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Biomedical subjects

B Sharrack

Publications and source records attributed to B Sharrack.

13 recordsLinked to original sources
PubMed2000

The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis.

We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.

Administration, Oral↗
PubMed1999

The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.

OBJECTIVE: To determine the effect of humanized monoclonal antibody against alpha4 integrin (reactive with alpha4beta1 integrin or very-late antigen-4) on MRI lesion activity in MS. METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-alpha4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment. RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated. CONCLUSIONS: Short-term treatment with monoclonal antibody against alpha4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.

Adult↗
PubMed1999

Randomized trial of interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To test the safety and efficacy of interferon beta-1a (IFN-beta) in treatment-resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). BACKGROUND: Current treatment regimens leave 4% to 30% of patients with CIDP with moderate or severe disability. IFN-beta has been reported as beneficial in one treatment-resistant patient. METHODS: Ten consecutive treatment-resistant patients were randomized in a double-blind, crossover design to receive placebo or IFN-beta (3 MIU for 2 weeks and then 6 MIU for 10 weeks) subcutaneously three times weekly, followed by 4 weeks without treatment, and then the opposite treatment for 12 weeks. The primary outcome measure was "clinically important" improvement by specified amounts in any three of eight clinical measures: timed 10-m walk, Ambulation Index, expanded Medical Research Council sum score, nine-hole peg test time, Functional Independence Measure, Hammersmith Motor Ability, a new Guy's Neurological Disability Scale, and the EuroQoL quality-of-life scale. These and motor median nerve conduction studies were measured before and after 12 weeks of each treatment. RESULTS: Clinically important improvement was observed in one patient while taking IFN-beta and two patients while taking placebo. There was no significant difference between IFN-beta and placebo in the change in any of the individual clinical or neurophysiological measures between the beginning and end of treatment. There were no serious adverse events. CONCLUSION: This trial shows that IFN-beta is safe but not efficacious in treatment-resistant CIDP.

Adjuvants, Immunologic↗
PubMed1999

The psychometric properties of clinical rating scales used in multiple sclerosis.

OullII;l y Many clinical rating scales have been proposed to assess the impact of multiple sclerosis on patients, but only few have been evaluated formally for reliability, validity and responsiveness. We assessed the psychometric properties of five commonly used scales in multiple sclerosis, the Expanded Disability Status Scale (EDSS), the Scripps Neurological Rating Scale (SNRS), the Functional Independence Measure (FIM), the Ambulation Index (AI) and the Cambridge Multiple Sclerosis Basic Score (CAMBS). The score frequency distributions of all five scales were either bimodal (EDSS and AI) or severely skewed (SNRS, FIM and CAMBS). The reliability of each scale depended on the definition of 'agreement'. Inter-and intra-rater reliabilities were high when 'agreement' was considered to exist despite a difference of up to 1.0 EDSS point (two 0.5 steps), 13 SNRS points, 9 FIM points, 1 AI point and 1 point on the various CAMBS domains. The FIM, AI, and the relapse and progression domains of the CAMBS were sensitive to clinical change, but the EDSS and the SNRS were unresponsive. The validity of these scales as impairment (SNRS and EDSS) and disability (EDSS, FIM, AI and the disability domain of the CAMBS) measures was established. All scales correlated closely with other measures of handicap and quality of life. None of these scales satisfied the psychometric requirements of outcome measures completely, but each had some desirable properties. The SNRS and the EDSS were reliable and valid measures of impairment and disability, but they were unresponsive. The FIM was a reliable, valid and responsive measure of disability, but it is cumbersome to administer and has a limited content validity. The AI was a reliable and valid ambulation-related disability scale, but it was weakly responsive. The CAMBS was a reliable (all four domains) and responsive (relapse and progression domains) outcome measure, but had a limited validity (handicap domain). These psychometric properties should be considered when designing further clinical trials in multiple sclerosis.

Activities of Daily Living↗
PubMed1999

The Guy's Neurological Disability Scale (GNDS): a new disability measure for multiple sclerosis.

A postal survey showed that the majority of 49 leading international neurologists involved with multiple sclerosis research felt that currently existing outcome measures for this illness were inadequate, and that there was a need for a new measure which should be patient orientated, multidimensional, and not biased towards any particular disability. The Guy's Neurological Disability Scale (GNDS) was subsequently devised as a simple and user-friendly clinical disability scale capable of embracing the whole range of disabilities which could be encountered in the course of multiple sclerosis. It has 12 separate categories which include cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and 'others'. The GNDS was found to be acceptable to neurologists and patients, reliable, responsive, and valid as a measure of disability. The scale was also found to be valid when applied by non-neurologists, over the phone, or via a postal questionnaire.

Clinical Trials as Topic↗
PubMed1997

Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subsets distribution and TNF alpha concentrations in multiple sclerosis.

We investigated in multiple sclerosis the difference between two commonly used oral and intravenous steroid regimens on the level of adhesion molecule expression on blood T lymphocytes, the distribution of circulating T cell subsets, and the concentration of serum tumour necrosis factor alpha. Venous blood samples were collected from a cohort of 22 patients with acute relapses who were participating in a randomised trial comparing intravenous methylprednisolone 1000 mg daily for 3 days with oral methylprednisolone 48 mg daily for one week, 24 mg daily for one week, and finally 12 mg daily for one week. There was a similar significant reduction of T cell LFA-1 surface expression and serum TNF alpha concentrations after 4 days of treatment with each regimen. There was no change in other lymphocyte adhesion molecules expression (ICAM-1, LFA-3 or CD2) at day 4, although LFA-3 and CD2 expression was moderately decreased at day 28 and day 90 respectively; nor was there any change in the distribution of lymphocyte subsets (CD4, CD8, and CD45RA, CD45RO), although a small decrease in CD45RO circulatory T cells was noted at day 28. This study suggests that some of the beneficial effects of glucocorticosteroids may be related to the inhibition of lymphocyte adhesion as well as the modulation of proinflammatory cytokines.

Administration, Oral↗
PubMed1996

Carcinoma and the peripheral nervous system.

An underlying carcinoma is an important differential diagnosis in peripheral neuropathy. While direct compression and infiltration of spinal roots or peripheral or cranial nerve trunks or branches can be identified easily when they occur in association with established malignancy, their diagnosis when they are presenting features may be difficult. In paraneoplastic sensory neuronopathy autoantibodies to neuronal antigens have become useful diagnostic markers for an underlying carcinoma, especially anti-Hu antibodies. Strong circumstantial evidence suggests that these antibodies form part of an autoimmune response which is responsible for the pathogenesis of some of these syndromes. Neuropathy appearing during the course of treatment of carcinoma may be due to radiation-induced damage or the neurotoxic effects of some chemotherapeutic agents. Neurotrophic factors are being investigated as a strategy for reducing the neurotoxic effects of these agents.

Combined Modality Therapy↗
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↗
PubMed1995

The association of hereditary neuropathies and heritable skeletal disorders.

We describe two patients with associations of hereditary neuropathies and heritable skeletal disorders not previously reported. The first patient had Marfan's syndrome and hereditary motor and sensory neuropathy Type 1. The second patient had Ehlers-Danlos syndrome, Klippel-Feil syndrome and tomaculous neuropathy.

Adolescent↗
PubMed1995

Drug trials in neuropathy.

Drug trials in peripheral neuropathy have used different outcome measures, the choice of which has depended on the nature of the neuropathy and the hypothesis being tested. The majority of the published trials have relied on measuring impairment (reflecting the desirable sensitivity of these outcome measures), and only few have used measures of disability or handicap. Drug trials in inflammatory neuropathy (GBS and CIDP), diabetic, paraproteinaemic, and toxic neuropathies have been discussed in this chapter, to illustrate the different therapeutic approaches used in the literature. Future drug trials in peripheral neuropathy should pay more attention to disability and handicap measures.

Aldehyde Reductase↗
PubMedDate not supplied

Reliability of distance estimation by doctors and patients: cross sectional study.

OBJECTIVE: To assess the reliability and accuracy of distance estimated by doctors and patients. DESIGN: Comparison between estimated and measured distances of six familiar sites around Guy's Hospital, London. SUBJECTS: 100 hospital consultants and 100 patients. MAIN OUTCOME MEASURES: Median (range) of estimated distances, and mean (SD) of the difference between estimated and measured distances. RESULTS: Both doctors and patients gave a wide range of estimates of distance. The estimates differed by up to 14.6-fold from the measured distances, and the difference between minimum and maximum estimates was up to 62.5-fold. CONCLUSION: Doctors and patients were inaccurate at estimating distances, which implies that estimates of distances walked are not reliable indicators of a person's health.

Cross-Sectional Studies↗