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I evaluated the value of adding a trisomy 18 screen to routine Down's screening and compared it with the benefits of atypicality screening. I studied 5080 unaffected pregnancies, 144 Down's syndrome and 190 non-Down's syndrome chromosome abnormalities (20 trisomy 13; 79 trisomy 18; 20 Turner's syndrome; 29 other sex chromosome abnormalities; 8 triploidy; and 34 miscellaneous). Using a one in 250 cut off, the Down's screen gave a screen positive rate of 4·07%; addition of atypicality without a trisomy 18 screen gave an extra 0·9% screen positives; trisomy 18 screening without atypicality gave an extra 0·51% screen positives; and atypicality screening after trisomy 18 screening gave 0·52% screen positives. Total screen positive rates were: Down's screening only, 4·07%; Down's screening + atypicality, 4·97%; Down's screening + trisomy 18 screen, 4·58%; Down's screening + trisomy 18 screen + atypicality, 5·09%. The detection rate for Down's syndrome using a one in 250 cut off was 58·9% and with addition of trisomy 18 and atypicality screening this increased to 59·3%, indicating that the extra screens add little to detection of Down's syndrome. For the other chromosomal abnormalities, Down's screening alone detected 22·6% of cases overall and addition of trisomy 18 and atypicality screening increased this to 49%. Examination of the marginal benefits of the extra screening tests revealed that the trisomy 18 screen was better at detecting chromosomal abnormalities than the Down's screen and that it would, therefore, be worthwhile adding this to all screening programs. Atypicality proved to be much less effective and it is suggested that this screen should only be applied in the early days of a screening program until sufficient data is available to design specific screens.

We describe an immunoblotting method for examining the electrophoretic properties of urinary Tamm-Horsfall protein. Using this method we tested frozen urine samples from a group of 37 thoroughly investigated recurrent idiopathic renal calcium stone formers and compared this with fresh urine from 19 non-stone forming laboratory staff. We found that there was a statistically significant different pattern of Tamm-Horsfall protein bands in the two sets of urines, with stone formers tending to have two bands and non-stone formers tending to have three bands. This could have been due to storage artefact and therefore a further group of 13 fresh urines from unselected renal stone formers was tested. A smaller proportion of these cases showed the two-band pattern, possibly because not all of this group were idiopathic calcium stone formers. This suggests that but does not prove that there is no significant storage artefact and that there may be an in vivoeffect causing stone formation.

1. Hypophosphatasia is a disorder characterized by low serum levels of alkaline phosphatase (ALP) and a range of skeletal deformities. The levels of a number of phosphorylated metabolites, namely phosphoethanolamine and pyrophosphate, are characteristically raised. Levels of pyridoxal-5′-phosphate (PLP) have also been reported to be raised. 2. Hypophosphatasia is a rare disease and experience of measuring PLP in patients is lacking. We have had the chance to look at PLP levels in four families with hypophosphatasia, specifically to examine the quantitative relationship between ALP and PLP which has not been described before. 3. We confirmed that PLP levels are raised in hypo-phosphatasia and related to the disease severity. A significant negative linear relationship was found between the log PLP and log ALP (log PLP = 5.99−2.76 log ALP; r = − 0.85, P < 0.001). 4. Measurement of PLP is simpler than some of the phosphorylated compounds, e.g. pyrophosphate. PLP may be a useful measure in patients with a suspected diagnosis of hypophosphatasia or for screening family members to detect potential heterozygotes and to monitor any response to therapy. 5. There did not appear to be any adverse clinical effects in relation to disturbed vitamin B6 metabolism in hypophosphatasia. 6. Vitamin B6 is used therapeutically in a number of conditions with monitoring of PLP levels. In these conditions PLP levels should be interpreted in conjunction with the prevailing serum ALP levels as the metabolism of these compounds is closely inter-related.

Recent advances in prenatal screening have led to the possibility that the risk of Down's syndrome associated pregnancy may be assessed by blood tests for maternal serum alphafetoprotein, human chorionic gonadotrophin (and possibly unconjugated oestriol) taken at 15–18 weeks of gestation.In neural tube defect screening correction of maternal serum alphafetoprotein for maternal weight has been recommended, although the precise method for weight correction is still under debate. We report an assessment of weight correction for maternal serum alphafetoprotein and human chorionic gonadotrophin based on 1408 singleton pregnancies and for unconjugated oestriol based on 197 singleton pregnancies. We demonstrate that weight correction of maternal serum alphafetoprotein and human chorionic gonadotrophin is statistically valid but that correction of unconjugated oestriol is not.

The underlying mathematical techniques behind the multivariate normal distribution are explained in principle and expanded in detail for up to three variables. The application of multivariate distributions to screening programs is described with particular reference to the calculation of risk ratios for the detection of Down's syndrome between 15 and 19 weeks of gestation.

No Abstract

A simple method which is practical for use in a routine clinical chemistry laboratory, for assay of vitamin B6 vitamers in serum is presented. The procedure uses a C18 (ODS) analytical column and fluorimetric detection (325 nm excitation, 400 nm emission) after post column derivatisation with pH 7.5 phosphate buffer containing lg/1 sodium sulphite. The mobile phase is pH 2.5, 0.067 mol/1 KH2PO4 adjusted with concentrated orthophosphoric acid and containing 125 umol/1 sodium hexanesulphonate as an ion pairing agent. Pyridoxamine 5'-phosphate is suggested for use as an internal standard when assaying human serum.

