The Opinions, Expectations and Experiences of Women with a Family History of Breast Cancer Who Consult Their GP and Are Referred to Secondary Care.

Objectives: The purpose of this work was to explore the views, expectations and experiences of the increasing number of women with a family history of breast cancer who present to their GP and are referred to secondary care. Methods: A prospective descriptive study was carried out with 193 women referred by their GP regarding a family history of breast cancer to a genetics clinic or breast clinic in Oxfordshire and Northamptonshire over a one-year period. Results: Women who presented to primary care about a family history of breast cancer wanted their GP to provide them with information (90%) and to discuss their risks of developing breast cancer (87%). Women often had unrealistic expectations of what they might expect from a referral to secondary care, especially with regards to being offered genetic testing. Within 1 month of attending the secondary care appointment, 11% of women had returned to see their GP regarding their family history and what had happened at the specialist clinic. Conclusions: Women want information and the opportunity to discuss their breast cancer family history concerns in a primary care setting. For women who are referred, information provision in primary care is important to ensure realistic expectations of the secondary care visit and to provide ongoing reassurance and support throughout the often lengthy referral process. For women who are not referred, information provision in primary care is even more important, as this may be their only source of information and advice. Copyright 2002 S. Karger AG, Basel

Hughlings Jackson's deductive science of the nervous system: a product of his thought collective and formative years.

This paper examines the life and work of John Hughlings Jackson (1835-1911), with particular attention to his early years in London, the "thought collective" into which he was initiated, and the consequent social ties, professional interests, hospital affiliations, scientific pursuits, aims, and ambitions that defined his medical career spanning almost half a century. There exists an abundant body of literature on Jackson, although it is far less extensive and substantive than his own writings (about 350 in number) in understanding his position and attitude concerning the study of diseases of the nervous system. This elucidation of the nature Jackson's pursuits throughout his career draws upon primary sources of information-the elaborate writings of Jackson himself and of his Victorian mentors and confreres. The latter constituted Jackson's thought collective, who contributed to a unique and previously undescribed document: Testimonials of Dr. J. Hughlings Jackson, M.D. (London, 1863). These medical men also contributed to the Medical Times and Gazette and belonged to the London Pathological Society and the New Sydenham Society. Jackson's thought collective and their shared beliefs and pursuits were instrumental in shaping Jackson's career as reflected by his later works. Jackson's professional pursuits and extensive writings marked a lifetime dedicated to developing a "Science of the Nervous System" according to a Millian-Spencerian form of deductive reasoning, to ultimately establish a rational basis for the treatment of nervous disease. Jackson and his contemporaries initiated and developed a deductive ideology and methodology that continue to be widely employed by neurologists today, and thus form the basis of the current neurological paradigm.

Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.

The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations.