The association between prior statin use and long-term outcomes after critical care admission.

BACKGROUND: Statins may have immunomodulatory effects that benefit critically ill patients. Therefore, we retrospectively examined the association between survival and the prescription of statins prior to admission to an intensive care unit (ICU), or high dependency unit (HDU), as a result of major elective surgery or as an emergency with a presumed diagnosis of sepsis. METHODS: We retrospectively studied critical care patients (ICU or HDU) from a tertiary referral UK teaching hospital. Nottingham University Hospitals have more than 2200 beds, of which 39 are critical care beds. Over a 5-year period (2000-2005), 414 patients were identified with a presumed diagnosis of sepsis, and 672 patients were identified who had planned ICU/HDU admissions following elective major surgery. Patients prescribed statins prior to hospital admission were compared with those who were not. Demographics, medical history, drug history, and Acute Physiology and Chronic Health Evaluation II scores were examined. Univariate and multivariate analyses were applied using the primary end point of survival at 5 years after admission. RESULTS: Patients prescribed statins prior to critical care admission were, on average, older and had higher initial Acute Physiology and Chronic Health Evaluation II scores and more preexisting comorbidities. Statins were almost invariably stopped following admission to critical care. Statin use was not associated with significantly altered survival during hospital admission, or at 5 years, for either patients with sepsis (9% vs 15%, P=.121; 73% vs 84%, P=.503, respectively) or postoperative patients (55% vs 58%, P=.762; 57% vs 63%, P=.390). CONCLUSIONS: Prior statin use was not associated with improved outcomes in patients admitted to critical care after elective surgical cases or with a presumed diagnosis of sepsis.

Influence of nonylphenol on the microbial community of lake sediments in microcosms.

In this study the impact of nonylphenol, an estrogenic degradation product of alkylphenol polyethoxylates, on the microbial community structure in contaminated sediments of aquatic microcosms using in situ hybridization with fluorescently labeled oligonucleotides probes was investigated. A positive correlation between nonylphenol concentration and cell numbers of bacteria and microfungi as well as an increase in the numbers of active bacteria was found. However, the ratio between total microorganisms and active bacteria remained unchanged. A large fraction of the cells could be identified using group specific oligonucleotide probes. A slight change in the composition of the microbial community structure was observed, with Gram-positive bacteria with high DNA G + C-content becoming more abundant at higher concentrations of nonylphenol.

Derivation of predicted No-effect concentrations for lindane, 3, 4-dichloroaniline, atrazine, and copper.

Environmental risk assessment is a key feature of regulations controlling the placing of new, and the maintenance of existing, chemicals products in the market place. For example, European Commission Directive 93/67/EC on Risk Assessment for New Notified Substances and Commission Regulation (EC) No. 1488/94 on Risk Assessment for Existing Substances requires that risk assessments be carried out for new and existing substances in the European Community. The process of environmental risk assessment seeks to determine the balance of probability of species and communities being damaged by chemical releases. The process relies upon a valid estimation of a predicted environmental concentration (PEC) in relevant environmental compartments and a predicted no effect concentration (PNEC) below which the organisms present in that compartment are unlikely to be significantly affected. If the PEC exceeds the PNEC there is a potential for damaging effects to occur. This article focuses on the determination of PNECs for risk assessment. Methods for determining a PNEC described in OECD Monograph 26 (1989, Report of the OECD Workshop on Ecological Effect Assessment, Paris, France, have been applied to data derived for the four chemicals lindane, 3,4-dichloroaniline, atrazine, and copper in a series of collaborative research projects funded by the European Commission.

Development of methods for evaluating toxicity to freshwater ecosystems.

This article presents a summary of a collaborative research program involving five European research groups, that was partly funded by the European Commission under its Environmental Research Program. The objective of the program was to develop aquatic toxicity tests that could be used to obtain data for inclusion at Level 2 of the Risk Evaluation Scheme for the Notification of Substances as required by the 7th Amendment to EC Directive 79/831/EEC. Currently only a very limited number of test methods have been described that can be used for this purpose and these are based on an even smaller number of test species. Tests based upon algae (Chlamydomonas reinhardi, Scenedesmus subspicatus, and Euglena gracilis), protozoa (Tetrahymena pyriformis), rotifera (Brachionus calyciflorus), crustacea (Gammarus pulex), and diptera (Chironomus riparius) were developed. The tests encompassed a range of end points and were evaluated against four reference chemicals: lindane, 3, 4-dichloroaniline (DCA), atrazine, and copper. The capacity of the tests to identify concentrations that are chronically toxic in the field was addressed by comparing the effects threshold concentrations determined in the laboratory tests with those determined for similar and/or related species and end points in stream and pond mesocosm studies. The lowest no-observed-effect concentrations (NOEC), EC(x), or LC(x) values obtained for lindane, atrazine, and copper were comparable with the lowest values obtained in the mesocosms. The lowest chronic NOEC determined for DCA using the laboratory tests was approximately 200 times higher than the lowest NOEC in the mesocosms.

Effects of point-source PCB contamination on breeding performance and post-fledging survival in the dipper Cinclus cinclus.

