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S J Jones

Publications and source records attributed to S J Jones.

At least 37 records · Page 2Linked to original sources

N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects.

Serum glutathione levels were assessed in a patient with genetically proven Unverricht-Lundborg disease (ULD) before and during treatment with the antioxidant N-acetylcysteine (NAC). Glutathione levels were low before treatment, and increased during treatment. This increase was mirrored by an improvement in seizures, but not in myoclonus or ataxia. Three other patients with clinically determined ULD showed a variable response and some notable side effects during treatment with NAC.

Acetylcysteine↗

The internal auditory clock: what can evoked potentials reveal about the analysis of temporal sound patterns, and abnormal states of consciousness?

Whereas in vision a large amount of information may in theory be extracted from instantaneous images, sound exists only in its temporal extent, and most of its information is contained in the pattern of changes over time. The "echoic memory" is a pre-attentive auditory sensory store in which sounds are apparently retained in full temporal detail for a period of a few seconds. From the long-latency auditory evoked potentials to spectro-temporal modulation of complex harmonic tones, at least two automatic sound analysis processes can be identified whose time constants suggest participation of the echoic memory. When a steady tone changes its pitch or timbre, "change-type" CP1, CN1 and CP2 potentials are maximally recorded near the vertex. These potentials appear to reflect a process concerned with the distribution of sound energy across the frequency spectrum. When, on the other hand, changes occur in the temporal pattern of tones (in which individual pitch changes are occurring at a rate sufficiently rapid for the C-potentials to be refractory), a large mismatch negativity (or MN1) and following positivity (MP2) are generated. The amplitude of these potentials is influenced by the degree of regularity of the pattern, larger responses being generated to a "deviant" tone when the pitch and time of occurrence of the "standards" are fully specified by the preceding pattern. At the sudden cessation of changes, on resumption of a steady pitch, a mismatch response is generated whose latency is determined with high precision (in the order of a few milliseconds) by the anticipated time of the next change, which did not in fact occur. The mismatch process, therefore, functions as spectro-temporal auditory pattern analyser, whose consequences are manifested each time the pattern changes. Since calibration of the passage of time is essential for all conscious and subconscious behaviour, is it possible that some states of unconsciousness may be directly due to disruption of internal "clocks"? Abnormal mismatch potentials may provide a manifestation of a disordered auditory time-sense, sometimes being abolished in comatose patients while the C-potentials and similar responses to the onset of tones are preserved. Both C- and M-potentials were usually found to be preserved, however, in patients who had emerged from coma and were capable of discriminating sounds. Substantially intact responses were also recorded from three patients who were functionally in a "vegetative" state. The C- and M-potentials were once again dissociated in a group of patients with multiple sclerosis, only the mismatch potentials being found to be significantly delayed. This subclinical impairment of a memory-based process responsible for the detection of change in temporal sound patterns may be related to defects in other memory domains such as working memory.

Acoustic Stimulation↗

Mismatch negativity to single and multiple pitch-deviant tones in regular and pseudo-random complex tone sequences.

OBJECTIVES: To determine whether the process responsible for the mismatch negativity (MMN) might be involved in the analysis of temporal sound patterns for information. METHODS: Synthesized musical instrument tones of 'clarinet' timbre were delivered in a continuous sequence at 16 tones/s, such that there was virtually no N1 potential to each individual tone. The standard sequence comprised 4 or 5 adjacent notes of the diatonic scale, presented either as a regularly repeated, rising pattern or pseudo-randomly. The deviant stimuli were 1-5 consecutive tones of higher pitch than the standards. RESULTS: A MMN was evoked by a single deviant tone, 1 or 5 semitones above the pitch range of the standards. The response to the 5-semitone deviant was significantly larger (mean of 7.3 microV) when the standard pattern was regular as compared with pseudo-random. The MMN latency, on the other hand, was only influenced by the magnitude of pitch deviation. A second MMN was evoked by a second deviant tone, immediately (SOA 62.5 ms) following the first. Further consecutive MMNs were not consistently evoked. CONCLUSIONS: The large amplitude of these MMNs can be attributed to the use of complex tones, continuous presentation and a rapid rate of pitch changes, such that no waveform subtraction was required. Over and above the probability with which each individual tone occurs in the standard sequence, the mismatch process is influenced by its temporal structure, i.e. can be regarded as a temporal pattern analyzer. Contrary to the findings of some other groups, we found that two consecutive deviants can evoke an MMN, even at high rates of presentation such that both occur within the postulated 'temporal window of integration' of ca. 170 ms. These findings suggest that the mismatch process might be involved in the extraction of sequential information from repetitive and non-repetitive sound patterns.

