Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.

Thermal analysis, nuclear magnetic resonance spectroscopy, and impedance spectroscopy of N,N-dimethyl-pyrrolidinium iodide: An ionic solid exhibiting rotator phases

N,N-dimethyl-pyrrolidinium iodide has been investigated using differential scanning calorimetry, nuclear magnetic resonance (NMR) spectroscopy, second moment calculations, and impedance spectroscopy. This pyrrolidinium salt exhibits two solid-solid phase transitions, one at 373 K having an entropy change, Delta S, of 38 J mol(-1) K-1 and one at 478 K having Delta S of 5.7 J mol(-1) K-1. The second moment calculations relate the lower temperature transition to a homogenization of the sample in terms of the mobility of the cations, while the high temperature phase transition is within the temperature region of isotropic tumbling of the cations. At higher temperatures a further decrease in the H-1 NMR linewidth is observed which is suggested to be due to diffusion of the cations. (C) 2005 American Institute of Physics.

Effect of sodium dodecylbenzene sulfonate on the motion of three-phase contact lines on the Wilhelmy plate surface

The combined approach of the molecular-kinetic and hydrodynamic theories for description of the motion of three-phase gas-liquid-solid contact lines has been examined using the Wilhelmy plate method. The whole dynamic meniscus has been divided into molecular, hydrodynamic, and static-like regions. The Young-Laplace equation and the molecular-kinetic and hydrodynamic dewetting theories have been applied to describe the meniscus profiles and contact angle. The dissipative forces accompanying the dynamic dewetting have also been investigated. The experiments with a Wilhelmy plate made from an acrylic polymer sheet were carried out using a computerized apparatus for contact angle analysis (OCA 20, DataPhysics, Germany). The extrapolated dynamic contact angle versus velocity of the three-phase contact line for Milli-Q water and 5 x 10(-4) M SDBS solution was experimentally obtained and compared with the combined MHD models with low and moderate Reynolds numbers. The models predict similar results for the extrapolated contact angle. SDBS decreases the equilibrium contact angle and increases the molecular jumping length but does not affect the molecular frequency significantly. The hydrodynamic deformation of the meniscus, viscous dissipation, and friction were also influenced by the SDBS surfactant. (c) 2005 Elsevier Inc. All rights reserved.

Shear deformation at 29% solid during solidification of magnesium alloy AZ91 and aluminium alloy A356

Partially solid commercial Al-Si and Mg-Al alloys have been deformed in shear during solidification using vane rheometry. The dendritic mush was deformed for a short period at 29% solid and allowed to cool naturally after deformation. Both alloys exhibited yield point behaviour and deformation was highly localised at the surface of maximum shear stress. The short period of deformation was found to have a distinct impact on the as-cast microstructure leading to fragmented dendrites in the deformation region of both alloys. In the case of the Mg-Al alloy, a concentrated region of interdendritic porosity was also observed in the deformation region. Concentrated porosity was not observed in the Al-Si alloy. (c) 2005 Elsevier B.V. All rights reserved.

Molecular orbital calculations of two-electron states for P-donor solid-state spin qubits

We theoretically study the Hilbert space structure of two neighboring P-donor electrons in silicon-based quantum computer architectures. To use electron spins as qubits, a crucial condition is the isolation of the electron spins from their environment, including the electronic orbital degrees of freedom. We provide detailed electronic structure calculations of both the single donor electron wave function and the two-electron pair wave function. We adopted a molecular orbital method for the two-electron problem, forming a basis with the calculated single donor electron orbitals. Our two-electron basis contains many singlet and triplet orbital excited states, in addition to the two simple ground state singlet and triplet orbitals usually used in the Heitler-London approximation to describe the two-electron donor pair wave function. We determined the excitation spectrum of the two-donor system, and study its dependence on strain, lattice position, and interdonor separation. This allows us to determine how isolated the ground state singlet and triplet orbitals are from the rest of the excited state Hilbert space. In addition to calculating the energy spectrum, we are also able to evaluate the exchange coupling between the two donor electrons, and the double occupancy probability that both electrons will reside on the same P donor. These two quantities are very important for logical operations in solid-state quantum computing devices, as a large exchange coupling achieves faster gating times, while the magnitude of the double occupancy probability can affect the error rate.

