No abstract

De novo mutations are rarely reported in BRCA1 and BRCA2. We report a proven BRCA1 de novo mutation in a woman diagnosed with young onset bilateral breast cancer with a limited family history.

We determined whether the cAMP-protein kinase A (PKA) pathway modulation of the cardiopulmonary reflex was caused by activation of 5-HT(4) receptors at the level of the nucleus tractus solitarii (NTS) of the anesthetized rat. NTS microinjection of 5-methoxytryptamine (5-MeOT, 2.25 pmol, n = 13), a 5-HT-receptor agonist, attenuated the cardiopulmonary reflex-evoked bradycardia and tachypnea. Microinjection of RS-39604 (4.5 pmol, n = 6), a selective 5-HT(4)-receptor antagonist, blocked the attenuating effect of 5-MeOT. NTS microinjection of 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP, 9 nmol, 45 nl, n = 10), a membrane-permeant analog of cAMP, significantly attenuated the reflex bradycardia and tachypnea. Rp-adenosine 3',5'-cyclic monophosphorothioate (4.5 nmol, n = 6), a cAMP-dependent PKA inhibitor, had no effect on the cardiopulmonary reflex when microinjected into the NTS alone but when given before a microinjection of either 8-BrcAMP (n = 6) or 5-MeOT (n = 6) blocked the attenuating effect on the reflex-evoked bradycardia. Thus stimulation of 5-HT(4) receptors within the NTS depresses the reflex bradycardia components of the cardiopulmonary reflex via a cAMP-dependent PKA pathway.

No abstract

Regional cancer genetics services in the UK base many of their risk assessments on the careful evaluation of a family history of disease. The pathological details of cancers in relatives can help refine this risk assessment and alter subsequent management. By analysing a variety of medical records, we surveyed how often a reported family history was discrepant from that recorded in the records, and how often this impacted on surveillance recommendations. Our survey analysed pathology confirmation and risk assessment in families over a 7-month period of referrals. 839 cancers were reported and 476 were independently confirmed. The accuracy of a reported family history differed depending on the reported site of a cancer and on the degree of relationship to the patient. Whilst the majority of reported cancers (84%) were confirmed, a change in risk assessment through pathology confirmation resulted in altered management in 20% of all referrals.