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H C Watt

Publications and source records attributed to H C Watt.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study.

BACKGROUND: Falls and fractures contribute to morbidity and mortality in bradykinetic rigid syndromes. METHODS: The authors performed a retrospective case notes review at the Queen Square Brain Bank for Neurological Disorders and systematically explored the relation between clinical features and falls and fractures in 782 pathologically diagnosed cases (474 with Parkinson's disease (PD); 127 progressive supranuclear palsy (PSP); 91 multiple system atrophy (MSA); 46 dementia with Lewy bodies (DLB); 27 vascular parkinsonism; nine Alzheimer's disease; eight corticobasal degeneration). RESULTS: Falls were recorded in 606 (77.5%) and fractures in 134 (17.1%). In PD, female gender, symmetrical onset, postural instability, and autonomic instability all independently predicted time to first fall. In PD, PSP, and MSA latency to first fall was shortest in those with older age of onset of disease. Median latency from disease onset to first fall was shortest in Richardson's syndrome (12 months), MSA (42), and PSP-parkinsonism (47), and longest in PD (108). In all patients fractures of the hip were more than twice as common as wrist and forearm fractures. Fractures of the skull, ribs, and vertebrae occurred more frequently in PSP than in other diseases. CONCLUSION: Measures to prevent the morbidity associated with falls and fractures in bradykinetic rigid syndromes may be best directed at patients with the risk factors identified in this study.

Accidental Falls↗
PubMed2005

A standardised method for measuring magnetisation transfer ratio on MR imagers from different manufacturers--the EuroMT sequence.

Magnetisation transfer ratio (MTR) is increasingly used to evaluate neurological disorders, especially those involving demyelination. It shows promise as a surrogate marker of disease progression in treatment trials in multiple sclerosis (MS) but the value measured is highly dependent on pulse sequence parameters, making it hard to include the technique in large multi-centre clinical trials. The variations can be reduced by a normalisation procedure based on the flip angle and timing of the presaturation pulse, but correction for parameters such as saturation pulse shape, amplitude, duration and offset frequency remains problematic. We have defined a standard pulse sequence, to include a standard presaturation pulse and set of parameters, which can be implemented on scanners from both General Electric and Siemens, and has also been used on Phillips scanners. To validate the sequence and parameters, six European centres measured MTR in the frontal white matter of normal volunteers. It was possible to measure MTR values in controls which were consistent to within approximately +/-2.5 percentage units across sites. This degree of precision may be adequate in many situations. The remaining differences between sites and manufacturers are probably caused by B1 errors.

Brain↗
PubMed2003

Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer's disease.

S100B is a predominantly astrocytic protein with dose-dependent cytotoxic and neurotrophic properties encoded on chromosome 21q22.3. Concentrations of S100B were measured in the cerebrospinal fluid (CSF) of 31 patients with Alzheimer's disease (AD), 36 patients with frontotemporal lobe dementia (FTLD) and 49 patients with other non-inflammatory neurological diseases. Additional CSF S100B concentrations were correlated with normalised brain volume measurements in AD and FTLD. CSF S100B was significantly higher in AD (Mean+/-standard deviation=0.4+/-0.2 ng/ml) and FTLD (0.42+/-0.19 ng/ml) patients when compared with control subjects (0.25+/-0.08, P<0.001). In patients with AD, S100B correlated negatively with normalised brain volume (R(S)=-0.53, P<0.001). No such correlation was found for FTLD patients. This study supports the concept that S100B is of pathological relevance for degeneration of the central nervous system in AD.

Adult↗
PubMed2003

Using Down syndrome serum screening results to predict low birthweight.

