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Biomedical subjects

S R Nelson

Publications and source records attributed to S R Nelson.

At least 19 recordsLinked to original sources

Vestibular and sensory interaction deficits assessed by dynamic platform posturography in patients with multiple sclerosis.

Vestibular impairments have not been routinely identified in patients with multiple sclerosis (MS), because of the confounding effects of deficits in other neural systems. In this study, 35 patients with MS were evaluated by means of a systematic alteration of the sensory environment (dynamic posturography) in order to identify those patients who became unstable when vestibular inputs were needed to maintain stance. Subjects were assigned to either a high-function (HF) or a low-function (LF) group on the basis of a functional status assessment score obtained prior to the posturography test. For the HF group, 30% (7/23) had abnormal posturography scores. Of those subjects, 3 had a vestibular dysfunction pattern or a somatosensory-vestibular impairment. In contrast, 58% of the LF group (7/12) had abnormal posturography scores. Nearly all of these LF patients (6/7) had a vestibular dysfunction pattern or a combined visual-vestibular or somatosensory-vestibular impairment. Posturography might serve as one method to evaluate the functional consequences of a vestibular deficit in patients with MS.

Adult

Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.

Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule.

Amyloid

Outcome of renal transplantation in hepatitis BsAg-positive patients.

Renal transplantation of patients with previous or ongoing hepatitis B virus infection has been tempered with a concern that immunosuppression may lead to viral replication and progressive liver damage. However, renal transplantation as therapy for end-stage renal failure in these patients improves quality of life and reduces the risk of body fluid exposure to their carers. To assess the long-term outcome of renal transplantation in hepatitis-BsAg-positive patients a retrospective study was carried out on the patients transplanted in this unit since 1969. Seventy-six patients received 98 grafts up to December 1991; follow-up was available on 68. Thirty-one of the 68 patients died; the causes of death were infective 23, cardiovascular 6, liver failure 4, pancreatitis 2, aspiration 1, GI haemorrhage 1, and stopped therapy 1. Serological markers of hepatitis B virus infection did not correlate with outcome. The risk of developing liver failure after renal transplantation appears small in the hepatitis-BsAg-positive patients and no patient should be denied a renal transplant on the basis of serological tests.

Adolescent

Evaluation of new high-performance calcium polyphosphate bioceramics as bone graft materials.

The purpose of this study was to evaluate the ability of a recently developed porous calcium polyphosphate bioceramic (CPB) to function as a bone graft substitute. After six weeks, postsurgical extraction of the mandibular first and second molars, alveolar ostectomies were performed bilaterally in five dogs. The ridge forms were then restored using the CPB implant material on one side and the autogenous bone obtained from the contralateral ostectomy site on the other. The graft and implant sites were retrieved after 4 months and decalcified and undecalcified sections were prepared for special staining (modified Attwood) and subsequent light microscopy and histomorphometry. In addition, the undecalcified sections were prepared for histometry using backscattered electron imaging (BSEI). Histologically, the CPB implants showed extensive vascularization and cellularity within an "invading" loose connective tissue matrix. On the opposite side, the loose connective tissue of the autografts showed hypovascularity and hypocellularity. Neither the implants nor the autografts showed any histologic evidence of an inflammatory reaction. Using light microscopic histomorphometry, the implants showed a higher incidence of union than the autografts. On BSEI histometry, the CPB implants showed significantly greater new bone formation than the autografts. This study reveals that porous CPB possesses certain characteristics essential for the "ideal" implantable bone substitute necessary for the repair of craniofacial and other bony defects.

Animals

The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products.

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.

Adult

Patterns of glucose use after bicuculline-induced convulsions in relationship to gamma-aminobutyric acid and mu-opioid receptors in the ventral pallidum--functional markers for the ventral pallidum.

Bicuculline-induced convulsions increased glucose use throughout the brain and sharply demarcated the ventral pallidum and globus pallidus. Glucose use in the nucleus accumbens also increased after bicuculline-induced convulsions, except for a circumscribed region in the dorsomedial shell. Since the projection from the nucleus accumbens to the ventral pallidum contains gamma-aminobutyric acid (GABA) and the opioid peptide, enkephalin, the pattern of increased glucose use in the ventral pallidum and nucleus accumbens after bicuculline-induced convulsions was compared to the topography of GABAA and mu-opioid receptors. The pattern of glucose use in the nucleus accumbens and ventral pallidum resembled the topography of GABAA, but differed from that of mu-opioid receptors. Bicuculline may disinhibit GABAergic efferents to the ventral pallidum resulting in a dramatic increase in glucose use within striatopallidal synaptic terminals as well as in local terminals of the pallidal projection neurons.

