Lithium treatment: prescribing and monitoring habits in hospital and general practice.

OBJECTIVES--To define current clinical practice of lithium prescribing and monitoring and to compare hospital based practice with general practice. DESIGN--Prospective study of doctors'' practice. SETTING--Psychiatric hospital day and outpatient facilities and general practices in Edinburgh and Midlothian district (population 600,000). SUBJECTS--458 patients taking lithium who had been stabilised and who remained as outpatients during the year of study. 219 were treated by their general practitioner and 190 by the hospital; 49 had shared care or care transferred during the study. MAIN OUTCOME MEASURES--Daily dose, duration of treatment, psychiatric diagnosis, mean annual serum lithium concentration, frequency of occurrence of and response to raised serum concentrations. RESULTS--Compared with hospital doctors general practitioners were more likely to prescribe lithium three or more times daily (43/219 (general practice) v 10/190 (hospital); chi 2 = 18.6, p = 0.001) and to estimate serum concentrations less frequently (4.5 v 5.3 measurements/year; t = 3.04, p = 0.003), and their patients were more likely to experience raised lithium concentrations (39/219 v 17/190; chi 2 = 6.8, p = 0.01). One third of doctors made no response to raised lithium concentrations in the next six weeks. CONCLUSIONS--General practitioners and hospital doctors care for similar types of patients and the stringency of lithium surveillance varies greatly among doctors. Certain aspects of practice give cause for concern and could be improved by following more uniform guidelines.     

Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase

Microglia are resident brain macrophages that become activated and proliferate following brain damage or stimulation by immune mediators, such as IL-1beta or TNF-alpha. We investigated the mechanisms by which microglial proliferation is regulated in primary cultures of rat glia. We found that basal proliferation of microglia was stimulated by proinflammatory cytokines IL-1beta or TNF-alpha, and this proliferation was completely inhibited by catalase, implicating hydrogen peroxide as a mediator of proliferation. In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide. IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase. Low concentrations of PMA or arachidonic acid (known activators of NADPH oxidase) or xanthine/xanthine oxidase or glucose oxidase (generating hydrogen peroxide) also increased microglia proliferation and this was blocked by catalase, showing that NADPH oxidase activation or hydrogen peroxide was sufficient to stimulate microglia proliferation. In contrast to microglia, the proliferation of astrocytes was unaffected by the presence of catalase. In conclusion, these findings indicate that microglial proliferation in response to IL-1beta or TNF-alpha is mediated by hydrogen peroxide from NADPH oxidase.     

An organic solvent–tolerant lipase from Streptomyces sp. CS133 for enzymatic transesterification of vegetable oils in organic media

The enzymatic route for biodiesel production has been noted to be cost ineffective due to the high cost of biocatalysts. Reusing the biocatalyst for successive transesterification cycles is a potential solution to address such cost inefficiency. However, when organic solvent like methanol is used as acyl-acceptor in the reaction, the biocatalyst (lipase) gets severely inactivated due to the inhibitory effect of undissolved methanol in the reaction medium. Thus, organic solvent–tolerant lipase is highly desirable for enzymatic transesterification. In response to such desirability, a lipase (LS133) possessing aforesaid characteristic was extracted from Streptomyces sp. CS133. Relative molecular mass of the purified LS133 was estimated to be 39.8 kDa by SDS-PAGE. Lipase LS133 was stable in pH range 5.0–9.0 and at temperature lower than 50 °C while its optimum lipolytic activity was achieved at pH 7.5 and 40 °C. It showed the highest hydrolytic activity towards long chain p-nitrophenyl palmitate with K_m and V_max values of 0.152 mM and 270.2 mmol min^?1 mg^?1, respectively. It showed non-position specificity for triolein hydrolysis. The first 15 amino acid residues of its N-terminal sequence, AIPLRQTLNFQAXYQ, were noted to have partial similarity with some of the previously reported microbial lipases. Its catalytic involvement in biodiesel production process was confirmed by performing enzymatic transesterification of vegetable oils with methanol.     

