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Biomedical subjects

R A Hughes

Publications and source records attributed to R A Hughes.

At least 19 recordsLinked to original sources
PubMed1996

A novel trial design to study the effect of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy.

Using a novel trial design, we prospectively examined the effect of intravenous immunoglobulin in seven patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a double-blind, placebo-controlled cross-over study. We suggest that the commonly used manual muscle testing and Rankin scale are not sufficiently sensitive to measure changes in CIDP and should not be used as isolated outcome measures. We propose a timed 10-m walk, the Nine-Hole Peg Test, the Hammersmith Motor Ability Score, and myometry as alternative measures which are valid, reliable and sensitive. Our trial design permitted the measurement of a treatment response in three responders despite different patterns of disability typical of the broad clinical picture seen in CIDP.

Adult↗
PubMed1996

The response of motoneurons to neurotrophins.

The ongoing search for neurotrophic factors for motoneurons has led to the identification of a number of molecules which regulate motoneuron survival and function. Among these factors, the neurotrophins brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 but not nerve growth factor (NGF), can prevent embryonic and postnatal motoneuron cell death in a variety of experimental paradigms. Analysis of expression of p75, trkB and trkC-components of the neurotrophin receptors-supports a potential physiological role for these factors as muscle- and glial-derived trophic factors for motoneurons. However, the survival of motoneurons during embryonic development is not reduced in the absence of BDNF, NT-3 or NT-4, as revealed by gene knockout experiments. This points to the involvement of additional trophic factors in the regulation of embryonic and postnatal motoneuron survival. The purpose of this review is to bring together the often prophetic observations from earlier studies-prior to the identification and characterization of these neurotrophins-with more recent results.

Animals↗
PubMed1996

Clinical scales for multiple sclerosis.

Many neurological rating scales have been suggested to assess the impact of multiple sclerosis on patients, but none has been universally accepted. The Kurtzke Extended Disability Status Scale has been the most widely used despite its imperfections. It combines disability and impairment, has moderate inter-rater reliability, and its overall score is heavily weighted toward ambulation. The Scripps Neurological Rating Scale attempts to quantify impairment as measured by the traditional neurological examination. However, this and other impairment scales lack direct relevance to patients' functional health status. The Ambulation Index and some of the quantitative upper limb dysfunction assessment methods are sensitive and reproducible, but they only measure limited aspects of the wide range of disabilities encountered in multiple sclerosis. Current scales of disability and activities of daily living, such as the Incapacity Status Scale and the Functional Independent Measure, are not sensitive to the type of change which occurs in multiple sclerosis. The relationship between abnormalities on magnetic resonance images of the brain and disability has been difficult to ascertain. Although recently developed imaging acquisition methods may demonstrate abnormalities which are more closely correlated with disability, the demonstration of prevention, stabilization or recovery from disability using clinical scales will remain the final arbiter of success in clinical trials. We suggest guidelines for an improved disability scale.

Disability Evaluation↗
PubMed1996

Intellectual impairment in neurofibromatosis 1.

Intellectual problems are a recognized feature of neurofibromatosis 1 (NF1) but their aetiology is unknown. We investigated the frequency, nature, severity and cause of intellectual impairment in NF1. We undertook neurological and psychometric assessments on 103 patients with NF1 and 105 controls equated for age, sex and socio-economic status. The mean full scale IQ was significantly lower in the NF1 than the control group, 88.6 (SD 14.6) compared with 101.6 (SD 14.2). However, the degree of intellectual impairment was mild and only 8% of NF1 patients had an IQ < 70. The NF1 patients also had significantly poorer reading skills and impaired short term memory. On a computerized performance test battery of complex tasks, the NF1 group had significantly slower mean reaction times and higher error rates than the controls. Overall the patients displayed impaired attention and were slow to develop and adapt strategies for complex and unfamiliar tasks. A particular profile of intellectual deficit did not emerge. The presence of neurological and/or medical complications was weakly associated with a lower mean full scale IQ in NF1 patients. Socio-demographic factors, age or sex differences and the presence of macrocephaly did not contribute to neurocognitive deficit in NF1.

Adolescent↗
PubMed1996

Antigen-presenting cells but not lymphocytes in the joint may indicate the cause of reactive arthritis.

T cells and antigen-presenting cells (APC) accumulate in the joint in reactive arthritis and there are reports that the T cells are a population selected for responsiveness to the causative agent. In this work, the latter view is questioned by detailed studies of the antigen specificities of the lymphocytes within the joint (SFMC) and peripheral blood (PBMC) of patients with reactive arthritis triggered by infection with Chlamydia trachomatis. Using a hanging-drop microculture system. SFMC displayed enhanced responses not only to antigens from the triggering organism, but also to other antigens, including PPD and tetanus toxoid, to which the patients were likely to have had prior exposure. No evidence was obtained for a dominant cross-reactive T-cell response to epitopes common to these antigen preparations, confirming the polyclonal nature of the infiltrate. In contrast to the broad specificity of the T-cell infiltrate, two experimental approaches indicated that APC within the joint carried chlamydial antigen. The failure of antigen-bearing APC to interact with T cells at this site may underlie the inability to clear microbial antigen from the joint.

