Approaching Social Security disability cases via "impairment listings".
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Disability Evaluation↗
Biomedical subjects
L R Williams
Publications and source records attributed to L R Williams.
Exogenous matrix precursors promote functional nerve regeneration across a 15-mm gap within a silicone chamber in the rat.
When silicone regeneration chambers are implanted empty, axonal regeneration fails if the interstump gap length is greater than 10 mm. Previous experiments using the 10-mm gap model demonstrated that regeneration success correlated with the dimension and/or consistency of the naturally formed acellular fibrin matrix. Both spatial and temporal parameters of regeneration could be stimulated through modifications of the fibrin matrix by prefilling the chambers at the time of implantation either with phosphate-buffered saline or plasma dialyzed against phosphate-buffered saline. In the present experiments, similar modification of matrix formation was found to promote successful regeneration across 15-mm and 20-mm interstump gap lengths. In addition, prefilling 15-mm-gap chambers with dialyzed plasma resulted in a 3.5-fold increase in the incidence of functional restitution detected at 8 weeks after implantation over the outcome with chambers prefilled with phosphate-buffered saline.
Animals↗
Nerve regeneration chamber: evaluation of exogenous agents applied by multiple injections.
In this laboratory, a silicone chamber model for peripheral nerve regeneration in adult rats has been developed and used to define basic principles of the regenerative events, such as the sequential stages being followed during 'spontaneous' regeneration in vivo and the role of neuronotrophic- and neurite-promoting factors as well as extracellular matrix molecules. Each of the defined stages seems amenable to experimental modulation. Previous attempts to enhance regeneration included increasing the volume of the nerve chambers along with the modification of fibrin matrix formation by prefilling with saline (PBS) or matrix precursors. We present here the results of a series of experiments on the effects of exogenous biochemical agents applied by multiple injections into these in vivo chambers. Out of a variety of agents screened, a mixture of laminin (L), testosterone (T), ganglioside GM 1 (G), and catalase (C) was shown to advance substantially the progress of regeneration in 16 day chambers, as compared to PBS-prefilled and PBS-injected controls. LTGC-treatment at day 0, 6, and 10 postimplantation caused an increasingly frequent occurrence of cellular elements in cross-sections obtained from the middle (S5) of the chambers (i.e. 5 mm from the proximal stump), which was 2-fold for vessels, 3-fold for Schwann cells, and 10-fold for axons. When only sections containing axons 3 mm from the proximal stump (S3) were compared in experimental and control groups, computerized area measurements also revealed an average 2-fold difference for the cross-sectional size of the whole regenerate, the endoneurium and the space occupied by blood vessels.
Animals↗
Loss of GABAergic neurons in medial septum after fimbria-fornix transection.
Neurons in the medial septum of the rat brain undergo retrograde degeneration after transection of their projection to the hippocampal formation, the fimbria-fornix. This cell death has been characterized for both Nissl-stained neurons and acetylcholinesterase-stained neurons. The major cell type in the medial septum is GABAergic, and many of these GABAergic neurons project to the hippocampal formation. Because the fimbria-fornix transection causes more neuronal death than can be accounted for by the loss of cholinergic neurons, we have sought to determine if the GABAergic neurons undergo a cell death similar to that reported for the cholinergic neurons. We report here that GABAergic neurons are indeed lost after the transection but the time course is considerably slower than that for the cholinergic neurons.
Animals↗
Exogenous fibrin matrix precursors stimulate the temporal progress of nerve regeneration within a silicone chamber.
The silicone chamber model permits the investigation of the cellular and molecular events underlying successful regeneration of the rat sciatic nerve across a 10 mm gap. When 25 microliter chambers are implanted prefilled with phosphate-buffered saline (PBS), it takes 5-7 days before sufficient fibrin matrix (derived from plasma precursors) accumulates naturally to form a complete bridge across the chamber gap; at 1 week postimplantation, cellular migration into the matrix from the nerve stumps is just beginning. The temporal progress of regeneration might be stimulated if a fibrin matrix, conducive to cell migration, was provided to the nerve stumps at or shortly after the time of chamber implantation. To test this hypothesis, chambers were prefilled, at the time of implantation, with different preparations of homologous plasma. A solution of 90% platelet-free plasma dialyzed against PBS (DP) formed a fibrin matrix by 24 hours postimplantation that, like the naturally formed matrix, had a predominantly longitudinal orientation. The temporal progress of regeneration was stimulated in the DP-prefilled chambers; at 17 days postimplantation, the extents of Schwann cell migration and axonal elongation were significantly greater than in the control system. In contrast, prefilling chambers with either non-citrated plasma or DP + calcium resulted in the generation of a matrix within 8 minutes that was composed of randomly oriented fibrin polymers. These matrices significantly retarded the progress of regeneration.
