Maternal leucocyte zinc deficiency at start of third trimester as a predictor of fetal growth retardation.

Leucocyte zinc concentrations were measured in 70 mothers at the beginning of the third trimester of pregnancy and compared with the weight centiles of their subsequently delivered babies. The median maternal leucocyte zinc concentrations rose progressively with weight centile. Thus the median leucocyte zinc concentration of the mothers delivering babies weighing below the 10th centile was 112 nmol/10(9) leucocytes and that of the mothers with babies weighing above the 90th centile was 229.5 nmol/10(9) leucocytes. A maternal leucocyte zinc concentration less than 120 nmol/10(9) leucocytes strongly predicted a baby weighing below the 10th centile (positive predictive value = 71.9%, negative predictive value = 91.5%, sensitivity = 64.3%, specificity = 81.8%). These findings suggest that maternal zinc concentration might have a role in antenatal screening, but larger studies are required.     

Do growth chart centiles need a face lift?

European height and weight growth charts commonly extend from the 3rd to the 97th centile, whereas in North America the extremes are usually the 5th and 95th centiles. There is no good reason for the difference, and neither chart is particularly useful for screening owing to the high false positive rate associated with a cut off based on the lowest centile. The World Health Organisation''s international growth reference uses cut offs based on standard deviation scores rather than centiles, which are more suitable for the extremes of growth status seen in the developing world. This chart, however, is incompatible with charts based on centiles. Here a unified growth chart is proposed: it has nine rather than seven centiles, and they are spaced two thirds of a standard deviation score apart rather than the more usual unit spacing. This gives a set of curves very like the conventional 3rd to 97th centiles, but with additional curves at 2.67 standard deviation below and above the mean (roughly the 0.4th and 99.6th centiles). The 0.4th centile is a more practical cut off for screening purposes than the 3rd or 5th centile.     

Growth and malnutrition in Ethiopia

This article focuses on anthropometric parameters as height for age, weight for age and weight for height, which are among the most used tools for assessing well-being of infants and children. Such data have been collected between 1992--1993 from samples of infants and children aged between 2 and 10 years from urban and rural areas of Ethiopia. Similar to many other reports from developing countries the great amount of malnourished children is preoccupying as reflected by about 15% of children below the 5th centile of weight for height and about 53% of children below the 5th centile of height for age and about 45% below the 5th centile of weight for age.     

Results of an experiment in systematic prenatal screening for neural tube malformations by assay of alpha fetoproteins in dried blood samples (12,480 pregnancies)

Measurement of alpha-fetoprotein (AFP) in eluate of dried blood was carried out in 12,480 pregnant women, between the 10th and 30th weeks of amenorrhea. In 348 cases, AFP level was greater than normal (greater than 99th centile). 225 control measurements were performed (123 women dropped out of the study). In 173 cases, the AFP level returned to normal (1.4% false positives). In 52 cases, AFP title remained above the 99th centile: in 8 cases, the fetus was malformed (4 anencephalics, 1 spina bifida, 1 hydrocephalus, 1 laparoschisis, 1 exomphalos). Of the 44 remaining cases, 26 were multiple pregnancies, 5 were cases of acute fetal distress, 7 false positives normalized when a second control was made, 5 false positives up to the end of pregnancy, and 1 spina bifida (normal ultrasound scan on two different occasions). During this prenatal screening, 7 false negatives (0.56%) not detected by AFP assay should be noted: 3 anencephalics, 2 spina bifida, 1 hydrocephalus, 1 exomphalos. In all cases except one, the AFP test was carried out too early (before the 10th week) or too late (after the 30th week). The authors stress that screening must be done during the precise period between the 16th and 20th weeks of amenorrhea, and that close collaboration with a competent ultrasonographist is necessary. In 5 cases of false negatives where AFP assay and ultrasound scan had been carried out, the two methods are compared. Measurement of AFP in eluate of dried blood thus seems a reliable test which could be the first stage in a plan for systematic prenatal screening for certain serious fetal malformations with high incidence (1,2% in the Midi-Pyrenees region).     