Acoustic Stimulation↗

The auditory C-process of spectral profile analysis.

OBJECTIVES: We here review the findings of several experiments, aimed at clarifying the functional role of the human auditory cortex in the processing of complex sound mixtures. METHODS: Long-latency auditory evoked potentials were recorded to abrupt changes in the pitch or timbre of continuous complex tones (synthesized musical instrument sounds). Changes were made at intervals of 0.5-4.5 s while the subjects read a magazine. RESULTS: The main response was a P1/N1/P2 complex which was maximal at the vertex and symmetrically distributed, consistent with origin in the supratemporal cortices of both hemispheres. To distinguish them from the conventional responses to brief pure tones, the potentials were named CP1 (c. 55 ms), CN1 (90 ms) and CP2 (165 ms). Responses to changes of pitch, where all the spectral components changed frequency, and to changes of timbre, where the frequencies remained the same but their energy levels changed, were very similar to one another. The response amplitudes were little affected by the magnitude of frequency changes in the range 6-100%, but were strongly influenced by the rate at which changes occurred (requiring at least 4 s for full recovery) and by the breadth of the changing frequency spectrum (the upper partials of the tone in sum contributing more than the fundamental). When the C-potentials were made refractory by a high rate of pitch changes (16/s) within a narrow frequency range, responses could still be elicited by infrequently interspersed changes of timbre. When the tones were split into their high and low partials, the responses to change in the two frequency bands combined roughly algebraically. CONCLUSIONS: The responses appear to represent a cortical process concerned with analysing the distribution of sound energy across the frequency spectrum ('spectral profile analysis'). This may be an important stage in the analysis of complex sound mixtures and in the perception of sound quality.

Adult↗

Ventriculoperitoneal shunt block: what are the best predictive clinical indicators?

AIMS: To evaluate the predictive value of symptoms, signs, and radiographic findings accompanying presumed ventriculoperitoneal (VP) shunt malfunction, by comparing presentation with operative findings and subsequent clinical course. METHODS: Prospective study of all 53 patient referrals to a paediatric neurosurgical centre between April and November 1999 with a diagnosis of presumed shunt malfunction. Referral pattern, presenting symptoms and signs, results of computed tomography (CT) scanning, operative findings, and clinical outcome were recorded. Two patient groups were defined, one with proven shunt block, the other with presumed normal shunt function. Symptomatology, CT scan findings, and the subsequent clinical course for each group were then compared. RESULTS: Common presenting features were headache, drowsiness, and vomiting. CT scans were performed in all patients. Thirty seven had operatively proven shunt malfunction, of whom 34 had shunt block and three shunt infection; 84% with shunt block had increased ventricle size when compared with previous imaging. For the two patient groups (with and without shunt block), odds ratios with 95% confidence intervals on their presenting symptoms were headache 1.5 (0.27 to 10.9), vomiting 0.9 (0.25 to 3.65), drowsiness 10 (0.69 to 10.7), and fever 0.19 (0.03 to 6.95). Every patient with ventricular enlargement greater than their known baseline had a proven blocked shunt. CONCLUSIONS: Drowsiness is by far the best clinical predictor of VP shunt block. Headache and vomiting were less predictive of acute shunt block in this study. Wherever possible CT scan findings should be interpreted in the context of previous imaging. We would caution that not all cases of proven shunt blockage present with an increase in ventricle size.

