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Meta-analysis of placebo controlled trials shows that antipsychotic drugs (APDs) are highly effective in reducing rates of relapse and rehospitalisation in people with schizophrenia (Leucht et al.,...

Distinct temporal regulation of neutrophil recruitment increases tissue I/R injury in males. Male and female rats were subjected to 30-min mesenteric ischemia followed by up to 2-h reperfusion. (A) Representative images of portions of male and female small intestine at the end of reperfusion, demonstrating redness and edema in males following I/R but no observable change in females. (B-C) Leukocyte/vessel wall interactions throughout reperfusion in mesenteric venules, measured by intravital microscopy: (B) Leukocyte adhesion and (C) number of tissue leukocytes at different distances away from venule (sham, n = 5 rats/group; I/R, n = 8 rats/group). (D) Circulating CD68+ monocytes in males and females during ischemia and reperfusion. Data are presented as mean ± sem. §P 0.05 by one-way ANOVA. (PDF 811 kb)

Objective: To evaluate the clinical performance of APC™II Victory Series™ (3M Unitek) brackets in direct orthodontic bonding with and without the use of primer. Design: A single-operator, two-centre prospective, non-inferiority randomized controlled clinical trial. Setting: The Orthodontic departments at the Leeds Dental Institute and St Luke’s Hospital, Bradford, UK. Ethical approval: Ethical approval was granted by Leeds (East) Research Ethics Committee on 18th of December 2009 (Reference 09/H1306/102). Protocol: The protocol was not published prior to trial commencement. Subjects and methods: Ninety-two patients requiring orthodontic treatment with fixed appliances were randomly allocated to the control (bonded with primer) or test groups (bonded without primer). Patients were randomly allocated to either the control or experimental group. This was performed by preparing opaque numbered sealed envelopes in advance using a random numbers table generated by a computer by an independent third party . Once the envelopes were opened, blinding of the operator and the patient was no longer possible due to the nature of the intervention. Patients were approached for inclusion in the trial if they qualified for NHS orthodontic treatment requiring fixed appliances and had no previous orthodontic treatment. Main outcome measures: Number of bracket failures, time to bond-up appliances, and the adhesive remnant index (ARI) when bracket failure occurred, over a 12-month period Results: Failure rate with primer was 11.1 per cent and without primer was 15.8 per cent. Bonding without primer was shown statistically to be non-inferior to bonding with primer odds ratio 0.95–2.25 ( P = 0.08). Mean difference in bond-up time per bracket was 0.068 minutes (4 seconds), which was not statistically significant ( P = 0.402). There was a statistically significant difference in the Adhesive Remnant Index − ARI 0 with primer 49.4 per cent, no primer 76.5 per cent, ( P < 0.0001). Limitations: As the study was only performed by one operator, the results can therefore only be truly be applied to their practice. Also this study was powered to ascertain if there was no difference between the 2 groups up to 5%, however orthodontists may consider a change in the bracket failure rate of 2% to be clinically significant. Conclusion: When bonding with APC™II Victory Series™ brackets without primer was shown statistically to be non-inferior to bonding with primer ( P =0.08). There was no significant difference in bond-up times. Bond failure was more likely to happen at the composite–enamel interface when bonded without a primer. Conflict of interest: No conflict of interest for all authors. Funding: No funding sources were used. Registration: Study was not registered on external databases.

Duration of untreated psychosis (DUP) is defined as the time from manifestation of the first psychotic symptom to initiation of adequate antipsychotic drug treatment. There are a number of factors, both clinical and social, that could determine the delay in the treatment of patients with first-episode psychosis. The reason for the delay could be in recognition of illness by patients themselves or their families and in whether the patients first presented to a primary care service. Such delays could have potential negative consequences and would prolong the suffering of patients and their carers. Long DUP may also have a negative impact on the long-term prognosis of these patients, although this association has not been conclusively demonstrated.1 Recognition of the predictors that prolong the DUP should have an impact on reducing DUP and potentially improving the long-term outcome.2 The essential role of an early intervention psychiatric team is to provide timely treatments as early as is practicable in the first episode of psychosis, thereby reducing the DUP. The social burden, negative health consequences, and stigma associated with this illness are thereby reduced. A previous study on pathways to care for first-episode psychosis3 found that patients with a long DUP (> 1 year) were young males with poor social network, social withdrawal, and a more deteriorating course. In this study, we determined the sociodemographic characteristics and early clinical course of first-episode psychosis patients under the care of a well-established early intervention team for psychosis in South Warwickshire. We compared the differences in these characteristics between those patients with a longer DUP (≥ 12weeks) and shorter DUP (< 12 weeks).

