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Biomedical subjects

N P Robertson

Publications and source records attributed to N P Robertson.

At least 19 recordsLinked to original sources
PubMed2004

Population based study of late onset cerebellar ataxia in south east Wales.

OBJECTIVE: To determine the prevalence and causation of late onset cerebellar ataxia (LOCA) in south east Wales, United Kingdom. METHODS: A population based study of LOCA was conducted in a defined geographical region with a total population of 742,400. Multiple sources of ascertainment were used to identify all cases prevalent on 1 January 2001. The inclusion criteria were: a predominantly progressive cerebellar ataxia with onset of symptoms at age > or = 18 years; and disease duration of > or = 1 year. Cases with known acquired ataxias, ataxic syndromes with associated prominent autonomic dysfunction and/or atypical parkinsonism suggestive of multiple system atrophy and disorders with ataxia as a minor feature were excluded. RESULTS: We identified 76 index cases of LOCA, of whom 63 were sporadic, idiopathic LOCA (ILOCA) and 13 were familial LOCA, of whom six had either spinocerebellar ataxia type 6, Friedreich's ataxia or dominant episodic ataxia. The mean annual incidence rate for the period 1999-2001 was 0.3/100,000 population/year. The crude prevalence rates were 8.4 per 100,000 (95% CI 7.2 to 11.6) for ILOCA and 1.8 per 100,000 (95% CI 0.8 to 2.7) for inherited LOCA. Of the 54/63 (85.7%) patients with ILOCA who were assessed, mean (SD) age at onset of symptoms was 53.8 (14.1) years (range 19 to 78) with a male:female ratio of 2.1:1. The mean disease duration was 8.7 (6.3) years (range 1 to 31). The most frequent presenting complaint was disturbance in gait (90.7%). One-third had a relatively pure cerebellar syndrome (33.3%) and two-thirds (66.7%) had additional extracerebellar neurological features. The majority (92%) were ambulant but only 9.3% were independently self-caring. CONCLUSION: This population based study provides insight into LOCA within a defined region and will inform decisions about the rational use of healthcare resources for patients with LOCA.

Adult↗
PubMed2001

Patterns of disease in concordant parent-child pairs with multiple sclerosis.

BACKGROUND: Although the exact etiology of MS remains elusive, there is good evidence that genetic factors play an important role. These factors are likely to be polygenic, exerting both independent and interactive effects on the expression of MS. They may determine susceptibility and/or shape the clinical course. METHODS: The authors studied clinical phenotype in 245 concordant parent-child pairs recruited from a national register of familial disease over a 10-year period. Data were examined in order to determine the effect of parental sex on expression of disease in the offspring. RESULTS: Allowing for the observed sex ratio of 2.6 F:1 M in this group of patients, sex pairings of parents and offspring were close to those expected. When assessed independently there was no evidence that either the sex of the affected offspring or the line of inheritance influenced disability, age at onset, or disease course. However, trends were observed toward greater disability and an increased frequency of primary progressive disease in offspring of affected fathers and an earlier age at onset in offspring of affected mothers. The highest mean Expanded Disability Status Scale score was observed in male offspring of affected fathers (5.64) and this group was also more likely to have primary progressive disease (OR 1.92). Thirty-one percent of families had an additionally affected offspring with no preferential maternal or paternal transmission. CONCLUSIONS: In offspring of concordant parent-child families with MS who are at high risk of inheriting increased numbers of susceptibility genes there is no evidence for a parent of origin effect distorting sex ratios in affected offspring, but parent of origin may influence disability and disease course as well as increasing the risk to additional offspring within the same family. The mechanism of these effects is not clear but may result from interactions between genes encoded at different loci (epistasis), which each independently influence susceptibility and phenotype.

Adolescent↗
PubMed1999

Urinary, faecal and sexual dysfunction in patients with multiple sclerosis.

