Biomedical subjects

P K Yu

Publications and source records attributed to P K Yu.

At least 19 recordsLinked to original sources

PubMed2004

Retinal toxicity of intravitreal tenecteplase in the rabbit.

AIM: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. METHODS: Tenecteplase (25-350 micro g in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. RESULTS: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 micro g. At a dose of 150 micro g ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 micro g and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. CONCLUSION: A dose of 50 micro g tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion.

Animals↗

PubMed2001

Spatial resolution of a stacked radiochromic film dosimeter.

PURPOSE: The spatial resolution of stacked radiochromic film dosimeters, which have increased sensitivity from a single layer radiochromic film detector, has been studied. METHODS: A 5-layer film which can easily be constructed provided a 4.3-times increase in sensitivity over a single layer film at 670 nm readout wavelength which meant that doses as low as 0.6 Gy could be measured with an accuracy of +/-4% with the stacked dosimeter. The spatial resolution was tested by comparison of the 80%/20% penumbral widths of a 5 x 5 cm 6 MV X-ray field. RESULTS: The MD-55-2 film measured the penumbral width as 3.0 mm whereas the 5-layer stack dosimeter measured the same penumbra as 3.2 mm. CONCLUSION: The stack dosimeter can provide useful in vivo information such as the position of a diverging beam edge for treatments around critical structures such as eyes during the first fraction of treatment.

Film Dosimetry↗

PubMed2001

Pathogenesis and intervention strategies in diabetic retinopathy.

Diabetic retinopathy is the leading cause of new blindness in the working-age population. If improved treatment regimens are to be developed it is crucial that the underlying pathophysiological mechanisms responsible for diabetic retinopathy are better understood. The multifactorial nature of the many pathways implicated in diabetic retinopathy requires a very detailed approach to elucidate the key mechanisms involved and their interactions in order to develop logical strategies aimed at therapeutic intervention. Fortunately, the streptozotocin rat model of diabetes displays many of the morphological and functional changes to the retinal vasculature that are evident in human diabetic retinopathy. This study reviews some of the recent experimental work by the authors in the streptozotocin rat, compares their findings to the human pathology and outlines potential new avenues for therapeutic intervention. In particular the improved understanding of which layers of the inner retina have the most stringent metabolic demands has helped identify which retinal layers are most susceptible to metabolic or hypoxic/ischaemic insult. It is concluded that improved treatment outcomes may ensue if the therapy is targeted at the appropriate tissue at specific stages of the disease.

Animals↗

PubMed2001

Radiochromic film dosimetry in water phantoms.

Radiochromic film is investigated for use in dosimetry in water phantoms as opposed to solid phantoms. Investigations are performed to measure the penetration rates of water into radiochromic film and to assess the effects on optical density that this penetration causes. The effects of film orientation during irradiation in water are also tested. Results show that only a small penetration rate is seen from water into the film which only affects the outer areas of the film, with penetration being less than 0.5 mm per hour. The optical density measurements of the film at 660 nm remain unchanged in the unaffected regions of the radiochromic film. Minimal effects are seen due to beam orientation in a water phantom as opposed to solid water phantoms in which an overestimation in dose is normally seen for parallel irradiation. Radiochromic film seems to be an adequate detector for dosimetry in a water phantom where high spatial resolution is needed and angle of beam incidence at the point of interest is important.

Dose-Response Relationship, Radiation↗

PubMed2001

Use of multiple layers of Gafchromic film to increase sensitivity.

This note investigates the increase of the sensitivity of radiochromic film by layering the film together. Investigations with up to five layers of radiochromic film placed together as a single dosimeter have allowed accurate two-dimensional dosimetry at low radiotherapy doses. The sensitivity of the response of the layered film increases with the number of layers, with the five-layer dosimeter increasing the change in optical density by 4.3 +/- 0.2 times that for a single layer film at 670 nm readout wavelength. Measurements in the penumbral region of a 6 MV x-ray beam show that the spatial resolution is slightly reduced with the layered film. The distance across the region from 20 to 80% of the maximum dose at the beam edge (20/80% penumbra) measured at 1.5 cm depth was measured as 3.1 +/- 0.3 and 3.5 +/- 0.3 mm for one and five layers, respectively. Thus no major reduction in spatial resolution was found by layering the film to five layers but the sensitivity was increased by 430% at 670 nm readout wavelength.

