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M Hayward

Publications and source records attributed to M Hayward.

At least 19 recordsLinked to original sources

Aortic stenosis in cardiovascular ochronosis.

Alkaptonuria (endogenous ochronosis) is a rare metabolic disorder caused by a deficiency of homogentisic acid oxidase, an enzyme responsible for the metabolic degradation of tyrosine. Patients with alkaptonuria commonly present with joint pain owing to degenerative arthritis. Other affected patients may present with pigmentation of the ear cartilage and sclera. This article reports a case of aortic stenosis associated with ochronosis in a 48-year-old man who presented with severe cardiac failure. He had no previous diagnosis of alkaptonuria, which was confirmed by mass spectrometry analysis of urine. The pathogenesis of cardiovascular ochronosis is unclear, but is probably related to the extensive extracellular deposits of ochronotic pigment in the cardiac tissue.

Aortic Valve Stenosis↗

In-vitro evaluation of the PALL Leukotrap Affinity Prion Reduction Filter as a secondary device following primary leucoreduction.

BACKGROUND AND OBJECTIVES: A filter (PRF1) designed to remove abnormal prion proteins from red-cell units has been developed. The purpose of this study was to evaluate the quality of red cells produced using this device. MATERIALS AND METHODS: Leucocyte-depleted red-cell units (CPD, CPD-A1 and CPD/SAGM) processed according to standard UK practices were filtered using PRF1. Filtered and control units were stored and sampled on day 1, day 7 and on the date of expiry and were tested using standard measures of red-cell quality. RESULTS: Filtered units were found to have significantly higher percentage haemolysis levels, lower haemoglobin levels and a smaller volume compared with controls. All results, however, were well within the permitted 0.8% haemolysis level at the end of storage and all units met the UK guidelines for haemoglobin and volume. The other test parameters measured showed no significant differences between the test and control units. CONCLUSIONS: The PRF1 filter was found to be easy to use and resulted in red-cell units that met all relevant UK and European Guidelines.

Erythrocyte Transfusion↗

Endurance enhancement related to the human angiotensin I-converting enzyme I-D polymorphism is not due to differences in the cardiorespiratory response to training.

Human physical performance is strongly influenced by genetic factors. We have previously reported that the I variant of the human angiotensin I-converting enzyme (ACE) gene is associated with greater endurance performance in mountaineers and Olympic runners and improved performance in army recruits. In this study we examined whether this effect is mediated by improvements in cardiovascular fitness with training in 58 army recruits homozygous for the insertion (I, ACE genotype II) or deletion (D, ACE genotype DD) allele. A submaximal and maximal exercise protocol was used to calculate both the heart rate/oxygen uptake (VO2) relationship and changes in maximal oxygen uptake (VO2max), respectively. There was no significant intergroup difference in VO2max at baseline (P=0.19) or after training (P=0.22). There was no difference between genotypes with training in the heart rate/VO2 elevation (P = 0.79 for the mean difference in mean adjusted heart rates). However, VO2 at all exercise intensities in the submaximal test was lower for all subjects after training and at 80 W the reduction in VO2 was greater for the II subjects compared to DD subjects [mean(SEM)] [1.6 (0.27) and 0.68 (0.27) ml kg(-1) min(-1), respectively; P = 0.02 for mean difference]. The I/D polymorphism may play a role in enhanced endurance performance but this is not mediated by differences in VO2max or the heart rate/VO2 relationship in response to training.

Exercise↗

A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.

This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.

Acetaminophen↗

Which event-related potentials reflect memory processing in a digit-probe identification task?