Firstly, to determine a satisfactory animal model for induction of intrarenal calcification, a study of four previously described animal models of intrarenal calcification was carried out which showed that intraperitoneal injection of 10% calcium gluconate into female Sprague-Dawley rats was most effective. We then investigated the hypothesis that dietary supplementation with essential fatty acids could reduce the intrarenal calcification developing as a result of intraperitoneal calcium injection. Using a combination of fish oil and evening primrose, oil, we demonstrated a significant difference in renal parenchymal calcification, which was 940±240 µg Ca/g dry weight renal parenchyma in unsupplemented animals and 320–370 ±55–65 µg Ca/g dry weight renal parenchyma in supplemented animals (means±SEM, P<0.005). It was also demonstrated that there was synergism between eicosapentaenoic acid (EPA) and ?-linolenic acid (GLA): dietary supplementation with a combined oil preparation containing 27 mg/ml EPA and 67 mg/ml GLA mixed as 2% with food was as effective as oils containing either 400 mg/ml EPA or 80 mg/ml GLA mixed as 4% of food.

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 α-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.

Sexually mature male goats were used to study the hemodynamics of penile erection. Contrast medium was injected into the internal pudendal artery and serial angiographs of the erection, and detumescence phases of the erection cycle. The flow of contrast medium injected after erection by electrostimulation was blocked at the caudal edge of the ischial arch just proximal to the origin of the deep arteries of the penis. It is suggested that the major valvular mechanism that makes the corpus cavernosum penis a closed system during erection is a mechanical compression of the internal pudendal arteries, deep arteries of the penis external to or within the tunica albuginea of the crus, and veins against the ischium by contraction of the ischiocavernosus muscles.

The corpus cavernosus penis (CCP) and electromyographic (EMG) activity of the external penile muscles were recorded during erection and ejaculation of the goat. The mean peak CCP pressures were 18, 83, and 7003 mm Hg for the quiescence, mild erection, and maximum erection stage of the penis. The contractions of the ischiocavernosus muscles (ICM) were in phase with the peak pressures of the CCP. Anesthesia of the ICM prevented the high peak CCP pressures, indicating that these muscles are the source of energy for the high pressure recorded.

Further data suggesting that assessment of atypicality may be a valuable addition to Down's syndrome screening is presented, based on results from 1521 unaffected pregnancies and 190 chromosomally abnormal pregnancies. For a 1 % increase in false positive rates (over the Down's screening-related false positives), it is estimated that the detection of non-trisomy 21 abnormalities may be enhanced by approximately 40%. These false positive and detection rates are similar to previous reports for specific trisomy 18 screens. Further work is necessary to prove whether a specific trisomy 18 screen, or an atypicality screen is preferable.

OLIGOSACCHARIDES composed of glucose and fructose units have been detected by various workers recently in extracts of Jerusalem artichoke, wheat flour, barley and agave. A number of oligosaccharides which are hydrolysed by invertase to glucose and fructose have now been found in ripe apricots. In one case a hexitol was also detected in the hydrolysis products.

MALIC and citric acids had been the only acids found in quantity in peaches1, but Peynaud2showed that they accounted for only 40−80 per cent of the total acidity. Hulme and Swain3, using paper chromatography, found that the pulp of the peach fruit contained an acid which had the same RF value as an unknown acid in apples, later shown to be l-quinic acid4. Using displacement chromatography on an anion-exchange resin, pure l-quinic acid has now been isolated from ripe peaches, in which it is sometimes the major acid.

Haas and Stadtman1separated an apricot concentrate (30 per cent solids) into cationic, anionic and neutral fractions and showed that browning occurred when any two fractions were combined and stored at 57° C. The reactions of individual cations, anions and neutral compounds in freeze-dried apricot puriée stored at 25° C. and 70 per cent relative humidity (79 per cent solids) have now been studied. After sixteen months/this material was a mid-brown colour. It contained 1-deoxy-1-(N-amino-acid)-fructoses2and traces of 2-deoxy-2-(N-amino-acid)-glucoses3, together with sucrose, glucose and (traces of) fructose half-esters of malic and citric acids. These compounds replaced almost quantitatively the apparent losses of free amino-acids and malic and citric acids. After allowing for these reactions, there was a loss of 11 m.moles of glucose and 8 m.moles of fructose per 100 gm. fruit solids. It appears that, at this relatively early stage of browning, the coloured compounds were formed from sugars without the incorporation of any significant amount of amino-acid or organic acid residues. If the 1-deoxy-1-(N-amino-acid)-fructoses were intermediates in browning, subsequent reactions must have included the release of the amino-acid4. The behaviour of glucose-6-phosphate5suggests that the malic and citric acid esters may also be important intermediates in browning.

ALTHOUGH furfural1is adsorbed on the weakly basic anion-exchange resin “Amberlite IR-4B”, the adsorption of sugars has not been reported; in fact, this resin has been used to de-ionize solutions prior to the estimation of sugars2. However, following the detection of traces of sugars in the acid fraction from fruit extracts, it has now been found that as much as 1 per cent of the glucose passed through a column of “Amberlite IR-4B” may be adsorbed on the resin.

MUCIC acid has only been recorded twice as occurring in natural products, namely, in putrified blood1and in the diffusion juice from sugar beet2. Pure mucic acid has now been isolated from sound ripe peaches and pears by methods which make it appear certain that the acid was present in the free state in the fresh fruit.

SPATH and Nikawitz1have investigated the behaviour of a base, C11H12ON2, termed peganine, which the firm of E. Merck (Darmstadt) isolated from the mother liquors of the alkaloids of Peganum harmala. A little later, Späth and Kuffner2found that peganine is identical with the base vasicine isolated from Adhatoda vasica, Nees, by Sen and Ghose3and more recently studied by Ghose, Krishna, Narang and Rây4; the name peganine therefore becomes superfluous.