Administrative incidence of psychosis assessed in an early intervention service in England: first epidemiological evidence from a diverse, rural and urban setting.

BACKGROUND: Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural-urban population. METHOD: A population-based study of FEP (ICD-10, F10-39) in people aged 17-35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings. RESULTS: A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5-56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1-3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization. CONCLUSIONS: Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.

Heterocyclic ortho-quinones, a novel type of Photosystem II inhibitors.

Members of the new chemical class of 7-substituted 6-bromo-benzo[4,5]imidazo[1,2alpha]pyridin-8,9-diones were found to be excellent inhibitors at the Q(B) site of the photosystem II D1 reaction center protein. The best inhibitors with pI(50)-values of >7 are: dimethyl-propyl, 7.05; i-pentyl, 7.36; t. butyl, 7.47; and i-propyl, 7.51. Displacement experiments with [14C]atrazine revealed that the 8,9-diones behave non-competitively in respect of Photosystem II herbicides and, hence, have to be considered as a new type of Photosystem II inhibitors. This notion is further corroborated by their inhibitory activity in D1 mutants of Chlamydomonas reinhardtii.

A comparison of albumin, polygeline and crystalloid priming solutions for cardiopulmonary bypass in patients having coronary artery bypass graft surgery.

This study was designed to assess the effect of different prime solution compositions on a patient's fluid balance, transfusion requirements, renal function and haemodynamic stability over the first 24 hours postbypass. Ninety-three patients presenting for first-time coronary artery bypass graft (CABG) surgery were randomly allocated to receive one of three prime solutions for the CPB pump: albumin (4.6%) + Plasmalyte (Group A, n = 32), polygeline (Hemaccel) + Plasmalyte (Group P, n = 29), or crystalloid (Plasmalyte) alone (Group C, n = 32). Patients, anaesthetists, surgeons and intensive care unit (ICU) staff were all blinded as to the solution type. The groups were demographically and haemodynamically similar. There were no differences between the groups with respect to white cell or platelet counts during the study. There was a significant difference in haemoglobin levels between the groups on weaning from CPB and on arrival in the ICU (Group C > Groups P and A, p < 0.001 for both times). There was no difference in blood transfusion requirements between any of the groups. During CPB, Group C required significantly more crystalloid than the other groups (p < 0.001). Urine output was significantly higher in Group C compared with Groups P and A at all time periods up to and including ICU 12 hours (p < 0.05). The use of frusemide was significantly higher in the ICU in Groups P and A (p < 0.01). There was a net gain of 3132 +/- 412 ml in Group C in 24 hour fluid balance, which was significantly higher than Group A (2166 +/- 223 ml, p = 0.04). Our results show that, in this patient population, there is no advantage in using a colloid-based prime solution over a purely crystalloid solution from a haemotologic or haemodynamic point of view for the first 24 hours after CPB. There appears to be an increase in extracellular fluid (ECF) retention in Group C, but this caused no related problems in the study period. On the other hand, diuretics (frusemide) needed to be given significantly less often in these patients to offset oliguria.

[3H]7-azido-4-isopropylacridone labels Cys159 of the bovine mitochondrial ADP/ATP-carrier protein.

Acridones (9-azaanthracen-10-ones), especially halogen-substituted acridone-carboxylic acids are efficient inhibitors of [14C]ADP binding to the bovine mitochondrial ADP/ATP-carrier protein. 7-Iodoacridone-4-carboxylic acid displaces [14C]ADP in a competitive manner, which indicates that both compounds share an identical binding site. Upon ultraviolet illumination, 7-azido-4-[1',2'-3H]isopropyl-acridone binds covalently to the ADP/ATP-carrier protein. By sequencing of its proteolytic fragments, radioactivity was detected in Cys159. This amino acid is located close to Lys162, a target of 2-azido-[alpha-32P]ADP [Dalbon, P., Brandolin, G., Boulay, F., Hoppe, J. & Vignais, P. V. (1988) Biochemistry 27, 5141-5149].

The acridones, new inhibitors of mitochondrial NADH: ubiquinone oxidoreductase (complex I).

Acridones (9-azaanthracen-10-ones) were found to be powerful inhibitors of mitochondrial NADH: ubiquinone oxidoreductase. Their inhibitory activity was best if an alkyl or alkyloxy substituent resided in the 4-position. Biological activity reached a maximum at a chain length of 9-10 A. Halogen substitution in position 7, but not in positions 6 and 7, further enhanced activity. 2-Alkylacridones were much less active. Inhibitory activity in a Quantitative Structure-Activity Relationship (QSAR) could be correlated to Verloop's STERIMOL parameters L and L2 (Verloop, A., Hoogenstraten, W. and Tipker, J. (1976) in Drug Design (Ariens, E.J., ed.), Vol. 7, pp. 165-207, Academic Press, New York). The QSAR could be further improved by inclusion of the lipophilicity parameter pi.

[125I]azido-ioxynil labels Val249 of the photosystem II D-1 reaction center protein.

Azido-ioxynil (3.5-diiodo-2-azido-4-hydroxy-benzonitrile) is a potent photosystem II inhibitor (pI50-value 7.38) and as effective as the parent compound ioxynil itself. [125I]azido-ioxynil exhibits specific binding to isolated thylakoids with a binding constant Kb = 7.14. Upon UV-illumination it binds covalently to thylakoids or photosystem II particles. It labels predominantly the 32 kDa D-1 photosystem II reaction center protein. A 41 kDa protein is only tagged in trace amounts. After proteolytic treatment of labeled D-1 protein with Staphylococcus aureus V8-protease two major and two minor fragments are obtained. Automated gas phase sequencing of a 7 kDa cleavage peptide revealed that Val249 is the primary target of azido-ioxynil binding. Compared to urea type herbicides, this places the ioxynil binding site in a different environment of the D-1 photosystem II protein.

Picrate as an inhibitor of photosystem II in photosynthetic electron transport.

2,4,6-Trinitrophenol (picric acid) is an effective inhibitor of photosynthetic electron transport (pI50 value 6.82). By means of artificial donor and acceptor systems its site of inhibition was located at the reducing side of photosystem II. In addition, picric acid also uncouples photophosphorylation but a much higher concentration is required than for inhibition of electron transport (pI50 value 4.40). By use of radioactivity labelled [U-14C]picric acid (spec. act. 2.1 Ci/mol) a binding constant of 0.25 microM and a number of binding sites of 2.84 nmol/mg chlorophyll was measured. This corresponds to one molecule of picric acid per 394 molecules of chlorophyll or one molecule per electron transport chain. Picric acid is competitively displaced from the thylakoid membrane by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (and functionally related compounds) and phenolic inhibitors as well. In this property picric acid, despite its phenol character, is distinct from other phenolic inhibitors.