Adolescent↗

Electrophysiological evidence for a defect in the processing of temporal sound patterns in multiple sclerosis.

OBJECTIVES: To assess the processing of spectrotemporal sound patterns in multiple sclerosis by using auditory evoked potentials (AEPs) to complex harmonic tones. METHODS: 22 patients with definite multiple sclerosis but mild disability and no auditory complaints were compared with 15 normal controls. Short latency AEPs were recorded using standard methods. Long latency AEPs were recorded to synthesised musical instrument tones, at onset every two seconds, at abrupt frequency changes every two seconds, and at the end of a two second period of 16/s frequency changes. The subjects were inattentive but awake, reading irrelevant material. RESULTS: Short latency AEPs were abnormal in only 4 of 22 patients, whereas long latency AEPs were abnormal to one or more stimuli in 17 of 22. No significant latency prolongation was seen in response to onset and infrequent frequency changes (P1, N1, P2) but the potentials at the end of 16/s frequency modulations, particularly the P2 peaking approximately 200 ms after the next expected change, were significantly delayed. CONCLUSION: The delayed responses appear to be a mild disorder in the processing of change in temporal sound patterns. The delay may be conceived of as extra time taken to compare the incoming sound with the contents of a temporally ordered sensory memory store (the long auditory store or echoic memory), which generates a response when the next expected frequency change fails to occur. The defect cannot be ascribed to lesions of the afferent pathways and so may be due to disseminated brain lesions visible or invisible on magnetic resonance imaging.

Adult↗

Thioridazine and sudden unexplained death in psychiatric in-patients.

BACKGROUND: Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown. AIMS: To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents. METHOD: A case-control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated. RESULTS: Sixty-nine case-control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P=0.004). There was no significant association with other individual antipsychotic drugs. CONCLUSIONS: Thioridazine alone was associated with sudden unexplained death, the likely mechanism being drug-induced arrhythmia.

Adolescent↗

Effect of diclofenac on cerebral blood flow velocity in patients with supratentorial tumours.

BACKGROUND: The aim of this investigation was to determine the effects of diclofenac on cerebral blood flow. Middle cerebral artery blood flow velocity was measured in nine patients with supratentorial tumours. METHODS: Using a transcranial Doppler ultrasound, we measured the baseline mean and systolic cerebral blood flow velocity. Measurements were repeated following administration of diclofenac 75 mg i.v. RESULTS: There was no significant change in cerebral blood flow velocity. All other physiological variables remained constant. CONCLUSION: Diclofenac does not cause a significant change in cerebral blood flow velocity in patients with supratentorial tumours.

Adult↗

Scalp potentials to pitch change in rapid tone sequences. A correlate of sequential stream segregation.

The object of the study was to look for a neurophysiological substrate of sequential auditory stream segregation. When a sequence of tones alternates rapidly between pitches separated by more than a few semitones, there is a tendency for it to be perceived as two independent "streams". We examined the scalp potentials evoked when the pitch interval abruptly changes, to see whether there are response parameters which might be correlated with sudden stream segregation and/or integration. For 3 s a continuous synthesized tone of "clarinet" timbre oscillated between pitches of F4 and F#4 (one semitone higher) at 16 notes/s, perceived as an integrated stream. The upper note was then raised to E5 (11 semitones above F4, perceived as segregated streams) for a further 3 s and the cycle was repeated 40 times. In a second condition also starting with oscillation between F4 and F#4, the upper note was lowered to E4 (one semitone below F4, still perceived as a single stream). Further conditions examined the changes between oscillations of 1 and 11 semitones down from E5, 1 and 23 semitones up from F4, and 10 and 11 semitones up from F4. Virtually no potentials were detectable during the periods of unchanging oscillation, but an N1/P2 complex was evoked on each change in the pitch interval. The N1 was termed "MN1" on account of its arguable relatedness to the mismatch negativity, recorded in a separate experiment using discontinuous tones at a much slower rate. The mean peak latency of the MN1 varied between 96 and 123 ms, the shortest latencies being recorded, not to the largest changes of pitch interval but to the widest pitch intervals between the new tone and the immediately preceding one. Therefore, although a causal relationship with streaming cannot necessarily be inferred, the MN1 latency appears to mark the degree of pitch contrast between consecutive tones, in correlation with the streaming effect.