Filter materials for phosphorus removal from wastewater in treatment wetlands—A review

This paper aims to collect and analyse existing information on different filter media used for phosphorus (P) removal from wastewater in constructed wetlands. The most commonly used materials are categorized as natural materials (considered in 39 papers), industrial byproducts (25 papers) and man-made products (10 papers). A majority of studies on sorbents have been carried out in lab-scale systems as batch experiments, and only very few studies have highlighted results on full-scale systems. Among the great variety of filter media studied, most of materials had a pH level >7 and high Ca (CaO) content. The highest P-removal capacities were reported for various industrial byproducts (up to 420 g P kg⁻¹ for some furnace slags), followed by natural materials (maximum 40 g P kg⁻¹ for heated opoka) and man-made filter media (maximum 12 g P kg⁻¹ for Filtralite). We found a significant positive Spearman Rank Order Correlation between the P retention and CaO and Ca content of filter materials (R² = 0.51 and 0.43, respectively), whereas the relation of P retention to pH level was weak (R² = 0.22) but significant. There is probably an optimal level of hydraulic loading rate at which the P removal is the highest. Additional important factors determining the applicability of filter materials in treatment wetlands such as saturation time, availability at a local level, content of heavy metals, and the recyclability of saturated filter media as fertilizer should be taken into consideration.     

The relative significance for stem elongation and flowering in Lolium temulentum of 3β-hydroxylation of gibberellins

In previous experiments with many gibberellins (GAs) and GA derivatives applied to Lolium temulentum L., quite different structural requirements were evident for stem elongation on the one hand and for the promotion of flowering on the other. Whereas hydroxylation at carbons 12, 13 and 15 enhanced flowering relative to stem growth, the reverse was the case at carbon 3 (L.T. Evans et al. 1990, Planta 182, 97–106). The significance of hydroxylation at carbon 3 is examined in this paper. The application of inhibitors of 3β-hydroxylation, including C/D-ring-rearranged GAs, reduced stem growth but, in the case of the two acylcyclohexanediones, increased the flowering response when applied on the inductive long day. Later applications of the acylcyclohexanediones, made after floral initiation had occurred, were inhibitory to flowering, suggesting that subsequent inflorescence development requires 3β-hydroxylated GAs. Applications of the 3α-hydroxy epimers of GA₁, GA₃ and GA₄ gave slightly less promotion of flowering in comparison with the 3β-hydroxy GAs, but far less promotion of stem elongation, except in the case of 3-epi-GA₄, which was comparable to GA₄. The 3α-hydroxy epimer of 2,2-dimethyl GA₄ gave less promotion of flowering than its 3β-hydroxy epimer but almost no promotion of stem elongation. The 3α-hydroxy epimers of GA₃ and 2,2-dimethyl GA₄ did not act as competitive inhibitors of the stem elongation elicited by GA₃ and 2,2-dimethyl GA₄, respectively. These results extend the differences in GA structure which favour flowering as opposed to stem elongation, and indicate that 3-hydroxylation and its epimeric configuration are of much greater importance to stem elongation than to flower initiation in Lolium.     

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10⁵ viral copies/ml in nasal lavage and 1.88 × 10⁵ viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.     

