Wide variation in surgical outcomes for acromegaly in the UK.

OBJECTIVE: Unsuccessful surgery for acromegaly has major consequences for the patient as well as financial consequences for the National Health Service (NHS). Surgical expertise affects the outcome. We have used the UK National Acromegaly Register to assess surgical outcomes in different centres to investigate whether these match the previously published case series. DESIGN: Retrospective and prospective observational study by analysis of anonymized national computer register records derived from individual clinical case records from 22 UK endocrine units and their associated pituitary surgical services. PATIENTS: Cases of acromegaly, presenting in 1970-2004, with levels of GH or IGF-1 (785 and 430 cases, respectively) recorded prior to transsphenoidal adenomectomy and in the 12 months postsurgery, before any subsequent pituitary surgery or radiotherapy. GH-lowering pharmacological therapy was permitted only if suspended for biochemical testing. MEASUREMENTS: Percentage of cases with 'safe' mean postoperative GH levels (< 5 mU/l) and/or IGF-1 in the age- and sex-adjusted normal range. RESULTS: 'Safe' GH, normal IGF-1, or both was achieved for 26%, 29% and 20% of extrasellar macroadenomas (> 1 cm), respectively, 39%, 39% and 29% of intrasellar macroadenomas, 56%, 51% and 37% of microadenomas (< 1 cm) and 39%, 39% and 28% of cases overall. In centres contributing more than 10 patients' data, rates of safe GH levels ranged from 20% to 68% and IGF-1 from 19% to 55%. Success rates in attaining safe postsurgical levels of GH improved only slightly in the UK between 1974 and 1999 but markedly thereafter. CONCLUSIONS: Surgical outcomes for acromegaly in UK centres vary widely and historically have not, except in a few centres, matched those of large published series, which mostly have a success rate around 60%. Results have, however, improved substantially since 2000 and in the most successful units match those of the best published series. Experience is an important determinant of surgical success in acromegaly and the very recent improvement in surgical results in the UK coincides with a trend to concentrate pituitary surgery in the hands of a smaller number of specialists. Therefore, patients should be offered surgery by a dedicated pituitary surgeon with a caseload sufficient to offer the prospect of safe postsurgical GH and IGF-1 levels for the majority of cases.

Heat stress lipids and schizophrenia.

The neurodevelopmental hypothesis of schizophrenia implicates abnormal or disrupted neural growth during embryogenesis. It is postulated here that stress-inducing agents acting upon a compromised cellular system resulting from abnormal plasma membrane lipids could effect the neuronal abnormalities observed in schizophrenia. The heat stress response is induced by exposure to hyperthermia as well as a variety of other agents. The response to these agents includes the cessation of most transcriptional and translational activities, accompanied by the induction of a highly specific set of proteins. A concomitant reduction in metabolic activity including cell cycle delays is also observed. Much of the enormous literature on the heat stress response concentrates on protein and DNA interactions, especially with regard to transcriptional control. However, a variety of lipids are intrinsically involved in the heat stress response. This paper will provide a brief introduction to the heat shock proteins and will explore the roles that lipids play in the heat shock response.

Neurogenesis in adult human.

This report describes neurogenesis in the adult human olfactory epithelium in vitro. Olfactory epithelium was collected at autopsy and by biopsy, and grown in serum-free medium. Basic fibroblast growth factor induced the differentiation of bipolar cells which were immunopositive for several neuronal proteins but not glial proteins. [3H]thymidine autoradiography confirmed that these neurones were born in vitro. The results demonstrate that the adult human olfactory epithelium retains the capacity for neurogenesis and neuronal differentiation, at least until the age of 72 years. It is now possible to examine neurones and neurogenesis in biopsies from patients with disorders that may involve a neurodevelopmental or neurodegenerative aetiology such as schizophrenia, bipolar disorder and Alzheimer's disease.

Comparative epidemiology of rotavirus, subgenus F (types 40 and 41) adenovirus and astrovirus gastroenteritis in children.

We report a 5 year prospective study of episodes of rotavirus, subgenus F adenovirus, and astrovirus gastroenteritis diagnosed by electron or immune electron microscopy in a single regional virology laboratory. Of 1426 total infections, the numbers in each category were 1117 (78.3%), 254 (17.8%), and 20 (7.9%), respectively. Using restriction endonuclease analysis or immune electron microscopy, all but 20 of the subgenus F adenovirus strains were classified as type 40 (n = 50) or type 41 (n = 184). Rotavirus and astrovirus infections were more prevalent in winter than summer, whereas subgenus F (either type 40 and 41) adenoviruses showed no seasonal variation in prevalence. The ratio of type 40 to all typable subgenus F adenoviruses declined between 1984 and 1986 and then increased again. Adenoviruses were relatively more important as causes of viral gastroenteritis in infants aged less than 6 months than in toddlers aged 12 months or more, but even in young infants more rotavirus than adenovirus infections were diagnosed. Our data confirmed the epidemiological differences between rotavirus, subgenus F adenovirus and rotavirus gastroenteritis and documented the shared epidemiological characteristics of type 40 or 41 adenovirus infections.

Comparison of gamma-radiation-induced accumulation of ataxia telangiectasia and control cells in G2 phase.

Recent reports from a number of laboratories have linked radiosensitivity in ataxia telangiectasia (A-T) to a large and prolonged block of some cells in G2 phase. Previous results from this laboratory, largely with one Epstein-Barr virus-transformed A-T lymphoblastoid cell line, presented evidence for a dramatic increase in the number of cells in G2 phase over controls during a 24-h period post irradiation. We describe here a study of the effect of gamma-radiation on G2 phase delay in several A-T cell lines. Based on previous results with several cell lines 24 h post irradiation was selected as the optimum time to discriminate between G2 phase delay in control and A-T cells. All A-T homozygotes showed a significantly greater number of cells in G2 phase, 24 h post irradiation, than observed in controls. A more prolonged delay in G2 phase after irradiation was seen in different A-T cell types that included lymphoblastoid cells, fibroblasts and SV40-transformed fibroblasts. At the radiation dose used it was not possible to distinguish A-T heterozygotes from controls.

Effect of caffeine on gamma-ray-induced G2 delay in ataxia telangiectasia.

Exposure of normal control and ataxia-telangiectasia (A-T) lymphoblastoid cell lines to ionizing radiation gives rise to an increase in the proportion of G2 phase cells. The size and extent of the G2 phase block is greater in A-T cells than in normal cells. Caffeine has a similar overall effect in control and A-T cell lines in reducing the G2 arrest observed after ionizing radiation. While the proportion of cells accumulated in G2 in A-T cells is considerably greater than in controls, addition of caffeine at the time of maximal G2 block brings about a return of G2 phase cell numbers to unirradiated values in 3 hours in both cell types. In normal control cells the caffeine-mediated decrease in G2 cells is reflected by an increase in mitotic cells. These mitotic cells have a higher frequency of chromosome aberrations compared to cells harvested in the absence of caffeine. Similarly in A-T cells addition of caffeine to irradiated cultures, delayed in G2 phase, increased the number of mitotic cells and the frequency of chromosome aberrations.