Acoustic Stimulation↗

The auditory 'C-process': analyzing the spectral envelope of complex sounds.

OBJECTIVE: To examine the hypothesis that auditory evoked potentials (AEPs) to pitch and timbre change of complex harmonic tones reflect a process of spectral envelope analysis. METHODS: AEPs were recorded to: (1) continuous tones of 'clarinet' timbre whose pitch abruptly rose or fell by 1 or 7 semitones every 0.5 or 1.5 s; (2) a cycle of 6 pitches changing every 0.5 s; (3) tones of constant pitch whose timbre (spectral envelope shape) changed periodically; (4) pitch change of high- and low-pass filtered 'clarinet' tones. RESULTS: The amplitudes of the 'change-N1' (CN1) potential peaking at ca. 90 ms and the following CP2 were influenced to a far greater degree by the time interval between changes, than by the magnitude of the change or by the time interval between occurrences of the same pitch. Amplitudes were also strongly dependent on the number of partials present, irrespective of whether they were increasing or decreasing in energy. The algebraic sum of the responses to pitch change of high- and low-pass filtered tones closely approximated the response to the unfiltered tone. CONCLUSION: The rate-sensitivity of the responses cannot be explained by the refractoriness of frequency-specific 'feature detector' neurones, but rather of a process (termed 'C-process') which analyzes amplitude modulations across the spectral envelope, the contribution of different frequency bands combining linearly in the scalp-recorded activity. On-going computation of the spectral envelope shape may be an important factor in maintaining the perceptual constancy of timbre.

Adult↗

PhyloBLAST: facilitating phylogenetic analysis of BLAST results.

PhyloBLAST is an internet-accessed application based on CGI/Perl programming that compares a users protein sequence to a SwissProt/TREMBL database using BLAST2 and then allows phylogenetic analyses to be performed on selected sequences from the BLAST output. Flexible features such as ability to input your own multiple sequence alignment and use PHYLIP program options provide additional web-based phylogenetic analysis functionality beyond the analysis of a BLAST result.

Internet↗

Long-term remyelination after optic neuritis: A 2-year visual evoked potential and psychophysical serial study.

Thirty-one patients were followed-up, at 3-month intervals for the first year and at 6-month intervals for the second year, after an episode of optic neuritis. The object was to confirm previous evidence for a progressive shortening of visual evoked potential (VEP) latencies and to determine whether this is associated with any change in the clinical ocular examination, visual fields or contrast sensitivity. VEP latencies were found to decrease significantly during both the first and (less strikingly) the second year, the most marked changes occurring between 3 and 6 months. Contrast sensitivity improved during the first 9 months, but subsequently tended (non-significantly) to deteriorate. A similarly transient improvement in central visual field sensitivity was seen in a subgroup of patients with clinically overt multiple sclerosis. In the data from the acutely unaffected fellow eyes, no significant changes in VEP parameters or functional indices were observed. The findings extend those of a previous study which showed significant shortening of VEP latencies between 6 months and 3 years without significant functional improvement. Over this period, a significant prolongation of VEP latencies occurred in the asymptomatic fellow eye, accompanied by contrast sensitivity deterioration. Taken in conjunction, the two studies suggest that recovery processes involving remyelination or, possibly, ion channel reorganization proceed for at least 2 years. The concurrent effects of insidious demyelination and/or axonal degeneration (also occurring in the fellow optic nerve) are initially masked by the recovery process, but gradually become more evident. The functional benefits of the long-term recovery process are relatively minor and are usually reversed within a few years. Nevertheless, it is suggested that long-term remyelination may perform an important role in protecting demyelinated axons from degeneration. Understanding the factors which promote long-term remyelination may have significant implications for therapy in multiple sclerosis.