Particle Accelerators↗

PubMed2001

Validation of blood product irradiation doses.

Dosimetry of blood irradiation using x-ray beams on a medical linear accelerator has been studied to evaluate the accuracy of a diode detector and the delivery achievable. Variations in applied doses for a standard dual field 6 MV x-ray are measured with a commercial diode detector. Results show that the diode detector measured applied in vitro doses to within 5.4% (2 standard deviations (2 SD)) of those calculated with a collapsed-cone convolution treatment-planning computer for a sample of 100 blood irradiations. Experiments involving the packing procedure of the blood products in the blood box were performed. It was found that a large proportion of the variation in the predicted and measured dose was due to the compacting of the scatter material at the base of the blood box (over a 6 month period) producing a higher density below the blood than originally scanned; hence an overall reduction of delivered dose was observed. The diode measurements (which provide an immediate printout) are recommended in conjunction with a film dosimeter such as radiochromic film, which still provides a back-up dose monitor and a visual reminder that the blood has been irradiated. It is also recommended that the blood box be completely evacuated of all scatter material every month and the base be carefully repacked to provide uniform scatter material.

Blood↗

PubMed2001

Visible dye light absorption properties of processed radiographic film.

The visible absorption spectra of Kodak X-Omat V film, which had been exposed to various doses of radiation, have been investigated to analyse the dosimetry characteristics of the film with various densitometers. Common densitometers can use fluorescent light (broad band visible), helium-neon (632 nm) or other spectra of specific bandwidth. The visible absorption spectra show a slight peak in absorption at approximately 580 nm and another at 630 nm caused by the base material of the film. The optical density of the film is shown to increase almost equally at all wavelengths within the visible region with increases in applied dose. By evaluating the results for the broad band spectra and specific wavelength optical density it is shown that a relatively uniform response is expected for all densitometers that work within the visible region as well as in selected infrared wavelengths. Thus similar optical density to dose response curves for X-Omat V radiographic film should be produced for all types of densitometers, no matter what type of light source is used for illumination. Thus it is most efficient to have a densitometer with a light source suitable for radiochromic film, which can also be used with radiographic film.

Absorption↗

PubMed2001

Tetrahydrobiopterin reverses the impairment of acetylcholine-induced vasodilatation in diabetic ocular microvasculature.

The purpose of this study is to test whether tetrahydrobiopterin, an essential cofactor in nitric oxide synthesis, can reverse endothelium dysfunction in diabetic ocular circulation. Using the streptozotocin-induced diabetic rat model and the isolated perfusion eye technique, the response to the acetylcholine (an endothelium-dependent vasodilator mediated by stimulated nitric oxide release) induced vasodilatation of the diabetic ocular vasculature before and after tetrahydrobiopterin administration was compared. Age matched normal rats were used for reference response. Six streptozotocin-induced diabetic rats and eleven control rats at 21.5 +/- 0.2 weeks and 21.2 +/- 2.1 weeks postinduction, respectively, were used. The dose response curve from the diabetic eyes was found to be significantly different from that of the control eyes (p < 0.001) with significantly reduced responses to 10(-4)M acetylcholine. After 30 min of administration of tetrahydrobiopterin to the diabetic eyes, however, the acetylcholine-induced vasodilatation response was significantly (p < 0.001) increased compared with the response prior to tetrahydrobiopterin administration. The vasodilatory response in the diabetic eyes after tetrahydrobiopterin administration was at a level that was comparable with the control response (p = 0.742). We have shown that acute administration of tetrahydrobiopterin is effective in reversing to control level the impaired acetylcholine-induced vasodilatory response at 21.5 +/- 0.2 weeks postinduction. Our result suggests that a decreased level of tetrahydrobiopterin in the eyes of the streptozotocin-induced diabetic rats may be responsible for the ocular vascular endothelium dysfunction.