Aims and MethodWe conducted a pilot study to determine patients' views on receiving a copy of the assessment letter sent to their general practitioner and to determine how psychiatrists' letter writing practice would be altered in the knowledge that patients would receive copies of such letters. Seventy-six consecutive new outpatients received copies of the initial assessment letter sent to general practitioners. Patients were asked to complete a short questionnaire on how the practice affected them. For each letter, psychiatrists were asked to provide details of anything of importance that had been omitted from the letter that in their normal practice they would have included.ResultsThere was a broad range of responses on how patients felt about the letters. Only two patients found the letters unhelpful, and 83% expressed a positive desire to continue receiving letters, even though initially 18% found the letter distressing. For 56 out of 76 patients, psychiatrists stated that they composed and sent out the letter to the GP in accordance with their usual practice and copied the letter to the patient in an unaltered form. For 17 patients, the psychiatrist stated that some information he/she would usually have included in the GP letter was omitted in the copy the patient received. In a further 3 cases, the psychiatrist sent no letter to the patient.Clinical ImplicationsPatients found it helpful to receive copies of their assessment letters. Psychiatrists might require training and reassurance about this policy before implementation.

Objective: To review the evidence base for the efficacy and tolerability of antipsychotic medication for the treatment of the first episode of schizophrenia. Data Source: MEDLINE databases were searched for published articles in English over the last 25 years, from January 1986 to January 2011, on choice of antipsychotic treatment for the first episode of schizophrenia, with an emphasis on efficacy and tolerability of antipsychotic drugs in the acute phase of psychotic illness. Study Selection: The keywords antipsychotic drugs and schizophrenia were used in combination with drug treatment, pharmacologic treatment, efficacy, and tolerability in addition to atypical antipsychotics, first-generation antipsychotics, second-generation antipsychotics, first-episode psychosis, and acute psychotic episode. Data Synthesis: At present, there is no convincing evidence to guide clinicians in choosing a single first-line antipsychotic that is effective in treating the positive and negative symptoms of the first episode of schizophrenia. Even though second-generation antipsychotic drugs offer potential benefits in terms of less extrapyramidal side effects and some benefits in treating negative, affective, and cognitive symptoms, these drugs are not without their own side effects. Conclusions: With the introduction of a number of second-generation antipsychotic drugs there have been significant advances in antipsychotic drug treatment over the last decade. Despite these advances, there are still a number of limitations in continued use of some antipsychotic medications due to their efficacy and tolerability issues in the acute and early maintenance phases of psychosis. Active research in this area would provide more promising results of improved efficacy and tolerability of antipsychotic medication.

In this paper, we describe the first example of a sustained galvanic coating deposited on a surface from a non-aqueous liquid. We present the surface characterization of electroless silver deposits on copper substrates from a solution of Ag(+) ions in an ionic liquid based on a choline chloride (ChCl) eutectic. Through a study of these deposits and the mechanism of formation using acoustic impedance spectroscopy (QCM), probe microscopy (AFM) and electron microscopy (SEM/EDX), we demonstrate that sustained growth of the silver deposit is facilitated by the porous nature of the silver. This is in contrast to the dip-coating reaction of silver ions in aqueous media, where the reaction stops when surface coverage is reached. Electroless silver deposits of up to several microns have been obtained by dip coating in ionic liquids without the use of catalysts of strong inorganic acids.

Interleukin-8 (IL-8) is produced by human decidual cells in culture, and may play a role in the initiation of parturition. beta-endorphin is released in significant amounts into the maternal and fetal circulation during labour. The effect of beta-endorphin on IL-8 production by human chorio-decidual cells in culture was investigated. Mixed cells were obtained from the decidual surfaces of 35 term placentas. The cells were plated out at 10x10(6) cells per well in Roswell Park Memorial Institute 1640 culture medium. After 48 h the cells were washed and incubated with either plain culture medium (control), 1 micromol/l progesterone, 1-100 nmol/l beta-endorphin or 1 nmol/l N-acetyl beta-endorphin. After 48 h, IL-8 concentrations were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Experiments were repeated in the presence of naloxone (1 micromol/l) and using calcium-deficient culture medium. Progesterone (P < 0.0002) and beta-endorphin (P < 0. 0005) significantly inhibited the production of IL-8. The inhibitory effect of beta-endorphin was blocked by naloxone and by using calcium-deficient medium. N-acetyl beta-endorphin had no significant effect on IL-8 production. These findings suggest that beta-endorphin has an inhibitory effect on IL-8 production by decidual cells, and that the effect is mediated via opioid receptors and is calcium-dependent.

Hypodontia: A Team Approach to Management (2010) Authors: John A. Hobkirk, Daljit S. Gill, Steven P. Jones, Kenneth W. Hemmings, G. Streven Bassi, Amanda L. O’Donnell, Jane R. Goodman Publisher: Wiley-Blackwell Price: £82.50 ISBN: 978-1-4051-8859-3 Pages:208 ‘Hypodontia: A Team Approach to Management’ is targeted at final year dental students, graduate students of a large number of dental specialities, and general dental practitioners with an interest in management of hypodontia. The book is 187 pages in length and is divided into 3 parts, with 3 sub-sections each. Tables emphasize key points and the work …

This paper describes an unusual case of caecal adenocarcinoma which had perforated through to the anterior abdominal wall. Colocutaneous fistula is an uncommon complication of colonic cancer which is more typically associated with sepsis and ischaemia of the bowel, inflammatory bowel disease and trauma. On rare occasions, as in this case, the colocutaneous fistula may be the initial presenting complaint.

