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Biomedical subjects

P K Yu

Publications and source records attributed to P K Yu.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dosimetry of blood irradiation with radiochromic film.

It has been shown that radiochromic film is an ideal dosimeter for assessment and verification of delivered dose to irradiated blood products. Using a parallel opposing two-field technique on a medical linear accelerator, blood is irradiated to diminish the risk of transfusion-associated graft vs. host disease (TA-GVHD). The blood products are irradiated in a Perspex blood box to an applied dose of 29.5-31.7 Gy. Verification of applied dose has been performed with thimble ionization chambers and radiochromic film. Radiochromic film results have matched absorbed dose measurements from ionization chambers at all sites within the 'active' treatment volume within +/-6% for a 95% confidence limit. Using a sample of 100 in-vitro measurements, radiochromic film has measured the average applied dose to blood products to be 30.95+/-2.6 Gy for two standard deviations. Like currently available 'irradiated' film labels, the radiochromic film also serves as a visible reminder that the blood products have been irradiated.

Blood↗
PubMed1998

Effect of betaxolol, timolol and nimodipine on human and pig retinal arterioles.

This study tested the hypothesis that the beta-adrenergic antagonists betaxolol and timolol, cause retinal arteriolar vasodilatation in addition to their ability to reduce intraocular pressure (IOP), and compared their vasodilatory ability with that of a known Ca2+ channel entry blocker nimodipine in donor human and pig isolated perfused retinal arterioles. This study was performed using a microperfusion technique specifically established to allow investigations in arterioles as small as the first order human and pig retinal arterioles (approximately 100 microns diameter). The scarcity of viable human tissue was overcome by the successful development of controlled rate freezing and cryopreservation techniques which were able to preserve the vascular responsiveness of the retinal arterioles, thus enabling multiple experiments to be performed on segments of retinal arterioles from each individual donor eye. Furthermore, relaxation by acetylcholine in noradrenaline contracted pig retinal arterioles showed that endothelial cell function was well maintained after cryopreservation (n = 8). Baseline diameters of retinal arterioles used in the main studies were: cryopreserved human 92.3 +/- 3.4 microns (n = 44), fresh pig 94.7 +/- 2.2 microns (n = 42), and cryopreserved pig 94.3 +/- 2.3 microns (n = 30). Precontraction with extraluminal endothelin-1 (ET-1) 10(-9) M reduced the diameters to 74.3 +/- 0.9%, 71.6 +/- 1.6% and 72.5 +/- 0.9% respectively. Intraluminally applied nimodipine and betaxolol caused a significant dose dependent dilatation (P < 0.001) in human retinal arterioles with a threshold of 10(-12) M. Timolol did not produce a significant dilatation in human arterioles. Timolol produced a small but significant dilatation in fresh and cryopreserved pig arterioles but the dilatation with betaxolol and nimodipine was significantly larger. The nimodipine and betaxolol dose response curves were not significantly different in human arterioles, but nimodipine produced significantly greater dilatation than betaxolol (P < 0.001) in fresh and cryopreserved pig arterioles. Both nimodipine and betaxolol were significantly more effective vasodilators than timolol (P < 0.001) in human and pig retinal arterioles.

Adrenergic beta-Antagonists↗
PubMed1998

Effects of read-out light sources and ambient light on radiochromic film.

Both read-out light sources and ambient light sources can produce a marked effect on coloration of radiochromic film. Fluorescent, helium neon laser, light emitting diode (LED) and incandescent read-out light sources produce an equivalent dose coloration of 660 cGy h(-1), 4.3 cGy h(-1), 1.7 cGy h(-1) and 2.6 cGy h(-1) respectively. Direct sunlight, fluorescent light and incandescent ambient light produce an equivalent dose coloration of 30 cGy h(-1), 18 cGy h(-1) and 0 cGy h(-1) respectively. Continuously on, fluorescent light sources should not be used for film optical density evaluation and minimal exposure to any light source will increase the accuracy of results.

Calibration↗
PubMed1998

Measurement of off-axis and peripheral skin dose using radiochromic film.

A radiotheraphy skin dose profile can be obtained with radiochromic film. The central axis skin dose relative to Dmax for a 10 x 10 cm2 field size was found to be 22%, 17% and 15.5% for 6 MV, 10 MV and 18 MV photon beams. Peripheral dose increased with increasing field size. At 10 MV the skin dose 2 cm outside the geometric field edge was measured as 6%, 10% and 17% for 10 x 10 cm2, 20 x 20 cm2 and 30 x 30 cm2 field sizes respectively. Off-axis skin dose decreased as distance increased from central axis for fields with Perspex block trays. For a 20 x 20 cm2 field, an approximately 5-8% drop in percentage skin dose was observed from central axis to the beam edge.