Acetylcholine↗

PubMed2000

Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications.

PURPOSE: The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. RESULTS: With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. CONCLUSION: Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy.

Adolescent↗

PubMed2000

Assessment of large single-fraction, low-energy X-ray dose with radiochromic film.

PURPOSE: To investigate the accuracy of in vivo dosimetry using radiochromic film for large single-fraction, low-energy irradiations. METHODS AND MATERIALS: Gafchromic MD-55-2 radiochromic film and LiF thermoluminescent dosimeters (TLDs) were placed in vivo on 25 patients to ascertain their effectiveness for assessment of dose. All patients received 10 Gy single fractions at energies ranging from 100 kVp (half-value layer [HVL] = 3.5 mm Al) up to 250 kVp (HVL = 2.3 mm Cu). Effects of small air gaps were also investigated using LiF TLDs and radiochromic film. RESULTS: Radiochromic film adequately measured applied dose for 25 patients in vivo with a standard deviation of 5.5% from prescribed dose. LiF TLDs recorded a standard deviation of 4.1% from measured to applied dose. Small air gaps which can be created under the film or TLDs during in vivo dosimetry were shown to have a measurable but minimal effect on results for gaps less than 5 mm. CONCLUSIONS: Gafchromic film has adequately measured applied dose in vivo at low energy for large 10 Gy single-fraction irradiation.

Fluorides↗

PubMed2000

Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats.

BACKGROUND: This long-term (2.3 years) study determines the temporal relationship between systemic glucose levels and the progression of diabetic retinopathy during the natural course of streptozotocin-induced diabetes in rats. METHODS: Of 367 rats, 200 were randomly assigned into a group injected with streptozotocin (50 mg.kg(-1)) and 167 into a control group. Subsets of the rats were killed at 6, 28, 40, 65, 90 and >100 weeks post induction to allow the severity of retinopathy to be assessed quantitatively and qualitatively by trypsin digests of the retinal vasculature. Concurrently blood glucose, body weight and death rate were monitored. RESULTS: Three glycemic phases were observed in the streptozotocin rats. In phase 1 (0 to 36-40 weeks) hyperglycemia was established and maintained. In phase 2 (36-40 to 84-90 weeks) normoglycemia was restored, and maintained during phase 3 (84-90 to 120 weeks). Control rats were normoglycemic throughout. The retinal microangiopathy was marked at 28 weeks during phase 1, developed more slowly in phase 2 and continued to worsen with loss of capillaries in all retinas and saccular microaneurysms present in 50% of retinas in phase 3. Cumulative death rate in streptozotocin rats also followed three phases, with maximum vulnerability occurring between 28 and 40 weeks. Body weight was significantly lower in streptozotocin rats throughout, increasing slowly in phase 1, then more rapidly during and after spontaneous glycemic recovery. CONCLUSION: The worsening retinopathy, despite sustained recovery to normoglycemia, implies that good glucose control alone does not stop the progression of the retinal microangiopathy at this late stage.

Animals↗

PubMed2000

Blood irradiation with accelerator produced electron beams.

Blood and blood products are irradiated with gamma rays to reduce the risk of graft versus host disease (GVHD). A simple technique using electron beams produced by a medical linear accelerator has been studied to evaluate irradiation of blood and blood products. Variations in applied doses for a single field 20 MeV electron beam are measured in a phantom study. Doses have been verified with ionization chambers and commercial diode detectors. Results show that the blood product volume can be given a relatively homogeneous dose to within 6% using 20 MeV electrons without the need to rotate the blood bags or the beam entry point. The irradiation process takes approximately 6.5 minutes for 30 Gy applied dose to complete as opposed to 12 minutes for a dual field x-ray field irradiation at our centre. Electron beams can be used to satisfactorily irradiate blood and blood products in a minimal amount of time.

