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Biomedical subjects

R B Bhisitkul

Publications and source records attributed to R B Bhisitkul.

16 recordsLinked to original sources

Vascular endothelial growth factor biology: clinical implications for ocular treatments.

Decades of research on vascular endothelial growth factor (VEGF) have reached fruition with the recent development of intravitreal anti-VEGF treatments for exudative age-related macular degeneration. VEGF is a critical regulator of angiogenesis and vascular permeability with diverse roles, both pathological and physiological, during development and adulthood. The aim of this article is to review aspects of VEGF biology that may be relevant to the clinical use of anti-VEGF agents in ophthalmology: molecular characteristics and isoforms of VEGF; its roles in vasculogenesis, vascular maintenance and angiogenesis; systemic effects of VEGF inhibition; and properties of current anti-VEGF agents.

Angiogenesis Inhibitors↗

Development of Microelectromechanical Systems (MEMS) forceps for intraocular surgery.

AIM: To develop silicon microforceps for intraocular surgery using Microelectromechanical Systems (MEMS) technology, the application of microchip fabrication techniques for the production of controllable three dimensional devices on the micrometre scale. METHODS: Prototype MEMS forceps were designed and manufactured for intraocular surgery. Scanning electron microscopy was used to evaluate device tip construction. Designs using both thermal expansion actuators and conventional mechanical activation were tested in human cadaver eyes and in vivo rabbit eyes to assess functionality in standard vitreoretinal surgery. RESULTS: MEMS forceps were constructed with various tip designs ranging from 100 mum to 2 mm in length. Scanning electron microscopy confirmed accurate construction of micro features such as forceps teeth as small as tens of micrometres. In surgical testing, the silicon forceps tips were effective in surgical manoeuvres, including grasping retinal membranes and excising tissue. The mechanical actuator design on a 20 gauge handle was more operational in the intraocular environment than the thermal expansion actuator design. While handheld operation was possible, the precision of the forceps was best exploited when mounted on a three axis micromanipulator. CONCLUSION: MEMS microforceps are feasible for conventional vitreoretinal surgery, and offer advances in terms of small scale, operating precision, and construction tolerance.

Animals↗

Bloom syndrome: multiple retinopathies in a chromosome breakage disorder.

AIM: To describe multiple retinal abnormalities in a patient with Bloom syndrome, including early macular drusen, diabetic retinopathy, and the onset of leukaemic retinopathy. METHODS: Clinical data were collected over 1 year of follow up, and ocular abnormalities in Bloom syndrome were reviewed from the literature. RESULTS: A 39 year old man with a rare autosomal recessive "chromosome breakage" syndrome was followed. A variety of ocular findings have been reported in Bloom syndrome; this patient had hard drusen in both maculae, non-proliferative diabetic retinopathy, and haemorrhagic retinopathy as a herald of acute lymphocytic leukaemia. CONCLUSIONS: Bloom syndrome is a rare disorder of genomic instability, in which a variety of ocular abnormalities have been found. Described here are multiple retinal manifestations arising from characteristic systemic associations of diabetes mellitus and leukaemia, as well as macular hard drusen.

Adult↗

Spontaneous central retinal artery occlusion in hemoglobin sickle cell disease.

PURPOSE: To describe a case of spontaneous central retinal artery occlusion in a young man with hemoglobin sickle cell disease. METHOD: Case report. RESULTS: A 31-year-old African-American man with a history of hemoglobin sickle cell disease developed sudden painless loss of vision in the right eye. Medical history was remarkable for the recent history of a mild painful crisis, but no other systemic illness or contributing factors. Central retinal artery occlusion was diagnosed with retinal whitening, cherry red spot, and delayed arteriovenous transit on fluorescein angiography. Over the ensuing week, the patient had visual recovery to 20/60 in the absence of therapeutic intervention. CONCLUSION: Central retinal artery occlusion has been reported in sickle cell hemoglobinopathies (ie, SS, S-thal, sickle trait, and sickle cell), but the association with sickle cell disease is rare. Most reports have described additional contributing factors, such as trauma or concomitant systemic illness, to help account for the central retinal artery occlusion. The present case suggests that sickle cell disease alone is sufficient for the development of central retinal artery occlusion.

Adult↗

Soccer ball-related retinal injuries: a report of 13 cases.

PURPOSE: To describe the clinical characteristics and management of retinal injuries caused by soccer ball impact as well as the mechanism of injury, prognostic features, risk factors, and possible prevention strategies. METHODS: Thirteen cases of soccer ball injuries from retina referral practices were retrospectively reviewed, with attention to the mechanism of associated ocular complications and the anatomic and visual outcomes. RESULTS: Soccer ball injuries occurred in both male and female patients (9 male, 4 female) with ages ranging from 8 to 21 years (median 14 years). These patients were observed from 0 to 64 months (median follow-up, 8 months). Four patients had traumatic macular holes, two eyes had retinal detachment associated with retinal dialysis, two had retinal tears associated with hemorrhage, one had a choroidal rupture, and one had only vitreous hemorrhage and Berlin's edema. Although six eyes had some degree of traumatic retinal pigment epitheliopathy, it was the primary diagnosis in only three. Visual acuity at presentation ranged from 20/20 to count fingers, with 7/13 (54%) having 20/200 or worse vision. Seven eyes underwent surgical procedures; the remainder were observed. Final visions ranged from 20/20 to count fingers, with 3/13 (23%) having 20/200 or worse vision. Six eyes (46%) improved by two or more lines by the last follow-up. CONCLUSION: Soccer ball-related ocular injuries disproportionately affect young players, are more frequent in females than previously reported, and have more severe visual consequences than previously recognized. Injury prevention strategies to minimize contact between the eye and the soccer ball may reduce the incidence and severity of eye injuries.