Antigen Presentation↗
PubMed1995

Campylobacter jejuni infection and Guillain-Barré syndrome.

BACKGROUND: Although infection with Campylobacter jejuni is recognized as a common antecedent of the Guillain-Barré syndrome, the clinical and epidemiologic features of this association are not well understood. METHODS: We performed a prospective case-control study in a cohort of patients with Guillain-Barré syndrome (96 patients) or Miller Fisher syndrome (7 patients) who were admitted to hospitals throughout England and Wales between November 1992 and April 1994. Bacteriologic and serologic techniques were used to diagnose preceding C. jejuni infection. RESULTS: There was evidence of recent C. jejuni infection in 26 percent of the patients with Guillain-Barré or Miller Fisher syndrome, as compared with 2 percent of household controls and 1 percent of age-matched hospital controls (P < 0.001). Of the 27 patients with C. jejuni infection, 19 (70 percent) reported having had a diarrheal illness within 12 weeks before the onset of the neurologic illness. No specific serotypes were associated with Guillain-Barré syndrome. C. jejuni infection was slightly more common in men (P = 0.14) and was more likely to be associated with a pure motor syndrome and a slower recovery (P = 0.03). The patients with preceding C. jejuni infection were more likely to have acute axonal neuropathy or axonal degeneration in association with acute inflammatory demyelinating polyradiculoneuropathy, and they had greater disability after one year (P = 0.02). C. jejuni infection was significantly associated with a poor outcome even after correction for other factors associated with a poor prognosis. CONCLUSIONS: Infection with C. jejuni often precedes the Guillain-Barré syndrome and is associated with axonal degeneration, slow recovery, and severe residual disability.

Campylobacter Infections↗
PubMed1995

Fibroblast growth factors regulate calcitonin gene-related peptide mRNA expression in rat motoneurons after lesion and in culture.

In this study, we have investigated the effect of fibroblast growth factors (bFGF and FGF-5) and brain derived neurotrophic factor (BDNF) on the expression of calcitonin gene-related peptide (CGRP) in rat motoneurons in vivo and in vitro. Following sciatic nerve transection in adult rats, the levels of alpha-CGRP and beta-CGRP mRNA were up- and down-regulated respectively in axotomized motoneurons, revealed by in situ hybridization histochemistry. Local administration of 1 microgram bFGF was able to entirely abolish the up-regulation of alpha-CGRP mRNA, and to further down-regulate beta-CGRP. These effects, albeit less pronounced, were still evident with 0.2 micrograms bFGF. In contrast, bFGF did not attenuate the lesion-induced decrease of choline acetyltransferase (ChAT) mRNA. Administration of BDNF did not significantly alter the expression of CGRP or ChAT mRNA in axotomized motoneurons. Both alpha- and beta-CGRP mRNAs could be detected by PCR in enriched motoneuron cultures prepared from rat embryos at embryonic day 14-15. Comparing the amplification of alpha- and beta-CGRP mRNAs with that of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in parallel samples, we found that cultures treated with FGF-5 had a lower ratio of alpha- and beta-CGRP mRNA to GAPDH mRNA, than did control or BDNF-treated cultures. BDNF, on the other hand increased alpha-CGRP and decreased beta-CGRP mRNA levels, though these effects were moderate compared with the effects of FGF-5. The results obtained in this study suggest that members of the FGF family of growth factors influence the expression of CGRP in rat motoneurons, and that the increase of this neuropeptide induced by axotomy may, at least in part, be due to deprivation of these target-derived factors.

Animals↗
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

Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection.

To clarify the association between Campylobacter jejuni (Cj) infection and antibodies to ganglioside GM1 (anti-GM1) in Guillain-Barré syndrome (GBS), we have carried out a prospective case-control study of 96 patients with GBS. Cj infection occurred in 25 (26%) patients. IgG and/or IgM anti-GM1 were identified in 24 (25%) patients and in 1 of 71 (1.4%) household controls (p < 0.001). Thirteen of the 25 (52%) Cj-positive patients had anti-GM1 compared with 11 of the 71 (15%) Cj-negative patients (p < 0.001). Neither the peak overall disability nor the 1-year disability differed between the anti-GM1-positive and anti-GM1-negative patients. However, patients with the combination of Cj infection and anti-GM1 positivity recovered more slowly than Cj/anti-GM1-negative patients (p = 0.05), were more likely to have axonal degeneration, and were significantly more disabled at the end of 1 year (p = 0.02). The presence of Cj infection is more important than anti-GM1 positivity in determining the extent of axonal involvement and, hence, prognosis. Since the presence of anti-GM1 is not a significant poor-prognostic factor, a search should be made for other properties of Cj infection that would account for its relationship to axonal degeneration.

Autoantibodies↗
PubMed1995

The aetiopathogenesis of giant cell arteritis.

In this review, current understanding of the aetiopathogenesis of giant cell arteritis is examined. Possible explanations for the late age of onset and striking responsiveness to steroid therapy.

Aging↗