Biomedical subjects

S M Hall

Publications and source records attributed to S M Hall.

At least 55 records · Page 3Linked to original sources

PubMed1998

Chronically denervated rat Schwann cells respond to GGF in vitro.

C-erbB receptor/neuregulin signalling plays a significant role in Schwann cell function. In vivo, Schwann cells up-regulate expression of c-erbB receptors in the first month after injury, but receptor expression is down-regulated with time to levels that are not detectable immunohistochemically. The inability of chronically denervated Schwann cells to respond adequately to signals derived from regenerating axons may be one reason why delayed repair of an injured peripheral nerve frequently fails. We have examined the effects of GGF on denervated Schwann cells in vitro. A modified delayed dissociation technique was used to obtain adult rat Schwann cells from the distal stumps of transected sciatic nerves which had been acutely (7 days) or chronically (2-6 month) denervated. We found that in vitro denervated Schwann cells invariably expressed p75NTR and c-erbB receptors. There was a progressive decrease in total cell yield and the percentage of cells with Schwann cell phenotype (p75NTR and/S-100 or/laminin or /GFAP or/c-erbB positive); proliferation rate; migratory potential; and expression of the cell adhesion molecules N-CAM and N-cadherin, with increasing time of denervation. Addition of GGF2 had a significant stimulatory effect upon Schwann cell proliferation and migration, and an increased proportion of Schwann cells expressed N-CAM and N-cadherin, suggesting that these responses were mediated via GGF/c-erbB signalling. Our results support the view that it may be possible to manipulate chronically denervated Schwann cells so that they become more responsive to signals derived from regrowing axons.

Animals↗

PubMed1997

Effects of delayed re-innervation on the expression of c-erbB receptors by chronically denervated rat Schwann cells in vivo.

We propose that chronically denervated Schwann cells may be less able to respond to axonal signals than their acutely denervated counterparts, and that this lack of sensitivity may be one reason why axons fail to regenerate into chronically denervated nerve stumps. To test this proposal we have used in situ hybridization, and quantitative and qualitative immunohistochemistry to compare the expression of c-erbB2 and c-erbB4 receptors in Schwann cells denervated for up to 6 months in vivo, with that seen in Schwann cells denervated for similar periods of time but then exposed to regenerating axons. The results were correlated with the extent of axonal regeneration in each experimental group as assessed from transverse sections which had been double-immunolabelled using anti S-100 and anti-beta tubulin III antibodies. Since c-erbBs are receptors for neuronally derived neuregulins we probed the appropriate axotomised DRG neurons for expression of GGF2 mRNA. When the denervated distal stumps were anastomosed to acutely transected proximal stumps, GGF expression in DRGs increased transiently during the first week: we assume that secreted GGF2 derived from regrowing axon sprouts would have been available to Schwann cells in all distal stumps. Endoneurial cell proliferation (predominantly Schwann cell proliferation); levels of expression of c-erbB receptors by Schwann cells, and the degree to which axons regenerated into the distal stumps all decreased as the period of prior denervation increased: the longer the time of denervation, the lower the expression of c-erbBs in Schwann cells, and the smaller the percentage of bands of Bungner which were re-innervated.

Animals↗

PubMed1997

Use of high dose benzodiazepines in alcohol and sedative withdrawal delirium.

The authors describe two patients who required massive doses of benzodiazepines to treat complicated alcohol and sedative withdrawal delirium. Some of the factors that contribute to difficulties in management are discussed. Finally, we describe the advantages and disadvantages of high dose pharmacologic management and controversies regarding psychopharmacologic management of such complex patients.

Adult↗

PubMed1997

Schwann cells responding to primary demyelination in vivo express p75NTR and c-erbB receptors: a light and electron immunohistochemical study.

We have used quantitative and qualitative light microscope immunohistochemistry to examine the expression of p75NTR and c-erbB receptors in Schwann cells in a demyelinating lesion induced by the intraneural injection of lysophosphatidyl choline (LPC). We report that levels of p75NTR, c-erbB2 and c-erbB4, as assessed using image analysis of immuno-peroxidase labelled sections, and c-erbB3, as assessed by eye, increased within each lesion site soon after the initiation of myelinolysis, peaked between 5 and 8 days after induction of demyelination and fell to undetectable levels at the onset of remyelination. Pre-embedding immunoelectron microscopy confirmed that Schwann cells ensheathing demyelinated axons were p75NTR positive. Immunolabel decorated overlapping processes of neighbouring Schwann cells, suggesting that in this context p75NTR could play a role in juxtacrine signalling between reacting cells. We conclude that upregulation of p75NTR and c-erbB receptors is a constitutive Schwann cell response to an acute disruption of the axon-Schwann cell relationship.

