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Biomedical subjects

J O'Rourke

Publications and source records attributed to J O'Rourke.

At least 73 records · Page 4Linked to original sources
PubMed1985

Fibrin: mediator of in vivo and in vitro injury and inflammation.

We examined the role that fibrin deposition and fibrin-associated factors (FAF) play in acute anterior segment inflammatory responses in the rabbit eye. It was demonstrated by immunofluorescence that fibrin represented a major component of the exudative meshwork deposited within the anterior chamber and on leukocyte surfaces therein. Using our in vivo model of endocular inflammation we next demonstrated that fibrin and fibrinogen-derived peptides, but not thrombin, induced inflammatory responses characterized by both leukocyte influx and endothelial cell injury. Fibrin formation within the anterior chamber induced a leukocyte influx consisting primarily of PMN's. Fibrinogen-derived peptides induced primarily a monocyte influx. This dichotomy suggests that multiple inflammatory mediators are elaborated or released during endocular fibrinogenesis and fibrinolysis. To investigate direct effects of fibrin deposition on the corneal endothelial cells (CEC) an in vitro "corneal cup" organ culture model was next developed. Studies comparing various types of mediators demonstrated that only fibrin- derived preparations directly induced CEC injury. Fibrin deposition may thus play multiple roles in endocular inflammation, including the modulation of leukocyte influx, and the direct mediation of corneal endothelial cell injury.

Animals↗
PubMed1985

Regulation of anterior chamber fibrinolysis.

Levels of plasminogen activator (PA), plasminogen (Plg), and antiplasmin activity (APli) were compared in feline aqueous humor obtained from normal eyes, eyes inflamed by chronic mycobacterial-induced uveitis (CMIU), opposite eyes, and in plasma. Fibrin-agar plate microassays were utilized to visually confirm the extent of differences in in vitro fibrinolysis, per se. Chromogenic peptide (S2251) microassays were utilized to quantify differences. Normal AH showed much more available PA than did plasma. However, when APli activity was first neutralized their levels of total PA were comparable. Available PA activity in both normal and CMIU AH was considerably amplified in the presence of trace amounts of free plasmin. Plasma failed to show this response. AH levels of circulating Plg and APli in normal eyes were far below plasma levels. During CMIU, total PA levels remained approximately normal while levels of Plg and APli were greatly increased. The net effect of these concurrent rises was that antiplasmin activity (APli) prevailed over free plasmin formation; i.e., in vitro fibrinolysis was suppressed. Plasma levels of PA, Plg and APli did not change during CMIU. Changes in the normal PA+Plg/APli balance induced by CMIU suggested a hypothetical model of AH fibrinolysis wherein exclusion of APli from the normal anterior chamber and the high levels attained during CMUI are posited as key determinants of AH fibrinolytic capability.

Animals↗
PubMed1984

Leukocyte-mediated injury to corneal endothelial cells. A model of tissue injury.

Although leukocyte-mediated cell injury has long been suggested as a major mechanism of general tissue injury in acute and chronic inflammation, only limited data have been developed to directly implicate leukocytes in ocular tissue injury. In an effort to unravel the role and mechanisms of leukocyte-mediated injury to the cornea, an isolated corneal cup model was developed. For this model, peripheral bovine leukocytes were added to isolated bovine corneal cultures (corneal cup) in vitro, after which endothelial cell damage and death were evaluated morphologically. In general, corneal endothelial cell swelling was observed within 5-10 minutes after leukocyte exposure, followed by detachment of the corneal endothelium at a 30-75-minute interval. Grossly, the detached endothelium appeared as a floating sheet. Using trypan blue dye exclusion, cells in the sheet were found to be nonviable. When examined ultrastructurally, the sheet was found to consist of leukocytes and endothelial cell debris. Light-microscopic examination of the corneal cup at 5-10 minutes after leukocyte action demonstrated extensive endothelial cell damage, as indicated by cell membrane thickening, cytoplasmic vacuolization, and changes in nuclear shape. These changes in the endothelial cells were confirmed by electron microscopy. Vacuolization and swelling of the endothelium appeared as the first changes, induced by leukocyte interactions with the endothelial cell layer. In general, the endothelial cell nucleus became convoluted, mitochondria swelled, and the endoplasmic reticulum became dilated. These changes become more pronounced as the endothelial cells become detached from the underlying Descemet's membrane. Leukocyte interaction with corneal epithelium, on the other hand, did not result in cell detachment, but only cell damage. These studies demonstrate the ability of leukocytes to denude Descemet's membrane of endothelial cells and destroy corneal endothelial cells in vitro. They also suggest that the corneal cup model system will enhance both morphologic and biochemical evaluation of the mechanisms and consequences of leukocyte-mediated injury to the cornea, and thereby provide new insights into the mechanisms of endocular inflammation and tissue injury in vivo.