The prevalence and nature of bladder and bowel dysfunction were examined in a population-based study of 221 patients with multiple sclerosis who returned postal questionnaires. This preliminary investigation was supplemented by personal review which also provided information on sexual dysfunction in 174 and laboratory and urodynamic tests in 152 participants. Thirty of 221 (14%) currently used an indwelling catheter, and 84 of the remaining 190 (44%) reported symptoms of urinary dysfunction, of which the most common were urgency and frequency. Thirteen of 144 (9%) patients had biochemical evidence of renal dysfunction, and 40 of 132 (30%) had infected urine samples. Eleven of 54 patients in whom investigation of upper urinary tract was thought to be appropriate demonstrated abnormalities. Sixty-four of 221 (29%) patients had experienced faecal incontinence, and 120 of 221 (54%) were constipated. Fifty-six of 68 (82%) men and 55 of 106 (52%) women reported a deterioration in sexual activity, the commonest symptoms being erectile failure in men and fatigue in women.

Constipation↗
PubMed1998

Urgent neurology out-patient referrals from primary health care physicians.

We retrospectively analysed patients seen in a rapid referral clinic to identify those with abnormalities genuinely requiring urgent assessment, and to evaluate the impact of the clinic on routine services. After advertising the availability of the service, 25% of telephone referrals from primary-care physicians led to identification of patients considered suitable for urgent evaluation. We assessed 350 patients over an 18-month period. After neurological review, relevant abnormalities were identified in 73%, and 33% were considered to have warranted urgent assessment. In addition, 74% required radiological evaluation and 14% had a neurophysiological procedure; 19.4% were admitted on the same day, 13% underwent CSF analysis and 34% required some form of therapeutic intervention. In retrospect, patients with a clinical history of > 11 days rarely warranted urgent referral. Visual failure and diplopia provided the highest correlation with patients deemed to require urgent assessment, and syncope and headache the lowest. Despite the number of patients reviewed, no effect was demonstrated on waiting times for standard out-patient review.

Adolescent↗
PubMed1998

Myasthenia gravis: a population based epidemiological study in Cambridgeshire, England.

OBJECTIVES: To perform a comprehensive survey of myasthenia gravis in the county of Cambridgeshire, England, establishing contemporary epidemiological data. METHODS: Cases were ascertained from multiple sources. Prevalent patients were visited and assessed by means of a standardised questionnaire and examination complemented by review of medical case notes. RESULTS: One hundred cases were identified in a population of 684000 (prevalence 15 per 100000 population, 95% confidence intervals (95% CIs) 12-18). Thirty eight new diagnoses were made over a five year period providing an incidence of 1.1/100000 population/year. The sex ratio was 2:1 F:M. After a mean follow up of 11.7 years, symptomatic disease was still restricted to ocular muscles in 25 patients. Thirty four of 100 patients underwent thymectomy a mean of 0.8 years after presentation, and a thymoma was present in 12. Highest remission rates were seen in patients presenting with generalised disease who underwent thymectomy but did not have a thymoma (27%). Cosegregation of an additional autoimmune disease occurred in 27 patients and in 24/49 (49%) women with onset<50 years of age. CONCLUSIONS: This, the second highest reported prevalence for myasthenia, is likely to be the result of optimum case ascertainment, increased disease duration, application of complex diagnostic tests, and the impact of an aging population leading to a relative increase in the prevalence of ocular myasthenia.

Adolescent↗
PubMed1998

Adult polyglucosan body disease associated with an extrapyramidal syndrome.

A 50 year old patient is described who presented with parkinsonism, frontal dementia, peripheral neuropathy, neurogenic bladder, and upper motor neuron signs. No improvement in objective measurements of extrapyramidal dysfunction were seen with an incremental apomorphine test or more prolonged oral dopamine challenge. Neurophysiology disclosed changes compatible with a diffuse axonal neuropathy and pathological examination of a length of sural nerve taken at biopsy showed multiple polyglucosan bodies characteristic of adult polyglucosan body disease (APGBD). This case underlines the diverse clinical presentation of this rare neurological disease and the importance of recognising the unusual association of clinical features in making the diagnosis. APGBD should be included in the differential diagnosis of parkinsonism unresponsive to dopaminergic therapy.

Adult↗
PubMed1997

Offspring recurrence rates and clinical characteristics of conjugal multiple sclerosis.