Adult↗

Changes in sports injuries to children between 1983 and 1998: comparison of case series.

BACKGROUND: Sports injuries sustained by children are worrying because they prevent and deter participation in physical activity. Before we can address such injuries we need to understand the size of the problem and whether there have been changes in occurrence. A study of sports injuries to children, carried out in a Cardiff Accident and Emergency department in 1983, provided the data against which to compare data gathered in 1998. METHODS: Data on all sports injuries to children aged 16 and under treated between September and December 1998 were compared with those reported for the same hospital, age group, injury and period in 1983. RESULTS: A total of 953 injuries were treated in 1998, representing an increase of 54 per cent [95 per cent confidence interval (CI) 44-64 per cent]. The male:female distribution remained constant and the majority of injuries were due to rugby and soccer. The number of females injured playing rugby and soccer increased and a wider range of sports led to injuries for both males and females. Amongst 10-15-year-olds injury risk increased from 1 in 78 for boys in 1983 to 1 in 22 in 1998 (p < 0.0001). For girls, the increase was from 1 in 117 to 1 in 55 (p < 0.0001). The number of soccer- and rugby-related fractures increased by 52 per cent (95 per cent CI 22-87 per cent). CONCLUSIONS: Sports injury rates have increased considerably over 15 years. With minimal population change, little variation in minor injuries and only small improvements in data capture, the main reason for change appears to be increased participation.

Adolescent↗

Changes in gene expression associated with developmental arrest and longevity in Caenorhabditis elegans.

Gene expression in a developmentally arrested, long-lived dauer population of Caenorhabditis elegans was compared with a nondauer (mixed-stage) population by using serial analysis of gene expression (SAGE). Dauer (152,314) and nondauer (148,324) SAGE tags identified 11,130 of the predicted 19,100 C. elegans genes. Genes implicated previously in longevity were expressed abundantly in the dauer library, and new genes potentially important in dauer biology were discovered. Two thousand six hundred eighteen genes were detected only in the nondauer population, whereas 2016 genes were detected only in the dauer, showing that dauer larvae show a surprisingly complex gene expression profile. Evidence for differentially expressed gene transcript isoforms was obtained for 162 genes. H1 histones were differentially expressed, raising the possibility of alternative chromatin packaging. The most abundant tag from dauer larvae (20-fold more abundant than in the nondauer profile) corresponds to a new, unpredicted gene we have named tts-1 (transcribed telomere-like sequence), which may interact with telomeres or telomere-associated proteins. Abundant antisense mitochondrial transcripts (2% of all tags), suggest the existence of an antisense-mediated regulatory mechanism in C. elegans mitochondria. In addition to providing a robust tool for gene expression studies, the SAGE approach already has provided the advantage of new gene/transcript discovery in a metazoan.

Animals↗

Variation of visual evoked potential delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis.