Adolescent↗

Lasers and diabetic retinopathy: the art of gentle destruction.

Laser retinal photocoagulation represents the primary therapy for the potentially blinding manifestations of diabetic retinopathy. Advances in laser therapy for diabetic eye disease have arisen from the convergence of laser technology and clinical ophthalmology. In this review, the basis of laser therapy in diabetic retinopathy is discussed. Included are the clinical characteristics, classification, and pathogenetic mechanisms of diabetic retinopathy. The principles of laser technology, variety of lasers currently available for therapy, and mechanisms of laser actions on retinal target tissues are introduced. The milestone clinical trials establishing the efficacy of laser therapy and the parameters for its clinical application in diabetic retinopathy are outlined.

Blindness↗

A voltage- and time-dependent rectification in rat dorsal spinal root axons.

1. Rat dorsal spinal roots were studied by the use of whole-nerve sucrose gap and intra-axonal recording techniques. A prominent time-dependent conductance increase as evidenced by a relaxation or "sag" in membrane potential toward resting potential was elicited in dorsal spinal roots by constant hyperpolarizing current pulses. The relaxation, or sag, indicative of inward rectification, reached a maximal level and then decayed during the current pulse. 2. The time-dependent sag elicited by hyperpolarization was reduced when Na+ or K+ was removed from the normal bath solution but was abolished with the removal of both Na+ and K+. Tetrodotoxin (TTX), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) did not affect the depolarization sag, suggesting that conventional voltage-dependent sodium and potassium channels do not underlie the inward rectification. 3. Cs+ in low concentrations completely abolished the inward rectification, whereas Ba2+ induced a partial block. 4. Current-voltage curves indicate that the magnitude of the depolarizing sag increases monotonically with increasing hyperpolarization. The time required to reach peak hyperpolarization, maximal sag potential, and the time between peak hyperpolarization and sag membrane potentials decreases with increasing levels of hyperpolarization. 5. The inward rectification is refractory to further stimulation during its decay phase, as revealed by paired-pulse protocols. This decay in inward rectification is both time and voltage dependent and is observed on a single axon level by the use of intra-axonal recording techniques as well as from whole-root recordings in the sucrose gap. 6. It is concluded that rat dorsal root fibers display a prominent time-dependent conductance increase in response to hyperpolarization that depends on both Na+ and K+ permeability and is blocked by Cs+. This rectification displays a decay phase that has not been previously described for similar conductances. It is argued that the Na+ component of this conductance is primarily responsible for stabilizing membrane potential near resting potential during periods of hyperpolarization.

Animals↗

Trophic influence of the distal nerve segment on GABAA receptor expression in axotomized adult sensory neurons.

The depolarizing action of gamma-aminobutyric acid (GABA), or the GABAA receptor agonist muscimol, on rat dorsal root (L4 and L5) fibers is attenuated following transection, but not crush, of the sciatic nerve. Following discrete nerve crush, axons actively regenerate and contact both the distal nerve segment and the peripheral target tissues. The aim of the present study was to distinguish between these two regions as possible sources of trophic support for retrograde maintenance of dorsal root GABA receptor sensitivity. A surgical procedure was employed to permit a delimited segment of axonal regeneration while prohibiting reestablishment of end organ innervation; the sciatic nerve was crushed and a ligature was placed 3 cm distal to the crush site. Under these conditions, the injury-induced decrement in the dorsal root GABA response, observed between 12 and 21 postoperative days, was significantly attenuated relative to that of ligated nerves, in which regeneration into the distal stump does not occur. The data suggest that nerve transection by ligation restricts trophic support for maintenance of GABA receptor expression in dorsal root ganglion (DRG) neurons. Furthermore, during regeneration the denervated distal nerve segment assumes a neurotrophic role in the maintenance of dorsal root GABA sensitivity, consistent with the hypothesis that growth factors derived from reactive Schwann cells may positively regulate the expression of receptors on axotomized sensory neurons.

Animals↗

Axonal GABA receptors are selectively present on normal and regenerated sensory fibers in rat peripheral nerve.

A sucrose gap chamber was used to study the effect of gamma-aminobutyric acid (GABA) on normal and regenerating rat peripheral nerve fibers. Sciatic nerves and dorsal roots were depolarized by GABA and the GABAA receptor subtype agonist muscimol, but not by the GABAB receptor subtype agonist baclofen. Ventral root fibers were not affected by these agents, suggesting a selective presence of axonal GABA receptors on sensory fibers of mammalian peripheral nerves. Regenerating dorsal and ventral root fibers were studied 13 to 20 days following nerve crush. The regenerated dorsal root fibers were depolarized by GABA or muscimol, but the regenerated ventral root fibers were not. These results indicate that GABA receptors are selectively present on normal mammalian sensory axons, and are reestablished on regenerated sensory axons.

Animals↗

Adenosine selectively blocks parallel-fiber-mediated synaptic potentials in rat cerebellar cortex.

Electrophysiological techniques were used to study the efficacy of adenosine in modulating synaptic transmission mediated from convergent parallel- and climbing-fiber inputs to Purkinje cells. Our results indicate that adenosine application leads to selective blocking of parallel fiber-mediated synaptic activity but not of climbing fiber activity. Adenosine does not alter the action-potential excitability properties of the parallel fibers. However, application of gamma-aminobutyric acid (GABA), which directly affects Purkinje cell dendritic membranes [Malenka, R. C. & Kocsis, J. D. (1982) J. Neurophysiol. 48, 608-621], leads to reduction of both parallel- and climbing-fiber synaptic activity. These results support the proposals that adenosine receptors in the cerebellar cortex are selectively localized on the nonmyelinated parallel fibers and that the blocking action of adenosine is the result of a mechanism other than direct alteration of axon excitability.

Adenosine↗