Biophysical Phenomena↗
PubMed1998

Intracellular structures of retinal vascular endothelium in normal and early diabetic rats.

PURPOSE: To determine whether the arrangement of microfilaments in retinal vascular endothelium is altered in early diabetes. METHODS: F-actin and nuclei of retinal vascular endothelial cells of normal and diabetic (28 weeks postinduction) rats were examined using confocal microscopy. RESULTS: An increase in the incidence of aberrant F-actin bundle arrangement in the diabetic retinal arteriole was observed, but there was no disruption of peripheral border F-actin. The diameter of superficial capillaries was increased in diabetic rats. CONCLUSION: These changes may be related to the endothelial dysfunction demonstrated in a previous pharmacological study.

Actins↗
PubMed1998

Quantification of retinal oxygen consumption changes from preretinal oxygen transients.

BACKGROUND: In the avascular retina of the guinea-pig all the oxygen supply is from the choroid. Under these circumstances we had proposed, on theoretical grounds, that a change in retinal oxygen consumption would modulate the preretinal oxygen level. METHODS: In the present study in guinea-pigs,the oxygen consumption of the outer retina was modulated by light-dark exposure while preretinal oxygen tension was monitored. RESULTS: The results were in complete agreement with the proposed mathematical models. CONCLUSION: The present study demonstrates that it is feasible to quantify oxygen consumption changes in a known retinal layer from measurements of preretinal oxygen tension.

Animals↗
PubMed1997

Heterogeneous endothelial cell structure along the porcine retinal microvasculature.

The pivotal role of the endothelial cell in the regulation of vascular tone has been well demonstrated in many vascular beds, including the retina. However, in the retina, little is known about how the structural elements of the endothelial cells are arranged along the arborisation pathway from artery to vein, the nature of which has been linked to functional heterogeneity in other vascular beds. The relative vulnerability of the retina to vascular based diseases, and the heavy reliance on local regulation of the retinal vasculature makes an improved understanding of such local regulatory mechanisms of significant clinical importance. The present study focuses on identifying differences in endothelial cells along the arborisation pathway in the porcine retinal vasculature. Enucleated pig eyes were arterially cannulated and perfused with fixative followed by double staining for F-actin microfilaments (rhodamine phalloidin) and nucleic acid (YO-PRO-1). The intact retina was then viewed by confocal microscopy. The distribution of F-actin, vessel diameter, endothelial cell size and shape, nucleus size and shape, and position within the cell were determined as a function of location along the vascular tree. The main retinal arterioles (A1) contained full length F-actin internal stress fibers which lay parallel to the long axis of the endothelial cell. Subsequent branches from the A1 arteriole (A2 and A3) showed fewer, shorter fibers, with none visible in the A4 and A5 branches, the capillaries, or in the venous side of the vasculature. All endothelial cells showed peripheral border staining of F-actin microfilaments which allowed the shape of the cell to be determined. All endothelial cells were elongated with the long axis parallel to the vessel, but the mean aspect ratio decreased from 10.9+/-0.5, s.e.m. in the A1 arterioles to 3.2+/-0.2 in the major veins (V1). The position of the endothelial cell nucleus relative to the cell was eccentric in the downstream direction in the A2-A5 arterioles, whilst centrally placed in the A1 arterioles and veins. The structural heterogeneity of endothelial cells along the pig retinal circulation suggests that functional heterogeneity of the endothelium may be involved in regulation of retinal blood flow.

Actin Cytoskeleton↗
PubMed1997

The electron-dose distribution surrounding an 192Ir wire brachytherapy source investigated using EGS4 simulations and GafChromic film.

The steep dose gradient around 192Ir brachytherapy wire implants is predicted by the EGS4 (PRESTA version) Monte Carlo simulation. When considering radiation absorbing regions close to the wire source, the accurate dose distribution cannot be calculated by the GE Target II Sun Sparc treatment-planning system. Experiments using GafChromic film have been performed to prove the validity of the EGS4 user code when calculating the dose close to the wire source in a low energy range.

Brachytherapy↗
PubMed1997

The dose distribution close to an 192Ir wire source: EGS4 Monte Carlo calculations.