OBJECTIVES: To compare the degree of visual evoked potential (VEP) delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis, to determine whether the differential involvement of parvocellular and magnocellular fibre types suggested by other studies is governed by retinotopic factors. METHODS: VEPs were recorded to reversal of 40' checks in the central (4 degrees radius) and the left and right surrounding regions of the visual field (as far as 10 degrees vertical and 14 degrees horizontal) in 30 patients recently recovered from the acute stage of optic neuritis, and in 17 age matched controls. RESULTS: In the control group, VEP latencies were similar to stimulation of the central and temporal regions of the macula, marginally shorter from the nasal region. In the patients with optic neuritis, VEPs were significantly more delayed from the central region, on average by about twice as much as from the nasal and temporal regions. Delays seen in some of the VEPs from the patients' fellow eyes tended to be more uniformly distributed. CONCLUSIONS: Although the central region of the macula is where the density of parvocellular innervation is greatest, there is no reason to suppose that the VEPs to stimulation of the nasal and temporal regions (almost all P100 activity arising from within the central 10 degrees ) are mediated by fibres of another type. Consequently it is suggested that the central fibres were most affected by demyelination, not on account of their belonging to the parvocellular type but because of their particular situation in the optic nerve. Centrally located fibres may experience greater exposure to factors causing demyelination, or fibres located closer to the edge of the plaque may undergo more effective remyelination in the first few weeks after the acute episode.

Adult↗

Aggressive behaviour in patients with schizophrenia is associated with catechol-O-methyltransferase genotype.

BACKGROUND: Evidence exists for an association between aggression and schizophrenia. Although the aetiology of aggression is multifactorial, three studies have reported associations between polymorphisms of the catechol-O-methyltransferase (COMT) gene and aggression in schizophrenia. AIMS: To replicate these findings in a larger sample using the Overt Aggression Scale (OAS). METHOD: A sample of 180 people with DSM-IV schizophrenia were rated for aggression using the OAS. Kruskal-Wallis and contingency table analyses were applied to the OAS results. RESULTS: The high-activity homozygotes showed significantly higher scores of aggression, whereas the heterozygotes showed significantly lower scores. The odds ratio for aggression for the high-activity homozygotes was 2.07 (95% Cl=1.03-4.15), whereas that for the heterozygotes was 0.54 (95% Cl=0.30-1.00). CONCLUSIONS; The high-activity COMT homozygote confers a higher risk of recorded aggression in schizophrenia. Heterozygotes had a significantly lower risk, which may represent an example of heterosis/heterozygote advantage.

Aggression↗

Overlapping functions of lysosomal acid phosphatase (LAP) and tartrate-resistant acid phosphatase (Acp5) revealed by doubly deficient mice.

To date, two lysosomal acid phosphatases are known to be expressed in cells of the monocyte/phagocyte lineage: the ubiquitously expressed lysosomal acid phosphatase (LAP) and the tartrate-resistant acid phosphatase-type 5 (Acp5). Deficiency of either acid phosphatase results in relatively mild phenotypes, suggesting that these enzymes may be capable of mutual complementation. This prompted us to generate LAP/Acp5 doubly deficient mice. LAP/Acp5 doubly deficient mice are viable and fertile but display marked alterations in soft and mineralised tissues. They are characterised by a progressive hepatosplenomegaly, gait disturbances and exaggerated foreshortening of long bones. Histologically, these animals are distinguished by an excessive lysosomal storage in macrophages of the liver, spleen, bone marrow, kidney and by altered growth plates. Microscopic analyses showed an accumulation of osteopontin adjacent to actively resorbing osteoclasts of Acp5- and LAP/Acp5-deficient mice. In osteoclasts of phosphatase-deficient mice, vacuoles were frequently found which contained fine filamentous material. The vacuoles in Acp5- and LAP/Acp5 doubly-deficient osteoclasts also contained crystallite-like features, as well as osteopontin, suggesting that Acp5 is important for processing of this protein. This is further supported by biochemical analyses that demonstrate strongly reduced dephosphorylation of osteopontin incubated with LAP/Acp5-deficient bone extracts. Fibroblasts derived from LAP/Acp5 deficient embryos were still able to dephosphorylate mannose 6-phosphate residues of endocytosed arylsulfatase A. We conclude that for several substrates LAP and Acp5 can substitute for each other and that these acid phosphatases are essential for processing of non-collagenous proteins, including osteopontin, by osteoclasts.

Acid Phosphatase↗