DNA binding-independent transcriptional activation of the vascular endothelial growth factor gene (VEGF) by the Myb oncoprotein

Myb is a key transcription factor that can regulate proliferation, differentiation, and apoptosis, predominantly in the haemopoietic system. Abnormal expression of Myb is associated with a number of cancers, both haemopoietic and non-haemopoietic. In order to better understand the role of Myb in normal and tumorigenic processes, we undertook a cDNA array screen to identify genes that are regulated by this factor. In this way, we identified the gene encoding vascular endothelial growth factor (VEGF) as being potentially regulated by the Myb oncoprotein in myeloid cells. To determine whether this was a direct effect on VEGF gene transcription, we examined the activity of the murine VEGF promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was found that WT Myb was able to activate the VEGF promoter and that a minimal promoter region of 120 bp was sufficient to confer Myb responsiveness. Surprisingly, activation of the VEGF promoter was independent of DNA binding by Myb. This was shown by the use of DNA binding-defective Myb mutants and by mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of Sp1 sites within this region abolished Myb-mediated regulation of a reporter construct, suggesting that Myb DNA binding-independent activation of VEGF expression occurs via these Sp1 binding elements. Regulation of VEGF production by Myb has implications for the potential role of Myb in myeloid leukaemias and in solid tumours where VEGF may be functioning as an autocrine growth factor. (c) 2006 Elsevier Inc. All rights reserved.

Pectinase production by solid fermentation from Aspergillus niger by a new prescription experiment

The Ordos Plateau in China is covered with up to 300,000 ha of peashrub (Caragana) which is the dominant natural vegetation and ideal for fodder production. To exploit peashrub fodder, it is crucially important to optimize the culture conditions, especially culture substrate to produce pectinase complex. In this study, a new prescription process was developed. The process, based on a uniform experimental design, first optimizes the solid substrate and second, after incubation, applies two different temperature treatments (30 degrees C for the first 30 h and 23 degrees C for the second 42 h) in the fermentation process. A multivariate regression analysis is applied to a number of independent variables (water, wheat bran, rice dextrose, ammonium sulfate, and Tween 80) to develop a predictive model of pectinase activity. A second-degree polynomial model is developed which accounts for an excellent proportion of the explained variation (R-2 = 97.7%). Using unconstrained mathematical programming, an optimized substrate prescription for pectinase production is subsequently developed. The mathematical analysis revealed that the optimal formula for pectinase production from Aspergillus niger by solid fermentation under the conditions of natural aeration, natural substrate pH (about 6.5), and environmental humidity of 60% is rice dextrose 8%, wheat bran 24%, ammonium sulfate ((NH4)(2)SO4) 6%, and water 61%. Tween 80 was found to have a negative effect on the production of pectinase in solid substrate. With this substrate prescription, pectinase produced by solid fermentation of A. niger reached 36.3IU/(gDM). Goats fed on the pectinase complex obtain an incremental increase of 0.47 kg day(-1) during the initial 25 days of feeding, which is a very promising new feeding prospect for the local peashrub. It is concluded that the new formula may be very useful for the sustainable development of and and semiarid pastures such as those of the Ordos Plateau. (c) 2005 Elsevier Inc. All rights reserved.

The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.

