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Biomedical subjects

M D Becker

Publications and source records attributed to M D Becker.

32 records · Page 2Linked to original sources
PubMed2000

Toward new therapies for ocular inflammation.

While the use of this type of therapy and its application are far from immediate clinical application, the theory to support this approach is plausible. Most forms of anti-inflammatory therapy employed for ocular inflammatory diseases including iritis, scleritis, and chorioretinitis are derived from the success of these therapies for other organ systems. Just as ophthalmologists have the unique opportunity to visualize the hallmarks of the immune response, so do ophthalmologists have the unique opportunity to test this therapeutic approach which we speculate could offer improved efficacy and specificity over current modalities. Technological advances have helped to create an exciting era in ophthalmology. We believe that this technology can eventually be applied to the treatment of inflammatory diseases involving other body systems, as well as those primarily involving the eye.

Animals↗
PubMed1999

In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal angiogenesis.

PURPOSE: Numerous investigations have stressed the significance of leukocytes in early angiogenesis. Leukocytes invade the cornea, and the location of their extravasation corresponds to the site of vessel ingrowth. The interactions between leukocytes and vascular endothelium are mediated by various proteins, including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated in vivo. METHODS: Corneal neovascularization was induced in New Zealand White rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS: Limbal vessels showed increased leukocyte adhesion 24 hours after pellet implantation: The number of rolling and sticking leukocytes was significantly increased compared with the number in control animals (P < 0.01). Treatment with anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in early angiogenesis. This model may serve for investigation of the significance of adhesion molecules by in vivo observation and quantification.

Animals↗
PubMed1998

In vivo fluorescence microscopy of corneal neovascularization.

PURPOSE: The purpose of our study establish an animal model to study the microcirculation in corneal neovascularization in the living animal atraumatically. METHODS: Corneal neovascularization was induced in New Zealand white rabbits by a standard micropocket assay utilizing pellets with 250 ng basic fibroblast growth factor. Anesthesia consisted of intramuscular injections of ketamine and xylazine. Intravital microscopy was performed without preparation of the cornea. Rhodamine 6G was used as fluorescent dye to stain leukocytes. Fluorescein-isothiocyanate-dextran served as plasma marker. Microcirculation analysis was done off-line by digital video imaging with special analysis software and included the following parameters: vessel diameters, blood velocity, and differentiation of leukocytes according to their interaction with endothelium into free-floating. rolling and sticking leukocytes. RESULTS: Vessel diameters in venular trunk vessels showed diameters of 54.0 +/- 13.3 microns with 1.1 +/- 0.5 mm/s flow; 29.4 +/- 16.3% of all leukocytes were attached to the vascular wall. The number of sticking leukocytes was found to be 17.8 +/- 36.0 cells/mm endothelial surface. Values are given for arteriolar trunk and branch as well as venular branch vessels. CONCLUSIONS: This method for in vivo microscopic observation and quantification of the vasculature of the ocular surface seems to be suitable for evaluation of microhemodynamic and leukocyte measurements in mature neovascular vessels. It allows atraumatic experiments without corneal preparation procedures which disturb the microcirculation. The results concerning microhemodynamics and adherence of leukocytes are in a range comparable to other microcirculation studies. This new model could provide insight into the pathophysiology of microcirculatory disorders of the anterior eye segment, e.g. during angiogenesis.

Animals↗
PubMed1998

Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor.

BACKGROUND: Ocular diseases caused by neovascularization are among the leading causes of blindness. No specific pharmacological treatment is available. Among potential drugs, thalidomide deserves special interest since a wide body of clinical experience exists. However, its antiangiogenic effect is controversial. We therefore investigated the effect of thalidomide on corneal angiogenesis induced by vascular endothelial growth factor (VEGF), which has a special role among angiogenic growth factors. METHODS: Corneal neovascularization was induced in NZW rabbits by an intrastromal pellet loaded with 500 or 750 ng VEGF. Animals received two daily feedings of 200 mg/kg thalidomide. RESULTS: Significant inhibition of corneal angiogenesis (P < 0.0001) was caused by the teratogenic dose of thalidomide after the 5th day of treatment and persisted for more than 16 days. No obvious side effects were recorded. CONCLUSIONS: Thalidomide has a significant antiangiogenic effect against VEGF-induced neovasclar growth. Together with earlier findings this observation indicates that the drug inhibits two angiogenic pathways which are mediated through integrin adhesion molecules.