OBJECTIVE: To investigate the use of prenatal maternal serum screening results for Down syndrome, for the prediction of low (<2500 g) and very low (<1500 g) birthweight. DESIGN: Record linkage of maternal serum screening results with the corresponding birth records. PARTICIPANTS: 42 259 women whose pregnancies had been screened for the risk of Down syndrome. SETTING: Three East London maternity units, between February 1989 and August 1998. RESULTS: Estimates were made of the effectiveness of single markers only for the prediction of low birthweight, and of multiple markers together with mother's weight and smoking habit. As reported previously, high levels of the single markers alpha-fetoprotein and total human chorionic gonadotrophin, inhibin A, and low levels of unconjugated oestriol were associated with low birthweight. However, the best prediction was obtained when multiple serum markers comprising alpha-fetoprotein, unconjugated oestriol, and inhibin A were used in combination together with mother's weight and adjustment for smoking habit. For a false-positive rate of 5%, this combination predicted 23% of low birthweight and 39% of very low birthweight babies, possibly the best method of prediction to date. CONCLUSION: Prediction of low birthweight derived from Down syndrome screening could be used, for little extra cost, to advise on place of delivery or to select candidates for randomised clinical trials of low birthweight prevention.

Adult↗
PubMed2003

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Adult↗
PubMed2001

Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging.

BACKGROUND AND PURPOSE: MR-based volumetric measures of cerebral structures are increasingly used for diagnostic purposes and to measure progression of atrophy. Variations in individual head size may be corrected by normalization with use of a total intracranial volume (TIV) measurement. The TIV also may be used to correct for voxel size fluctuations in serial studies. The TIV should be measured from the same images used for structural volumetry, usually T1-weighted imaging. The objectives were to show that normalization with TIV reduces interindividual variation, to develop and validate a simple protocol for measuring TIV from T1-weighted MR images, and to apply TIV normalization to serial brain measures in controls and subjects with Alzheimer disease (AD). METHODS: We measured TIV with a semiautomated segmentation technique on T1- and T2-weighted MR images in 55 controls, 10 AD patients, and two persons at risk of familial AD. Whole-brain volumes also were measured and normalized with TIVs. RESULTS: The TIV normalization of cross-sectional brain volumes significantly reduced interindividual variation; the coefficient of variation (CV) was reduced from 10.0% to 6.0% in controls (P <.001). The TIVs measured on T1-weighted images had low variability (CV, 0.16%) and did not differ significantly from those measured on T2-weighted images (P =.16). The TIV normalization of serial brain-volume measurements reduced interimage differences caused by voxel-scaling variations (CV reduced from 1.3% to 0.5%, P =.002) in 10 controls and five AD patients. CONCLUSION: Structural volumes should be normalized with a TIV, measured cross-sectionally, to reduce interindividual variation, and longitudinally with a concurrent measurement, to reduce subtle interimage differences. This may have important implications in progression studies.

Adult↗
PubMed2000

Adding free to total prostate-specific antigen levels in trials of prostate cancer screening.

We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.

Case-Control Studies↗
PubMed1999

Integrated screening for Down's syndrome based on tests performed during the first and second trimesters.

BACKGROUND: Both first-trimester screening and second-trimester screening for Down's syndrome are effective means of selecting women for chorionic-villus sampling or amniocentesis, but there is uncertainty about which screening method should be used in practice. We propose a new screening method in which measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by Down's syndrome. METHODS: We used data from published studies of various screening methods employed during the first and second trimesters. The first-trimester screening consisted of measurement of serum pregnancy-associated plasma protein A in 77 pregnancies affected by Down's syndrome and 383 unaffected pregnancies and measurements of nuchal translucency obtained by ultrasonography in 326 affected and 95,476 unaffected pregnancies. The second-trimester tests were various combinations of measurements of serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A in 77 affected and 385 unaffected pregnancies. RESULTS: When we used a risk of 1 in 120 or greater as the cutoff to define a positive result on the integrated screening test, the rate of detection of Down's syndrome was 85 percent, with a false positive rate of 0.9 percent. To achieve the same rate of detection, current screening tests would have higher false positive rates (5 to 22 percent). If the integrated test were to replace the triple test (measurements of serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin), currently used with a 5 percent false positive rate, for screening during the second trimester, the detection rate would be higher 85 percent vs. 69 percent), with a reduction of four fifths in the number of invasive diagnostic procedures and consequent losses of normal fetuses. CONCLUSIONS: The integrated test detects more cases of Down's syndrome with a much lower false positive rate than the best currently available test.