Pesticides of Potential Ecological Concern in Sediment from South Florida Canals: An Ecological Risk Prioritization for Aquatic Arthropods

A two-tier ecological risk assessment was conducted for pesticides monitored in sediment at 36 sampling sites in south Florida freshwater canals from 1990–2002. For tier 1, we identified the chemicals of potential ecological concern (COPECs) as DDT, DDD, DDE, chlordane and endosulfan based on their exceedence of sediment quality standards at 20 sites. For 12 sites with data on the fraction of organic carbon in sediments, whole sediment concentrations of COPECs were converted to pore water concentrations based on equilibrium partitioning. In tier 2, a probabilistic risk assessment compared distributions of pore water exposure concentrations of COPECs with effects distributions of freshwater arthropod response data from laboratory toxicity tests. Arthropod effects distributions included benthic and non-benthic arthropod species for chlordane (n = 9), DDD (n = 12), DDE (n = 5), DDT (n = 48), and endosulfan (n = 26). The overlap of predicted pore water concentrations and arthropod effects distributions was used as a measure of risk. DDE was the most frequently detected COPEC in sediment at the 12 sites. Chlordane was present at only one site. The mean 90th centile concentration for pore water exposure was highest for endosulfan and lowest for DDT. The estimated acute 10th centile concentration for effects was highest for chlordane and lowest for DDD. The probability of pore water exposures of COPECs exceeding the estimated 10th centile concentrations for species sensitivity distributions of arthropod acute toxicity data was between 0 and 1%. The estimated NOEC 10th centile concentration from arthropod chronic toxicity distributions was exceeded by the estimated 90th centile concentration for pore water distributions at three sites. Endosulfan had the highest potential chronic risk at S-178 in the C-111 canal system, based on the probability of pore water exposure concentrations exceeding the arthropod estimated chronic NOEC 10th centile at 41%. The COPEC with the next highest probability of exceeding the chronic NOEC 10th centile was DDD at 17.7% and 19.8% in the Everglades Agricultural Area (at S-2 and S-6). DDT had minimal potential chronic risk. Uncertainties in exposure and effects analysis and risk characterization are discussed.     

Aquatic Risk Assessment of Metals in Sediment from South Florida Canals

A major watershed restoration effort is underway in south Florida, yet there are significant gaps in scientific information on exposure and risks of contaminants to its natural resources. We conducted a two-tier aquatic screening-level ecological risk assessment for metals that were monitored in sediment at 32 sampling sites in south Florida freshwater canals from 1990–2002. For tier 1, the chemicals (or metals) of potential ecological concern (COPECs) were identified as arsenic, cadmium, chromium, copper, lead, nickel and zinc based on their exceedences of Florida sediment quality guidelines at 10 sites. For tier 2, we used a probabilistic risk assessment method to compare distributions of predicted pore water exposure concentrations of seven metal COPECs with distributions of species response data from laboratory toxicity tests to quantify the likelihood of risk. The overlap of pore water concentrations (90th centile for exposure) for metal COPECs and the effects distributions for arthropods (10th centile of LC50s) and all species (10th centile of chronic NOECs) were used as a measure of potential acute and chronic risks, respectively. Arsenic (25%) in the Holey Land tracts, in Broward County north of Everglades National Park (ENP), and chromium (25%) in the C-111 freshwater system, at the east boundary of ENP, were the most frequently detected COPECs in sediment. Antimony (6%), zinc (6%) and lead (5%) were the least frequently detected COPECs in sediment. The 90th centile concentrations for bulk sediment were highest for zinc (at S-178) and lead (at S-176) in the C-111system. The 90th centile concentration for pore water exposure was highest for arsenic in the Holey Land tracts and lowest for cadmium and chromium. The estimated acute 10th centile concentration for effects was lowest for copper and arthropods. The probabilities of pore water exposures of copper exceeding the estimated acute 10th centile concentration from the species sensitivity distributions (SSD) of acute toxicity data (for arthropods) were 57 and 100% for copper at S-177 and S-178 in the C-111 system, respectively. The probability of pore water exposures of copper exceeding the estimated NOEC 10th centile concentration from the SSD of chronic toxicity data (for all species) was 93 and 100% for copper at S-177 and S-178, respectively. Uncertainties in exposure and effects analysis and risk characterization are identified and discussed. The study presents a straightforward approach to estimate exposure and potential risks of metals detected in sediment from south Florida canals.     

Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience.