Despite widespread information on the incidence and biochemical effects of polychlorinated biphenyls (PCBs) in birds, field studies of effects on population processes are still scarce. This is particularly so in passerines. We therefore assessed breeding performance and post-fledging survival in dippers, Cinclus cinclus, breeding along the Afon Mule, a Welsh river where previous work indicated locally elevated PCB concentrations. We hypothesised that marked toxicological effects, including endocrine disruption, would be detectable as altered clutch-size, hatching success, nest success, brood-size, post-fledging survival or recruitment to the breeding population. Congener-specific analysis of PCBs in failed and deserted dipper eggs during 1990-93 revealed that geometric mean concentrations were four to 20 times higher along the Mule than elsewhere in Wales, UK. PCB signatures also varied highly significantly from other locations, with congeners 138, 153 and 180 dominant at the contaminated site, but 118 or 170 more frequent in eggs elsewhere. Subsequent analysis of surface runoff confirmed a small breaker's yard as a point source. Neither laying dates, clutch-sizes, brood-sizes, nest failure nor hatching failure along the contaminated Mule (n=46 breeding attempts and 218 eggs) differed significantly from dippers along adjacent reference rivers (n=82 breeding attempts and 315 eggs) or Welsh rivers as a whole (n=332 breeding attempts and 1534 eggs). Subsequent recaptures of breeding dippers ringed initially as nestlings were nearly identical between the Mule (7.7% of 182 nestlings), the reference set (7.5% of 323 nestlings) and all other Welsh rivers (7.3% of 2821 nestlings). These data illustrate the value of congener-specific analysis of bird's eggs in indicating local PCB sources. The data show also that PCBs can occur in dipper eggs at total concentrations of 0.49 (geometric mean)-1.29 (upper quartile) microg g(-1) wet mass without effects on breeding performance and survival. These values are below those at which biochemical or reproductive effects on other passerines have been detected, but above current concentrations in any other population of European dippers for which PCB data are available. Population effects by PCBs on European dippers are therefore unlikely. Survivors from locally contaminated sites like that in our study might allow field assessments of second-generation effects on breeding performance in wild birds that have developed under PCB exposure.

PCBs and PCDD/Fs in lake sediments of Grosser Arbersee, Bavarian Forest, South Germany.

Despite their environmental importance, there are still relatively few historical studies of the environmental occurrence of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), especially in middle Europe. Trends in PCBs and PCDD/Fs were, therefore, assessed in lake sediments of the Grosser Arbersee over the past 130 years (1860-1990). Ballschmiter-PCB concentrations (congeners # 28, 52, 101, 138, 153, 180) increased between 1946 and 1972 from 4.2 to 32.0 microg kg(-1) dry wt, but have since decreased to 25.6 microg kg(-1) dry wt. High chlorinated PCB congeners reached their maxima earlier (1968-1972) than low chlorinated congeners (1985-1991). These trends were consistent with patterns expected from the production and use of PCBs and their precursors. PCDD/F concentrations increased between 1950 from 0.6 microg kg(-1) dry wt to 2.3 microg kg(-1) dry wt in 1977, falling to 1.7 microg kg(-1) dry wt by 1993. PCDF concentrations exceeded those of PCDD until 1968, but afterwards PCDDs (especially OCDD) were predominant. These patterns suggest that domestic heating and waste combustion were the most likely sources, but pollution from local industries, such as metal smelting and glass production, might also have been involved. The data provide a valuable case study from central Europe which confirms the overall declining trends of PCB and PCDD/F contamination shown elsewhere.

A pond mesocosm study to determine direct and indirect effects of lindane on a natural zooplankton community.

We assessed the threshold concentrations for toxic effects by lindane on a zooplankton community using mesocosms in a natural pond. Enclosures (1000 litres) were treated to give mean concentrations of 0, 2, 6, 12, 18, 24, and 50 microg litre(-1) over a test period of 39 days. Larvae of the phantom midge Chaoborus flavicans showed a high susceptibility to lindane and were virtually eliminated from enclosures with > or =12 microg litre(-1) 4 days after application. Populations of cyclopoid nauplii (Eucyclops serrulatus) were reduced at a lindane concentration of 2 microg litre(-1) and showed high mortality after 11 days exposure to > or =6 g litre(-1). No lindane-induced effects could be seen in the cladoceran species Daphnia longispina and Chydorus sphaericus. Rotifer species were probably not directly affected by lindane; however loss of the principal predator Chaoborus was accompanied by an increase in the numbers of Asplanchna priodonta. A simultaneous decrease in Keratella quadrata possibly reflected predation since its decline showed no dose-response relationship with lindane and it is among the major prey of Asplanchna. Such complex secondary effects, occurring through trophic interactions between a predator and two co-occurring prey, would not have been predicted from single-species toxicity tests. These, and effects on cyclopoid populations that occurred predominantly through the mortality of nauplii, demonstrate the value of toxicological studies on natural communities. We conclude that a combination of laboratory and field investigations, coupled with mono-species and community assessments, provide the best route for understanding the effects of toxicants such as lindane for regulatory purposes.

Toxicity of lindane to freshwater insect larvae in compartments of an experimental pond.

The acute and chronic toxicities of lindane to larvae of the freshwater insects Chironomus riparius Meigen, Chaoborus flavicans (Meigen), and Sigara striata (L.) were investigated in mesocosm compartments of an experimental pond. The following median lethal concentrations (LC50s) were determined: 240-hr LC50 of 2.0 micrograms lindane liter-1 for second instar C. riparius, 72-hr LC50 of 6.5 micrograms lindane liter-1 for fourth instar C. riparius, and 96-hr LC50s of 4.0 and 3.9 micrograms lindane liter-1 for fourth instar C. flavicans and fourth or fifth instar S. striata, respectively. Lindane significantly reduced the growth over 10 days of second instar C. riparius compared to that of the control at the treatment concentrations where larvae survived (1.0, 2.5, and 7.0 micrograms lindane liter-1). A significant increase in the median emergence time in comparison to that of the control was observed for C. riparius exposed to 0.8 and 2.0 micrograms lindane liter-1, with higher concentrations causing 100% mortality. The findings compare well with previously reported laboratory data on the toxicity of lindane to insects and support the methodology and results of a laboratory growth test for C. riparius.