BACKGROUND: There has been no previous systematic study of conjugal multiple sclerosis. This study of conjugal pairs with complex traits investigated disease transmissibility and the genetic contribution to frequency and clinical course. METHODS: We studied 45 conjugal pairs concordant for multiple sclerosis from 58 pairs recorded in a national register of familial disease, 86 offspring of the 45 pairs were individually assessed for clinical evidence of neurological disease; those over age 16 underwent cranial magnetic resonance imaging. Clinical features were compared in 33 pairs in whom neither member had symptoms before they met. FINDINGS: Of the 86 offspring, five (6%) had clinically definite multiple sclerosis. A further five children had either characteristic imaging abnormalities or clinical symptoms consistent with demyelination, but did not meet the criteria for clinically definite disease. There was no evidence of clinical concordance, clustering at year of onset, or distortion of the expected pattern of age of onset in the second affected spouse from 33 pairs. The crude recurrence in children of conjugal pairs (1 in 17) is significantly higher than previously reported population-based risk for offspring of single affected parents (1 in 200). INTERPRETATION: Taken with the low prevalence of multiple sclerosis in the spouses of affected individuals, and the lack of concordance for age at onset in these families, the disparity in crude recurrence between children of conjugal pairs and those of single affected parents shows that the recurrence risk in children is determined by genetic factors inherited from both parents.

Adolescent↗
PubMed1996

Age-adjusted recurrence risks for relatives of patients with multiple sclerosis.

Familial aggregation is a cardinal epidemiological feature of multiple sclerosis, but few investigators have systematically examined recurrence risks for relatives of affected individuals in the United Kingdom. As part of a cross-sectional study of multiple sclerosis in Cambridgeshire, pedigree details were taken on 674 probands. Sex-specific, crude and age-adjusted recurrence risks were assessed amongst relatives of probands, applying a statistical model based on the observed age at onset of affected individuals and providing risks for clinical counselling. Details on year of birth, present age or age at death, and disease status were available on 11 391 relatives of successive probands. Nineteen percent of patients reported an additionally affected relative; 128 non-proband affected relatives were identified and the highest risk was observed for sisters. There was a systematic reduction in relative risk with genetic distance from the proband and no preferential recurrence for maternal or paternal relatives.

Adult↗
PubMed1996

Clinical concordance in sibling pairs with multiple sclerosis.

As part of a linkage study, we obtained clinical, demographic, and genetic information on 210 families with siblings concordant for multiple sclerosis (MS). Twenty-eight pairs were excluded and information was incomplete in a further 16 pairs; intrafamilial comparisons of the clinical course are reported on the remaining 166 families (155 pairs and 11 trios) in whom complete data sets were available. The demographic characteristics were comparable to those of recently performed prevalence studies in the United Kingdom, supporting the application of results in these families for genetic linkage studies in MS. We observed no significant correlation for age at onset after correction for selection bias but found a minor correlation for year at onset, which we speculate is due to earlier recognition of symptoms in second affected siblings. There was no pair-wise concordance for presenting symptoms or disability at time of assessment. However, there was a strong correlation for disease course and to a lesser degree for gender. In addition, the familial recurrence rate was 33%, almost twice that previously recorded in a local prevalence study. These results suggest that the etiology of MS involves random exposure to an, as yet unidentified, environmental trigger and the clinical features of familial disease are modified by inherited factors. That the risk of developing MS is not spread uniformly among families has important implications for the counseling of individuals with familial disease.

Female↗
PubMed1990

Cytotoxic and hemolytic effects of Tritrichomonas foetus on mammalian cells.

Geographically distinct lines of Tritrichomonas foetus were assayed for their ability to cause cytotoxicity in nucleated mammalian cells and lysis of bovine erythrocytes. T. foetus was highly cytotoxic toward a human cervical cell line (HeLa) and early bovine lymphosarcoma (BL-3) but displayed low levels of cytotoxicity against African green monkey kidney (Vero) cells. In addition to variation in the extent of cytotoxicity toward different targets, differences in the levels of cytotoxicity in the same nucleated target occurred with different parasite lines. Whole T. foetus, unfractionated whole-cell extracts, and parasite-conditioned medium (RPMI 1640 without serum) all caused lysis of bovine erythrocytes. Lytic activity in the conditioned medium was substantially reduced by repeated freezing and thawing or heating to 90 degrees C for 30 min. Damage of mammalian target cells by live T. foetus could be reduced by the presence of protease inhibitors; however, such inhibitors did not diminish the lytic effects of conditioned medium. These results suggested that proteolytic enzymes were necessary for the lytic mechanism of the live parasites but were not required once lytic factors were released into the parasite-conditioned medium. They further suggested that the lytic molecules were either proteins or had proteinaceous components.