Adolescent↗
PubMed1999

The target plot: a new way of displaying the performance of a screening test.

OBJECTIVES: To produce a graphical method to represent the performance of a screening test that illustrates the prevalence of the disorder being screened for, as well as its discriminatory potential. CONCEPT: A target plot was constructed in which the risk of the disorder is represented by a series of concentric circles of constant risk (isorisks) equivalent to specified false positive rates, with the highest risk in the centre and lower risks spreading outwards towards the circumference. Dots were drawn to represent cases of the disorder; these were of a size such that their total area as a proportion of the area of the whole target plot equalled the prevalence of the disorder in the screened population. The discriminatory power of the test was seen as the clustering of dots around the centre or bull's eye of the target. The detection rate could be estimated as the proportion of dots which fell within the isorisk corresponding to a specified false positive rate. APPLICATION: The target plot was applied to second trimester antenatal screening for Down's syndrome using different combinations of screening markers, and also to screening for ischaemic heart disease using protein components of cholesterol (apolipoproteins A I and B and Lp(a) lipoprotein), systolic blood pressure, and smoking status. DISCUSSION: The efficacy of the different methods of screening for Down's syndrome is readily apparent using the target plot, as is the poorer performance of screening for ischaemic heart disease. CONCLUSIONS: The target plot is a simple and quantitative way of displaying the performance of a screening test that may be useful in teaching and educational material.

Audiovisual Aids↗
PubMed1999

Fetal loss in Down syndrome pregnancies.

It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated. We present new data on the spontaneous fetal loss in Down syndrome pregnancies from the National Down Syndrome Cytogenetic Register (1989-1996). We compare our results with published results of other studies on the subject to obtain a summary estimate. We exclude one study from the meta analysis due to incorrect methodology resulting in an overestimate of fetal loss. Based on the combined data (i) between the time of chorionic villus sampling and term an estimated 43 per cent (95 per cent CI: 31-54 per cent) of pregnancies ended in a miscarriage or still birth, (ii) between the time of amniocentesis and term an estimated 23 per cent (95 per cent CI: 19 28 per cent) of pregnancies ended in a miscarriage or still birth, and (iii) 12 per cent (95 per cent CI: 2-23 per cent) of births were stillborn or resulted in a neonatal death.

Abortion, Spontaneous↗
PubMed1999

SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. International Prenatal Screening Research Group.

We conducted a study to determine the value of serum pregnancy-specific beta-1-glycoprotein (Schwangerschafts protein 1, SP1) as an antenatal screening test for Down syndrome in the first trimester. Serum samples collected from women at 8 to 14 weeks of pregnancy, immediately prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from 96 women with Down syndrome pregnancies (cases) and from 480 women with unaffected pregnancies (controls). Cases and controls were ascertained at 21 obstetric centres in nine countries. Each case was matched with five controls for maternal age (same five-year age groups), duration of storage of the serum sample (same calendar year) and gestational age (usually the same week of pregnancy). The levels of SP1 were lower in pregnancies associated with Down syndrome: the median level was 0.86 multiples of the median level in the controls (95 per cent confidence interval 0.76 to 0.97). This difference, though statistically significant, was not large enough for SP1 to be a useful marker in screening, at least from 10 weeks onwards where most of our data lie.

Biomarkers↗
PubMed1998

Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.

BACKGROUND: Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position. METHODS: In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design). RESULTS: Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons. CONCLUSIONS: Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.

Adult↗
PubMed1998

Screening for Down syndrome at 14 weeks of pregnancy.

To investigate whether statistical parameters used in Down syndrome screening between 15 and 22 weeks of pregnancy can be used at 14 weeks, we assayed alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and inhibin-A in 16 pregnancies with Down syndrome in the 14th week of pregnancy and expressed values in multiples of the normal median. The median and standard deviation values for these 16 pregnancies were not materially different from those published for 15-22 weeks. It is reasonable, therefore, to offer Down syndrome screening using these markers starting at 14 completed weeks of pregnancy instead of 15 weeks. It needs to be recognized, however, that serum AFP measurement for neural tube defect screening is less effective at this time than between 16 and 18 weeks of pregnancy.

