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Summary Objective To assess cerebrovascular mortality in a UK cohort of patients with pituitary adenoma known to have increased incidence of cerebrovascular accidents (CVA). Methods A total of 334 patients treated at the Royal Marsden Hospital (RMH) between 1962 and 1986 with surgery and postoperative radiotherapy were followed up via the NHS Central Register (NHSCR) to identify deaths and emigrations. The causes of death were assessed by NHSCR-based death certificates and coded according to the 9th revision of ICD. Follow-up was censored at age 85, on emigration or cancellation of NHSCR. Thirteen patients could not be traced. A total of 4982 person-years was accumulated in the cohort. Expected numbers of deaths were computed from the national age-, sex- and period-specific mortality rates for England and Wales. Results In the pituitary adenoma cohort, 128 deaths were observed compared to 80·9 expected [relative risk (RR) of death 1·58 (95% CI: 1·32–1·90)]. There were 33 cerebrovascular deaths compared with 8·04 expected (RR 4·11, 95% CI 2·84–5·75). Three deaths were from subarachnoid haemorrhage compared to 0·54 expected (RR 5·51, 95% CI 1·14–16·09). There was an increased cerebrovascular mortality in women (RR 6·93, 95% CI 4·29–10·60) compared to men (RR 2·4, 95% CI 1·24–4·20; P = 0·002) and in patients having debulking surgery (RR 5·19, 95% CI 3·50–7·42) compared to biopsy/no surgery (RR 1·33, 95% CI 0·27–3·88; P = 0·02). The RR in patients with nonsecretory tumours was 3·65 (95% CI 2·26–5·58), compared with 5·23 (95% CI 2·25–10·30) in secretory tumours (P = 0·4). The effect of age at radiotherapy was not significant (P = 0·4). Conclusion Patients with pituitary adenoma treated with surgery and radiotherapy have an increased risk... [ABSTRACT FROM AUTHOR]

Examines the role of radiotherapy in the management of patients with pituitary adenoma. Use of stereotactic radiosurgery; Effective preservation of normal pituitary function; Risk of radiation necrosis.

dUTPases are a ubiquitous family of enzymes that are essential for all organisms and catalyse the breakdown of 2-deoxyuridine triphosphate (dUTP). In Bacillus subtilis there are two homotrimeric dUTPases: a genomic and a prophage form. Here, the structures of the genomic dUTPase and of its complex with the substrate analogue dUpNHpp and calcium are described, both at 1.85 A resolution. The overall fold resembles that of previously solved trimeric dUTPases. The C-terminus, which contains one of the conserved sequence motifs, is disordered in both structures. The crystal of the complex contains six independent protomers which accommodate six dUpNHpp molecules, with three triphosphates in the trans conformation and the other three in the active gauche conformation. The structure of the complex confirms the role of several key residues that are involved in ligand binding and the position of the catalytic water. Asp82, which has previously been proposed to act as a general base, points away from the active site. In the complex Ser64 reorients in order to hydrogen bond the phosphate chain of the substrate. A novel feature has been identified: the position in the sequence of the ;Phe-lid', which packs against the uracil moiety, is adjacent to motif III, whereas in all other dUTPase structures the lid is in a conserved position in motif V of the flexible C-terminal arm. This requires a reconsideration of some aspects of the accepted mechanism.