OBJECTIVE--To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis. DESIGN--Four year prospective study of two tier screening strategy. First tier: immunoreactive trypsinogen measured in dried blood spot samples from neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (delta F508, delta I506, G551D, G542X, and R553X) in samples with immunoreactive trypsinogen concentrations in highest 1% and in all neonates with meconium ileus or family history of cystic fibrosis. SETTING--South Australian Neonatal Screening Programme, Adelaide. SUBJECTS--All 88,752 neonates born in South Australia between December 1989 and December 1993. INTERVENTIONS--Neonates with two identifiable mutations were referred directly for clinical assessment and confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates identified as carriers of cystic fibrosis mutation were counselled and offered genetic testing. MAIN OUTCOME MEASURES--Identification of all children with cystic fibrosis in the screened population. RESULTS--Of 1004 (1.13%) neonates with immunoreactive trypsinogen > or = 99th centile, 912 (90.8%) had no identifiable mutation. 23 neonates were homozygotes or compound heterozygotes; 69 carried one identifiable mutation, of whom six had positive sweat tests. Median age at clinical assessment for the 29 neonates with cystic fibrosis was 3 weeks; six had meconium ileus and two had affected siblings. 63 neonates were identified as carriers of a cystic fibrosis mutation. Extra laboratory costs for measuring immunoreactive trypsinogen and direct gene analysis were $A1.50 per neonate screened. CONCLUSION--This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone.     

Simplified radioimmunoassay for aldosterone using antisera to aldosterone-γ-lactone

A simplified, non-chromatographic method for aldosterone-γ-lactone (2) radioimmunoassay is described, using a high titer aldosterone-γ-lactone antibody. This method takes six working hours for completion; the blanks are below the sensitivity of the assay (0–10 pg), and the intra and interassay coefficient of variation is 4.9% and 8.2% respectively. There is no significant variation with different plasma volumes assayed and the plot of added and assayed aldosterone gives a slope of 0.983. The negligible cross reactivity with other steroids and lactones eliminates the problem of interference by these substances.     

Increased saliva oestriol to progesterone ratio before preterm delivery: a possible predictor for preterm labor?

Saliva oestriol, oestradiol, and progesterone concentrations were measured in 23 women who went into spontaneous preterm labour. The patients fell clinically and biochemically into two groups. The 13 who went into preterm labour with intact membranes had a saliva oestriol to progesterone ratio greater than one in every case and greater than the 95th centile for their length of gestation in 12 cases; by contrast, all those who went into spontaneous preterm labour after prolonged rupture of the membranes had an oestriol to progesterone ratio less than one and below the 50th centile for their period of gestation in the one to four days before delivery. Saliva oestradiol to progesterone ratios were randomly distributed throughout the normal range in both groups. It appears that preterm labour without prior prolonged rupture of the membranes is, like term labour, preceded by an increase in the saliva oestriol to progesterone ratio. It may therefore be possible to use this ratio to predict preterm labour.     

采用三次样条拟合胎儿体格发育指标百分位数参考值

目的:生长发育评价标准的最佳形式是年龄别百分位数,然而,目前我国缺乏胎儿的孕周别体格发育指标百分位数评价标准,影响了胎儿宫内生长发育水平的准确评价,本研究拟建立陕西省正常单胎妊娠孕妇胎儿体格发育指标百分位数参考标准。方法:以陕西省西安、汉中、延安5所大型综合医院超声科或妇产科超声室为数据采集点,选择2010-01-01到2010-12-31间进行常规孕期检查的正常单胎妊娠胎儿的超声测量数据,随机抽取一次测量结果,共收集到6832个单胎正常妊娠胎儿的超声测量数据。采用三次样条法对陕西省孕16-41周正常单胎妊娠胎儿的双顶径、腹围、股骨长百分位数进行拟合。结果:三次样条拟合胎儿的双顶径、腹围、股骨长百分位数,各百分位数的决定系数均在0.95以上,均方差均在各指标重复测量的容许误差内,拟合结果满意。计算出了胎儿的孕周别双顶径、腹围、股骨长的P3、P10、P25、P50、P75、P90、P97百分位数。结论:三次样条兼顾了曲线拟合中的拟合优度和光滑度,能更好的实现曲线拟合的目的。所建立的孕周别胎儿体格发育指标百分位数符合胎儿宫内生长发育规律,为胎儿宫内生长发育的准确评价提供了科学、准确的评价工具,可用于产科临床和研究工作中。     

Identification of insulin receptor systems: assessing the impact of model selection and measurement error on precision of parameter estimates using Monte Carlo study