Animals↗
PubMed1989

Tumor cell invasion of three-dimensional matrices of defined composition: evidence for a specific role for heparan sulfate in rodent cell lines.

The abilities of rodent tumor cell lines; B16BL6, ND and LT dietary variants of B16BL6, +SA, RT7-4bs and RT7-4bLs to invade composite collagen I gels containing heparin, chemically modified heparins, heparan sulfate, chondroitin sulfate, hyaluronic acid, dextran, dextran sulfate, laminin and collagen IV were investigated, and compared to the invasion of plain collagen I gels. The presence of heparin or heparan sulfate most generally promoted tumor cell invasion of the gels, with more aggressive invasion being noted for the more metastatic variants examined. Of the chemically modified heparins tested, carboxyl-reduced heparin promoted matrix invasion by B16BL6 and +SA cells to the greatest degree. Hyaluronic acid marginally promoted invasion by +SA and RT7-4bs primary cells while, in these collagen I based gels laminin only promoted matrix invasion by primary +SA cells to a very limited degree. The tumor cell lines attached relatively poorly to heparan sulfate substrates compared to the other glycosaminoglycans tested, and the primary tumor cell lines also attached relatively poorly to collagen I. As expected, highly metastatic variants showed greater attachment to laminin than did their less metastatic counterparts. Apart from the negative correlation of cellular attachment to heparan sulfate substrates with invasiveness towards heparan sulfate containing gels, no other relationships emerged linking attachment rates with invasive activities for particular complex gel compositions. Our results suggest an important role for heparan sulfate, and possibly also tissue heparin, in promoting tumor cell invasion of extracellular matrices. Results from complex gels containing dextran or dextran sulfate failed to support the hypothesis that GAG sulfation is important to cellular invasion. The activity of the chemically modified heparins in promoting invasion, when present as components of these model matrices, suggests that part of the anti-metastatic activity of these compounds, when preincubated with tumor cells prior to intravenous inoculation, could result from interference with tumor cell extravasation.

Animals↗
PubMed1988

Heat shock-like polypeptides of the sporozoites and merozoites of Eimeria bovis.

Heat shock proteins (hsps) are a group of highly conserved polypeptides found in a wide variety of organisms. Polypeptides of sporozoites and merozoites of Eimeria bovis, blotted onto nitrocellulose, were probed with antibodies to artificially constructed peptides representing portions of the cDNA-generated fragment of pf75, the 75K hsp of merozoites of Plasmodium falciparum. Polypeptide antigens of sporozoites and merozoites of E. bovis with molecular weights of 46K, 71-72K, and 75K reacted with antibodies against pf75, indicating that they are hsp70 (the 70K family of hsps) or hsp70 cognates (noninducible proteins homologous to hsps). Radiolabeling with 125I and treatment with antibodies against pf75 detected a 71K antigen on the merozoite surface. Hsps in sporozoites of E. bovis are either constitutive or evoked by treatment at 37 C for in vitro excystation. If hsp70 is mandatory for parasite survival, it may prove to be an appropriate antigen for a vaccine against bovine coccidiosis.

Animals↗
PubMed1987

A rapid analytical technique for flow cytometric analysis of cell viability using calcofluor white M2R.

Analysis of dead versus live cells is shown to be possible using Calcoflour White M2R (CFW), a fluorescent brightener. Comparison of CFW with both propidium iodide (PI) and fluorescein diacetate (FDA) was performed on a FACS 440 dual laser flow cytometer on several populations of cultured rat and mouse cell lines, peripheral leukocytes, splenocytes, diatoms, and plant protoplasts. As a measure of cell viability, staining results with CFW were strongly associated with PI (correlation coefficient of 0.9886) and FDA (inverse correlation coefficient of 0.9647). With plant and algal cells, controls are necessary as CFW does stain live cells to some extent. CFW (excitation: UV, emission max: 435 nm) can be used in conjunction with two-color immunofluorescence analysis using fluorochromes excited at 488 nm with no interference.

