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T M Reynolds

Publications and source records attributed to T M Reynolds.

At least 91 records · Page 5Linked to original sources
PubMed1995

The effects of gestation dating on the calculation of patient specific risks in Down's syndrome screening.

In Down's syndrome screening using biochemical markers, the marker concentrations are adjusted for the gestational age of the fetus, since they are known to change with gestational age. This adjustment is performed by referring to the population median of each marker for the appropriate gestational age group. The measurement of gestational age is subject to error, whatever method is used, and the population median used is actually the median of a mixture of distributions for different true gestational ages. We show how the proportions in this mixture can be estimated and how the true median corresponding to a given true gestational age can be estimated. For simplicity, we consider the case of using a single marker, namely maternal serum alpha-fetoprotein, and show that the usual estimation method has considerable bias. The effect of this mixture on the calculation of patient-specific risks is discussed and we show that detection rates can be improved by allowing for this error in the dating process. The overall detection rate is increased by about 1%. The increase in detection rate is age-dependent and for some maternal ages the increase is of the order of 5%. The comparative effects of different methods for dating are discussed.

Biomarkers↗
PubMed1993

The frusemide test: simple screening test for renal acidification defect in urolithiasis.

Urinary pH was first labelled as a risk factor for patients with recurrent calcium stone disease of the renal tract in 1978. The standard diagnostic test for patients with a history of stones, who appear to have urinary acidification defects is the ammonium chloride test. However, the performance of this test results in significant morbidity, particularly nausea and vomiting, and as a result there is little enthusiasm for screening for such defects. We describe a screening test that may be used to determine which patients require more definitive testing. It involves an oral dose of frusemide (40 mg) followed by half-hourly urine sampling for pH. For the detection of a renal tubular acidification defect, the frusemide test had sensitivity = 100%, specificity = 82%, predictive value of a positive result = 40%, predictive value of a negative result = 100%, screening efficiency = 84%, and there was no morbidity. During the ammonium chloride test 80% of the patients vomited or felt very nauseated.

Ammonium Chloride↗
PubMed1993

Assessment of atypicality: an adjunct to prenatal screening for Down's syndrome that facilitates detection of other abnormalities.

Current software used for assessment of the risk of Down's syndrome may give misleading risk estimates if applied to other abnormalities. Often the abnormality is reflected in maternal serum alpha-fetoprotein and human chorionic gonadotrophin levels and is then translated into a low risk for Down's syndrome that may not be recognized as significantly atypical of normality. We regard this as a serious deficiency in the current Down's syndrome risk reporting algorithm, and suggest a modification that allows the problem to be overcome.

Algorithms↗
PubMed1993

All MoMs are not equal: some statistical properties associated with reporting results in the form of multiples of the median.

The statistical procedure for discriminating between a Down syndrome or neural tube defect (NTD) fetus and a normal fetus relies, to a great extent, on the reporting of maternal serum alpha-fetoprotein (MSAFP), hCG, and uE3 results in the form of multiples of the median (MoMs). Further, threshold MoMs values for MSAFP, such as 2.5 MoMs, are often used to define a reference range to identify an NTD fetus. We show that a constant threshold-MoMs cutoff for MSAFP values actually refers to different percentiles of MSAFP levels at different gestational ages and that the combining of MoMs values between centers and gestational ages, such as suggested by Wald et al. for deriving a patient-specific risk index, is highly questionable. The results presented in this paper are quite general and will apply to all situations where MoMs are used.

Down Syndrome↗
PubMed1993

Age-specific detection and false-positive rates: an aid to counseling in Down syndrome risk screening.

OBJECTIVE: To determine whether the serum screening test for Down syndrome provides equal detection efficacy for women of all ages, to improve the data available for patient counseling both before testing and afterward in the event of a positive result. METHODS: We examined the effect of age on Down screening by generating a set of "normal" and "Down syndrome" likelihood ratios by computer simulation. The expected false-positive and detection rates were derived for different age groups by counting the proportion of cases in which the likelihood ratio could modify the age-specific risk to be greater than the cutoff risk of one in 300 (equivalent to an incidence of 3.33 per 1000). The predictive value of a positive result was calculated using Baye's theorem. RESULTS: Detection rates, false-positive rates, and predictive values were shown to be age-dependent. CONCLUSIONS: Knowledge of the age dependency of Down syndrome screening results may be useful in explaining to patients that the Down screen can only detect a proportion of cases and that a negative result does not guarantee normality. This knowledge may also be helpful in minimizing psychological stress, as a positive result indicates only a small chance that the fetus will have Down syndrome.

Adolescent↗
PubMed1992

Ultrasonographic dating of pregnancy causes significant errors in Down syndrome risk assessment that may be minimized by use of biparietal diameter-based means.

OBJECTIVES: Gestational dates assessed by ultrasonographic measurement of fetal dimensions are usually quoted in terms of complete weeks because the uncertainty of ultrasonographic measurement is approximately +/- 7 days. This study examines the effect of ultrasonographic dating on Down syndrome risk assessment. STUDY DESIGN: The effect of small changes in measured biparietal diameter resulting in a change in estimated gestational week and the benefits of a more precise measure of fetal gestational age (raw biparietal diameter) are examined mathematically. RESULTS: If maternal serum alpha-fetoprotein and human chorionic gonadotropin are used to assess Down syndrome risk, risks assessed with ultrasonographically determined dates may be less than or equal to 45% too high for fetuses with biparietal diameter at the lowest end of the size band and less than or equal to 22% too low with biparietal diameter at the top of the size band. If the results for maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol are used, these figures become less than or equal to 150% and less than or equal to 60%, respectively. CONCLUSION: If ultrasonography is used to assess gestational age, the raw biparietal diameter and not the estimated week of gestation must be used to derive means for calculation of multiples of the mean.

Down Syndrome↗
PubMed1992

Hip fracture patients may be vitamin B6 deficient. Controlled study of serum pyridoxal-5'-phosphate.

Deficiency of vitamin B6 in rats may result in defective bone formation, possibly due to decreased activity of the enzyme ornithine decarboxylase which requires pyridoxal-5'-phosphate (PLP) as a co-factor and is responsible for production of intracellular putrescine, a metabolic regulator. We studied 3 groups of patients (62 fit ambulant out-patients, 21 elective arthroplasty patients, and 20 hip fracture patients) and assayed their PLP status by high performance liquid chromatography. The reference range derived from the out-patients was 13-106 nmol/L. 3 of the arthroplasty group and 10 of the fracture group had serum PLP concentrations less than 13 nmol/L (P < 0.01). We conclude that PLP may be an etiologic factor in hip fracture by virtue of its role in the activity of a key regulatory protein.

Adult↗