Spatial correlograms of soil cover as an indicator of landscape heterogeneity

Soil cover, which is one of the most informative and integrative landscape factors, can be used for the analysis of landscape patterns. We studied the spatial autocorrelation (Moran's I) of raster format soil maps (1:10,000; 10 m pixel size) in 35 study areas representing all landscape regions in Estonia. The carbonate concentration of soils, volumetric soil moisture (%) and the depth of the groundwater table were taken into consideration in compiling a scale of contrast of 17 soil groups. We introduce a simple characteristic based on spatial correlograms: a half-value distance lag, h_I = 0.5—a distance where Moran's I drops below 0.5. Spatial autocorrelation decreased very rapidly in the case of heights with a very heterogeneous landscape composition, showing low values of h_I = 0.5 (<100 m in all 6 study areas). In uplands and depressions, the spatial autocorrelation also decreased relatively rapidly (h_I = 0.5 < 200 m). In most of the plains, coastal lowlands, sea islands and inland paludified lowlands, the values of Moran's I did decrease slowly with increasing lag, being >200 m in all forest and bog areas with complex topographical conditions due to the variety of glacial landforms and peatlands. All of the eight FRAGSTATS landscape metrics studied demonstrated significant correlations with h_I = 0.5, whereas five of them – Contrast Weighted Edge Density (CWED); Percentage of Like Adjacencies (PLADJ), Edge Density (ED), Patch Density (PD) and Mean Patch Area Distribution (AREA_MN) – had Spearman Rank Order Correlation values higher than 0.8. Landscapes with high ED, PD, and CWED values have a low autocorrelation: PD, ED, and CWED correlated negatively with h_I = 0.5. PD, ED, and CWED decreased and PLADJ increased with the power-law relationship with increasing h_I = 0.5. Spatial autocorrelation is lower in landscapes with complex structure and high contrast. The positive relationship with PLADJ indicates the same. Thus, spatial correlograms of potential landscape structure based on soil cover analysis can be used for the characterization of human-influenced landscape (land use) structure.     

Fit for purpose? A case study: validation of immunological endpoint assays for the detection of cellular and humoral responses to anti-tumour DNA fusion vaccines

Clinical trials are governed by an increasingly stringent regulatory framework, which applies to all levels of trial conduct. Study critical immunological endpoints, which define success or failure in early phase clinical immunological trials, require formal pre-trial validation. In this case study, we describe the assay validation process, during which the sensitivity, and precision of immunological endpoint assays were defined. The purpose was the evaluation of two multicentre phase I/II clinical trials from our unit in Southampton, UK, which assess the effects of DNA fusion vaccines on immune responses in HLA-A2+ patients with carcinoembryonic antigen (CEA)-expressing malignancies and prostate cancer. Validated immunomonitoring is being performed using ELISA and IFNγ ELISPOTs to assess humoral and cellular responses to the vaccines over time. The validated primary endpoint assay, a peptide-specific CD8+ IFNγ ELISPOT, was tested in a pre-trial study and found to be suitable for the detection of low frequency naturally occurring CEA- and prostate-derived tumour-antigen-specific T cells in patients with CEA-expressing malignancies and prostate cancer. This paper is a Focussed Research Review based on a presentation given at the Sixth Annual Meeting of the Association for Immunotherapy of Cancer (CIMT), held in Mainz, Germany, 15–16 May 2008.     

Colonisation and mass rearing: learning from others

Mosquitoes, just as other insects produced for the sterile insect technique (SIT), are subjected to several unnatural processes including laboratory colonisation and large-scale factory production. After these processes, sterile male mosquitoes must perform the natural task of locating and mating with wild females. Therefore, the colonisation and production processes must preserve characters necessary for these functions. Fortunately, in contrast to natural selection which favours a suite of characteristics that improve overall fitness, colonisation and production practices for SIT strive to maximize only the few qualities that are necessary to effectively control populations.However, there is considerable uncertainty about some of the appropriate characteristics due to the lack of data. Development of biological products for other applications suggest that it is possible to identify and modify competitiveness characteristics in order to produce competitive mass produced sterile mosquitoes. This goal has been pursued - and sometimes achieved - by mosquito colonisation, production, and studies that have linked these characteristics to field performance. Parallels are drawn to studies in other insect SIT programmes and aquaculture which serve as vital technical reference points for mass-production of mosquitoes, most of whose development occurs - and characteristics of which are determined - in an aquatic environment. Poorly understood areas that require further study are numerous: diet, mass handling and genetic and physiological factors that influence mating competitiveness. Compromises in such traits due to demands to increase numbers or reduce costs, should be carefully considered in light of the desired field performance.     

AB5 toxins: structures and inhibitor design

High-resolution crystal structures of AB₅ toxins in their native form or in complex with a variety of ligands have led to the structure-based design and discovery of inhibitors targeting different areas of the toxins. The most significant progress is the development of highly potent multivalent ligands that block binding of the toxins to their receptors.