Animals↗

PubMed1996

An immuno-electronmicroscopical study of the distribution of laminin within autografts of denatured muscle.

We have used an immunogold post-embedding technique to examine, qualitatively and quantitatively, the distribution of laminin along sarcolemmal basal laminae of variously treated muscle autografts placed in transected rat sciatic nerves. We found that freeze-thawing or heating to 60 degrees C prior to grafting did not affect laminin labelling density along the sarcolemmal basal laminae, either at the time of preparation or 7 days after grafting. In sharp contrast, heating to 80 degrees C significantly reduced laminin labelling density. These findings are consistent with our earlier work showing that frozen-thawed or 60 degrees C muscle autografts both support axonal regeneration, whereas 80 degrees C grafts do not, and add further support to the view that laminin is a functionally important molecule in nerve regeneration. We have compared immunostaining using 10 nm gold particles with silver enhancement of 5 nm gold particles: although labelling density was higher in the silver-enhanced preparations, there was no increase in background labelling. Although empty sarcolemmal basal lamina tubes were frequently highly infolded, there was no evidence of preferential labelling of either 'peaks' or 'troughs' of the infolded basal laminae.

Animals↗

PubMed1996

Mood management and nicotine gum in smoking treatment: a therapeutic contact and placebo-controlled study.

Earlier research indicated that a 10-session mood management (MM) intervention was more effective than a 5-session standard intervention for smokers with a history of major depressive disorder (MDD). In a 2 x 2 factorial design, the present study compared MM intervention to a contact-equivalent health education intervention (HE) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD. Participants were 201 smokers, 22% with a history of MDD. Contrary to the earlier findings, the MM and HE interventions produced similar abstinence rates: 2 mg gum was no more effective than placebo. History-positive participants had a greater increase in mood disturbance after the quit attempt. Independent of depression diagnosis, increases in negative mood immediately after quitting predicted smoking. No treatment differences were found in trends over time for measures of mood, withdrawal symptoms, pleasant activities and events, self-efficacy, and optimism and pessimism. History-positive smokers may be best treated by interventions providing additional support and contact, independent of therapeutic content.

Adult↗

PubMed1996

The changing clinical pattern of Reye's syndrome 1982-1990.

OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.

Aspirin↗

PubMed1996

Effect of cold preservation on pulmonary arterial smooth muscle cells.

The efficacy of preservation fluids on the cytoskeleton and contractile function of porcine pulmonary arterial smooth muscle (SM) cells during cooling and rewarming was evaluated, using EuroCollins solution (EC), University of Wisconsin solution (UW), Marshall's solution (MS), and tissue culture growth medium (GM). Functional studies included passive distensibility and contraction to prostaglandin F2a (PGF2a) in arterial rings and wrinkling of silicone membranes by cooled-rewarmed cultured SM cells. Immunofluorescence measurements were made of actin brightness in cooled arterial rings. Cultured SM monolayers were stained with antibodies to SM alpha-actin, SM myosin, and tubulin. In cooling, all solutions resulted in increased arterial distensibility, whereas EC and MS reduced cell wrinkling. With the use of all solutions, actin cables thinned, myosin filaments dissociated, and microtubules depolymerized. During rewarming, resistance to imposed tension increased in all arterial rings. After GM,ED, and MS preservation, contraction to PGF2a increased. Wrinkling increased and actin-myosin cables shortened after GM and EC; after UW, wrinkling decreased and actin-myosin cables thinned. No recovery occurred after MS. Thus the type of preservation solution influenced contractility during preservation and after rewarming. The absence of spontaneous contraction in cells cooled in UW may be advantageous.

Actins↗

PubMed1995

Toxoplasmosis in England and Wales 1981 to 1992.

