Computer support for interpreting family histories of breast and ovarian cancer in primary care: comparative study with simulated cases

ObjectivesTo evaluate the potential effect of computer support on general practitioners'' management of familial breast and ovarian cancer, and to compare the effectiveness of two different types of computer program.DesignCrossover experiment with balanced block design.ParticipantsOf a random sample of 100 general practitioners from Buckinghamshire who were invited, 41 agreed to participate. From these, 36 were selected for a fully balanced study.InterventionsDoctors managed 18 simulated cases: 6 with computerised decision support system Risk Assessment in Genetics (RAGs), 6 with Cyrillic (an established pedigree drawing program designed for clinical geneticists), and 6 with pen and paper.ResultsRAGs resulted in significantly more appropriate management decisions (median 6) than either Cyrillic (median 3) or pen and paper (median 3); median difference between RAGs and Cyrillic 2.5 (95% confidence interval 2.0 to 3.0; P<0.0001). RAGs also resulted in significantly more accurate pedigrees (median 5) than both Cyrillic (median 3.5) and pen and paper (median 2); median difference between RAGs and Cyrillic 1.5 (1.0 to 2.0; P<0.0001). The time taken to use RAGs (median 178 seconds) was 51 seconds longer per case (95% confidence interval 36 to 65; P<0.0001) than pen and paper (median 124 seconds) but was less than Cyrillic (median 203 seconds; difference 23. (5 to 43; P=0.02)). 33 doctors (92% (78% to 98%)) preferred using RAGs overall. The most important elements of an “ideal computer program” for genetic advice in primary care were referral advice, the capacity to create pedigrees, and provision of evidence and explanations to support advice.ConclusionsRAGs could enable general practitioners to be more effective gatekeepers to genetics services, empowering them to reassure the majority of patients with a family history of breast and ovarian cancer who are not at increased genetic risk.     

Telomerase-directed molecular therapeutics

The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3. Traditionally, surgery, chemotherapy and radiotherapy have been the primary choice of treatment for patients with malignant tumours. Despite advances in the use and development of conventional cytotoxic agents, the cure rate remains disappointing in most patients with advanced disease of the common solid tumours. Consequently, the development of novel anti-cancer therapies is a high priority in cancer medicine. In recent years, a new generation of cancer therapies has emerged, based on a growing understanding of the molecular events that contribute to malignant transformation. A major difference between normal and cancer cells is the ability of cancer cells to multiply in an unrestricted and ungoverned fashion. In this context, there is considerable interest in elucidating the mechanisms that allow this unrestricted proliferation and that ultimately result in immortal cancer cells. It is now clear that the enzyme telomerase confers immortality on cells in most types of cancer. With the cancer cell reliant on telomerase for its survival, telomerase represents an extremely attractive mechanism-based target for the development of new cancer therapeutics.     

The variability of the hepatitis B virus genome: statistical analysis and biological implications

A statistical analysis of the nucleotide sequence variability in 14 published hepatitis B virus (HBV) genomes was carried out using parametric and nonparametric methods. A parametric statistical model revealed that the different regions of the genome differed significantly in their variability. The conclusion was supported by a nonparametric kernel-density model of the HBV genome. Genes S, C, and P, region X, the precore region, and the pre-S2/pre-S1 regions were ranked in order of increasing variability. In many instances, conserved regions of the genome identified with sequences of known function in HBV biology. However, other characterized regions (such as pre-S) showed much variability despite the involvement of their encoded peptides in specific functions. Point mutations that may result in the formation of stop codons and amino acid changes may affect the clinical picture of HBV infection and may be reflected in atypical serological patterns.      

Defining the gigantopterid concept: a reinvestigation of Gigantopteris (Megalopteris) nicotianaefolia Schenck and its taxonomic implications

Reinvestigation of the first described gigantopterid plant, Gigantopteris (Megalopteris) nicotianaefolia Schenk ex Potonié, 1902 from the Permian of China, has been conducted using the original specimens documented in 1883. The application of new techniques has permitted a comprehensive review of their morphology. This study represents the first photographic record of Schenk's specimens and provides a standardised terminology to describe them. This species of Palaeozoic leaf megaphyll is characterised by its pinnate venation, with tertiary veins that anastomose, and give rise to branches that may be of the same or higher order. These anastomosed branches form a reticulum of irregular polygonal meshes, within which higher order veins anastomose and again form meshes. On examination of Schenk's original specimens only one, MB.Pb.2002/989, can be assigned to Gigantopteris nicotianaefolia, and this is herein designated the lectotype. The remaining specimens described by Schenk are reassigned to cf. G. nicotianaefolia, cf. Gigantopteris sp., Gigantonoclea sp. or cf. Gigantonoclea sp. This re‐analysis of Schenk's specimens has led to an emended diagnosis of both the genus Gigantopteris and the species G. nicotianaefolia. Current evidence suggests that Gigantopteris nicotianaefolia is restricted to the southern floral regions of Cathaysia, as typically are other species of this genus. Fertile specimens of Gigantopteris are unknown, and the status of these plants as a natural group relies upon a combination of their complex foliar physiognomy, stratigraphic range, and geographical distribution. This study indicates that the genera GigantopterisGigantonoclea form the basis of the gigantopterid concept. These two genera share characters of leaf morphology including megaphylls with eucamptodromous venation across which extends a continuous lamina, and higher order veins, third order or above, that arise from the secondary veins and anastomose to form complex meshes. These genera are distinguished in that the venation of Gigantopteris is far more complex than that of Gigantonoclea, with a greater number and complexity of vein orders, the penultimate and ultimate of which form meshes within meshes, and of these the finest may terminate in blind endings.     

Submerged growth of the cultivated mushroom,Agaricus bisporus

Agaricus bisporus grew well in submerged culture in a medium containing malt extract, phosphate, and casein. Moderate growth occurred in defined media containing glucose, asparagine, phenylalanine, vitamins and minerals. Other amino acids did not stimulate growth. Growth was stimulated by vegetable oils, partly due to utilization of the oils, and partly to a more complex mechanism. Oleates had the same effect as vegetable oils; palmitates a lesser one. In shaken flasks maximum yield was reached after 22–24 days and in stirred and aerated fermentors after 8–10 days. Besides dry weight of mycelium, laccase activity was determined. The latter determination is suitable for a rapid estimation of the growth in routine experiments. The flavour of the mycelium was like that of mushrooms but weaker. It was strongest in standing liquid cultures and on solid media. The mycelium grown in submerged culture was suitable as spawn for mushroom culture. Presented at the First International Mycological Congress, Exeter, 7–16 September 1971, and at the Meeting of the Netherlands Society for Microbiology, Rotterdam, 8 December 1971. We thank the Mushroom Experiment Station, Horst, the Netherlands, for kindly supplying the compost for fructification experiments and Mr. P. Arntz, M.Sc., for advice in the fermentor work. F. IJ. Dijkstra is indebted to the Royal Netherlands Fermentation Industries (Gist-Brocades), Delft, for a research grant.