IDENTIFICATION OF NEURODEVELOPMENTAL ABNORMALITY AT FOUR AND EIGHT MONTHS BY THE MOVEMENT ASSESSMENT OF INFANTS

The predictive validity of infant neuromotor evaluation by the Movement Assessment of Infants (MAI) was investigated in low-birthweight infants. Motor performance at four and eight months was examined in relation to neurodevelopmental outcome at 18 months of age. Correlations were equally strong between total MAI risk scores at four and eight months and performance on the Bayley Scales. Muscle tone observations were more discriminating at four months, and automatic reactions and volitional movement were most predictive at eight months. The MAI was highly sensitive to neurodevelopmental abnormality at four and eight months and more sensitive than the Bayley Motor Scale; both assessment tools had lower specificity at eight months. The high false-positive rate is attributed to transient neuromotor abnormalities and immaturity of motor function in low-birthweight infants with normal outcome.     

Prognostic significance of oestrogen and progestogen receptor activities in breast cancer

The prognostic significance of the tumour activities of 2 steroid receptors, those for oestrogen (ER) and for progestogen (PgR), has been studied in 372 patients with breast cancer, in whom follow-up was available for 2-6 years (median 41 months). Of 252 patients with operable disease, 75.8 per cent had ER-positive tumours and 46.4 per cent had PgR-positive tumours, though a small additional fraction (6.3 per cent) had an equivocal PgR assay result. For the 236 patients with unequivocal receptor status, the relationships between disease-free interval or overall survival and receptor activity and other factors were evaluated by univariate and multivariate analyses. The latter revealed that only tumour size, node status, menstrual status and ER status related significantly to both disease-free interval and survival, though adjuvant therapy also related to disease-free interval, and tumour grade related to survival. It is concluded that measurements of PgR activity do not add to the prognostic significance of ER status.     

TNO-6 has no effect in gastrointestinal cancer: N-acetyl-glucosaminidase shows renal damage

Twenty-five patients, 16 with gastric cancer and nine with colonic cancer, received TNO-6 30 mg m-2 every four weeks. No objective tumour response was recorded. Nausea and vomiting occurred in 21 patients and was severe in 17. Severe marrow suppression developed in five patients. Renal function was unaffected in all but one patient who developed renal failure, probably as a result of septicaemia. However, the renal tubular enzyme N-acetyl-beta-D-glucosaminidase was measured in six patients and showed a rise in all. In this study TNO-6 had no anti-tumour activity in gastrointestinal malignancy, but produced significant renal tubular damage.     

Possibilities and limitation of prenatal diagnosis and carrier determination for Duchenne and Becker muscular dystrophy using cDNA probes.

Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal.