Margaret M. Esiri

Classical pituitary apoplexy : clinical features, management and outcome

The term classical pituitary apoplexy describes a clinical syndrome characterized by sudden headache, vomiting, visual impairment and meningismus caused by the rapid enlargement of a pituitary adenoma usually due to haemorrhagic infarction of the tumour. Most published reports looking at the clinical features and management of pituitary apoplexy have not differentiated between patients with clinical and subclinical apoplexy, the latter diagnosed at surgery. Furthermore, little is reported on the clinical outcome, in particular visual and endocrinological, and the role of radiotherapy. The purpose of this study was to observe not only the clinical presentation but also the possible predisposing events, investigations, management, clinical outcome as well as the role of radiotherapy in patients presenting with classical pituitary apoplexy.

The ACE gene and Alzheimer's disease susceptibility

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimers disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOEε4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE andACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and IDACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DIv DD 1.33, 95% CI=1.14-1.53, p=0.0002).

Expression analysis of cyclins in pituitary adenomas and the normal pituitary gland.

The molecular events involved in pituitary tumour development are still poorly understood. The cyclins play an important role in the control of the cell cycle during cell proliferation and over‐expression of the cyclins has been shown in many different tumour types. The aim of this study was to investigate whether, in comparison to the normal gland, ectopic expression of cyclins occurs in pituitary tumours, and whether differences in cyclin expression are seen with different pituitary tumour types or in association with different tumour behaviour. In contrast to work on cyclin D there are no published data on cyclin B, A and E in human pituitary tumours.

The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease.

Alzheimers disease (AD) pathology is characterized by β-amyloid plaques and neurofibrillary tangles. Studies of autosomal dominant early-onset AD mutations suggest that β-amyloid overproduction is sufficient to cause AD. Recently, the BACE gene, which encodes β-secretase, the rate limiting enzyme in β-amyloid formation, has been identified. Since this gene is a strong candidate gene for late-onset AD because of its function, we have characterized its genomic organization and identified two polymorphisms. Neither of these polymorphisms were associated with AD risk in genetic association studies comparing autopsy-confirmed late-onset AD cases and age-matched non-demented controls. Thus, we find no evidence that this locus influences risk for late-onset AD.

Genetic association of an LBP-1c/CP2/LSF gene polymorphism with late onset Alzheimer's disease

OBJECTIVES The only locus unequivocally associated with late onset Alzheimers disease (AD) risk is APOE. However, this locus accounts for less than half the genetic variance. A recent study suggested that the A allele of the 3′UTR biallelic polymorphism in theLBP-1c/CP2/LSFgene was associated with reduced AD risk. Samples were diagnosed predominantly by clinical rather than pathological criteria. We have sought to replicate this finding in a series of necropsy confirmed, late onset AD cases and non-demented controls. METHODS The 3′UTR polymorphism in theLBP-1c/CP2/LSFgene was typed in 216 necropsy confirmed AD cases and 301 non-demented controls aged >73 years. RESULTS We found differentLBP-1c/CP2/LSFallele distributions in our AD cases and controls (p=0.048); the A allele was associated with reduced AD risk. The allele and genotype frequencies observed in our cases and controls were similar to those previously reported. No significant effects emerged when the data were adjusted for age, sex, or apoE ε4 carrier status. CONCLUSIONS Our data supportLBP-1c/CP2/LSFas a candidate gene/risk factor for AD and provide justification for future studies to investigate the role of this gene in Alzheimers disease.