Auditory and visual event-related potentials (ERPs) generated by digit-probe identification and matching in a modified Sternberg paradigm have been recorded in 37 healthy subjects with the aim of identifying the potentials which best reflect the memory processes associated with this task. We analysed the effects of memory load (one, three or five digits to memorise), probe type (probe digit present or absent from the preceding memory set) and recording site, on the ERPs. With conventional methods of determining component amplitudes and latencies, the main effects of increasing memory load on the major positive wave varied according to stimulus modality-there was an amplitude decrease for the auditory ERPs and a latency increase for the visual ERPs. However, subjective component identification methods may be prone to errors when comparing responses recorded under different stimulus conditions. Waveform changes with increasing memory load may be misinterpreted as latency (or amplitude) effects if non-analogous potentials are compared. Further, component analysis may provide only partial information, because of its relative insensitivity to sustained amplitude shifts. For these reasons, an objective computer method was used to determine the mean amplitudes for multiple '50 ms' epochs. This showed, for both auditory and visual stimuli, that the main effect of increasing memory load was a 'negative amplitude shift'. It was seen between 315 and 525 ms for auditory stimuli and between 210 and 472 ms for visual stimuli and could be distinguished from other ERP features that were sensitive to stimulus modality. These changes are either specific to the memory processes involved in carrying out this task or reflect other parallel processing which covaries with memory processing.

Adult↗

"Familial Parkinson's disease"--a case-control study of families.

BACKGROUND: Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of "familial PD" (fPD). METHODS: 81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined. RESULTS: On examination, 8 persons, said to be "normal" by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100,000 versus 1190/100,000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100,000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree. CONCLUSIONS: "Familial parkinsonism" cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a "negative" family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population-regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.

Adult↗

Working memory impairment in early multiple sclerosis. Evidence from an event-related potential study of patients with clinically isolated myelopathy.

Auditory and visual event-related potentials were recorded during a short-term memory task in 24 patients who had recently presented with symptomatically and clinically isolated spinal cord syndromes suspected to be due to multiple sclerosis, and in 24 matched control subjects. Event-related potentials (ERPs) were recorded during two sequential components of the working memory task, first the temporary active memorizing of sets of digits and secondly, their subsequent manipulation, namely digit-probe recognition and matching. The patients' reaction times were slower and showed larger increments than those of the control subjects as the number of items to be memorized was increased. The patients' ERPs during both memorizing and probe matching/recognition phases differed significantly from control subjects for both auditory and visual presentations. The more marked changes were seen in a subgroup of eight patients who had the lowest levels of performance on a battery of general tests of memory and who also made significantly more errors in the working memory task as the memory load increased. In this subgroup, the abnormalities of the ERPs during recognition and matching tests occurred in the component of the response that has been shown to be sensitive to memory loading in healthy control subjects. This study provides objective evidence of subclinical working memory dysfunction in patients at an early stage of demyelinating disease, i.e. when they first present with clinically isolated spinal cord lesions and before they have developed symptoms of cognitive or memory dysfunction. The defect at this early stage is either restricted to processes involved in the formation of a memory trace or, more probably, involves both trace formation and the mechanisms that underly recognition ('retrieval') and matching of memory traces in working memory.

Adult↗

Technetium-99m sestamibi uptake in human breast carcinoma cell lines displaying glutathione-associated drug-resistance.

An in vitro study was designed to evaluate the uptake of sestamibi (MIBI) in P-glycoprotein (Pgp) and glutathione-associated (GSH) multidrug-resistant (MDR) cell lines. MIBI uptake was studied in various human breast carcinoma cell lines, i.e. in wild-type (MCF7/wt) cells, in adriamycin-resistant (MCF7/adr) cells which express Pgp and in melphalan-resistant (MCF7/mph) cells with increased levels of GSH. The effects of buthiomine sulphoximine (BSO) and verapamil on MIBI uptake were also studied in the MCF7/mph and MCF7/adr cells respectively. The cells were incubated for 1 h with a dose of 0.1 MBq thallium-201 and technetium-99m MIBI. Both MIBI and 201Tl uptakes were higher for MCF7/mph cells than for the other cells studied. The mean MIBI uptake in MCF7/adr cells was significantly lower than that in MCF7/wt cells (1.9%+/-0.5% vs 3. 1%.0.6%; P <0.01). Verapamil treatment increased the MIBI uptake in MCF7/adr cells (to 2.6%.0.3%; P <0.05). Treatment of MCF7/mph cells with BSO resulted in a significant reduction in GSH content (from 243.2+/-81.1 nmol/mg protein to 17.6+/-4.4 nmol/mg protein; P <0. 001). However, MIBI uptake in BSO-treated and untreated MCF7/mph cells was similar (4.43%+/-0.5% and 5.93%+/-1.7%, respectively; P >0. 1). This study suggests that the uptake of MIBI is not diminished by glutathione-associated drug resistance and that MIBI uptake in a tumour sample does not necessarily indicate that a cancer is sensitive to drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The health-wealth connection: racial differences.

