St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

Low expression of the cell cycle inhibitor p27Kip1 in normal corticotroph cells, corticotroph tumors, and malignant pituitary tumors.

Abstract: The cell cycle is regulated by a number of inhibitors, including p27 Kip1 (p27), which belongs to the kip1 family. By binding to the cyclin/cyclin-dependent kinase complexes, it regulates progression of G1 to S phase in the cell cycle. It has been reported that p27 knockout mice develop multiorgan hyperplasia and intermediate lobe pituitary tumors secreting ACTH. Previously, we and others have been unable to show any consistent change in messenger RNA expression or genomic mutations for p27 in human corticotroph adenomas. However, dysregulation at the protein level has been reported in nonendocrine tumors, and we, therefore, investigated the expression of p27 in a range of benign and metastatic pituitary tumors. We studied a total of 107 pituitaries, including normal pituitary (n 5 20), Cushing’s disease (n 5 21), acromegaly (n 5 19), nonfunctioning adenomas (n 5 18), prolactinomas (n 5 7), TSH-omas (n 5 2), FSH-omas (n 5 6), aggressive tumors showing invasiveness and recurrence (n 5 9), and metastatic pituitary carcinomas (n 5 5). Using standard immunohistochemical techniques with a highly specific monoclonal antibody, p27 expression was determined quantitatively as the percentage of cells showing strongly positive, weak, or negative staining. In each sample, ;500 cells were analyzed. We also analyzed normal pituitaries using double-labeling for p27 and each of the pituitary hormones to characterize the expression of p27 in each cell type. p27 was expressed in normal pituitary cells; in tumors expressing GH, prolactin, TSH, and FSH; and in aggressive tumors, but markedly reduced expression of p27 was seen in corticotroph tumors and pituitary carcinomas. In the normal pituitary, somatotroph, lactotroph, and thyrotroph cells showed strong p27 staining, whereas normal corticotroph cells showed a much lower level of p27 staining (P , 0.001). Somatotroph, lactotroph, gonadotroph, and thyrotroph adenomas showed a lower level of p27 expression compared with normal somatotrophs (P 5 0.02), lactotrophs (P 5 0.03), gonadotrophs (P 5 0.01), and thyrotrophs, respectively, whereas the lower level of p27 expression present in normal corticotrophs virtually disappeared in corticotroph adenomas (P 5 0.001). We conclude that pituitary adenomas show a lower level of p27 protein expression than the normal cells from which they are derived, with malignant transformation leading to complete loss of p27 immunoreactivity. Corticotrophs are quite different to other pituitary cell types in terms of p27 immunoreactivity because both normal and tumorous corticotrophs have low p27 staining, and we speculate that this may relate to their inherent control mechanisms. (J Clin Endocrinol Metab 84: 3823‐3830, 1999)

Presentation and progress of childhood diabetes mellitus: a prospective population-based study

Abstract: We surveyed the clinical presentation, initial management and subsequent course of a prospectively registered, population-based cohort of 230 patients with Type 1 (insulin-dependent) diabetes mellitus diagnosed before age 21 years in the Oxford Regional Health Authority area in 1985 and 1986. Clinical details from the time of diagnosis were available on 219 patients. Thirty-four (16%) were in severe ketoacidosis with pH less than 7.10 or plasma bicarbonate less than 10 mmol/l, and 21 (10%) had mild to moderate ketoacidosis with pH 7.10–7.35 or plasma bicarbonate 10–21 mmol/l. One child died in ketoacidosis. Presentation in severe ketoacidosis was most common in children under age 5 years (p<0.05), and ketoacidosis of any degree was less frequent in older children (0.05< p<0.01) and those with a parent or sibling with diabetes (p<0.01). Within 4 years of diagnosis, 55 of 211 patients (26%) experienced severe hypoglycaemia, which in 31 (15%) led to one or more admissions. Readmission for unstable glycaemic control excluding acute hypoglycaemia occurred at least once within 1 year of diagnosis in 13% and within 4 years in 28%, and was more common in girls, in children aged less than 10 years at diagnosis, and those with a history of severe hypoglycaemia. A second cohort of 97 similar patients was recruited in 1990. The rates of admission at diagnosis (79%), severe ketoacidosis (13%) and mild to moderate ketoacidosis (13%) did not differ from the 1985/1986 cohort. Despite recent developments in diabetes management and a high level of clinical ommitment at participating centres, ketoacidosis remains a common presentation of childhood diabetes, and hypoglycaemia is unacceptably frequent in the years following diagnosis. Greater public and medical awareness of the presenting features of diabetes in young children is needed to reduce the frequency of ketoacidosis at presentation, while hypoglycaemia remains a major obstacle to good glycaemic control.