The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase.

X-linked dominant disorders that are exclusively lethal prenatally in hemizygous males have been described in human and mouse. None of the genes responsible has been isolated in either species. The bare patches (Bpa) and striated (Str) mouse mutations were originally identified in female offspring of X-irradiated males. Subsequently, additional independent alleles were described. We have previously mapped these X-linked dominant, male-lethal mutations to an overlapping region of 600 kb that is homologous to human Xq28 (ref. 4) and identified several candidate genes in this interval. Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles. Quantitative analysis of sterols from tissues of affected Bpa mice support a role for Nsdhl in cholesterol biosynthesis. Our results demonstrate that Bpa and Str are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype. They also expand the spectrum of phenotypes associated with abnormalities of cholesterol metabolism.

Tumor localization using fundus view photography for episcleral plaque therapy.

The accurate localization of ophthalmic tumors on the scleral surface is important when calculating radiation dose to the tumor and adjacent structures from episcleral I-125 plaques. This is particularly true for tumors close to the fovea or optic nerve. A fundus view diagram of the eye is often used by ophthalmologists to describe the size and shape of the tumor perimeter as well as its geographical location on the retinal surface. There is, however, an inherent inaccuracy associated with the use of a hand drawn diagram to obtain physical measurements. A computer planning program has been developed which uses CT and a digitized photographic montage of the posterior hemisphere to estimate the size and location of posteriorly located tumors. A simple phantom was constructed to test the software and a direct comparison made between planned versus measured tumor size and location in an excised eye.

Substandard and falsified anti-tuberculosis drugs: a preliminary field analysis.

SETTING: Pharmacies in 19 cities in Angola, Brazil, China, Democratic Republic of Congo, Egypt, Ethiopia, Ghana, India (n = 3), Kenya, Nigeria, Russia, Rwanda, Thailand, Turkey, Uganda, United Republic of Tanzania and Zambia. OBJECTIVE: To assess the quality of the two main first-line anti-tuberculosis medicines, isoniazid and rifampicin, procured from private-sector pharmacies, to determine if substandard and falsified medicines are available and if they potentially contribute to drug resistance in cities in low- and middle-income countries. DESIGN: Local nationals procured 713 treatment packs from a selection of pharmacies in 19 cities. These samples were tested for quality using 1) thin-layer chromatography to analyze levels of active pharmaceutical ingredient (API), and 2) disintegration testing. RESULTS: Of 713 samples tested, 9.1% failed basic quality testing for requisite levels of API or disintegration. The failure rate was 16.6% in Africa, 10.1% in India, and 3.9% in other middle-income countries. CONCLUSIONS: Substandard and falsified drugs are readily available in the private marketplace and probably contribute to anti-tuberculosis drug resistance in low- and middle-income countries. This issue warrants further investigation through large-scale studies of drug quality in all markets.

What use is the human genome for understanding the mouse?

Having a working draft of the human genome sequence is proving invaluable to mouse genetic and genomic studies, providing a useful stepping-stone towards the finished sequence of the mouse genome.

Regional organisation of neonatal intensive care in the North-west.

From January 1976 to July 1978, 234 ill neonates were transported to the regional neonatal intensive care unit (ICU) of St Mary's Hospital, Manchester, from 26 maternity hospitals three to 120 miles (4.8-193.1 km) away. Ninety per cent were transferred from 15 hospitals within a 30-mile (48.3 km) radius of the ICU. Most referring hospitals had more than 2000 births a year and offered good nursing supervision of high-risk neonates in conventional special care baby units (SCBUs). In 200 of the 234 babies respiratory symptoms precipitated referral, hyaline membrane disease being the most common final diagnosis. Altogether 143 babies received definitive mechanical ventilation, and most of them were ventilated in the ambulance en route to the ICU. The neonatal survival rates for all babies and for those who received mechanical ventilation were 61% and 45% respectively. Lethal inoperable malformations and tentorial tears accounted for 23 of the 92 deaths.A crisis-orientated referral service directed towards the treatment of babies with impending or actual respiratory failure needs close collaboration between the regional ICU and referring SCBUs, with parallel development of their facilities and skills. A complementary but distinct pattern of referral is necessary to cater for those high-risk but not critically ill babies who are born in hospitals that lack staff and facilities to provide the vigilant and anticipatory care that is so necessary.

Technical and nursing roles in patient care for photorefractive surgery.

1. The University of Ottawa Eye Institute is conducting clinical research protocols using the excimer laser. The state-of-the-art technology currently available ensures an ever-evolving role for the staff, and working as a team allows the patient the best possible care experience. 2. The role of the technologist (at Ottawa Eye Institute) includes ensuring the basic laser maintenance and calibration of the energy levels delivered by the laser; carrying out pre- and postoperative patient testing according to protocols; and assisting with the surgical procedure. 3. The role of the nurse (at Ottawa Eye Institute) includes ensuring the informed consent form has been signed and patient education been given.

Comparative genome sequence analysis of the Bpa/Str region in mouse and Man.

The progress of human and mouse genome sequencing programs presages the possibility of systematic cross-species comparison of the two genomes as a powerful tool for gene and regulatory element identification. As the opportunities to perform comparative sequence analysis emerge, it is important to develop parameters for such analyses and to examine the outcomes of cross-species comparison. Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region. We identified 11 genes in mouse and 13 genes and two pseudogenes in human. In addition, we compared the mouse and human sequences using pairwise alignment and searches for evolutionary conserved regions (ECRs) exceeding a defined threshold of sequence identity. This approach aided the identification of at least four further putative conserved genes in the region. Comparative sequencing revealed that this region is a mosaic in evolutionary terms, with considerably more rearrangement between the two species than realized previously from comparative mapping studies. Surprisingly, this region showed an extremely high LINE and low SINE content, low G+C content, and yet a relatively high gene density, in contrast to the low gene density usually associated with such regions.