Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques.

This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 Å. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 Å with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.

Validation of THIN data for non-melanoma skin cancer.

BACKGROUND: The Health Improvement Network (THIN) database began in 2003. It consists of anonymised records from over 300 general practice computer systems and is likely to be valuable for research, planning and strategic issues in health care, but it is important to establish completeness and accuracy of the data. AIM: To investigate the validity of THIN data for non-melanoma skin cancer (NMSC). We defined NMSC as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: Using Read codes we extracted THIN database records of first-recorded diagnoses of NMSC from 1 January 1996 to 31 December 2003. Searches for SCC were unable to distinguish between skin tumours of this type, and SCC at any other site. From our dataset for BCC, 40 patient records were selected at random, and a questionnaire sent to their corresponding practice, asking if they had been referred to hospital/dermatology clinic, and how the diagnosis of BCC had been confirmed. RESULTS: All the patients in the sample were referred to a hospital or dermatology clinic: 37/40 (93%) had the diagnosis of BCC confirmed, either by a letter from the hospital or a pathology report, a finding that we have reported previously. One patient's diagnosis was confirmed as SCC, and the other two either died or moved away before diagnosis could be confirmed. The 38 patients with diagnoses confirmed were all treated in hospital or dermatology clinic. CONCLUSIONS: Data for BCC are sufficiently accurate for research. It is also likely that these data will prove valuable for quality management. It is not possible currently to obtain accurate data for SCC of the skin from the THIN database. This seems not to be a problem with the THIN database itself, but attributable to the Read coding scheme being, in practice, unable to allow differentiation between SCCs of different organs.

Trends in incidence of skin basal cell carcinoma. Additional evidence from a UK primary care database study.

We determined the trends in incidence of skin basal cell carcinoma (BCC) using a primary care population-based cohort study in the UK. 11,113 adults with a BCC diagnosis were identified from a total of 7.22 million person-years of data between 1996 and 2003 from the Health Improvement Network database. From a random subsample of BCC cases identified from the database, 93% were confirmed by hospital letter and/or pathology report. The incidence of BCC was 153.9 per 100,000 person-years (95% CI 151.1, 156.8) and was slightly higher in men as compared to women (Incidence Rate Ratio 1.10, 95% CI 1.06, 1.14). There was a 3% increase year on year across the study period (IRR 1.03, 95% CI 1.01, 1.04), with the largest increase in incidence seen in the 30-39 year age groups, although this did not reach statistical significance. Our study indicates 53,000 new cases of BCC are estimated every year in the UK and figures are continuing to rise on a yearly basis. Incidence rates are highest for men and in particular in the older age categories. These findings are consistent with those reported for various other populations. We have also found an increase in incidence in ages 30-39, which may suggest a cohort effect of increasing ultraviolet exposure in successive younger generations. This may have a huge public and service impact in future years in countries such as the UK, with predominantly fair-skinned population, with high leisure exposure to ultraviolet light. Our findings underline the need for more elaborate preventive measures.

Coronary heart disease prevention and age inequalities: the first year of the National Service Framework for CHD.

BACKGROUND: The National Service Framework for Heart Disease sets national standards and defines service models for coronary heart disease (CHD). Little is known about the impact of this intervention on age inequalities. AIM: To determine the changes in the uptake of coronary prevention measures before and after the first year of implementation of the National Service Framework for Coronary Heart Disease, and to compare these changes in uptake of coronary prevention in patients aged 75 years and over with younger patients. DESIGN OF STUDY: Repeated cross-sectional survey using routinely collected data. SETTING: Seventeen general practices in 17 primary care groups in the Trent Region. METHOD: All registered patients at baseline and follow-up aged >/=35 years were categorised into three groups: those with either coronary heart disease or a history of stroke; those with diabetes or hypertension who were not in in the first group; and the remaining population. Data from electronic records was collected to show differences in the proportions of patients with coronary risk factors recorded in the previous year. Data was also collected about differences in the proportions of patients with adequate disease control measures. RESULTS: Improvements were demonstrated in the recording of coronary risk factors and of disease control measures. However, compared with patients aged <75 years, older patients were significantly less likely to have a serum cholesterol level recorded at baseline; to be on lipid lowering drugs; to be on beta blockers post myocardial infarction and to have well controlled blood pressure. These differences persisted at follow-up. CONCLUSION: There have been substantial improvements in both the recording of coronary risk factors and disease control measures following the implementation of the National Service Framework for Coronary Heart Disease. However, there needs to be an effort to strengthen the focus on the care of older patients.