An extensive Monte Carlo study has been carried out in order to study the effect of measurement error on the precision of parameter estimates of an insulin binding system. Hypothetical radioimmunoassay experiments were generated for insulin binding to erythrocytes. The design of experiments followed strictly the protocol of real experiments. Randomly generated error was added to the synthetic data. The standard technique, a weighted non-linear regression analysis, was employed to re-estimate parameters of a model of two receptor sites and a model of negative co-operativity. As the original parameter values were known, the differences between original and estimated values was studied for (a) measurement error in the range from 0-17%, (b) random initial estimates and (c) error-free non-specific binding. In addition, analytical estimates of parameter precision were compared with the true between-experiment variation of parameter estimates. At the measurement error of 12%, a one site model is recommended to estimate the high affinity population of the two sites model. Plausible results can be expected in 90% of experiments, the between-experiment variation being approximately 30%. The model of two receptor sites gives approximately two thirds of plausible results. The high affinity population can be estimated with the between-experiment variation of 40%, the low affinity population is virtually unidentifiable with the between-experiment variation of approximately 100% and parameter estimates biased to higher values. Only half of the results obtained from the model of negative co-operativity are plausible, the variation in parameter estimates ranges from 90-150% and estimates are biased to higher values. At the level of 12% measurement error, random initial estimates do not significantly affect the estimation process, provided initial estimates are selected from a feasible range. At the same measurement error, the error-free non-specific binding does not improve the results, indicating that the mean of six replicates may be taken as a reliable estimate of non-specific binding. The analytical estimates of the coefficient of variation systematically underestimates the true between-experiments coefficient of variation, the difference has been found to be about 50%.     

大杯香菇辐射选育新株系主要营养价值的遗传分析

对大杯香菇中20个（品种和辐射选育新株系）的蛋白质营养价值6项评价指标进行了遗传变异分析、相关性分析和主成分分析.结果表明,变异系数最大的为氨基酸比值系数分,达到22.70％;其次为氨基酸评分,变异系数为18.08％;其它变异系数较小分别为化学评分、生物价、营养指数和必需氨基酸指数为4.18％、3.76％、3.37％和...     

Growth profile of rural Meitei children of Manipur state of India

Patterns of growth in 10 anthropometric measurements among the rural Manipuri children (N=425), aged 5 to 14 years, with poor socio-economic backgrounds are reported. The anthropometric dimensions include weight, stature, sitting-height, head, chest and midupper-arm circumferences, biepicondylar widths of humerus and femur, and triceps and biceps skinfolds. Except skinfolds, the boys measured more than the girls in all measurements at all ages, except from 10 to 12 years in weight, stature, sitting-height, and chest and mid-upper-arm circumferences. Across all ages, the girls had thicker fat folds. Up to 12 years, the children lie approximately on the 10th centile of NCHS in stature and weight. The arm circumferences was below the 3rd centile of the Dutch children, until 11 years. The triceps fat fold fluctuated between 10th and 25th centiles of US whites. The rural Meiteis were taller and heavier than rural Burmese and urban Meiteis. The overall growth performance of the rural Meitei children was poor as compared to US, Urban Chinese, and well-nourished Indian children.     

Grip Strength across the Life Course: Normative Data from Twelve British Studies

Introduction

Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.

Methods

We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).

Results

Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.

Conclusion

This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.     

A quantitative method for the measurement of membrane affinity by polydiacetylene-based colorimetric assay

The measurement of membrane affinity is an important early screening step during drug discovery. However, classical methods for membrane affinity measurement are tedious and difficult to implement in high-throughput screening. This article describes a quantitative method for the measurement of membrane affinity by colorimetric assay based on polydiacetylene (PDA) sensors. Prepared lipid/PDA chromatic vesicles were used to model cell membranes. By measuring the colorimetric response of the chromatic vesicles when drug-membrane interactions occurred, membrane affinity constant K(b) could be calculated using a simple quantitative model. Under optimized preparation conditions, the calculated log(K(b)) values exhibited an in-batch relative standard deviation (RSD) of less than 4% and a between-batch RSD of less than 8% for all three reference compounds. The logarithm of K(b) of the six β-blockers exhibited excellent linear correlation with the logarithm of the liposome/water partition coefficient (K(m)) with R(2)=0.9793. For neutral compounds, the log(K(b)) of n-fatty alcohols correlated with the logarithm of the n-octanol/water partition coefficient (K(oct)) with a linear correlation coefficient R(2)=0.9833. This work provides a simple, convenient, and reproducible method for the rapid measurement of membrane affinity and presents important implications for high-throughput screening.     