Animals↗
PubMed1983

Demonstration of inflammatory mediator-induced inflammation and endothelial cell damage in the anterior segment of the eye.

Although some investigations have demonstrated the ability of inflammatory mediators, including vasopermeability and chemotactic factors, to induce acute inflammatory reactions in vivo, little is known about the response of various elements of the anterior segment to the direct effects of inflammatory mediators. These studies were initiated to develop models for the investigation of inflammatory responses in this region of the eye. Acute inflammatory reactions were induced within the rabbit anterior chamber by intracameral injection of 50 microliters of various inflammatory mediators and were evaluated by clinical grade, leukocyte influx into the aqueous humor, and morphologic changes in the corneal endothelium. Peak responses were recorded following injection of 10(-4) M formyl-methionyl-leucyl-phenylalanine (fMLP); 5 ED50 C5fr; 0.5 mg/ml C5; undiluted anti-red blood cell (RBC) serum; and 10(-5) M histamine. The number of leukocytes per milliliter of aqueous humor induced by each mediator was quantitated by comparison with the number of leukocytes induced by buffer instillation into a separate group of rabbits (mediator-induced influx/buffer-induced influx). Comparisons were made 24 hours after instillation of mediators. The results of these studies were as follows: buffer alone, 1.0; fMLP, 3.1 C5fr, 61.0; C5, 8.7; anti-RBC, 91.0; and histamine, 24.0. Clinical grades correlated well with these ratios. In addition, differences were noted when the time kinetics of acute responses induced by two different mediators (10(-4) M fMLP, a synthetic preformed chemotactic factor; and a 1:5 dilution of anti-RBC, which binds to vascular and corneal endothelial cells) were directly compared over 48 hours. Responses induced with fMLP peaked between 5 and 8 hours and resolved rapidly, whereas anti-RBC-induced responses peaked between 8 and 12 hours and resolved very slowly. Histopathologic analysis indicated that both fMLP and anti-RBC induced a similar sequence of changes in the corneal endothelium. Within 2-3 hours after instillation of either mediator, the endothelial cells exhibited prominent vacuolization/retraction phenomena. At the peak of leukocyte influx PMNs filled these vacuoles, then migrated back into the aqueous humor within several hours. Normal morphologic features were recovered following clearance of leukocytes from the anterior chamber. We believe that these models will be useful in identifying the roles of individual mediators in acute and chronic endocular inflammation and in the injury of corneal endothelium.

Animals↗
PubMed1982

Fluorescein appearance time curves. Continuous recordings of iris and anterior chamber dye flow contours.

Fluorescein appearance time (FAT) curves were recorded at 5-s intervals from the feline iris and anterior chamber using a modified video-frame store unit. Anterior chamber washout slopes were also recorded following intracameral injection. The iris FAT interval following intravenous injection was maximally 5 s. Passage of the dye bolus then appeared during the next 10 s, followed by a rapid (100-s) rise to maximum levels. In contrast to the iris, anterior chamber FAT curves recorded from the pupillary space showed an approximate two-minute delay after injection (mean = 1.92 +/- 0.360 minutes), followed by a gradual (20-minute) rise to maximum recordable levels. The mean anterior chamber washout rate following intracameral injection of 10(-6) g/mL of dye levels was 2.323% +/- 0.810%/min. There are potential applications of the method and a need for shorter recording intervals.

Animals↗
PubMed1982

Evidence of impaired anterior segment fibrinolytic activity in chronic uveitis.

Purified homologous fibrinogen (2.4-9.4 mg) was injected intracamerally in cat eyes at approximate six months intervals for up to 30 months in order to assess, in vivo, the long-term impact of chronic uveitis on anterior segment fibrinolytic capability. Normal and acutely inflamed eyes responded with slow clotting, small clot formation and rapid lysis (2-3 days). Chronically inflamed eyes showed rapid clotting, larger clots and much slower lysis, with BCG-induced uveitis much slower than endotoxin-induced uveitis. Suppression of plasminogen activator levels within aqueous humor of chronically inflamed eyes was indicated, using modified fibrin plate methods. The normal balance between fibrinolysis and fibrinogenesis within tissues bounding the anterior chamber is apparently tilted in favor of the latter function when inflammation is prolonged.

