for the repair of retinal lesions over an extended post-traumatic period as well as revealing the wide developmental window for harvesting retinal tissue for the purpose of intravitreal transplantation.

Aging↗

Peripheral nerve implant effects on survival of retinal ganglion layer cells after axotomy initiated by a penetrating lesion.

A lesion paradigm involving a small penetrating incision made through the sclera, choroid and retina of the adult rat eye creates a unique environment for the study of the damaged retina. More specifically, the dependable formation of a small focal retinal lesion makes this an ideal model for the determination of conditions that may stimulate retinal regeneration, wound repair and/or cell survival. Our previous studies have indicated that the placement of a desheathed peripheral nerve implant (PNI) into the lesioned adult rat eye: (1) initiated the rescue of retinal tissue that would normally die due to trauma; and (2) maintained the thickness and organization of most retinal layers adjacent to the lesion site, particularly the retinal ganglion cell layer (RGL). We report in the present work that a more detailed analysis of the RGL revealed a significant increase in the survival of axotomized neurons within this layer in the presence of a PNI over an 8-week post-implantation period. More specifically, there was a 60% loss of control RGL cells axotomized by the lesion 3 weeks previously in contrast to only a 30% loss in those tissues exposed to a PNI. Additional RGL cell size distribution studies point to the fact that the PNI appeared to affect the increased survival of cells greater than or equal to 70 micron2. Also the PNI effect demonstrated a specificity of response when tested against the influence of a tendon or suture implant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A prospective study of giardiasis and water supplies in Colorado.

A prospective study of 484 visitors to Vail and Aspen/Snowmass, Colorado, was conducted to determine the risk of acquiring giardiasis. Of the 259 visitors to Vail, no cases of giardiasis were confirmed and only one of 12 water filtrates were positive for Giardia cysts. Of 225 visitors to Aspen/Snowmass two cases of giardiasis were confirmed and 12 of 20 water filtrates were positive for Giardia cysts. The regular occurrence of Giardia cysts in Aspen and Snowmass water was associated with lower rates of giardiasis acquisition than reported during outbreaks of waterborne giardiasis.

Colorado↗

Peripheral nerve implantation into a penetrating lesion of the eye: stimulation of the damaged retina.

A small penetrating incision made through the sclera, choroid and retina of the adult rat eye creates a unique lesion paradigm. More specifically, by one to two weeks after the incision the wound area stabilizes, leaving a clean inflammation-free degeneration gap or 'die-back zone' (200-300 microns wide) between the cut edges of the intact retina. The dependable formation of a small focal retinal lesion makes this an ideal model for the determination of conditions that may stimulate retinal regeneration, wound repair and/or cell survival. In other words, material may be injected or placed into the lesion site and the retina analyzed for responses to such treatments. Accordingly, the placement of a desheathed peripheral nerve implant (PNI) into the lesioned adult rat eye initiated the rescue of retinal tissue that would normally die due to trauma. In addition, the cut edges of the retina just lateral to the PNI actually touched and fused together, thus demonstrating a wound closure or healing phenomenon which was not observed in control situations. Also the thickness and organization of most retinal layers at the site of lesion were maintained at intact control levels in the presence of the PNI. However, controls not containing the PNI exhibited dramatic reductions in total and individual retinal layer thickness for up to approximately 500 microns lateral to the lesion site. Through the use of a double lesion paradigm, it was also determined that the wound repair phenomena could be influenced over a distance by (a) putative diffusable factor(s) elaborated or initiated by the PNI.

Animals↗

Newborn rat retinal cells transplanted into a retinal lesion site in adult host eyes.

We report the successful grafting of embryonic (newborn) rat retina into a lesion site (die-back zone) of an adult retina with a corresponding 90-100% survival rate. A penetrating lesion was made through the sclera, choroid and retina on the superior surface of the host eye and closed with microsutures. The lesion site was either allowed to stabilize for 5 weeks or immediately received a retinal graft. Retinas were removed from 1-day-old neonate donors, drawn through a small gauge needle and injected into the fresh or stabilized lesion site. Host animals were sacrificed and the eyes processed for light, scanning- and transmission-electron microscopic analysis at 1, 2, and 4 weeks after grafting. Analysis of sections through grafted tissue within the lesion site revealed that the neonatal cells not only survived at all times examined but also continued their development reminiscent of normal littermate controls. Examination of 4-week grafts revealed a laminar pattern similar to adult ganglion cell, inner plexiform, inner nuclear, and outer plexiform layers as well as developing photoreceptor neurons. The grafted tissue could easily be delivered into the retinal lesion site where it established a pattern of retinal layers within the die-back zone. In addition, the plexiform areas of the graft appeared to integrate with those of the host. The age of the adult retina lesion transplantation site had little effect on the graft/host integrative phenomenon. These studies show for the first time a method utilizing immature retinal grafts to fill and/or bridge the wound area of the lesioned adult mammalian retina. These observations also demonstrate the utility of using this model for the study of numerous retinal developmental phenomena.

Animals↗

Responses to exercise in children with sickle cell trait.

To determine whether responses to exercise in children with sickle cell trait (AS) are different from those of normal children, we performed dynamic cycle ergometer stress testing in 48 children with AS, aged 4 to 21 years. We compared these data with those obtained from 184 healthy black children. No subject with AS demonstrated definite ischemia on the exercise ECG, but four (8.3%) had equivocal ischemia. Population statistics derived from Z score values showed that the subjects with AS had lower exercise values for heart rate and work load than the controls. The BP response to exercise was normal in subjects with AS. Since no ischemia or complications occurred, exercise in subjects with AS appears to be safe. Further studies are needed to define the mechanism for the impaired pulse rate and work load variables.

Adolescent↗