Relevance of IGF-I, IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficient children and adolescents

BACKGROUND: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. AIM/METHOD: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. RESULTS: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. CONCLUSION: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.     

Determination of total phenylalanine and galactose from a sample of dry blood on paper filter: its application on neonatal screening

Neonatal screening programs for metabolic disorders are recommended especially for phenylketonuria and congenital hypothyroidism. The present study was designed to adapt, develop and evaluate a SUMA method for total galactose (Gal) and phenylalanine (Phe) measurement on filter paper blood specimens. A single 5 mm disk with blood was deproteinized with methanol-acetone and eluted with distilled water. Ten microliters of the extract was transferred to one well of a ultramicroELISA plate, and the reaction solution was added to determine Phe level. The remaining extract was used for the GAL determinations. The method showed good linearity in a 0-50 mg/dl concentration range for Phe and 0-60 mg/dl for Gal. The detection limit was 0.14 mg/dl for Phe and 0.9 mg/dl for Gal. Reproducibility was assessed with filter paper blood specimens containing Gal and Phe at low, middle and high levels. Intraassay coefficients of variation were 10%, 7.5%, 6.22%, and 8.5%, 7%, 5%, respectively, whereas interassay coefficients of variation were 9.54%, 6%, 7% and 6%, 4.6%, 5.6%, respectively. In 1,000 samples from newborns, four samples of Phe and two samples of Gal showed a concentration below the threshold set for each assay. This method provides a rapid means to survey for a low incidence disease (i.e., galactosaemia: incidence, 1/30,000), in existing phenylketonuria analysis programs, where an incidence of 1/10,000), easily justifies the cost of mass screening.     

Predicting fetal death by measuring oestrogen:creatinine ratios on early morning samples of urine.

Total oestrogens were measured, on a creatinine basis, by a fully automated method in 75 000 early morning specimens of urine from 5429 women. Among the 5241 pregnancies in which the oestrogen:creatinine ratio was normal there were 11 fetal deaths (0-21%). But there were 57 fetal deaths (30-3%) among 188 patients with ratios below the fifth centile. When delivery took place before the ratio decrease to below the fifth centile a live baby was born in every one of 59 pregnancies. Apart from its effectiveness in predicting fetal death, the test has a high degree of precision and can be performed swiftly, and cheaply. For these reasons the assessment of fetoplacental function by measuring the urinary:creatinine ratio could become a convenient and inexpensive part of antenatal care that could be extended to every pregnant woman without making many further demands on obstetricians'' time.     

Determination of amitriptyline-n-oxide,amitriptyline and nortriptyline in serum and plasma by high-performance liquid chromatography

A method for the determination of amitriptyline-N-oxide, amitriptyline and nortriptyline in serum and plasma has been developed. After extraction from serum or plasma the drugs were analysed by high-performance liquid chromatography.The detection limit was 10 ng/ml (2 ml serum or plasma actually used). The coefficient of variation for all three compounds was below 10%.Amitriptyline-N-oxide was found in rat plasma after an oral dose (10 mg/kg) of amitriptyline-N-oxide.     

Determination of pyridinium crosslinks in plasma and serum by high-performance liquid chromatography

A chromatographic method for the determination of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in serum and plasma is described. The analytical procedure involved plasma or serum purification by ultrafiltration (20 000 relative molecular mass cut-off) under centrifugation at 2500 g for 4 h, as an innovative step. Analysis was done by isocratic high-performance liquid chromatography with fluorescence detection. The linearity of the method was tested from 0.6 to 15 pmol/ml and 0.12 to 3 pmol/ml for Pyr and Dpyr, respectively. The detection limit was 60 fmol/ml for both crosslinks. Except for Dpyr in plasma (coefficient of variation 19.9%), intra-assay variation was always below 10% in serum and plasma. The method has been applied to the quantification of crosslinks in serum and plasma of healthy volunteers and also in mouse and rat plasma. Serum proved to be the most suitable biological fluid for the systemic measurement of these compounds in humans and under the experimental conditions used, contained an average of 3.62 ± 0.65 and 0.7 ± 0.18 pmol/ml Pyr and Dpyr, respectively.