Blood↗

PubMed2000

Verification of lung dose in an anthropomorphic phantom calculated by the collapsed cone convolution method.

Verification of calculated lung dose in an anthropomorphic phantom is performed using two dosimetry media. Dosimetry is complicated by factors such as variations in density at slice interfaces and appropriate position on CT scanning slice to accommodate these factors. Dose in lung for a 6 MV and 10 MV anterior-posterior field was calculated with a collapsed cone convolution method using an ADAC Pinnacle, 3D planning system. Up to 5% variations between doses calculated at the centre and near the edge of the 2 cm phantom slice positioned at the beam central axis were seen, due to the composition of each phantom slice. Validation of dose was performed with LiF thermoluminescent dosimeters (TLDs) and X-Omat V radiographic film. Both dosimetry media produced dose results which agreed closely with calculated results nearest their physical positioning in the phantom. The collapsed cone convolution method accurately calculates dose within inhomogeneous lung regions at 6 MV and 10 MV x-ray energy.

Algorithms↗

PubMed2000

Ultraviolet radiation dosimetry with radiochromic film.

Radiochromic film is tested for its broad-band response to ultraviolet (UV) B (290-320 nm) and A (320 nm400 nm), visible and infrared radiation produced by a solar simulator and examined for dosimetry in ultraviolet radiation. Results show that MD-55-2 radiochromic film in solar and fluorescent light sources responds almost exclusively to broad-band UVA radiation with negligible colouration from UVB, visible and low level infrared radiation. A second order polynomial function approximates the change in optical density at 660 nm wavelength for film colouration with exposure to UVA from white light fluorescent and solar UV with exposures measured with a dedicated UVA dosimeter. Using a double exposure technique as used in radiation dosimetry where the film is firstly irradiated to a known UV dose, radiochromic film can be used as a quantitative measure of UVA exposure.

Calibration↗

PubMed2000

Acetylcholine-induced relaxation in rat ocular vasculature.

Endothelial cell function is often evaluated by the assessment ofendothelium-dependent relaxation to acetylcholine. The purpose of this study was to characterize the acetylcholine-induced vasodilator responses in the intact ocular vasculature tree in isolated perfused rat eyes. At a fixed perfusion flow rate (5 microl/min), the resultant perfusion pressure reflected the total vascular resistance of the perfused vasculature. The baseline vascular resistance, and hence perfusion pressure, was manipulated by perfusion with high concentrations of potassium Krebs (60, 90, or 124 mM). The response to bolus administration of acetylcholine (10(-8) to 10(-4) M) was then assessed over a range of perfusion pressures. Acetylcholine induced a dose-dependent relaxation response which was larger in magnitude with increased levels of induced vascular tone. The relationship between the size of the acetylcholine-induced response and the baseline perfusion pressure was essentially linear with a correlation coefficient of 0.86 at 10(-5) M and of 0.88 at 10(-4) M acetylcholine. Our results suggest that, in the isolated perfused rat eye, the initial vascular tone has to be considered when evaluating endothelial cell function by acetylcholine-induced relaxation.

Acetylcholine↗

PubMed2000

Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat.