A Monte Carlo simulation using the PRESTA version of the EGS4 code has been employed as an investigative tool to calculate the absorbed dose in water close to 192Ir wire implants. It has been shown that a treatment planning system, such as GE Target II, using the Sievert integral and the Meisberger polynomial is only able to reproduce the Monte Carlo results at radial distance of 1 mm and farther away. The Sievert integral used with the Meisberger polynomial is proven to be in good agreement with the Monte Carlo generated data at distances between 1 mm and 1 cm.

Brachytherapy↗
PubMed1997

Measurement of vasoactivity in the guinea-pig choroid.

PURPOSE: A perfusion system for studying the vasoactive properties of the guinea-pig choroid is described. METHODS: The principle of operation is that the vascular resistance of the entire vascular network of an isolated, perfused eye can be monitored by recording the pressure required to deliver a constant flow of perfusate through the network. Delivery of the pharmacological agent of interest into the perfusate stream and the subsequent determination of the magnitude of any induced pressure changes allows the vasoactive potency of various agonists to be assessed. RESULTS: The baseline vascular resistance was 1.35 +/- 0.16 mmHg min/microL (mean +/- SEM; n = 10) and the mean response to intraluminal delivery of 124 mmol/L K+ Krebs was an increase in resistance of 297 +/- 67%. Vasoactive responses were sustainable for more than 8 h. CONCLUSIONS: This system will now be used to study the vasoactive properties of the guinea-pig choroid in greater detail.

Animals↗
PubMed1996

Asymmetrical response of the intraluminal and extraluminal surfaces of the porcine retinal artery to exogenous adenosine.

The relative effects of exogenous adenosine applied intraluminally or extraluminally were compared on first-order pig retinal arteries in an isolated perfused artery preparation. First-order retinal arteries with at least one side branch were cannulated and perfused at a constant flow in an environmentally-controlled organ bath on the stage of an inverted microscope. Vessels were precontracted with 10(-4) methoxamine applied extraluminally, which produced a sustained contraction. Then, either extraluminal or intraluminal adenosine was added in increasing concentrations from 10(-9) to 10(-3) M. During these procedures continuous measurements of external vessel diameter were made. The average external diameter of the retinal arterial segments used was 127.6 +/- 2.3 microns (n = 13). Extraluminal methoxamine (10(-4) M) constricted the vessels to 77.9 +/- 2.0% (n = 9) and 78.8 +/- 0.8% (n = 4) of the control value for the vessels later exposed to extraluminal and intraluminal adenosine respectively. Extraluminal adenosine caused a dose-dependent dilatation which commenced between 10(-7) M and 10(-6) M, and reached a percentage dilatation of 22.6 +/- 1.8% (n = 9) at 10(-3) M. For concentrations of 10(-4) M and above, spontaneous oscillations in diameter were observed for extraluminally-applied adenosine with an average period of 0.46 +/- 0.02 (n = 9) cycles per minute. The average percentage diameter oscillation was +/- 7.1% of the mean diameter. In contrast, intraluminal adenosine failed to cause dilatation or spontaneous oscillations at all concentration values, although the dilatory ability of these vessels was confirmed by intraluminal application of the Ca2+ channel blocker verapamil. In conclusion this study has demonstrated that the two sides of the retinal artery wall are differentially sensitive to adenosine, with the intraluminal route being ineffective. In vivo, in hypoxic or ischemic situations, adenosine is released by extraluminal neural tissue and minimizes tissue damage, partially by acting as a signaller of metabolic status to the vasculature leading to vasodilatation and hence increased local blood flow. This study shows that delivery of adenosine for therapeutic purposes through an intraluminal route is not a feasible proposition. This isolated, perfused artery technique has considerable potential to improve our understanding of uptake mechanisms, metabolism and vasoactivity of the retinal vessel wall.

Adenosine↗
PubMed1996

Intraretinal oxygen distribution and choroidal regulation in the avascular retina of guinea pigs.

