Sorption of phthalate esters and PCBs in a marine ecosystem

Dialkyl phthalate esters (DPEs) are widely used industrial chemicals with octanol-seawater partition coefficients ranging between 10(1.80) for dimethyl phthalate to 10(10.0) for diiso-decyl phthalate, indicating a propensity to sorb strongly to particulate matter in aquatic environments. Sorption plays a key role in controlling the long-term fate of DPEs in aquatic systems and exposure to organisms in aquatic food-webs. However, field observations of the sorption of many commercial DPEs do not exist. To characterize the sorptive nature of DPEs in a real-world aquatic ecosystem, we measured concentrations of DPEs congeners, commercial DPE mixtures, and 10 polychlorinated biphenyls (PCBs) in water, suspended sediments, and bottom sediments of a marine inlet. Sorption coefficients of spiked and native DPEs and PCBs between suspended sediments and water indicate that the apparent sorptive nature of DPEs and PCBs is substantially greater than expected from K(ow)-based sorption models. Particulate and dissolved organic matter showed similar (i.e., not statistically different) sorption affinities for native analytes. The apparent fraction of the total aqueous concentration of DPEs that is freely dissolved and absorbable via the respiratory tract of aquatic organisms varied from virtually 100% for DMP to 0.0003% for C10. The observed decline in concentration of most DPEs between suspended and bottom sediments, compared to an increase in the concentration of high Kow PCBs, suggests that the rate of desorption and degradation of DPEs exceeds that of organic carbon mineralization and contributes to the previously observed lack of biomagnification of DPEs in the aquatic food-web of this system.     

Currently available hypolipidaemic drugs and future therapeutic developments

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.     

Intracellular location of inapparently infecting Chlamydia in synovial tissue from patients with Reiter's syndrome

Culture of Chlamydia trachomatis from synovial tissues/fluids from Reiter's syndrome (RS) patients frequently yields negative results. However, we have identified chlamydial RNA at that site in such patients, suggesting that viable organisms may be present. Here we define the cellular location of chlamydia within the synovium via in situ hybridization. Using a chlamydial ribosomal RNA-directed probe, we show that synovial tissue from culture-negative RS patients gives strong hybridization which is often localized to a subsynovial cell layer, rather than to the synovial lining; in some cases, hybridizing cells are dispersed through the synovium. All hybridization signal is located within host cells, indicating that infectious extracellular elementary bodies are rare or absent. These data confirm the extensive intracellular presence of inapparent chlamydia in the synovia of RS patients and provide some insight into the usual culture negativity of synovial tissues for the organism.     

Variation in the survival of women with breast cancer in Scotland. The Scottish Breast Cancer Focus Group and The Scottish Cancer Therapy Network

We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation.