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Biomedical subjects

D H Miller

Publications and source records attributed to D H Miller.

At least 343 records · Page 19Linked to original sources
PubMed1994

Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions.

Serial proton magnetic resonance spectroscopy (MRS), was carried out at 1-2 monthly intervals on eight patients with multiple sclerosis who presented with evidence of a large acute cerebral white matter lesion. An MRS was obtained from acute lesions (volumes of interest 4-12 ml), which at presentation showed gadolinium-diethylenetriamine penta-acetic acid enhancement, and from similar volumes of normal appearing white matter lateral to the lesion and nearer the scalp. Follow-up ranged from 4 to 9 months (mean 6 months). Short echo spectra from acute enhancing lesions invariably showed the presence of large resonances at 0.9 and 1.3 p.p.m. compared with normal appearing white matter and healthy age matched controls, indicating that these peaks were not the result of voxel contamination from scalp fat. These resonances, which probably represent lipid products of myelin breakdown, were detected in lesions which had been enhancing for < 1 month and remained elevated for a mean of 5 months (range 4-8 months). The results provide evidence that short echo proton MRS can detect myelin breakdown products and that myelin breakdown occurs during the initial inflammatory stage of lesion development. The ratio of N-acetylaspartate (NAA) (a neuronal marker) relative to creatine was reduced in acute lesions and in normal appearing white matter. In six of the lesions studied there was, however, a subsequent rise in the NAA/creatine ratio indicating that axonal loss is not the only mechanism of reduction in the NAA/creatine ratio.

Adult↗
PubMed1994

Magnetic resonance imaging in degenerative ataxic disorders.

MRI of the brain was performed in 53 patients with a variety of degenerative ataxias and related disorders and 96 control subjects. Atrophy of intracranial structures was not seen in patients with the pure type of hereditary spastic paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's ataxia there was atrophy of the vermis and medulla. The MRI features of early onset cerebellar ataxia with retained reflexes were variable, and suggest heterogeneity. In autosomal dominant cerebellar ataxias, most patients had cerebellar and brainstem atrophy, probably reflecting the pathological process of olivopontocerebellar atrophy; there was no clearly defined group with both clinical and imaging features of isolated cerebellar involvement. The MRI abnormalities in idiopathic late onset cerebellar ataxia were predominantly those of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and imaging features of brainstem abnormalities were discordant in several patients. Pure cerebellar atrophy was associated with slower progression of disability. Cerebral atrophy was common in the late onset ataxias. Cerebral white matter lesions, although usually few in number, were observed in significantly more patients than controls, particularly those aged over 50 years.

Adolescent↗
PubMed1994

A placebo-controlled trial of isoprinosine in patients with multiple sclerosis.

Isoprinosine was used under double-blind, randomised, and placebo-controlled conditions in 52 patients with relapsing/remitting or progressive multiple sclerosis. All patients received pulsed treatment with methylprednisolone. There was no significant effect of treatment on clinical disability or the accumulation of MRI abnormalities, after correction of results for multiple comparisons. It is concluded that isoprinosine is not effective therapy for multiple sclerosis.

Administration, Oral↗
PubMed1994

British Isles survey of multiple sclerosis in twins: MRI.

64/105 subjects who have a twin with multiple sclerosis included in a study of clinical concordance also underwent MRI of the brain. 8/23 monozygotic and 1/41 dizygotic co-twins from this subgroup were clinically concordant of whom 8/9 had MRI appearances typical of multiple sclerosis. Of the 48 clinically discordant twins aged less than 60, abnormalities on MRI were detected in 6/15 (40%) monozygotic and 13/33 (39%) dizygotic twins compared with 7/37 (19%) healthy age-matched controls. Abnormalities on MRI typical of multiple sclerosis (defined by the Fazekas criteria) were, however, present in only 2/15 (13%) monozygotic and 3/33 (9%) dizygotic twins and 0/37 controls. These results suggest that about 10% of monozygotic and dizygotic twins have "subclinical multiple sclerosis". It is likely that most of the MRI abnormalities seen in clinically discordant twins, however, represent incidental pathology.

Adolescent↗
PubMed1994

Benign form of multiple sclerosis: MRI evidence for less frequent and less inflammatory disease activity.

