Making every SAR point count: the development of Chemistry Connect for the large-scale integration of structure and bioactivity data

The increase in drug research output from patent applications, together with the expansion of public data collections, such as ChEMBL and PubChem BioAssay, has made it essential for pharmaceutical companies to integrate both internal and external 'SAR estate'. The AstraZeneca response has been the development of an enterprise application, Chemistry Connect, containing 45 million unique chemical structures from 18 internal and external data sources. It includes merged compound-to-assay-to-result-to-target relationships extracted from patents, papers and internal data. Users can explore connections between these by searching using drug names or synonyms, chemical structures, patent numbers and target protein identifiers at a scale not previously available.     

Influence of the birth attendant on maternal and neonatal outcomes during normal vaginal delivery: A comparison between midwife and physician management

BACKGROUND: The purpose of this study was to compare the obstetric outcome of low-risk maternity patients attended by certified midwives with that of low-risk maternity patients attended by obstetricians. PATIENTS AND METHODS: Obstetric outcome of 1352 midwife patients was compared with that of 1352 age- and parity-matched physician patients with normal spontaneous vaginal delivery at the Department of Obstetrics and Gynecology of the University Hospital Vienna during the period from January 1997 to July 2002. Our analysis was restricted to a sample of low-risk pregnant women. Women with medical or obstetric risk factors were excluded. RESULTS: A significant decrease in the use of oxytocin (p=0.0001) was observed in women who selected a midwife as their primary birth attendant compared with women in the physician group. In both groups most women gave birth in a supine position; however, significantly more alternative birth positions were used by midwife patients (p = 0.0001). Concerning perineal trauma, a significantly lower rate of episiotomies (p = 0.0001) and perineal tears of all degrees (p=0.006) were found in midwife patients. When analyzing severe postpartum hemorrhage and postpartum infections, there were no significant differences between the two groups (p > 0.05). Concerning neonatal outcome, there were no significant differences in APGAR score < 7 at 5 minutes (p > 0.05). Our data clearly show the ability of certified midwives to successfully provide prenatal care and delivery to low-risk maternity patients, with neonatal outcomes comparable to those of physician patients. The use of certified midwives supervised by obstetricians may provide the optimum model for perinatal care, particularly for those women who are low-risk maternity patients, leaving physicians free to attend to the high-risk elements of care.     

Tissue microarray analysis of EGFR and HER2 oncogene copy number alterations in squamous cell carcinoma of the larynx

Purpose To evaluate EGFR and HER2 copy number changes and to assess their significance to tumor progression in a large group of patients with larynx cancer through the construction of a tissue microarray (TMA) consisting of 1,385 biopsies.Methods Fluorescent in situ hybridization (FISH) was applied to analyze the tumors. FISH was successful for EGFR in 1,080 (77.98%) and for HER2 in 683 (49.31%).Results HER2 was amplified in 1.02% of cases. Amplification did not correlate with the tumor phenotype-clinical stage, and grade. The low frequency of amplification of HER2 oncogene in larynx tumors showed that the mechanism responsible for the high level of receptor overexpression still remains unclear in the majority of cases. Amplification of EGFR was found in 10.37% of cases. The analysis revealed a lack of correlation between amplification of the oncogenes and the tumor phenotype. We observed a lack of difference between the samples of primary tumors and advanced disease carcinomas—tumors with regional/distant metastases and recurrent tumors regarding oncogene amplification.Conclusion These results suggest that EGFR amplification is a relatively rare event in larynx carcinogenesis that obviously does not predispose to tumor progression.     

Detection of free antielastin antibodies among diabetic children.

Antibodies to elastin breakdown products are found in the serum of all human subjects and correlate with their respective serum peptide levels. The presence of these antielastin antibodies (AEAbs) and the corresponding antigens in circulation leads to the formation of circulating immune complexes (CICs). The aim of this study was to determine if the serum levels of free AEAbs (not bound in CICs) correlate with the development of vascular complications in diabetic children. To this end, we used a method for detecting immune complexes (complement inhibition factor [CIF]-enzyme-linked immunosorbent assay [ELISA]) in combination with an ELISA for detection of AEAbs. The levels of free immunoglobulin G (IgG) AEAbs were studied in the sera of 54 diabetic children (mean age 12.3+/-4 years; diabetes duration 5.2+/-3.7 years). Thirty-two of the children had vascular complications (group 1), and 22 were without vascular complications (group 2). Twenty healthy children (mean age 13.6+/-4.2 years) were used as controls. The diabetics showed statistically significant higher levels of free AEAbs (0.490 E492+/-0.244 E492 vs 0.307 E492+/-0.081 E492; p = .02) compared with the control group. In group 1, free AEAbs showed statistically significant higher levels than controls (0.523+/-0.269 vs 0.307+/-0.081; p = .016). Eighteen of 54 (33%) patients were positive for free AEAbs (13 of 32 [41%] in group 1 and 5 of 22 [22%] in group 2). Free AEAb levels in all diabetics showed a correlation with systolic blood pressure (r = .44; p = .01), diastolic blood pressure (r = .46; p = .009), total cholesterol (r = .33; p = .05), triglycerides (r= .38; p = .03), high-density lipoprotein (r= -.46; p = .009), serum fructose (r= .43; p = .001), and microalbuminuria (r= .41; p = .002). Patients who had vascular pathology showed a correlation of free AEAbs with microalbuminuria (r= .434; p= .026), serum fructose (r= .63; p = .0004), hemoglobin A1c (r= .392; p = .043), and triglycerides (r= .456; p = .025). These findings suggest that elevated levels of free IgG AEAbs are associated with the development of diabetic vascular complications in children.