A novel application of high-dose (50 kGy) gamma irradiation for demineralized bone matrix: effects on fusion rate in a rat spinal fusion model

BACKGROUND CONTEXT: The safety of allograft material has come under scrutiny because of recent reports of allograft-associated bacterial and viral infections in tissue recipients. Gamma irradiation, although being one of the most effective ways of terminal sterilization, has been shown to affect the biomechanical properties of allograft bone. It may also have detrimental effects on the osteoinductivity of allograft material such as demineralized bone matrix (DBM) by the denaturation of proteins because of heat generated by irradiation. Sterilization of DBM material is an important variable in processing graft materials. This is considered to be one of the factors leading to different fusion rates observed with different commercially available DBM products, as the sterilization procedure itself may affect the osteoinductivity of the material. Currently, there is no ideal sterilization technique that limits the detrimental effect on osteoinductivity and fusion rates. PURPOSE: To evaluate the effects of a range of hydrogen peroxide exposures with or without the controlled high-dose gamma irradiation after processing with radioprotectant solutions (Clearant radiation sterilization procedure) on the fusion rates of human DBM. STUDY DESIGN: A prospective in vivo animal study. METHODS: Eighty mature athymic nude female rats were used for this study, which formed 10 equal groups. Human DBM exposed to hydrogen peroxide for different time periods (0, 1, 6, and 24 hours) was divided into two major subgroups. One group was further treated with controlled high-dose radiation using radioprotectants (radiation treated), whereas the other group was frozen immediately without specific treatment (non-radiation treated). Both radiation-treated and non-radiation-treated DBM material from each group of hydrogen peroxide exposure times were implanted between L4 and L5 transverse processes of the rats forming eight test groups including eight animals in each. The remaining 16 rats were divided into two additional groups to form negative (only decortication, n=8) and positive (bone morphogenetic protein [BMP]-2, n=8) control groups. The rats were evaluated for fusion by radiographs (2, 4, and 8 weeks), manual palpation (8 weeks), and histological analysis after sacrificing. Comparison of fusion rate among all groups was made using these three evaluation methods. RESULTS: Increasing the time period of hydrogen peroxide (0, 1, 6, or 24 hours) exposure for preparation of DBM from bone allograft did not affect the fusion rates significantly (p<.05), although there was a trend toward decreasing fusion rates with longer exposure times. When the hydrogen peroxide washed DBM preparations were also radiation treated, the resulting fusion rates were again not significantly different (p<.05). Agreement among fusion detection methods was found to be high. CONCLUSIONS: Hydrogen peroxide processing was not detrimental to fusion rates. The additional terminal sterilization technique with special gamma irradiation protocols (Clearant process) also did not decrease the fusion rates but could provide an additional margin of safety.     

Ratio of transverse to longitudinal resistivities of isolated cardiac muscle fiber bundles

The ratio of transverse to longitudinal resistivities (рt/р1) of isolated cat cardiac muscle bundles (papillary muscles and ventricular trabeculae) composed of parallel fibers was measured and compared with frog sartorius muscles. Similar measurements made on a physical model representing such bundles of parallel fibers, consisting of layers of glass rods orderly packed with Ringer solution filling the interstices, gave a рt/р1 of 7. This ratio averaged 11 for cardiac muscle and 21 for skeletal muscle, indicating that in both muscles the transverse conductivity and effective diffusion coefficient are much less than the longitudinal values. Equilibration of cardiac muscle in ten-fold diluted Ringer (sucrose to isotonicity) to raise the resistance of the interstitial fluid (ISF) 8.5-fold raised р1 6.3-fold, but hardly affected р1, so that рt/р1 was markedly reduced to 2.0. In sartorius, the high-resistance solution had much less of an effect on р1 or on рt/р1. Equilibration in hypertonic Ringer (2 X isotonicity with sucrose) raised р1 and lowered рt slightly in both types of muscles, resulting in a small decrease in рt/р1. Calculations of the ratio of the resistance of the cellular pathway to that of the extracellular pathway averaged 20 for cardiac muscle compared to only 0.82 for skeletal muscle. The data indicate that the longitudinal current path through the myocardial cells is high in resistance compared to that through the ISF, suggesting that the intercalated disks are high-resistance membranes. The resistivity of the disk membranes averages 576 Ω-cm², assuming a 6.4-fold increase in surface area due to convolutions; this value approaches that of the sarcolemma, and is much higher than the maximum (2 Ω-cm²) allowable for significant DC electrical coupling to occur between contiguous cells. The fact that the extracellular fluid of a parallel-fibered muscle bundle itself acts as a cable could account for the observation that measurements of the tissue length constant by extracellular application of current give large values; thus, such measurements cannot be used to determine the resistance of the cell junctions in muscles composed of short cells.     

Color perception under chromatic adaptation: "supersensitivity" with dim backgrounds

The amounts of 540 nm light and 660 nm light that when mixed result in a yellow (neither reddish nor greenish) percept remain in constant ratio, regardless of the total retinal illumance level of the mixture. A similar result holds if the mixture is superimposed upon a very dim 660 nm adapting field, except that a larger proportion of 540 nm light is required than in the dark (contrary to an effect of receptor desensitization, which would result in a smaller proportion of 540 nm light). Mixtures of 460 and 579 nm lights that give yellow/blue equilibrium percepts show the same effect: under very dim 579 nm adaptation, a larger proportion of 460 nm light is required than in the dark. These results cannot be accounted for by cone sensitivity reduction nor by a postreceptoral restoring effect; they reveal an additional mechanism of adaptation.     

Squamous papilloma of esophagus

Four additional cases of squamous papilloma of the esophagus are reported. They were diagnosed and resected endoscopically by the excisional biopsy technique and confirmed histologically. A brief survey of the literature is included. This report is presented to stress the recognition and clinical implications of this entity.     

Diazepam-induced changes in tardive dyskinesia: suggestions for a new conceptual model

Using an ABA' research design, the effects of a benzodiazepine gamma-aminobutyric acid (GABA)-ergic agent, diazepam, on various aspects of tardive dyskinesia (TD) were investigated in 21 patients. Videotaped recordings of the examinations were rated blind on the Abnormal Involuntary Movements Scale. In nonsedating amounts, diazepam had a significant anti-TD effect, especially in terms of limb dyskinesia. A significant portion of the therapeutic effect persisted after the medication was withdrawn. The results suggest that diazepam has a specific anti-TD action and that in some cases it may be able to produce a somewhat lasting correction of the deranged neurobiological mechanisms in TD. Since the main sites of action of benzodiazepines and the highest concentrations of benzodiazepine-linked GABA receptors are in the limbic and cortical structures that provide principal sources of inputs to the basal ganglia, it is suggested that the supra-striato-pallidal mechanisms of voluntary movement control should be considered in understanding the pathogenesis and treatment of TD.