Data from two serial studies comparing the MRI activity of two groups of 11 patients, one with early relapsing-remitting (mean disease duration 3.5 years), the other benign (mean disease duration 22 years) multiple sclerosis are presented. Those with benign disease developed fewer new or enlarging lesions, and such lesions that occurred had a lower incidence of gadolinium enhancement, a marker of inflammation. These results, when considered in conjunction with other published studies, suggest that both the frequency of new lesions and the amount of inflammation within them influence the development of disability in multiple sclerosis.

Adult↗
PubMed1994

Sleep problems in multiple sclerosis.

Twenty-eight consecutive patients with multiple sclerosis (MS) were clinically evaluated to determine the presence of sleep-related disorders. There were 12 males and 16 females aged between 22 and 67 with disability ranging between 1.5 and 8.5 on Kurtzke extended disability status score (EDSS). Fifteen patients (54%) reported sleep-related problems. These included difficulties initiating sleep and/or frequent awakenings due to spasms or discomfort in the legs (8 patients), difficulty in initiating or maintaining sleep (3), habitual snoring (4) and nocturia (1). All-night oximetry was performed and the tracings analysed for the number of dips in oxygen saturation (SaO2) or more than 4%. Three patients showed significant sleep-related oxygen desaturation (> 5 dips of > 4% SaO2/h). Subsequent polysomnography performed in 2 of the 3 patients with significant oxygen desaturation confirmed the presence of sleep apnoea. MRI analysis of brain stem regions showed abnormalities in 20/22 cases. The 3 patients showing nocturnal oxygen desaturation had MRI brain stem lesions, but their locations were variable and their general appearance not different from that seen in the 17 without sleep apnoea. Sleep disturbance in MS is common but poorly recognised. It is usually due to leg spasms, pain, immobility, nocturia or medication. It is much less commonly associated with nocturnal respiratory insufficiency.

Adult↗
PubMed1994

The British Isles survey of multiple sclerosis in twins.

During a 27-month recruitment period, we identified 146 individuals with multiple sclerosis (MS) who have a twin. A single clinician interviewed and examined 105 pairs of twins, and we confirmed zygosity using minisatellite probes. Including two suspected cases, 11 of 44 (25%) monozygotic twin pairs were concordant compared with two of 61 (3%) dizygotic twin pairs--two of 33 (6%) like-sexed and zero of 28 (0%) opposite-sexed. MRI was performed in 64 of 105 co-twins, and showed abnormalities consistent with demyelination in 13% of monozygotic and 9% of dizygotic co-twins who were clinically unaffected. These findings are similar to the results of most previous studies of MS in twins in which zygosity was not unequivocally established and where the majority of clinically unaffected co-twins were not studied by MRI; the difference in concordance rates in monozygotic and dizygotic twins indicates a significant genetic component in the etiology of MS.

Adolescent↗
PubMed1994

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis.

We performed semiautomated quantitative measurement of brain magnetic resonance imaging (MRI) abnormalities seen at presentation and at 5-year follow-up in 84 patients presenting with an acute clinically isolated syndrome of the optic nerves, brainstem, or spinal cord suggestive of multiple sclerosis (MS). At follow-up, 34 (40%) had developed clinically definite and four (5%) clinically probable MS. Patients who developed MS during follow-up had a higher lesion load at presentation than those who did not. There was a strong correlation of the MRI lesion load at presentation with both the increase in lesion load over the next 5 years and disability at follow-up. Increasing initial lesion load correlated with a decreasing time to development of MS clinically (r = -0.328, p < 0.05). At follow-up, disability and brain lesion load were strongly correlated in patients who had developed MS. These results establish that MRI at presentation with clinically isolated syndromes suggestive of MS is useful in predicting the subsequent clinical course and the development of new MRI lesions. This suggests that quantitative brain MRI will be helpful in selecting patients with early clinical MS for treatment trials and for subsequent monitoring of their response to treatment.

Adolescent↗
PubMed1994

Neuroimaging in multiple sclerosis.

Modern neuroimaging, and in particular magnetic resonance imaging (MRI), has made a major contribution to the assessment of patients with multiple sclerosis. Brain MRI is the single most useful diagnostic investigation, and recent improvements in the quality of spinal cord imaging make MRI of this region a powerful tool in the evaluation of patients with undiagnosed myelopathies or with probable multiple sclerosis but equivocal findings on brain imaging. Putative MR markers of inflammation and axonal loss have, respectively, provided new insights into the mechanisms of relapse and remission on the one hand and persistent disability on the other. Monthly MRI is a powerful method for screening new therapies in relapsing-remitting and relapsing-progressive disease, but because of the uncertain relationship between short-term MRI activity and long-term disability, definitive trials should continue to have primary clinical endpoints.