O2-sensitive microelectrodes were used to measure PO2 as a function of depth through the retina and choroid of anesthetized and artificially ventilated guinea pigs. The guinea pig retina is of particular interest, because it has a typically mammalian structure but no retinal circulation; it relies totally on choroidal delivery of O2 and other nutrients. Measurements of intraretinal O2 distribution in an avascular mammalian retina have not previously been reported. Under normal ventilation conditions, PO2 decreased monotonically from the choroid (33.6 +/- 2.9 mmHg, n = 11) to near zero (0.4 +/- 0.1 mmHg) at the retina-vitreous boundary. The inner half of the retina had an average PO2 of only 0.6 +/- 0.1 mmHg. Stepwise increases in inspired O2 (from 20 to 40 to 60 to 80 to 100%) had surprisingly little effect on choroidal PO2. Rapid changes (20-100%) produced overshoot-type responses in the choroid before recovery to levels only slightly above those found in normoxia. This indicates the presence of an active O2-regulatory mechanism in the guinea pig choroid. Addition of CO2 (5%) to O2 ventilation appeared to break down this control mechanism and led to dramatic and sustained increases in PO2 throughout the retina and choroid. The demonstration of an O2-regulating mechanism in the guinea pig choroid that maintains choroidal PO2 well below that in the systemic arterial blood, coupled with the observation of very low O2 levels throughout the inner retina, suggests that the O2 requirement of the inner retina in the guinea pig is small and that O2 levels in the choroid are deliberately constrained.

Animals↗
PubMed1996

Direct vasodilatory effect of insulin on isolated retinal arterioles.

PURPOSE: To test the hypothesis that insulin has a direct vasodilatory effect on retinal arteries and their branches and to investigate the mechanisms involved. METHODS: Segments of porcine retinal arteries were dissected, cannulated, and perfused. Vessel diameter was measured continuously on-line. Vessels were precontracted to 66% +/- 0.9% (SEM, n = 148) of their original diameter by perfusing with 124 mM K(+)-Krebs solution. Dose-response curves to insulin (2 to 2000 microU/ml) were compared for extraluminal (EL), intraluminal (IL), and combined IL-EL application. The effect of cyclooxygenase and nitric oxide synthase inhibition on the insulin response was determined, as was Ca2+ channel involvement. RESULTS: EL insulin alone had no significant effect on vessel diameter. IL insulin produced a dose-dependent dilatation of 5.6% +/- 2.9% (n = 22) of the K+ contracted diameter at 200 microU/ml and up to 12.4% +/- 3.6% (n = 22) by 2000 microU/ml, whereas combined IL-EL insulin application caused dilatation at all concentrations, rising to 15.1% +/- 2.9% (n = 44) at 200 microU/ml and 19.7% +/- 3% (n = 44) at 2000 microU/ml. IL indomethacin (5 x 10(-5) M) had no significant effect on the insulin-induced dilatation, whereas IL L-NAME (10(-4) M) inhibited insulin dilatation completely. The addition of EL verapamil (10(-6) M) during insulin-induced dilatation resulted in further dilatation to 37.8% +/- 4.2% (n = 18). However, the addition of insulin to verapamil-dilated vessels caused no further dilatation. Exposure to EL insulin while the IL K+ contraction dose-response curve was measured had no effect. Results in main arteries and branches did not differ. CONCLUSIONS: The IL application of insulin dilates potassium-contracted pig retinal arteries. This effect was enhanced by the EL presence of insulin, which did not result in dilatation when it was administered alone. The dilatation response was mediated by nitric oxide but not by prostaglandins. There was some evidence for the involvement of Ca2+ channels in insulin-induced dilatation. These results imply that insulin is a vascular regulator in normal conditions and may have relevance to the vascular changes occurring in diabetes and hypertension in the retina.

Animals↗
PubMed1995

Altered vasoactivity in the early diabetic eye: measured in the isolated perfused rat eye.

The effect of 4 weeks streptozotocin-induced diabetes on ocular vascular resistance responses to noradrenalin (NA), adrenalin (A), phenylephrine (PHE), isoproterenol (ISOP), prostaglandin F2 alpha (PGF2 alpha). 5-hydroxytryptamine (5-HT) and angiotensin II (ANG II), was determined using a newly-developed, isolated, arterially-perfused rat eye preparation, by comparing responses from control and diabetic eyes. After extensive preliminary experiments to establish optimum parameters, the ophthalmic artery of enucleated control and diabetic rat eyes was cannulated and the retinal and uveal vasculature perfused at a constant flow with Na(+)-Krebs solution after streptozotocin-induced diabetes had been established for 4 weeks. The eyes were maintained in an environment-controlled organ bath. Perfusion pressure was monitored as increasing log M concentrations of agonists were added to the perfusate. Total ocular resistance could be calculated from knowledge of flow and pressure. In control eyes, NA, A, PHE, PGF2 alpha, and 5-HT all produced dose-dependent increases in total vascular resistance, with the following order of potency: NA = A > 5-HT > PHE = PGF2 alpha at 10(-4) M. The ocular circulation was not sensitive to isoproterenol and angiotensin II. In diabetic eyes responses to NA, A, PGF2 alpha and 5-HT were altered. Diabetic responses to NA and A had lower thresholds with larger resistance increases at low concentrations. However, the rate of increase in resistance with concentration was more gradual in diabetic eyes so that at 10(-4) M control responses were larger. Diabetic resistance responses to PGF2 alpha had the same threshold as in control eyes, but were greater in magnitude with an earlier peak at 10(-4) M. In contrast diabetic resistance responses to 5-HT were reduced, peaked at a lower resistance at 10(-4) M, but had the same threshold as those in the control eye. Basal vascular resistances in control: 3.14 +/- 0.32 mmHg min microliter-1 (n = 28), and diabetic eyes: 3.44 +/- 0.19, mmHg min microliter-1 (n = 36), were not significantly different. Vasoactivity in the early diabetic eye is disturbed with the effective balance between different agonists altered in favour of catecholamines at physiological concentrations. This may be related to the early changes in blood flow and oxygen distribution already reported in the rat eye, as well as changes to autonomic function. The isolated perfused rat eye is a valuable technique for investigating such vascular reactivity in animal models of retinal disease.