We have examined laboratory reports of toxoplasmosis received by the PHLS Communicable Disease Surveillance Centre between January 1981 and December 1992 in order to describe epidemiological trends in the three main clinical manifestations of toxoplasmosis-lymphadenopathy, eye disease, and neurological disease; and the two most important risk groups-fetuses and people whose immunity is impaired. The total numbers of reports each year did not change significantly between 1981 and 1992 and were similar to the numbers between 1976 and 1980, but different trends emerged in each subgroup. Reports of acute lymphadenopathic toxoplasmosis declined in children and young adults and eye disease associated with toxoplasmosis fell markedly in all age groups. Reports of neurological disease and severe toxoplasmosis complicating impaired immunity, due mainly to HIV infection or transplant surgery, rose. Reports of infections diagnosed in pregnancy rose steeply in the late 1980s although reports of congenital toxoplasmosis were no more common than in 1975 to 1980. Reports of acute toxoplasmosis came mainly from southern England. The emergence of these diverse trends from apparently unchanging totals emphasises the importance of surveillance systems capable of discrimination.

Adult↗

PubMed1995

A survey of health education material for the primary prevention of congenital toxoplasmosis.

We have assessed health education material for the prevention of congenital toxoplasmosis in terms of its epidemiological and clinical information and preventive advice. Nineteen leaflets and booklets were evaluated: fourteen were produced locally, ten for patients and four for professionals; and five were distributed nationally, including two sponsored booklets and one produced by the Department of Health. Material was compared with 'standards' derived from recently published reviews of toxoplasmosis and the Department of Health's booklet. The amount of information about toxoplasmosis, and the advice on how to avoid it, differed widely. Some booklets contained factual errors and some of the advice was impractical and even hazardous. Booklets contained on average between a fifth and a half of the standard desired for epidemiological and clinical information and preventive advice. Leaflets devoted to toxoplasmosis were more informative than general guides. Presentation was assessed informally: medical terminology inappropriate for a 'lay' audience was used, booklets were published in English only, and the date of publication was not printed. Health education is an important means of primary prevention of disability caused by congenital toxoplasmosis. Our study suggests that it has not received the scientific appraisal and commitment needed to make it effective.

Health Education↗

PubMed1995

Chronic relapsing axonal neuropathy: a first case report.

A relapsing and remitting axonal polyneuropathy developed in a woman at age 47. Serial electrophysiological studies showed that the amplitudes of compound muscle action potentials and sensory action potentials were reduced but conduction velocities were only mildly slowed. F wave latencies were normal and there was no evidence of conduction block. Two sural nerve biopsy specimens showed changes supportive of axonal neuropathy. Repeated responses to prednisolone alone and later prednisolone and azathioprine suggested that inflammatory, possibly autoimmune, processes were important in this case of chronic relapsing axonal neuropathy.

Action Potentials↗

PubMed1995

Self-efficacy and illicit opioid use in a 180-day methadone detoxification treatment.

Self-efficacy ratings coincided with illicit opioid use across the 3 phases of a 180-day methadone detoxification treatment. Efficacy ratings increased after patients received their first dose of methadone, did not change while they were maintained on a stable dose of methadone, and declined during the taper as they attempted to face high-risk situations without the full benefit of methadone. Efficacy ratings measured at a point before a phase of treatment predicted illicit opioid use across that phase. For clarification of the relation between self-efficacy and illicit opioid use, 3 conceptual models proposed by J.S. Baer, C.S. Holt, and E. Lichtenstein (1986) were tested. Self-efficacy influenced subsequent drug use in parallel with previous behavior, but this influence was found only at the start of the stabilization phase and immediately before the start of the taper phase. These findings highlight the usefulness of the self-efficacy concept for the treatment of opioid addiction.

Adult↗

PubMed1995

Social relationships and abstinence from cocaine in an American treatment sample.

In an extension of earlier work relating social-relationship variables to post-treatment abstinence from abused drugs, 104 cocaine users were studied for 6 months after completing drug treatment. Social-relationship variables included social integration, perceived support and social-network cocaine use. The effects of social relationships on cocaine abstinence tended to be conditional on race. Greater social integration predicted abstinence for Caucasian Ss (n = 54), but not African-Americans (n = 50). Similar results occurred for perceived support. Social network drug-use data also showed race differences: the absence of current cocaine users and the presence of former users predicted abstinence only for Caucasians. Interpretation of these findings is complicated by the relationship we observed between race and route of cocaine administration, with African-American Ss far more likely than Caucasians to be crack smokers or injection users as compared to intranasal users. The effects of race could not be disentangled from the effects of route. Future studies of social relationships and cocaine abstinence should focus on identifying social factors that are protective for African-Americans and for smokers/injectors. Such studies are critical precursors to designing successful social-support interventions.

