The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs.

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.     

Dietary fat intake and plasma lipid levels in adolescents.

The relationship between dietary fat intake and fasting plasma lipid levels was assessed in 35 female and 19 male adolescents recruited from two local education authority schools in Norwich, UK. Dietary intakes were assessed using a 7-day weighed dietary record method, coupled with the collection of duplicate diets. Fat and energy intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Fasting plasma lipid levels (total, HDL and LDL cholesterol and triglycerides) were measured and compared with total dietary lipids and fatty acid intakes. The average proportion of energy consumed as fat was higher than is currently considered desirable but lower than previous studies have reported for adults. Mean serum total cholesterol values were 4.2 (SEM 0.1) mmol for females and 4.5 (SEM 0.2) mmol for males; this difference was not statistically significant. In male subjects the dietary fatty acid profiles were significantly correlated with several parameters of plasma lipid status which are thought to be risk factors for coronary heart disease, and in particular with the ratio of total:HDL cholesterol.     

Evidence for in vivo incorporation of D-lactate into peptidoglycan precursors of vancomycin-resistant enterococci.

The VanA ligase encoded by the vancomycin resistance plasmid pIP816 of Enterococcus faecium BM4147 condenses D-alanine with various D-2-hydroxy and D-2-amino acids in vitro. D-Lactate added to the culture medium restored the vancomycin resistance of a strain that does not produce the VanH dehydrogenase and therefore appears to be a substrate of VanA in vivo.     

Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67

Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information.     

Inferior vena caval stent filter

New inferior vena caval filters for percutaneous placement were made by attaching filter wires similar to those in the bird's nest inferior vena caval filter onto expandable metallic stents. These stents formed a base on which to anchor the filter to the wall of the inferior vena cava. The stent filter can be introduced through a 12- to 13-French catheter sheath system. The system was successfully tested in 13 dogs.     

Medical imaging of fetal ventriculomegaly

Five cases of fetal ventriculomegaly are described in detail. Following ultrasonography, either computerized tomography or magnetic resonance imaging was used in an attempt to clarify the structural pathology of the ventriculomegaly. In two patients, a precise diagnosis was achieved while a probable diagnosis was established in a third patient. The diverse etiology of fetal ventriculomegaly in these five cases demonstrates that ancillary medical imaging may be necessary to achieve diagnostic precision prior to therapeutic intervention.     

The complex enterprise of modelling prenatal exposure to cigarettes: what is ‘enough’?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement.
Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.     

Incremental versus maximum bite advancement during twin-block therapy: a randomized controlled clinical trial.

The aim of this study was to evaluate the effectiveness of incremental and maximum bite advancement during treatment of Class II Division 1 malocclusion with the Twin-block appliance in the permanent dentition. It was performed at 3 district general hospitals in the United Kingdom with 4 operators. Two hundred three patients, 10-14 years old, were randomized. Control patients had the initial bite taken edge-to-edge for appliance construction with a standard Twin-block. Experimental patients had 2 mm initial bite advancement and subsequent 2 mm advancements at 6 weekly intervals with a Twin-block appliance incorporating advancement screws. Data were collected at the start and the finish of Twin-block treatment. The use of incremental advancement of the Twin-block did not confer any advantages in terms of process and outcome of the treatment. However, patient compliance was influenced by operator and patient age. The duration of treatment was influenced by operator and initial overjet. Incremental bite advancement produced no advantages over maximum advancement.