Angiotensin II↗
PubMed1995

A comparison of two photon planning algorithms for 8 MV and 25 MV X-ray beams in lung.

We report results of a comparison of two photon planning algorithms, the Clarkson Scatter Integration algorithm and the Equivalent Tissue-air Ratio algorithm, using a simple lung phantom for 8 MV and 25 MV X-ray beams of field sizes 5 cm x 5cm and 10 cm x 10 cm. Central axis depth-dose distributions were measured with a thimble chamber or a Markus parallel-plate chamber. Dose profile distributions were measured with TLD rods and films. Measured dose distributions were then compared to predicted dose distributions. Both agorithms overestimate the dose at mid-lung as they do not account for the effect of electronic disequilibrium. The Clarkson algorithm consistently shows less accurate results in comparison with the ETAR algorithm. There is additional error in the case of the Clarkson algorithm because of the assumption of a unit density medium in calculating scatter, which gives an overestimate in the effective scatter-air ratios in lung. For a 5 cm x 5 cm field, the error of dose prediction (Dpredicted-Dmeasured) for 25 MV x-ray beam at mid-lung is 15.8% and 12.8% for Clarkson and ETAR algorithm respectively. At 8 MV the error is 9.3% and 5.1% respectively. In addition, both algorithms underestimate the penumbral width at mid-lung as they do not account for the penumbral flaring effect in low density medium. It is very important for medical physicists, radiation therapists and clinicians to be aware of the limitation of their radiotherapy treatment planning systems.

Algorithms↗
PubMed1994

Vasoactivity of intraluminal and extraluminal agonists in perfused retinal arteries.

PURPOSE: To evaluate the vasoactive response of isolated perfused arteries of the pig to K+ and adrenergic agonists and to compare the effects of intraluminal (IL) and extraluminal (EL) drug delivery. METHODS: A new microperfusion system was developed, in which short lengths of porcine retinal arteries (outer diameter 90.4 +/- 2.7 microns) were cannulated at both ends and perfused at a controlled rate (5 microliters/min) with outflow through a single side branch. The diameter of the vessel and the intraluminal pressure were monitored, and the effect of intraluminally and extraluminally applied agonists was determined. Endothelial cell function and the integrity of the blood retinal barrier was verified. RESULTS: Consistent vasoactive responses were obtained from most vessels. The resting diameter of the vessel was not greatly influenced by changes in flow rate or intraluminal pressure over the physiological range. Adrenaline and noradrenaline caused dose-dependent contractions, which were larger when applied intraluminally than they were when applied extraluminally. The largest contraction for adrenaline was 19.0% +/- 2.1% (n = 13) IL and 8.4% +/- 1.5% (n = 13) EL, and for noradrenaline, 17.8% +/- 1.9% (n = 13) IL and 6.8% +/- 1.1% (n = 13) EL. The IL contraction to 124-mM K+, 19.0% +/- 1.6% (n = 21), was also greater than that for EL application, 5.0% +/- 1.0% (n = 13). We found that the existence of myogenic contractions was restricted to the special case in which vessels with no branches were pressurized under zero flow conditions. CONCLUSIONS: Pig retinal arteries exhibited asymmetry in their responses to adrenergic agonists and K+, with contractions significantly larger when the drug was applied to the intraluminal surface rather than the extraluminal surface. This asymmetry may reflect an important property of retinal vessels. Microperfusion systems of this type may prove valuable in developing a better understanding of control mechanisms in retinal circulations.

Adrenergic alpha-Agonists↗