Animals↗
Rat aorta isografts possess nerve regeneration-promoting properties in silicone Y chambers.
Recent investigations using synthetic entubation materials have demonstrated that nerve regeneration across a gap requires peripheral nervous tissue as a distal component within the chamber. Regeneration fails if the distal end of the regeneration chamber remains open to the environment, or is filled with tendon or skin. These results are contrary to those of Weiss and Taylor (1944) who used homologous aorta as a chamber material and found that regeneration was successful across a gap regardless of the distal tissue, even in the branches of the aorta that were closed or open. In the present report, silicone Y chambers were implanted with the distal branch remaining open, or filled with pieces of nerve, tendon, or isologous aorta. A homogenous fibrin matrix formed in all the chamber branches by 1 week postimplantation. At 4 weeks, regeneration across a 10-mm gap failed in the chamber branches that were open or filled with tendon. However, regeneration was successful in those branches containing aorta or nerve. These experiments strongly support the hypothesis that aorta tissue, like peripheral nervous tissue, is a source of regeneration-promoting materials. The results provide a probable explanation for and a reconciliation of the discrepancies between the earlier observations of Weiss and Taylor and those of more recent investigators.
Animals↗
A small-gauge cannula device for continuous infusion of exogenous agents into the brain.
A method is described for the construction of an intraventricular or intraparenchymal cannula device, which when connected to an Alzet osmotic pump, can be used for the continuous infusion of experimental solutions into the brain. A 33-gauge, stainless-steel cannula is encased within a dental acrylic stabilization platform prior to stereotaxic implantation, and after implantation, the platform is glued to the animal's skull using cyanoacrylate adhesive. This procedure provides for the long-term stability (at least 4 weeks) of the small-gauge cannula without the need for additional stabilization skull screws, thus minimizing damage to surrounding tissues by the cannula and postsurgical trauma to the animal. Using the stock model 2002 Alzet pump to infuse artificial cerebral spinal fluid at a flow rate equal to 0.5 microliter/h, an inflammatory tissue reaction around the cannula tip was consistently found after 2 weeks of continuous intraparenchymal infusion. However, the inflammatory reaction could be significantly reduced or eliminated by decreasing the flow rate to approximately 0.25 microliter/h, using a modified Alzet pump. Alternatively, the stock 0.5 microliter/h pump could be used without causing parenchymal damage if the cannula tip was implanted into the lateral ventricle.
Animals↗
An interlaboratory study of an EPA/Ames/Salmonella test protocol.
7 laboratories participated in a collaborative study to evaluate an EPA standard protocol for the Ames test. The study utilized Salmonella typhimurium (strains TA98 and TA100) and 3 metabolic activation levels (0%, 2%, and 10% S9 in the S9 mix). 6 pure chemicals and 2 complex mixtures were tested as coded unknowns. Ability to obtain qualitative results in agreement with published data was less (% agreement) than that reported in an earlier study (% agreement) by de Serres and Ashby (1981) in which each laboratory used its own protocol. The conclusion from analysis of the quantitative data from this interlaboratory Ames study was that both intralaboratory and interlaboratory variations were substantial. Results for the same substance varied by an order of magnitude or more (CV of 115%) when the mutagenic response was measured as the slope of the dose response in revertants/microgram. Taking interlaboratory variation into account, one chemical must be more than an order of magnitude more mutagenic than another (ratio of slopes greater than 10) to have only an even chance of finding a statistically significant difference between the two chemicals at the 5% level. Such large variations must be taken into account when evaluating Ames/Salmonella data.