Animals

The osmotic/calcium stress theory of brain damage: are free radicals involved?

This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx of calcium (i.e., calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.

Amino Acids

Enhanced surgical exposure for the high extracranial internal carotid artery.

The need for enhanced surgical exposure for the high extracranial (Zone III) internal carotid artery is not uncommon. In certain circumstances, the posterior border and angle of the mandible may interfere with access to the distal internal carotid artery (ICA). The use of modified mandibular osteotomies has provided vascular surgeons in our institution with improved exposure of the ICA in selected cases. The intraoral sagittal split and extraoral vertical ramus osteotomies of the mandible allow manipulation of the posterior border and angle of the mandible with low morbidity and minimal postoperative complications. These procedures can be performed for both dentate and edentulous patients without the need for intermaxillary fixation. This paper introduces these modifications and discusses the benefits over previously described methods of mandibular manipulation.

Carotid Artery, Internal

Effects of polymerization contraction in composite restorations.

Post-gel polymerization contraction of resin composite induces contraction stresses at the composite-tooth bond and in surrounding tooth structure. Strain gauges have been shown to be an effective method for measuring linear post-gel polymerization contraction of composites. A new model was developed in which the composite sample was bonded to and circumscribed by an acrylic ring. The model simulates a composite restoration surrounded by dentine. A strain gauge measured the deformation of the ring while a second strain gauge simultaneously recorded the dimensional change of the sample. Stresses placed on the acrylic ring as a result of polymerization contraction of the composite were calculated, based on the strains on the ring and the ring's material properties. Four composites (Heliomolar, Vivadent, Tonawanda, NY, USA; Herculite XR, Kerr Manufacturing Co., Romulus, MI, USA; P-50, 3M Co., St Paul, MN, USA; Silux Plus 3M Co.) were evaluated for polymerization contraction strain and stress on the surrounding acrylic ring during polymerization. At the end of the 60 s light application, Heliomolar demonstrated significantly lower post-gel contraction (0.12 per cent, P less than 0.05) when compared to the other materials. When the strain reached an equilibrium at the end of 14 min Heliomolar continued to demonstrate lower post-gel contraction, however this was not statistically significant at P less than 0.05. When the contraction stress on the surrounding acrylic ring was considered, P-50 rapidly developed and produced the largest stress values (1.7 MPa) at the end of the light application while Heliomolar produced the lowest stress values (0.3 MPa). These values, however, were not significantly different when evaluated statistically.(ABSTRACT TRUNCATED AT 250 WORDS)

Composite Resins

Serum amyloid P component in chronic renal failure and dialysis.

A normal reference interval for serum amyloid P component (SAP) concentration in the serum was established in 500 healthy adult individuals (274 women, 226 men), by electroimmunoassay calibrated with standards of highly purified, isolated SAP. The mass of SAP in these was determined from the extinction coefficient of SAP at 280 nm measured here precisely for the first time by spectrophotometry and cryogenic drying. The mean (SD, range) SAP concentration was significantly lower in women: 24 mg/l (8, 8-55), compared to 32 mg/l (7, 12-50) in men (P less than 0.001). In renal insufficiency patients, 38 with chronic renal failure, 79 on hemodialysis and 66 on continuous ambulatory peritoneal dialysis, the mean values for SAP concentration were all significantly higher than normal (range of means, 39-59 mg/l in men and 35-42 mg/l in women), but did not correlate with serum creatinine, duration of dialysis or the presence of an acute phase response. The metabolism of SAP is thus altered in renal failure and is not normalized by dialysis, but it is not clear whether this is relevant to the pathogenesis of dialysis related arthropathy and amyloidosis.

Adult

Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component.