Chorionic Gonadotropin↗
PubMed1998

The pattern of maternal serum inhibin-A concentrations in the second trimester of pregnancy.

Maternal serum inhibin-A concentration is a useful marker in prenatal screening for Down syndrome in the second trimester. We measured inhibin-A concentrations in 4304 pregnancies without Down syndrome between 14 and 22 weeks of pregnancy to determine the median values according to gestational age. There was a U-shaped pattern of inhibin-A concentration against gestational age with a minimum concentration at 17 weeks and 1 day (120 days). We suggest that screening centres use a quadratic equation when estimating their normal median inhibin-A level, constraining the shape of the curve and fixing the lower point of the curve to occur at 120 days, but allowing its position in relation to the vertical inhibin-A axis to be set according to the local data. This approach will systematically allow for the changing inhibin-A concentration without introducing the instability of deriving a fresh quadratic equation for each screening centre and each time a centre's medians are revised.

Biomarkers↗
PubMed1998

Serum triglyceride: a possible risk factor for ruptured abdominal aortic aneurysm.

BACKGROUND: We aimed to determine the relationship between ruptured abdominal aortic aneurysm (AAA) and serum concentrations of lipids and apolipoproteins. METHODS: A cohort of 21 520 men, aged 35-64 years, was recruited from men attending the British United Provident Association (BUPA) clinic in London for a routine medical examination in 1975-1982. Smoking habits, weight, height and blood pressure were recorded at entry. Lipids and apolipoproteins were measured in stored serum samples from the 30 men who subsequently died of ruptured AAA and 150 matched controls. RESULTS: Triglyceride was strongly related to risk of ruptured AAA. In univariate analyses the risk in men on the 90th centile of the distribution relative to the risk in men on the 10th (RO10-90) was 12 (95% confidence interval [CI] : 3.8-37) for triglyceride, 5.5 (95% CI: 1.8-17) for apolipoprotein B (apoB) (the protein component of low density lipoprotein [LDL]), 0.15 (95% CI : 0.04-0.56) for apo A1 (the protein component of high density lipoprotein [HDL]), 3.7 (95% CI: 1.4-9.4) for body mass index and 3.0 (95% CI: 1.1-8.5) for systolic blood pressure. Lipoprotein (a) (Lp(a)) was not a significant risk factor (RO10-90 = 1.6, 95% CI: 0.6-3.0). In multivariate analysis triglyceride retained its strong association. CONCLUSION: Triglyceride appears to be a strong risk factor for ruptured AAA, although further studies are required to clarify this. If this and other associations are cause and effect, then changing the distribution of risk factors in the population (by many people stopping smoking and adopting a lower saturated fat diet and by lowering blood pressure) could achieve an important reduction in mortality from ruptured AAA.

Adult↗
PubMed1998

Alternative methods of maternal weight adjustment in maternal serum screening for Down syndrome and neural tube defects.

Serum markers used in screening for Down syndrome and neural tube defects are often adjusted to take account of the effect of maternal weight on the marker levels. The standard adjustment procedure is based on a linear relationship between the marker concentration, expressed as the log of the multiple of the median (MOM), and maternal weight on a linear scale. It has been proposed that maternal weight adjustment may be better performed using a linear relationship between marker concentration expressed in MOM and the reciprocal of maternal weight. In a dataset of 8905 singleton pregnancies in white women without Down syndrome or neural tube defects we compared the two methods of weight adjustment and found that both were satisfactory and neither had an obvious advantage over the other. In the analysis it was noticed that hCG levels in very heavy women (> 120 kg) were higher than expected from the decreasing linear trend with maternal weight--a result that was statistically highly significant (p < 0.01) but for which we have no explanation. In screening it will have virtually no effect because the finding was restricted to only the 0.3 per cent of the heaviest women.

Biomarkers↗
PubMed1997

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases.

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.

Adult↗