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Biomedical subjects

D J Worthington

Publications and source records attributed to D J Worthington.

At least 19 recordsLinked to original sources
PubMed2000

Maternal serum screening for trisomy 18: assessing different statistical models to optimize detection rates.

We have evaluated three alternative models for trisomy 18 screening using the maternal serum markers alpha-fetoprotein (AFP) and intact human chorionic gonadotrophin (hCG). Using data from 46 affected pregnancies and 48 150 unaffected pregnancies, we calculated distribution parameters for AFP and hCG multiples of the median (MoMs) and the factor comprising AFP MoMxhCG MoM. The trisomy 18 risk at mid-trimester was then calculated using either bivariate analysis of AFP and hCG MoMs or univariate analysis of AFP MoMxhCG MoM. The observed detection rates and positive rates obtained using either published distribution parameters or those derived from the West Midlands population were compared for each model. Using fixed cut-offs for AFP and hCG of 0.66 and 0.40 MoMs resulted in a detection rate of 28.3% for a 0.5% false positive rate (FPR). Using published parameters, the univariate analysis model had a slightly higher detection rate of 32.6% for a 0.5% FPR (cut-off 1:248) compared to the bivariate model which was 28.3% (cut-off 1:239). Locally derived distribution parameters significantly improved the detection rate for the bivariate model for FPRs between 0.4-1.3% but worsened it below 0.4%. For the univariate model there was little difference in detection whether local or published parameters were used. Thus, we have confirmed that trisomy 18 screening using two markers can be a worthwhile addition to Down screening.

Chorionic Gonadotropin↗
PubMed1999

Evaluation of different weight correction methods for antenatal serum screening using data from two multi-centre programmes.

Weight correction of serum markers is widely used when screening for Down's syndrome and open neural tube defects (NTD) because marker concentrations decrease with increasing maternal weight. Log-linear regression is frequently used for determining weight correction factors, but recently reciprocal-linear regression has been suggested to have advantages. We compared both methods of weight correction using data from two screening programmes carried out by this laboratory, one using alpha-fetoprotein (AFP) and total human chorionic gonadotrophin (HCG) (n = 129,143) and the other, AFP and free beta-HCG (n = 39,982). The reciprocal-linear method fitted the data more closely but did not significantly alter the detection rate or screen positive rate (SPR) for Down's syndrome or NTD with either dataset. Without correction, women heavier or lighter than average weight had significantly different SPRs for Down's syndrome and NTD compared with those weighing close to the median weight. Both correction methods smoothed out the variability in the SPR for Down's syndrome to a similar degree, but reciprocal-linear regression was much better at reducing the variability in SPR for NTD and its use is therefore worthwhile.

Biomarkers↗
PubMed1999

Second trimester levels of pregnancy associated plasma protein-A in cases of trisomy 18.

In a study of 70 cases of trisomy 18 and 450 matched controls in the second trimester we have measured the maternal serum levels of the analytes alpha feto protein (AFP), free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A). We have found the median multiple of the median (MoM) of maternal serum free beta-hCG to be significantly lower (0.327) than normal, as was the level of AFP (0.600). Levels of PAPP-A were reduced even further (0.108). Of the markers associated with trisomy 18 at this time PAPP-A was the most discriminatory, being lower than the 5 per cent centile of normal in 93 per cent of cases, compared with 57 per cent of cases for free beta-hCG and 32 per cent of cases for AFP. Combining free beta-hCG and PAPP-A or all three markers with maternal age would have the ability to detect 74 per cent of cases at a 0.5 per cent false positive rate (or 64 per cent at a 0.1 per cent false positive rate). Unlike in cases of trisomy 21, the low PAPP-A values observed in the first trimester are continued into the second trimester. Whether the good discriminatory power of PAPP-A can be realized in second trimester screening programmes will depend on developing two stage screening algorithms. This approach is unlikely to be better than the excellent detection rates achievable with free beta-hCG, PAPP-A and nuchal translucency in the first trimester.

Adult↗
PubMed1993

Dual analyte immunoassay in neural tube defect and Down's syndrome screening: results of a multicentre clinical trial.