To the Editor: Refractory depression is common in clinical practice. At least 30% of patients fail to respond to initial antidepressant therapy.1 In patients who have failed 1 course of antidepressants, there is evidence from 9 randomized controlled trials suggesting that approximately 50% of treatment-refractory patients do respond to lithium augmentation compared with placebo (p < .001).2 The British Association for Psychopharmacology guidelines recommend that patients be treated with 2 antidepressants before an augmentation strategy is used.3 Our aim was to review the evidence for use of lithium in those patients who are resistant to treatment with 2 or more antidepressants at recognized therapeutic doses. Method. A systematic review was undertaken of placebo-controlled, double-blind, randomized trials of lithium that assess its effectiveness in treatment-resistant depression. English-language studies of adults (aged 18 years or older; both sexes), suffering from major depressive disorder diagnosed by the International Classification of Diseases, Tenth Revision (ICD-10), the Diagnostic Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or Research Diagnostic Criteria (RDC) were included. The following keywords were used: lithium OR Camcolit OR Carbolith OR Duralith OR Eskalith OR Licarbium OR Liskonum OR Litarex OR Lithane OR Lithocarb OR Lithizine OR Lithonate OR Lithotabs OR Manialith OR Phasal OR Priadel OR Quilonorm OR Quilonum OR Li-Liquid OR resistant depression OR refractory depression OR treatment resistant depression OR treatment non respon(*) depression OR lithium augment(*). Exclusion criteria were bipolar depression, previous prescription of lithium, co-morbid schizophrenia, or drug and alcohol dependence. All participants should have received 2 antidepressants at recognized therapeutic doses (eg, 150 mg of imipramine daily) for a minimum of 4 weeks. Participants in the active arm should have received at least 4 weeks of lithium treatment at a minimum plasma level of 0.4 mmol/L or a dose of 600 mg daily. The search included the computerized databases of the Cochrane Library, MEDLINE/PubMed (1966+), EMBASE (1980+), CINAHL (1982+), and PsycINFO (1974+). Reference lists were hand searched along with major books. Pharmaceutical companies were contacted. Leading researchers and experts in the field were also contacted. Methodological quality was categorized as (A) adequate, (B) uncertain, or (C) inadequate. Results. A total of 12 randomized controlled trials involving lithium augmentation for resistant depression were identified, of which only 14 had ensured a trial of 2 antidepressants. There was little information given in the published reports regarding the methods used to achieve random allocation. Thus, on the basis of the published reports, the studies initially received a B rating according to the Cochrane criteria. In the 1 study that included 2 antidepressants,4 there were 18 patients in the lithium augmentation arm, of whom 2 dropped out. The proportion who responded to lithium augmentation in the completer and intent-to-treat (ITT) analyses were 12.5% and 11.1%, respectively. There was no statistically significant difference in scores on the 17-item Hamilton Rating Scale for Depression. The lithium group achieved a mean reduction of 6.3/5.5 points (completer/ITT). The mean reduction in the placebo group was 6.5/5.8 points (completer/ITT) (p = .91). The mean blood lithium level at week 2 was 0.63 mmol/L (range, 0.3–1.4 mmol/L) and at week 6 was 0.61 mmol/L (range, 0.6–0.9 mmol/L). The duration of the trial was 6 weeks. In the recent Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study,5 there was no placebo group, and, as there was no significant difference to T3 augmentation (which has not yet been demonstrated as being effective for treatment-resistant depression), we cannot conclude that either lithium or T3 is an effective augmentation strategy for patients who are resistant to at least 2 antidepressants. There is limited evidence to support the use of lithium augmentation after 2 or more failed antidepressant therapies. More research needs to be undertaken to compare lithium augmentation with other augmentation strategies. Those patients who have failed to respond to 2 or more antidepressants are a difficult group to treat.

Electron impact mass spectra have been recorded for helium nanodroplets containing water clusters. In addition to identification of both H(+)(H(2)O)(n) and (H(2)O)(n)(+) ions in the gas phase, additional peaks are observed which are assigned to He(H(2)O)(n)(+) clusters for up to n=27. No clusters are detected with more than one helium atom attached. The interpretation of these findings is that quenching of (H(2)O)(n)(+) by the surrounding helium can cool the cluster to the point where not only is fragmentation to H(+)(H(2)O)(m) (where mor = n-1) avoided, but also, in some cases, a helium atom can remain attached to the cluster ion as it escapes into the gas phase. Ab initio calculations suggest that the first step after ionization is the rapid formation of distinct H(3)O(+) and OH units within the (H(2)O)(n)(+) cluster. To explain the formation and survival of He(H(2)O)(n)(+) clusters through to detection, the H(3)O(+) is assumed to be located at the surface of the cluster with a dangling O-H bond to which a single helium atom can attach via a charge-induced dipole interaction. This study suggests that, like H(+)(H(2)O)(n) ions, the preferential location for the positive charge in large (H(2)O)(n)(+) clusters is on the surface rather than as a solvated ion in the interior of the cluster.