The usefulness of acetic acid wash and chemiluminescent illumination (Vizilite) in the visualization of oral mucosal white lesions

A diligent and careful examination of the mouth and oral structures has been historically deficient in revealing premalignant and malignant oral lesions. Conventional screening practice for oral neoplastic lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualization is the principal strategy used to find patients with lesions at risk for malignant transformation; hence, any procedure which highlights neoplastic lesions should aid the clinician. This pilot study examined the usefulness of acetic acid wash and chemiluminescent light (Vizilite) in enhancing visualization of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of a white lesion, were prospectively screened with Vizilite, and an incisional biopsy performed for a definitive diagnosis. The age, sex, and smoking status of all patients were recorded, and all lesions were photographed. The visibility, location, size, border, and presence of satellite lesions, were also recorded. The Vizilite tool enhanced intraoral visualization of 26 white lesions, but it could not distinguish between epithelial hyperplasia, dysplasia, or carcinoma. Indeed, all lesions appeared ‘‘aceto-white’’, regardless of the definitive diagnosis. On one occasion, Vizilite aided in the identification of a satellite lesion that was not observed by routine visual inspection. Vizilite appears to be a useful visualization tool, but it does not aid in the identification of malignant and potentially malignant lesions of the oral mucosa.

On the solute coupling at the moving solid/liquid interface during equiaxed solidification

Integral mass conservation was widely accepted for the solute coupling to solve solute redistribution during equiaxed solidification so far. The present study revealed that the integral form was invalid for moving boundary problems as it could not represent the mass balance at the moving interface. Accordingly, differential mass conservation at the solid/liquid interface was used to solve solute diffusion for spherical geometry. The model was applied for hydrogen diffusion in solidification to validate that the hydrogen enrichment was significant and depended on the growth rate. (c) 2006 American Institute of Physics.

A transgenic mouse model that recapitulates the clinical features of both neonatal and adult forms of the skin disease epidermolytic hyperkeratosis

Keratins are the major structural proteins of keratinocytes, which are the most abundant cell type in the mammalian epidermis. Mutations in epidermal keratin genes have been shown to cause severe blistering skin abnormalities. One such disease, epidermolytic hyperkeratosis (EHK), also known as bullous congenital ichthyosiform erythroderma, occurs as a result of mutations in highly conserved regions of keratins K1 and K10. Patients with EHK first exhibit erythroderma with severe blistering, which later is replaced by thick patches of scaly skin. To assess the effect of a mutated K1 gene on skin biology and to produce an animal model for EHK, we removed 60 residues from the 2B segment of HK1 and observed the effects of its expression in the epidermis of transgenic mice. Phenotypes of the resultant mice closely resembled those observed in the human disease, first with epidermal blisters, then later with hyperkeratotic lesions. In neonatal mice homozygous for the transgene, the skin was thicker, with an increased labeling index, and the spinous cells showed a collapse of the keratin filament network around the nuclei, suggesting that a critical concentration of the mutant HK1, over the endogenous MK1, was required to disrupt the structural integrity of the spinous cells. Additionally, footpad epithelium, which is devoid of hair follicles, showed blistering in the spinous layer, suggesting that hair follicles can stabilize or protect the epidermis from trauma. Blisters were not evident in adult mice, but instead they showed a thick, scaly hyperkeratotic skin with increased mitosis, resulting in an increased number of corneocytes and granular cells. Irregularly shaped keratohyalin granules were also observed. To date, this is the only transgenic model to show the typical morphology found in the adult form of EHK.

A controlled trial comparing the efficacy of rice-based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis

A prospective randomized trial was conducted to compare the efficacy of a rice-based oral rehydration solution (ORS) with glucose ORS in infants and children under 5 years of age with acute diarrhoea and mild to moderate dehydration (<10%). One hundred children presenting to a large metropolitan teaching hospital were eligible for entry to the study and were randomized to receive rice ORS or glucose ORS. Outcome measures were stool output (SO), duration of illness (DD) and recovery time to introduction of other fluids (RTF) and diet (RTD). Significant differences were found for all outcome measures in favour of the rice ORS group. Mean SO was lower (160 vs 213 mt; P<0.02), mean DD was reduced (17.3 vs 24.3 h; P = 0.03) and median RTF was decreased (12.7 vs 18.1 h; P< 0.001) in the rice ORS group compared with the glucose ORS group. The median rime to introduction of diet and mean length of hospital stay showed similar significant reductions. Our study has shown rice ORS to be an acceptable alternative to glucose ORS in young children and have shown that it is significantly more effective in reducing the course of diarrhoeal illness and the time taken to return to normal drinking and eating habits.