This article examines the theoretical connection between health capital and financial capital in an economic life-cycle model, exploring possible explanations for racial differences in capital accumulation behavior. Using data from the Health and Retirement Survey, detailed descriptive analysis and a comparison of regression models for health and financial capital are presented. The results, although preliminary and based on cross-section data, suggest possible racial differences in the connection between health and wealth and deserve further study.

Black or African American↗

The pathology of the lower leg muscles in pure forefoot pes cavus.

Enlargement of the peroneus longus muscle is a common occurrence in patients with forefoot pes cavus, and may contribute to the cavus deformity. The present study compares the morphology of up to five lower leg muscles from 17 patients with forefoot pes cavus with those of normal muscles. Eight cases had an identifiable neurogenic cause for the cavus. In four cases of hereditary motor-sensory neuropathy, the tibialis anterior showed more severe damage than the peroneus longus. In two cases of cerebral palsy, fibre atrophy and increased oxidative enzyme activity were observed. In nine clinically idiopathic cases, the histological appearances ranged from normal to generalised fibre atrophy or hypertrophy in individual muscles. There was a trend for the mean fibre area to be greater in peroneus longus than in tibialis anterior in six of the idiopathic group of patients. The muscle cross-sectional area on magnetic resonance imaging was correlated closely with the mean fibre area measured on tissue sections. In idiopathic forefoot pes cavus, fibre hypertrophy in peroneus longus (relative to tibialis anterior) may contribute to the cavus deformity. Muscle fibre hyperplasia may contribute to the peroneal muscle enlargement in Friedreich's ataxia. In none of the cases was peroneus longus enlargement due to fat or fibrous tissue replacement.

Adolescent↗

Is "memory-scanning" time in the Sternberg paradigm reflected in the latency of event-related potentials?

The time taken to scan short term memory for a target (probe) digit in the Sternberg paradigm is thought to be reflected in the latency of a major positive wave in the associated event-related potentials. In the present study we have recorded and analysed reaction time and event-related potentials to a digit probe identification task in 37 healthy subjects. Using methods similar to those of earlier studies, we have confirmed the previously reported relationship between memory set size and the apparent latency of the major positive wave. However, analysis of the responses of individual subjects showed that increasing set size had no consistent effects on this wave. One-third of the subjects showed no latency change with increasing set size. In the other subjects, possible latency changes were invariably associated with wave form changes, suggesting that impression of latency shifts may arise from a comparison of non-analogous waves. We suggest that the most significant effect of increasing set size, in the majority of subjects, is a negative amplitude shift which overlaps and distorts a variable section of the major positive wave. In these subjects, an apparent shift in the latency of the major positive wave could be attributed to a combination of attenuation of earlier contributions and relative preservation of later subpeaks, with the result that the dominant positive waves at different levels of memory load are not analogous. By contrast, reaction time increased with set size in all subjects, irrespective of the presence or absence of associated wave form changes. Whereas the reaction time changes with increasing memory load in our study support the original concept of memory scanning, we found no consistent relationship between the latency of event-related potentials generated by this digit probe identification task and memory load. While the presence or absence of a latency shift in some subjects may be open to interpretation, our findings do not support the hypothesis that the latency of the major positive waves is an index of the time involved in memory scanning.

Adult↗