Long-term haemodialysis is frequently complicated by amyloid deposition in which the fibrils consist of beta 2-microglobulin. Dialysis-related amyloid disease causes extensive morbidity and has been associated with deaths in some cases. All amyloid deposits contain amyloid P component that is derived from the normal circulating protein, serum amyloid P component (SAP). We have used scintigraphic imaging after injection of 123I-labelled SAP to assess the distribution of amyloidosis in 38 patients receiving long-term haemodialysis for end-stage renal failure. There was focal localisation of tracer at all sites where histological examination confirmed amyloid deposition. Splenic uptake was seen in 12 patients, indicating splenic amyloidosis, but there was no evidence of other visceral involvement. 6 control subjects who had been dialysed for under 1.5 years showed no localisation of tracer, nor was there any uptake of 123I-labelled human serum albumin in 3 long-term dialysis patients with histologically confirmed amyloidosis and positive 123I-SAP images. Negative scans were also obtained in 5 patients who had been transplanted 0.8-2.4 years previously, despite past evidence of dialysis arthropathy (5) and histologically proven amyloidosis (4). 123I-SAP scintigraphy may be helpful as a non-invasive method for both the diagnosis and monitoring of dialysis-associated amyloidosis.

Amyloidosis

Isolation and characterization of the integral glycosaminoglycan constituents of human amyloid A and monoclonal light-chain amyloid fibrils.

Amyloid fibrils were isolated by extraction in water from the livers and spleens of four patients who had died of monoclonal, light-chain (AL)-type, systemic amyloidosis and one with reactive systemic, amyloid A protein (AA)-type amyloidosis. Each fibril preparation contained 1-2% by weight of glycosaminoglycan (GAG) which was tightly associated with the fibrils and not just co-isolated from the tissues with them. After exhaustive digestion of the fibrils with papain and Pronase, the GAGs were specifically precipitated with cetylpyridinium chloride and were identified by cellulose acetate electrophoresis and selective susceptibility to specific glycosidases. All the preparations contained approximately equal amounts of heparan sulphate and dermatan sulphate. There was no evidence for the presence of chondroitin sulphate or other GAGs. Fine structural analysis by oligosaccharide mapping in gradient polyacrylamide gels, following partial digestion with specific glycosidases, showed very similar structures among the heparan sulphates and the dermatan sulphates, respectively. GAGs were also extracted by solubilizing amyloid fibrils in 4 M-guanidinium chloride followed by CsCl density-gradient ultracentrifugation. Although a minor proportion of the GAG material obtained in this way was apparently in the form of proteoglycan molecules, most of it was free GAG chains. The presence in amyloid fibrils of different types, in different organs and from different patients of particular GAG classes with similar structures supports the view that these molecules may be of pathogenic significance.

Amyloidosis

Lithium modifies convulsions and brain phosphoinositide turnover induced by organophosphates.

Inositol-1-phosphate (Ins1P), an index of phosphoinositide (PI) turnover, was measured in frontal and piriform cortices, caudate, thalamus, hippocampus and cerebellum in saline or LiCl (5 m Eq./kg) pretreated rats 60 min. after graded doses of DFP, paraoxon, or soman. DFP only produced bursts of convulsive activity whereas both paraoxon and soman produced prolonged tonic-clonic convulsions. All three organophosphates (OP) produced convulsions at a lower dose in LiCl than in saline pretreated rats. Regional Ins1P correlated better with the presence or absence of convulsions than with the dose of paraoxon or soman. This was true both in saline and LiCl pretreated rats. In saline pretreated non-convulsing rats, there was a cholinergic increase (1.5-2.0 X) in Ins1P in all brain regions except cerebellum after OP injection. In saline pretreated convulsing rats, there was a marked seizurogenic further increase in Ins1P; highest in caudate (8 X) and cortex (6 X). In LiCl pretreated nonconvulsing rats, the OP-induced cholinergic increase in Ins1P was significant only in caudate, thalamus and hippocampus. In LiCl pretreated convulsing rats, the further seizurogenic increase in Ins1P was less than in saline pretreated rats except in thalamus and hippocampus. Thus, OP produce both a cholinergic and a seizurogenic increase in PI turnover. These data suggest that increased PI turnover in the hippocampus may indicate a lithium-induced lowering of the seizure threshold for OP in limbic regions.

Animals