Adult↗

PubMed1995

Vascular changes and demyelination induced by the intraneural injection of tumour necrosis factor.

Several observations suggest that tumour necrosis factor (TNF) plays a role in demyelination, although direct evidence for this is lacking. We have examined ultrastructurally rat sciatic nerves injected with TNF-alpha or TNF-beta: the effects of the two cytokines were found to be qualitatively similar. One day after injection nerves were oedematous and contained many inflammatory cells. Leucocytes were adherent to the walls of endoneurial vessels and sometimes were packed into the sub-endothelial layer apparently occluding the vascular lumen. Occasional myelinated axons were associated with macrophages and showed signs of myelin damage. By 3 days the inflammatory changes had diminished: some axons were degenerating or demyelinating. By 6-7 days, the vascular changes had resolved, and the endoneurium contained significant numbers of demyelinating and degenerating axons. Control nerves, which received injections of vehicle, showed no vascular changes and either no, or significantly fewer, degenerating or demyelinating axons. We conclude that the intraneural injection of TNF produces inflammatory vascular changes within the endoneurium, together with demyelination and axonal degeneration. We have also observed demyelination and degeneration in a preliminary study of the effects of TNF-alpha in mice. These findings may be relevant to the pathogenesis of demyelinating diseases such as Guillain-Barré syndrome.

Animals↗

PubMed1995

Level of functioning, severity of illness, and smoking status among chronic psychiatric patients.

It was hypothesized that chronic psychiatric patients who had quit smoking would be more functional and have lower Brief Psychiatric Rating Scale (BPRS) scores than those who continued to smoke. We interviewed 300 chronic psychiatric patients followed in the community. Fourteen percent were former smokers and nearly 11% had never smoked. Fifty-six percent of the sample were current smokers who had no intention of quitting, 13% were considering quitting, and 6% were seriously preparing to quit or had actually quit for a short period. When compared with current smokers, former smokers were more likely to live independently (p < .026) and less likely to have a drug or alcohol problem (p < .013). A random sample of current smokers were compared with former smokers on the BPRS. Former smokers had lower total BPRS scores (p < .03), and lower withdrawal/retardation subscale scores (p < .0058) than current smokers. We concluded that better functioning patients who smoked would be more likely to quit.

Adult↗

PubMed1995

Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.

The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli.

Base Sequence↗

PubMed1995

Repeat users of substance abuse services at a VA Medical Center.

To examine patterns of use of acute walk-in services by substance abusers, the authors studied demographic characteristics and type of substance abuse among 1,838 patients treated at a Veterans Affairs substance abuse triage unit. They found that African-American and male substance abusers appeared most likely to return for triage services. Among heroin users, the strongest predictor of return was gender. Among alcoholics, homelessness was the sole predictor of return. No predictors were found for cocaine users. The authors conclude that the relationship between return rates and type of substance abuse needs further study.

Adult↗

PubMed1994

Survey of local policies for prevention of congenital toxoplasmosis.

District policies for the primary and secondary prevention of congenital toxoplasmosis in England, Wales, Jersey, and the Isle of Man were surveyed in 1992. Consultants in communicable disease control were asked to describe past, present, and proposed prenatal screening programmes and current health education policies. One hundred and eighty-seven out of 196 districts responded to a postal questionnaire. One district had a prenatal screening programme for toxoplasmosis and five were discussing possible programmes. Over half (55%) had never had a programme or considered introducing one and 68 (36%) districts had decided against screening. Fifty-four per cent of districts had health education policies on toxoplasmosis, and most of these provided leaflets in antenatal clinics. A sample of districts that in 1992 were considering or had not ruled out screening was followed up in February 1994. None had implemented a screening policy. All but one district, therefore, are following the recommendation by a working group of the Royal College of Obstetricians and Gynaecologists that prenatal screening for toxoplasmosis should not be introduced in the United Kingdom. The value of current health education policies in the primary prevention of congenital toxoplasmosis needs to be assessed.

Female↗