Analysis of Variance↗
Exogenous administration of neuronotrophic factors in vivo protects central nervous system neurons against axotomy induced degeneration.
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Acetylcholinesterase↗
The distribution of intracellular alkali metals in Reference Man.
A review of recent literature and a re-analysis of data used in Publication 23 of the International Commission on Radiological Protection (ICRP) have revealed several problems regarding the distribution of the predominantly intracellular alkali metals potassium, rubidium and caesium in ICRP Reference Man. In this paper we re-evaluate the distribution of the intracellular alkali metals in humans and we offer an approach for selecting reference concentrations for the organs of a typical adult human. For non-skeletal tissues, reference values for K, Rb and Cs are determined as a trimmed weighted mean of reported values remaining after studies involving apparently questionable populations or measurement techniques have been eliminated. The skeleton is treated as a special case, with explicit consideration being given to the heterogeneous distribution of these elements among different regions and different types of skeletal tissue. The most significant suggested changes for the intracellular alkali metals are for Rb in the skeleton and total body. ICRP Reference Man has a total Rb content of 0.68 g, compared with our estimate of only 0.25 g, and a skeletal Rb content of 0.21 g, compared with our estimate of only 0.013 g. This has important dosimetric implications for radiorubidium, because the retention model for Rb given in ICRP Publication 30 assigns a large portion of an intake to the skeleton on the basis of the large skeletal Rb content assigned to Reference Man in ICRP Publication 23.
Body Composition↗
Work and health around the world.
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Accident Prevention↗
Purification of adult rat sciatic nerve ciliary neuronotrophic factor.
The ciliary neuronotrophic factor (CNTF), a protein required for the survival of cultured avian embryonic parasympathetic ciliary ganglionic neurons, was recently purified from extracts of selected chick intraocular tissues. Here we report the purification of a mammalian CNTF activity from extracts of adult rat sciatic nerve using a fractionation procedure similar to that employed for isolating chick eye CNTF. About 2 micrograms of CNTF protein can be obtained from each 1.5 g batch of nerve tissue. Like the chick CNTF, the mammalian factor displays trophic activity for dorsal root and sympathetic as well as ciliary ganglionic neurons. The nerve CNTF activity differs from its chick counterpart in molecular weight and chromatographic behavior on ion-exchange columns. Unlike purified nerve growth factor (NGF), nerve CNTF activity is insensitive to anti-NGF antibodies and is unable to support the survival of 8-day chick embryo dorsal root ganglion neurons.
Animals↗
Descending thoracic aorta-to-femoral artery bypass.
Descending thoracic aorta-to-femoral artery grafts were placed in 13 patients who had abdominal aortas deemed undesirable for surgical treatment. These included seven patients in whom an infected aortic graft had been removed for primary graft infection (three) or aortoduodenal fistula (four). These patients had been treated initially with axillary-femoral grafts. In five other patients, this approach was used following failure of at least two previous aortofemoral grafts. The remaining patient was so treated following multiple complex abdominal operations. The surgical technique involves a posterolateral, seventh interspace thoracoabdominal incision with a transdiaphragmatic retroperitoneal tunnel to the left groin. There was no operative mortality. The mean follow-up of all patients was 22 months (range, one to 44 months). All grafts remained patent except one, which was removed because of ascending groin infection. Three patients died, at 24, 29, and 44 months postoperatively, respectively. Reasonable perioperative morbidity and reliable patency make this an attractive technique for the conversion of axillofemoral bypasses and, when reentry of the abdominal cavity is undesirable, laparotomy is avoided.
Aorta, Thoracic↗
Supine exercise testing in the selection of suprainguinal versus infrainguinal bypass in patients with multisegmental arterial occlusive disease.
Proper assessment of aortoiliac disease requires hemodynamic evaluation during lower extremity vasodilatation. Two tests that meet this criterion, intraarterial papaverine injection and supine exercise of the lower extremities, were compared in 35 extremities of 27 patients. Hemodynamic improvement as measured postoperatively was used as the standard for comparison. Ergometer and papaverine tests were 100 percent and 94 percent accurate, respectively, had sensitivities of 100 percent and 100 percent, specificities of 100 percent and 93 percent, positive predictive values of 100 percent and 75 percent, and negative predictive values of 100 percent and 100 percent. The lower accuracy rate for the papaverine test was the result of two borderline (false-positive) examinations. The ergometer test is more accurate but less applicable than the papaverine test. Routine papaverine testing with adjunctive ergometer testing is a highly accurate method of assessing the hemodynamic significance of aortoiliac disease.