We report a multicentre clinical field trial of a novel dual analyte enzyme immunoassay method for the simultaneous measurement of alpha-fetoprotein (AFP) and free beta-human choriogonadotropin (hCG) in the same microtitre well. The assay was shown to have good technical performance in the hands of all trial centres, with between assay coefficients of variation better than 10% for both analyte across the whole of the assay ranges. The method compared well with single analyte measuring procedures and produced acceptable performance as judged by external quality assurance criteria. Recovery of added analyte and analyte dilution curves also showed acceptable performance. In clinical evaluation of a large set of neural tube defect cases, good clinical discrimination from unaffected cases was observed using AFP. With over 150 Down's syndrome cases, the combination of AFP and free beta hCG confirmed the high detection rates achievable using this marker combination, with detection rates in excess of 70% in early gestation. We conclude that the combination of clinically superior markers coupled with technologically innovative assay design will lead to more efficient Down's screening programmes.

Adolescent↗
PubMed1989

Laboratories respond differently to the same clinical request.

A survey of 19 clinical chemical laboratories, undertaken to determine what tests would normally be done in response to a number of common clinical requests (e.g. 'plasma electrolytes please'), revealed wide variations in test patterns. It is suggested that laboratories must bear some of the responsibility for unnecessary testing, and that new strategies are needed to persuade laboratories to adopt more cost-effective test patterns.

Adult↗
PubMed1988

Neuroblastoma--when are urinary catecholamines and their metabolites 'normal'?

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

Adolescent↗
PubMed1988

Urinary catecholamines and their metabolites in management of neuroblastoma.

Measurements of urinary total catecholamines expressed as dopamine (TC) and their metabolites, total metadrenalines (TM) and 3-methoxy-4-hydroxy mandelic acid (HMMA) were made on 24-h urine collections from 56 previously untreated children with neuroblastoma. All results were expressed as a ratio to the creatinine excretion and were compared with "smoothed" age-related reference ranges derived from results in 704 children with other illnesses. Urinary catecholamines/metabolites excretion was elevated in 55 of the 56 patients, the exception being a baby with opsomyoclonus. TC was raised in 47, HMMA in 41, and TM in 37. Eleven patients had elevations of one parameter (TC in 10, HMMA in 1), 15 had 2 elevated levels, and 29 had elevations of all three. The TM level was the least contributory, as in no patient was it the only parameter elevated. Serial measurements were performed in 40 children, and the results correlated closely with the clinical progress of the disease and in some children permitted early detection of recurrence.

Catecholamines↗
PubMed1986

A direct assay for pyridoxal 5'-phosphate using pig heart apo-aspartate transaminase.

The development of a simple enzymatic method for the determination of blood and plasma pyridoxal 5'-phosphate (PLP) using pig heart apo-aspartate transaminase (apo-AST) is described. The technique requires three steps: sample extraction using perchloric acid, a binding step in which PLP in the sample extract is attached to the apo-AST and the enzymatic assay of the reconstituted holo-AST. PLP extracts were analysed with and without a known concentration of added PLP to correct for variation in recovery between different specimens. Procedures are outlined for manual and automatic analysis of the PLP extracts. Using the KONE Clinical Analyser after the extraction step, it is possible to measure enzyme activity in 100 specimens (i.e. 400 tubes) in a 5 h period. Results are shown from 185 healthy women aged 20-45 years, in which plasma PLP concentrations ranged from 5 to 165 nmol/L, and 142 men and 56 women in government service aged 17-64 years, whose plasma PLP ranged from 8 to 169 nmol/L. Values less than 20 nmol/L are believed to indicate vitamin B6 deficiency and the method is able to measure 5 nmol/L.

Adolescent↗
PubMed1983

Can the biochemical responses to a beta 2-adrenoceptor stimulant be used to assess the selectivity of beta-adrenoceptor blockers?