Animals↗
PubMed1987

Comparison of basement membrane matrix degradation by purified proteases and by metastatic tumor cells.

We have examined the nature of biochemical degradation of an isolated basement membrane matrix (bovine lens capsule) using different methodologies. The first strategy was quantitation of the release of surface-bound 125I and a second the documentation by SDS-PAGE of the appearance of putative cleavage products and the loss of high-molecular-weight components from the matrix. Basement membrane matrix bands resolved on SDS-PAGE were identified by their protease sensitivities as well as by Western immunoblots using monoclonal antibodies developed for this study. Radioiodinated components were found predominantly at positions on the gel equivalent to 160-200 kd and 400 kd proteins. Since these labeled moieties were sensitive to bacterial collagenase digestion and stained with anticollagen type IV antibodies, they were determined to represent various configurations of collagen type IV. Several other lower-molecular-weight bands also stained with the anticollagen IV antibodies. Monoclonal antibodies reactive with laminin exhibited a complex staining pattern on the gels, which included the expected 200 and 400 kd components. We confirmed that lens capsule basement membrane contained only a single heparan sulfate glycosaminoglycan species, and tumor cell-induced glycosaminoglycan degradation within the basement membrane matrix was detected using cellulose acetate electrophoresis. Distinctive putative cleavage products were resolved on SDS-PAGE gels from matrices subjected to digestion by a variety of purified proteases as well as by metastatic tumor cells or their conditioned media. Tumor cells of different histiotypes produced different characteristic cleavage patterns, suggestive of the existence of several pathways of matrix degradation. Overall, primary tumor cells exhibited a greater degradative activity towards the basement membrane matrix than did long-term tissue culture-passaged cells. The same tumor cell line could exhibit considerably different patterns of both protein and glycosaminoglycan degradation depending on recent culture history. The relevance of these biochemical studies to the pathogenesis of malignant neoplasms is shown by: 1) the evaluation of degradative activities of B16 tumor cell populations exhibiting enhanced lung-colonizing phenotypes, and 2) the ability of a known antimetastatic moiety with antiprotease activity (Haementeria leech species salivary gland extract) to protect matrix components from degradation by tumor cell-conditioned medium.

Animals↗
PubMed1985

tris(Hydroxymethyl)aminomethane: an artifact detected as an aminotetrose by gas chromatography/mass spectrometry.

The monosaccharide content of the ethanol-soluble moiety of crude polysaccharide fractions of the tapeworm Hymenolepis diminuta and the blood fluke Schistosoma mansoni was investigated by gas-liquid chromatography of alditol acetate derivatives. A prominent, unusual peak was found, and mass spectrometry suggested identification as an aminotetrose, a four-carbon aminosugar reported only once in the past 15 years [D. A. Cumming, C. G. Hellerquist, and O. Touster (1981) J. Biol. Chem. 256, 7723-7726]. The unknown molecule was found to be tris(hydroxymethyl)aminomethane (Tris), whose acetylated derivative has a mass spectrum identical to that of an aminotetrose. The source of the Tris was traced to buffers used in conjunction with polysaccharide isolation.

Amino Sugars↗
PubMed1985

Isolation and characterization of glycosaminoglycans from Schistosoma mansoni.

Tegumental tissues of paired adult Schistosoma mansoni were removed by treatment with Triton X-100 and recovered by centrifugation. The chloroform-methanol insoluble residues of this isolated tegumental fraction and of the denuded carcasses were analysed for glycosaminoglycan (GAG) and sialic acid contents. Treatment with GAG-specific enzymes followed by electrophoretic analysis showed that both the carcass and tegument contained heparin and/or heparan sulfate, chondroitin sulfate and hyaluronic acid. All these except hyaluronic acid were present in the tegumental fraction. Based on uronic acid content, about 73% of the total GAG was in the tegumental membrane, 15% in the tegmental matrix and the remaining 12% was in the carcass. The presence of heparin-like polysaccharide may present entrapment of the schistosoma by the hosts' blood-clotting process.

Animals↗