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Biomedical subjects

G Orr

Publications and source records attributed to G Orr.

31 records · Page 2Linked to original sources

Calmodulin supports the force-generating function in desensitized muscle fibers.

Externally added calmodulin (CaM) restored Ca2+ regulation for the tension development by skeletal muscle fibers of hamster and rabbit desensitized by the troponin C (TnC) extraction treatment. CaM produced this action by combining with the TnC-denuded sites in the fiber. However, the binding properties differed strikingly from TnC: unlike TnC, CaM binding required the continued presence of Ca2+ and the bound portion was completely released with EGTA in the physiological milieu. The maximal uptake was 1.7 g of CaM/kg of muscle in the present study. The apparent Ca2+ sensitivity for force development with 200 micrograms/ml CaM in the solution was lower than in the native fiber or in the TnC-loaded fiber. The apparent association constant for CaM binding to the TnC-denuded sites was found as 4.9 x 10(5) M-1, and the extrapolated maximum force (Fmax) with CaM was close to PO. The intrinsic CaM level in intact muscle was also measured and was 18.6 mg/kg, amounting to about 1% of the total TnC or the CaM uptake by TnC-denuded fibers. The intrinsic CaM was not dislodged by EDTA treatment, indicating tight binding and suggesting that it exists in a separate pool from the vacated TnC sites adsorbing externally added CaM. The stringent Ca+ dependence of the CaM adsorption to TnC sites in the regulatory complex in the fiber supports the view that the evolutionary replacement of residues in the amino terminus helix portion of the "EF-hand" motif of site IV may be critical for the functional specialization by TnC.

Animals↗

Morphologic observations on experimental subretinal neovascularization in the monkey.

Subretinal neovascularization is a poorly understood and potentially disastrous feature of many eye diseases. We used light and electron microscopy to study the sequence of events that lead to the formation of new vessels after laser photocoagulation of the retina and choroid of primates. In this animal model there is a rapid development of new blood vessels; one day after photocoagulation, endothelial cell degeneration and thrombus formation were observed in the capillaries, venules and arterioles of the choroid around the center of the lesion. Re-endothelialization began in some thrombosed choroidal vessels, with migration of the activated endothelial cells within the old basement membrane. Two days after photocoagulation, re-endothelialization was observed in almost all thrombosed choroidal vessels, and the initial stage of the endothelial cell budding was observed in the pre-existing choroidal vessels; this was especially prominent in venules with pericytes. Three days after photocoagulation, not only the endothelial cells in pre-existing vessels but also those in re-endothelialized vessels showed budding and lumen formation. The lumen of vessels was formed by the budding of adjacent endothelial cells that were coupled by transient intercellular junctions. Mitotic figures were frequently found in the endothelial cells distal to the growing tip. Five to eight days after photocoagulation, many new vessels extended into the subretinal space.

Animals↗

Aqueous concentrations of fluorouracil after intravitreal injection. Normal, vitrectomized, and silicone-filled eyes.

Treatment of postoperative vitreoretinopathy with combined intravitreal fluorouracil and liquid silicone may result in increased corneal and retinal toxicity. We therefore investigated the movement of carbon 14-labeled fluorouracil from the vitreous into the anterior chamber in normal rabbit eyes and in eyes filled with either balanced salt solution or silicone after vitrectomy and lensectomy, with or without preservation of the anterior capsule. Only 0.56% of intravitreally injected fluorouracil was recovered from the anterior chamber over a four-hour period in normal eyes. This impermeability was partly maintained if the anterior capsule was retained (9.98%), particularly if the eye contained silicone (2.52%). The greatest amount was recovered when both lens capsules were removed (43.7%). Corneal toxicity is most likely to occur in this situation.

Animals↗

Relative permeability of retina and retinal pigment epithelium to the diffusion of tritiated water from vitreous to choroid.

The movement of intravitreally injected tritiated water from the vitreous to the choroid was accelerated by the removal of intervening retina. Both rate of transfer and peak choroidal levels of the tracer were increased, but the proportion of the intravitreal dose recovered was unaltered. In contrast, the movement of tritiated water after diffuse damage to the retinal pigment epithelium by sodium iodate was similar to that of control eyes. The main resistance to the diffusion of this tracer from the vitreous to the choroid is the retina. The differential permeability of the retina and the retinal pigment epithelium may have a role in normal retinal adhesion.

Animals↗

A case of congenital triple valve disease.

We report a case of congenital triple valve stenosis with dominant pulmonary valve disease, sparing the aortic valve, presenting at the age of 51 years with progressive shortness of breath and central cyanosis. At post mortem, no intracardiac right to left communication could be demonstrated.

Female↗

Alternatives to total parenteral nutrition in the critically ill patient.

Alternatives to total parenteral nutrition (TPN) can play an invaluable role in the support of the critically ill patient. However, the efficacy of this depends on: (1) early nutritional assessment; (2) sequential nutritional assessment as dictated by the clinical condition of the patient; (3) careful estimation of requirements based on calculated energy expenditure and use of the "stress-index"; (4) early use of enteral feedings in combination with peripheral and central intravenous routes, especially with the use of "feeding modules" to provide patient's specific concentrated diet; (5) use of intravenous fat as an isotonic supplement to dextrose in the presence of carbohydrate intolerance; (6) avoid overfeeding as rigorously as underfeeding; (7) continued clinical trials to determine optimal nutritional/metabolic support of the critically ill.

Amino Acids↗

Low-dose clozapine for the treatment of Parkinson's disease in a patient with schizophrenia.

Clozapine is known to be beneficial for the treatment of dopamine agonist-induced psychotic states in patients with Parkinson's disease (PD). Many reports have suggested that it may also be efficacious for the treatment of parkinsonian tremor. We describe a patient with schizophrenia in whom early-onset PD appeared after treatment with antipsychotic drugs. When the parkinsonian symptoms proved resistant to anticholinergic agents, we introduced a trial with up to 50 mg clozapine daily, which yielded a prompt and dramatic response. Thereafter, the parkinsonian symptoms reappeared each time the patient discontinued clozapine and rapidly disappeared on its repeat initiation. There was also a marked improvement in his psychotic and depressive symptoms. This report suggests that some patients with concomitant schizophrenia and PD-a difficult treatment challenge-may benefit from clozapine treatment alone for both disorders.

Adult↗