Diagnostic Imaging↗
PubMed1994

The rationing of intensive care.

Meeting the challenges of allocating critical care resources in the fairest way possible depends upon the development of a standardized strategy for apportioning ICU services in times of limited supply. Two main approaches are emerging to handle these challenges. The first, rationing, requires the development of specific guidelines for determining ICU admission and discharge policies. The second approach involves improving the efficiencies of the care giving system itself. Either approach requires the establishment of a standard of care that reduces the potential for personal biases into the decision making process.

Age Factors↗
PubMed1993

Failure of 3,4-diaminopyridine to reverse conduction block in inflammatory demyelinating neuropathies.

3,4-Diaminopyridine was administered to 6 patients with inflammatory demyelinating neuropathies in whom partial conduction block was demonstrable. Four had Guillain-Barré syndrome and 2 had chronic inflammatory demyelinating neuropathy. Nerve conduction studies were performed before the administration of a single oral dose of 3,4-diaminopyridine, and at regular intervals thereafter. Neither resolution of conduction block nor clinical benefit were seen.

4-Aminopyridine↗
PubMed1993

Database for serial magnetic resonance imaging in multiple sclerosis.

The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.

Brain↗
PubMed1993

The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome.

A 5-year follow-up study was performed on 70 Caucasian patients presenting with isolated neurological syndromes of the optic nerve, brain stem, or spinal cord to assess the risk of progression to MS. The influence on patient prognosis of HLA-DR and -DQ alleles and presentation with disseminated brain lesions, demonstrated by MRI scanning, was determined. Clinical progression to MS was observed in 61% of optic neuritis patients, 50% of patients with a brain-stem syndrome, and 35% of patients with a spinal cord disturbance. MS and the isolated clinical syndromes were positively associated with DRB1*1501, DQA1*0102, and DQB1*0602; the frequency of these alleles in the latter group was intermediate between that seen in MS patients and healthy controls. Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025). The data suggest that these HLA alleles are involved in susceptibility to initial demyelinating lesion formation and are important in the subsequent development of MS in MRI-positive patients.

Adult↗
PubMed1993

Conversion to small-incision phacoemulsification: experience with the first 50 eyes.

Conversion from extracapsular cataract surgery to small-incision phacoemulsification is inevitably associated with a learning curve. Retrospective analysis of one surgeon's learning curve was carried out on the first 50 consecutive operations using small-incision phacoemulsification. Parameters were evaluated, including postoperative acuity and astigmatism at eight days, three weeks, three months, and six months. A comparison of the results of the first 25 operations and the subsequent 25 showed statistically significant differences only in acuity at eight days and cylinder at three months. The most frequent complication was corneal edema lasting at least one week. With careful preparation, proper patient selection, and meticulous technique, the learning curve for converting from extracapsular surgery to small-incision phacoemulsification does not necessarily increase the complication rate.

Aged↗
PubMed1993

The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study.

A 5-year follow-up study was performed on 89 patients who had undergone brain magnetic resonance imaging (MRI) at presentation with an acute clinically isolated syndrome of the optic nerves, brainstem or spinal cord of a type suggestive of multiple sclerosis. At presentation, MRI was abnormal, revealing one or more asymptomatic cerebral white matter lesions in 57 (64%), and was normal in 32 (36%). At follow-up, progression to clinically definite multiple sclerosis had occurred in 37 out of 57 (65%) with an abnormal MRI and one out of 32 (3%) with normal MRI. Human leucocyte antigen (HLA) typing was performed in 70 patients and cerebrospinal fluid (CSF) was examined at presentation in 36. The presence of HLA-DR2 antigen or cerebrospinal fluid oligoclonal IgG bands were both associated with a significantly increased risk of progression to multiple sclerosis, but MRI was much more powerful in predicting outcome. The presence of four or more MRI lesions at presentation was associated with a higher rate of progression to multiple sclerosis, more frequent development of moderate or severe disabilities and a greater number of new MRI lesions at follow-up. The results indicate that brain MRI at presentation with a clinically isolated syndrome suggestive of multiple sclerosis is a powerful predictor of the clinical course over the next 5 years. This observation, combined with an ability to detect other sometimes treatable disorders which can also cause such syndromes, suggests that MRI is the investigation of choice in evaluating this group of patients.

Adolescent↗