PURPOSE: To measure the intraretinal oxygen environment at different stages in the Royal College of Surgeons (RCS) rat model of retinal degeneration to determine whether changes in oxygen level are an important aspect of the disease. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of depth through the retina of anesthetized, mechanically ventilated RCS rats at ages ranging from postnatal day (P)20 to P104. The oxygen profiles were correlated with histologic observations of the cellular changes within the dystrophic retinas and compared with those in RCS-rdy(+) control animals and published values in normal mature rats. RESULTS: Although the youngest rats studied exhibited some differences in intraretinal oxygen distribution compared with mature animals, the distribution in dystrophic RCS rats at P20 was not significantly different from that in age-matched control subjects. However, the intraretinal oxygen distribution in dystrophic RCS rats was clearly affected after approximately P30, reflecting a loss of photoreceptor oxygen consumption consistent with histologic observations. In contrast, oxygen uptake by the inner retina was still evident long after the loss of photoreceptors was essentially complete. CONCLUSIONS: There was no significant tissue hypoxia during photoreceptor degeneration in the dystrophic RCS rat. The changes in intraretinal oxygen distribution are consistent with the loss of outer retinal oxygen uptake but the preservation of inner retinal oxygen metabolism.

Animals↗

PubMed1999

Systemic and ocular vascular roles of the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers.

This review addresses whether the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers cause vasoactive effects in the retinal and other ocular vasculatures, as they do in other tissues. The potent vasodilating effects of Ca2+ entry blockers on ocular vessels have recently been demonstrated in in vivo and in vitro studies, implying that the maintenance of ocular vascular tone relies almost exclusively on extracellular Ca2+. Ca2+ entry blockers may potentially play a role in relaxing the retinal, long posterior ciliary, and ophthalmociliary arteries to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present. The beta-adrenergic antagonists are discussed with reference to their antihypertensive role, their effect on other vascular beds, and finally what is known of their effect in the ocular vasculature. The emerging evidence that particular selective beta-adrenergic antagonists, such as betaxolol, are also potent Ca2+ channel entry blockers in other vascular beds is presented. Betaxolol has been shown to induce vasodilatation in the retinal and other ocular vascular beds, although studies have shown that beta1-adrenergic receptors are sparse in these vascular beds. This implies that an alternative mechanism must be responsible for betaxolol-induced vasodilatation. Evidence is presented that betaxolol vasodilates via its potent Ca2+ channel entry blocking properties, and its potency and ability to vasodilate are compared with those of nimodipine and timolol, as well as with those of other Ca2+ channel entry blockers. Important areas for future research in this area are discussed.

Adrenergic beta-Antagonists↗

PubMed1999

Increased incidence of tongue cancer after primary radiotherapy for nasopharyngeal carcinoma--the possibility of radiation carcinogenesis.

The aim of this study was to define the risk of tongue and other aerodigestive tract cancers developing after primary radiation therapy for nasopharyngeal carcinoma (NPC). A cohort of 903 patients with non-disseminated NPC given radical radiotherapy between 1984 and 1989 was studied for the incidence of tongue cancer and other malignancies during follow-up. A contemporary cohort of 87 patients with tongue cancer, without a history of NPC, was studied for demographic data, cigarette smoking and alcohol consumption habits. These were then compared with all the NPC patients and with the NPC patients who later developed tongue cancers. There was a significantly increased number of tongue cancers following radiotherapy for NPC. The risk of developing tongue cancer after radiotherapy for NPC was 0.13% per patient per year. There was no increase in the number of other malignancies. The association between NPC and tongue cancer was that of a non-random temporal sequence with tongue cancers following NPC but not in the reverse order. The demographic data and smoking and alcohol consumption history of the 7 NPC patients who subsequently developed tongue cancer were significantly different from the de novo tongue cancer patient population. The absence of common aetiological factors between NPC and tongue cancer and the non-random sequence of tongue cancers occurring after NPC suggests that these seven tongue cancers could be radiation induced. The estimated radiation dose received by the part of the tongue developing cancer was substantial and significantly higher than the dose to the cancer-free tongue. An increase of tongue cancers after radiotherapy for NPC is reported and arguments are made in support of the hypothesis that these were radiation-induced malignancies. We suggest a decrease in the volume of tongue included within the planning target volume of NPC in the absence of oropharyngeal and/or parapharyngeal infiltration. Awareness of the association should make early diagnosis of this likely radiation-induced cancer possible.

Adolescent↗