Administration, Oral↗
PubMed1998

Lung volumes before and after lung volume reduction surgery: quantitative CT analysis.

The volume and severity of pulmonary emphysema in individual lungs were measured by means of quantitative computed tomography (CT) studies in 28 patients (14 women, 14 men, median age 65 yr) who underwent either bilateral (n = 15) or unilateral (n = 13) lung volume reduction surgery (LVRS). Spirometric, total body plethysmographic, and CT data (at TLC and RV) were correlated before and after LVRS. Lung volumes determined by CT correlated well with volumes obtained by total body plethysmography (p < 0.0001). For individual lungs after LVRS, CT-derived mean lung capacity decreased 13% and residual volume 20% (p < 0.00001 for each), while mean total functional lung volume (TFLV, defined as the volume of lung with CT attenuation greater than -910 Hounsfield units) increased 9% (p < 0.01), and the mean ratio of the air space to tissue space volume (V(AS)/V(TS)) decreased more at RV (23%) than at TLC (14%) (p < 0.0005 for each). In contrast, unilateral LVRS did not affect exhalation from the unoperated lung (2% reduction in RV, p = NS). The magnitude of the postoperative response (CT-derived TLC, RV, TFLV, V(AS)/V(TS)) of each operated lung was comparable for unilateral and bilateral LVRS. Thus, a lung's response to LVRS was independent from that of the contralateral lung. Moreover, postoperative alterations in TFLV and FEV1 correlated significantly (r = 0.80, p < 0.0001), which suggests that the expansion of functioning tissue may contribute to the mechanism by which LVRS palliates airway obstruction.

Aged↗
PubMed1991

Amino acid sequence modulation of gramicidin channel function: effects of tryptophan-to-phenylalanine substitutions on the single-channel conductance and duration.

Linear gramicidins with one, two, or three Trp----Phe substitutions in the gramicidin A sequence form beta 6.3-helical channels that have widely varying conductances and average durations. The variations in single-channel conductance and average duration are uncoupled. The single-channel conductance decreases as a monotonic function of the number of Trp----Phe substitutions, and the relative conductance decrease induced by a given Trp----Phe substitution is only weakly affected by substitutions at other positions. These results suggest that each Trp influences the conductance independently, most likely through electrostatic interactions between the Trp dipole(s) and the permeant ion (as was deduced previously for aromatic side-chain substitutions at position one [Koeppe, R. E., Mazet, J.-L., & Andersen, O. S. (1990) Biochemistry 29 (2), 512-520]). Trp----Phe substitutions exert a complex, nonadditive influence on average duration as well as the energetics of heterodimer formation. These changes are presumably due to sequence-specific differences in the channel's surface chemistry--which may be related to ability of the Trp indole NH moieties to form hydrogen bonds with the lipid backbone oxygens and/or interfacial H2O.

Amino Acid Sequence↗
PubMed1979

Augmentation mammaplasty associated with a severe systemic illness.

A case report of a systemic, near-fatal illness possibly related to augmentation mammaplasty with silicone gel prostheses is presented. Twenty-four hours after the augmentation procedure, the patient, a 32-year-old woman, developed a high fever followed by diffuse arthritis, renal failure, and bilateral pulmonary infiltrates. Shortly after removal of the prostheses, the patient's condition improved dramatically. Samples from blood, urine, sputum, and breast pockets collected at the time of prosthesis removal demonstrated silicone polymers. Evidence is presented that indicates the illness was not of infectious origin.

Acute Kidney Injury↗
PubMed1978

Errors remaining in unit dose carts after checking by pharmacists versus pharmacy technicians.

The accuracy of pharmacists and pharmacy technicians in checking unit dose carts was compared. One-half of the unit dose patient medication drawers, for a 92-bed medicine service in a 450-bed teaching hospital, were checked by pharmacy technicians and the remaining by pharmacists. These drawers then were checked again to determine the number and type of checking errors committed by technicians and pharmacists. During the 10-day study, carts checked by pharmacists contained over twice as many errors (1.85%) as similar carts checked by technicians (0.87%). The results suggest that pharmacy technicians could probably be trained to perform the cart-checking task in unit dose drug distribution systems. Time-extended studies should be done to determine if technician performance is maintained after the novelty of the task wears off.

Drug Packaging↗