Characteristics of glaucoma drainage implants during dynamic and steady-state flow conditions

OBJECTIVE: This study aimed to ascertain whether the Optimed, Krupin, and Ahmed drainage devices function as valves that vary resistance depending on flow conditions to maintain pressure within a desired range. STUDY DESIGN: Experimental study. INTERVENTION: The three devices and a control cannula were submerged in fluid and perfused with balanced salt solution using a computer-driven apparatus that continuously monitors flow (Q) and pressure (P). In one set of experiments, the flow rates were maintained at 2, 5, 10, 25, or 50 microliters/min until steady-state pressures were achieved. In another set of experiments, the flow rate was increased linearly from 0 to 100 microliters/min over 15 to 20 minutes. MAIN OUTCOME MEASURES: The resistance of each implant was calculated from the first set of experiments by dividing the change in pressure (P) by the change in flow (Q) between successive perfusion rates. Flow-pressure curves were plotted from the experiments in which perfusion rate was increased linearly. RESULTS: Resistance remained relatively constant for the cannula (0.18-0.24 mmHg/microliter/min), the Krupin (0.09-0.25 mmHg/microliter/min), and the Optimed implants (0.04-0.08) throughout the tested flow rates. For the Ahmed device, conversely, resistance decreased proportionally (2.86-0.05 mmHg/microliter/min) to the increase in flow. When flow rate was increased linearly from 0 to 100 microliters/min, the Optimed and Krupin devices as well as the cannula generated a linear pressure response with a constant slope. The pressure in the two devices increased at a rate of 0.11 mmHg/microliter compared to 0.23 mmHg/microliter/min for the cannula. The flow-pressure curve for the Ahmed implant was distinct with a steep initial pressure rise and an essentially constant pressure of 12 mmHg thereafter. CONCLUSION: The Optimed and Krupin devices displayed resistance and pressure responses to various flow conditions that were similar to those of a cannula or flow resistor. In these devices, resistance remained relatively stable and pressure increased linearly with flow. The Ahmed device, conversely, functioned as a valve that closely regulated pressure within a desired range by decreasing or increasing resistance as a function of flow.     

In vivo targeting of acute myocardial infarction with negative-charge, polymer-modified antimyosin antibody: use of different cross-linkers

BACKGROUND: Cell surfaces and intercellular matrixes contain acidic residues, making them negatively charged. Antibodies are basic, positively charged glycoproteins. Therefore the potential for nonspecific ionic interaction exists, which could increase the background activity. Modification of antibodies with negatively charge-modified polymers have been shown to reduce this nonspecific background activity. This study was performed to investigate the appropriateness of different cross-linkers used covalently to link the chelating negatively charge-modified polylysine to antimyosin Fab (AM-Fab). The cross-linking was performed through peptide (AM-I) or thioether (AM-II) bonds. The in vitro evaluation of the immunointegrity and the in vivo assessment were performed to investigate the potential for reduction of nontarget background activity. Furthermore, the role of the charge of the polymers (whether completely negatively charge modified by succinylation [AM-IIs] or only partially negatively charge modified [AM-IIns]) was also assessed. METHODS AND RESULTS: All polymer-modified preparations (AM-I, AM-IIs, and AM-IIns) retained the immunoreactivities relative to the unmodified or conventional diethylenetriaminepentaacetic acid-coupled AM-Fab as assessed by radioimmunoassay or enzyme-linked immunosorbent assay. These polymer-modified preparations labeled with 111In were assessed in 13 rabbits with acute experimental myocardial infarction. Acute infarcts were produced by 40 minutes of left anterior descending coronary artery occlusion followed by reperfusion. At between 10 and 30 minutes of reperfusion, 10.4 +/- 1.8 mBq 111In-AM-I (10 to 20 micrograms; n = 7) or 11.4 +/- 2.3 mBq 111In-AM-II (n or ns) (20 to 25 micrograms; n = 6) was administered intravenously. Gamma imaging was performed in the left lateral position and arterial blood samples were withdrawn serially for the next 3 hours. At the end of the final imaging session, AM-I uptake was determined to be 1.09% +/- 0.11% (mean percent injected dose per gram myocardium +/- SEM) in 20 infarcted myocardial segments from seven rabbits, compared with 0.031% +/- 0.003% in 20 normal myocardial segments (infarct/normal myocardial ratio 53.9 +/- 18.41). The mean percent injected dose of 111In-labeled thioether-linked AM-Fab preparations in nine infarcted myocardial segments from each group was 0.067% +/- 0.008% (infarct/normal myocardial ratio 9.0 +/- 1.5) and 0.144% +/- 0.011% (infarct/normal myocardial ratio 10.2 +/- 1.9) with AM-IIs (n = 3) and AM-IIns (n = 3), respectively (p < 0.0001). The non-target organ distribution of the AM-I and AM-IIs was similar. AM-IIns preparation resulted in high non-target organ activities. CONCLUSIONS: This study shows that the charge of the antibody can be manipulated favorably by cross-linking with negatively charged polymers, which results in the reduced in vivo non-target organ activities. Charge modification does not adversely affect the apparent affinity of the antibody. However, the type of cross-linkers used may significantly influence the in vivo stability of the modified antibody preparations for target organ visualization. These data may find potential application in future clinical imaging protocols.     

Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.     

The effects of prednisolone on the cutaneous tuberculin response in patients with corticosteroid-resistant bronchial asthma

We have used the classical tuberculin cutaneous delayed hypersensitivity immune response to investigate the effects of corticosteroids on mononuclear cell function in nine subjects with corticosteroid-resistant asthma (CRA) and six subjects with corticosteroid-sensitive asthma (CSA), who demonstrated sensitivity to intradermal purified protein derivative (PPD) of Mycobacterium tuberculosis. In a double-blind, crossover, placebo-controlled study, patients were given oral prednisolone or placebo, starting on day 0, and a predetermined intradermal dose of PPD on day 7. On day 9 the site of the induration was measured and biopsied for immunohistochemical analysis. There was no difference in skin induration between the CSA and CRA groups during the placebo arm of the study (p = 0.38). Prednisolone significantly suppressed the cutaneous induration (p, 0.003) in the CSA group but not in the CRA group. As compared with placebo, the number of macrophages (p = 0.018), eosinophils (p = 0.009), and T memory cells (p = 0.009) was suppressed by prednisolone in the CSA group but not in the CRA group. No significant suppression of the number of neutrophils or monocytes/immature macrophages was induced by prednisolone in either group. There was no difference in intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 expression in blood vessels or epidermis between the CSA and CRA groups, with no suppression by prednisolone in either group. These findings suggest a defect in the responsiveness of cellular immune mechanisms to the suppressive effects of corticosteroids in steroid-resistant asthma. The differential suppressive effects of corticosteroids on cellular recruitment in the PPD response between the individuals with CSA and those with CRA are not due to modulation of expression of endothelial adhesion molecules.