Animals↗
PubMed1978

Continuous in vivo recordings of intraocular capillary and aqueous humor flows.

Multiple-point recordings of the initial slopes of xenon 133 and human serum albumin I125 washout from various ocular regions were utilized to visualize changes in capillary and aqueous humor bulk flow in vivo. Preservation of slope linearity is essential for sensitive responsiveness of recordings to flow change. Linearity is enhanced by the initial slope approach in which stability of physiological values and drug effects are maintained and slopes are closely fitted to multiple points. As examples of intraocular flow changes which may be observed and computed from such slopes, responses recorded in forty feline washout studies are presented and the fundamentals of washout recording interpretation are discussed.

Animals↗
PubMed1977

Mechanism of head and neck response to -Gx impact acceleration: a math modeling approach.

Mathematical modeling has attained wider acceptance in recent years. In particular, the use of computer programs to simulate the dynamic response of a human in a crash situation has become an attractive alternative to full-scale experimental testing. This paper analyzes data on the dynamic response of the living human head and neck to -Gx impact acceleration, where the motion of the subject's head and neck in the midsagittal plane was monitored with inertial instrumentation and high-speed photography for confirmation. The Calspan "3D Computer Simulator of Motor Vehicle Crash Victims" was used to predict expected responses for the deceleration pulses employed. These estimates were compared to the fully instrumented human test runs. The standard 15-segment and 14-joint representation of the occupant was modified to include two sternoclavicular joints, increasing the articulation in the upper torso. Analysis of the data indicated that muscular activity in the head and neck seemed to be evident and does influence motion of the head, even at relatively high (10-G peak, 530 G/s onset) acceleration levels. Simulation of muscular contraction, using a spring-damper arrangement, improved the results significantly. Additionally, possible limitations to head-to-neck motion, such as ligament restrictions, were also modeled.

Acceleration↗
PubMed1976

Emergency management of acute congestive glaucoma using an anterior chamber microsyringe and needle.

A microsyringe-needle assembly is described for use in aspiration and microinfusion procedures in the anterior chamber. Assets of a lancet pointed 30-gauge needle, surface anesthesia, and fine control of ocular pressure and aqueous humor volume are stressed. Use of the assembly for emergency treatment of acute congestive glaucoma, surgical paracentesis, aqueous sampling, and drug infusion are described. Drug volumes and concentrations must be maintained at levels which do not damage corneal endothelium.

Acute Disease↗
PubMed1975

Corticosteroid therapy for the pregnant asthmatic patient.

Corticosteroids were used during seventy pregnancies in 55 asthmatic patients. In this series there was one spontaneous abortion and 71 live births (including two sets of twins). There was no maternal, fetal, or neonatal deaths. On the basis of recorded gestation, slightly more premature births were noted in this series than would be expected in the general population. However, there was no increased incidence of toxemia, uterine hemorrhage, or congenital malformations when compared to the general population, Corticosteroids, when indicated for the treatment of severe asthma, do not appear to noticeably increase the risk of maternal or fetal complications, and thus should not be contraindicated in pregnancy.

Abnormalities, Drug-Induced↗
PubMed1975

The administration of radiographic contrast media to patients with a history of a previous reaction.

Ninety-five patients were seen in consultation for previous reactions which their physicians considered as possible contraindications for the use of radiographic contrast media (RCM). Twenty-seven patients received no further studies because of a lack of sufficient indication to do them. The previous incidents in 26 were such that they were not classified as immediate generalized reactions (IGRs). Two of these patients had IGRs with repeat RCM (7.7%). Forty-two patients had previous reactions considered to be IGRs and medical problems such that repeat administration of RCM appeared essential for diagnosis. After pretreatment with diphenhydramine, 43 repeat procedures were performed in these patients followed by reactions, generally mild, in 7 (16%). Five of these were classified as IGRs (11.8%). The data on 264 similar patients in the literature were also reviewed. There appeared to be a higher incidence of IGRs to RCM in patients with a good history of a previous reaction than in the general population, but no severe reactions or fatalitics occurred in this entire series. The results showed that repeat studies in patients with previous reactions to RCM may be done, provided that there is careful evaluation of the initial reaction, the need for the diagnostic study, and provided appropriate precautions are taken prior to the procedure.

Adult↗