The extent to which beta-adrenoceptor blocking drugs counteract the biochemical responses to an infusion of terbutaline, a beta 2-adrenoceptor agonist, has been investigated. In this study the beta 1-selectivity of metoprolol was compared with the non-selective beta-adrenoceptor blocker propranolol. The hypokalaemia produced by an infusion of terbutaline was reduced by low dose (50 mg) and high dose (200 mg) metoprolol and by low dose (40 mg) and high dose (160 mg) propranolol. The effects of propranolol on terbutaline induced hypokalaemia were more marked than those of metoprolol at both low dose (P = 0.01) and high dose (P = 0.05). Furthermore low dose metoprolol had less effect than high dose metoprolol (P = 0.05). The serum potassium appeared to rise slightly after propranolol. Low and high doses of both beta-adrenoceptor blockers markedly reduced the terbutaline-induced hyperglycaemia, but the differences between the two drugs were not statistically significant.

Adrenergic beta-Agonists↗
PubMed1982

Responsiveness to beta-adrenergic receptor stimulation: the effects of age are cardioselective.

1 To examine the influence of age on beta-adrenergic receptor mechanisms, we have observed the cardiovascular, bronchial and metabolic effects of an intravenous infusion of the beta-adrenoceptor agonist terbutaline in healthy young and elderly female subjects (mean ages 20.9 and 72.1 years respectively). 2 There was a highly significant fall in systolic blood pressure in the elderly, in contrast to the rise in systolic pressure seen in the young subjects. A similar fall in diastolic pressure occurred in both groups, indicating comparable beta-adrenoceptor-mediated vasodilatation. The fall in mean arterial pressure was significantly greater in the old than in the young subjects. The increase in heart rate was significantly less in the elderly. 3 Changes in plasma glucose and potassium during the infusion were similar in the two groups. 4 The observed abnormality of myocardial sensitivity to beta-adrenergic receptor stimulation, which is not associated with a generalized blunting of beta-adrenoceptor mediated effects, may significantly impair autonomic cardiovascular regulation in the elderly.

Adolescent↗
PubMed1982

Cardiovascular and metabolic effects of terbutaline.

Terbutaline is a selective beta 2 agonist used predominantly in the treatment of asthma. Since beta-mediated responses increase heart rate, dilate peripheral arteries, modify carbohydrate metabolism and the uptake of electrolytes into cells, the administration of terbutaline might be expected to produce widespread effects. In this study the intravenous administration of 0.5 mg terbutaline over 60 mn has been shown to produce marked changes without upsetting the volunteers. Heart rate, systolic blood pressure and plasma glucose all increase; diastolic pressure and serum potassium decrease. The data suggests that the terbutaline infusion may be a useful tool for the investigator. The results also quantitate some of the side effects which may result from the intravenous administration of a therapeutic dose of terbutaline given to asthmatics or to pregnant women to reduce uterine activity and delay childbirth.

Adult↗
PubMed1981

Erythrocyte deformability in sickle-cell crisis.

A serial study of erythrocyte deformability, plasma viscosity, and whole-blood viscosity has been made during 10 sickle-cell vaso-occlusive crises. The peak serum lactate dehydrogenase level was used to confirm the duration of crisis and the rheological changes were compared with 19 estimations made on the same patients when asymptomatic. Erythrocyte deformability, measured by filtration of washed erythrocytes through polycarbonate filters of 5 microgram pore size, was significantly reduced on day 1 of crisis and, in one additional patient, this occurred 24 h before the onset of pain. There was no increase in irreversibly-sick-led-cell counts and plasma- and blood-viscosity did not increase significantly until day 5 of crisis, in parallel with the acute-phase rise in plasma fibrinogen. Measurement of erythrocyte filterability is therefore a valuable technique for investigating the pathogenesis of the early stages of sickle-cell crisis.

Adolescent↗
PubMed1981

Efficiency of haematological screening tests for detecting disease.

A new "intermediate' reference (normal) range for the erythrocyte sedimentation rate has been compared with published "low' and "high' reference ranges in a study of 354 hospital patients. The "intermediate' range showed superior balance between sensitivity and specificity in the detection of disease-induced plasma protein abnormalities and and gave a test efficiency of 81.9%; this reference range can therefore be recommended for routine use in the diagnostic laboratory. Four other screening tests (whole-blood viscosity, plasma viscosity, zeta sedimentation ratio, and C-reactive protein level) were compared in the same 354 patients. Whole-blood viscosity proved to be unsuitable as a screening test (efficiency 44.8%) but the three other tests showed good balance between sensitivity and specificity and gave a test efficiency of 74.4-79.7%.

Blood Protein Disorders↗