Aorta, Abdominal↗
Retrograde cell changes in medial septum and diagonal band following fimbria-fornix transection: quantitative temporal analysis.
Complete unilateral fimbria-fornix transections, including the overlying cingulate cortex, were administered to female rats. At time points from 1 day to 6 weeks, the septal-diagonal band region was examined using acetylcholinesterase histochemistry, Cresyl Violet cell staining, and choline acetyltransferase biochemistry. As early as 1 day following the transection a decrease in acetylcholinesterase positive cell body staining was observed in the medial septum; however, no loss of Nissl-stained neurons was measured in Cresyl Violet stained sections until 1 week after the lesion. Maximal loss of acetylcholinesterase-positive cells, as visualized after irreversible acetylcholinesterase inhibition, was measured at 1 week, and no further change was observed at time points up to 6 weeks after operation. The loss of acetyltransferase-positive cells was greatest in the medial septal area (-65%) and the vertical limb of the diagonal band (-55%). Little cell loss was measured in the horizontal limb of the diagonal band. This is consistent with the known projections of these cell bodies. Remaining acetylcholinesterase-positive cell bodies in the medial septum had shrunk by about 20% (measured as the diameter along the major axis). A marked neuronal cell loss (about 50%) was demonstrable in the medial septum and vertical limb of the diagonal band in the Cresyl Violet-stained sections, too. A pile-up of acetylcholinesterase-stained material was observed in the dorsal-lateral quadrant of the septal area just proximal to the lesion at 1 day following transection. This pile-up occurred in the medial septum and diagonal band area up to 1 week following the transection, and had nearly disappeared by 2 weeks post-transection. Choline acetyltransferase biochemical activity, measured in samples of whole septum, decreased significantly at 1 day but subsequently returned to control levels. By 2 weeks following transection, an increase in acetylcholinesterase-positive stained fibers was observed in the dorsal-lateral quadrant of the septum, ipsilateral to the lesion relative to the contralateral septum. This response, which was interpreted as sprouting from the lesioned axons proximal to the transection, probably accounted for the rise in choline acetyltransferase biochemical activity in the whole septum following the reduction on the first day.
Acetylcholinesterase↗
Hair transplantation producing arteriovenous fistulization.
Arteriovenous fistula formation is a rare complication of the punch graft technique of hair transplantation. This report describes a large donor site arteriovenous fistula that was clearly demonstrated on arteriography. Operative correction was guided by precise directional Doppler ultrasound localization of the fistulous communication, thus avoiding a large disfiguring incision.
Adult↗
Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection.
Neurons in the rat medial septum (MS) and vertical limb of the diagonal band of Broca (VDB) undergo a rapid and severe cell death after transection of their dorsal projection to the hippocampus by aspiration of the ipsilateral fimbria fornix and supracallosal striae. By 2 weeks posttransection, the extent of neuronal loss was 50% of the total neurons and 70% of the cholinergic neurons in the MS and 30% of the total neurons and 40% of the cholinergic neurons in the VDB. We hypothesized that (i) the death was due to the loss of a hippocampus-derived neuronotrophic factor, and (ii) exogenous nerve growth factor (NGF) might provide trophic support to the MS/VDB cholinergic neurons, in light of recent reports that the septal diagonal band cholinergic neurons are responsive to NGF and that NGF is present and produced in the hippocampus. In the present study, we attempted to prevent the transection-induced neuronal death by continuous infusion of exogenous 7S NGF (1 microgram/wk) through an intraventricular cannula device. We report here that NGF treatment significantly reduces both the total neuronal and cholinergic neuronal death found 2 weeks after fimbria fornix transection; there was a sparing of 50% of the neurons in the MS and essentially 100% of those in the VDB that otherwise would have died. We conclude that NGF also has a protective effect on noncholinergic neurons since calculations indicate that 80% of the NGF-affected neurons are noncholinergic.
Animals↗