The Resilient Families program: promoting health and wellbeing in adolescents and their parents during the transition to secondary school.

Resilient Families is a school-based prevention program designed to help students and parents develop knowledge, skills and support networks to promote health and wellbeing during the early years of secondary school. the program is designed to build within-family connectedness (parent--adolescent communication, conflict resolution) as well as improve social support between different families, and between families and schools. It is expected to promote social, emotional and academic competence and to prevent health and social problems in youth.

The BEST plus approach to assisting families recover from youth substance problems

The Best plus program is a whole-of-family therapy option for families to address not only youth substance abuse issues, but also challenging and antisocial adolescent behaviours. It uses an evidence-based strategy that can be implemented widely in the community, and is proving to be a popular and relevant framework for professionals to engage and assist families in reducing adolescent problem behaviours. Evaluations indicate that the program is an effective forum for parents and siblings of adolescent drug abusers to redevelop positive family environments that encourage responsible behaviour and recovery from drug abuse.

Levels and family correlates of positive adolescent development: A cross national comparison

The article examines the levels of positive school engagement, and family characteristics associated with engagement, in adolescents in Australia and the United States. There are several modifiable family characteristics related to positive behavior. These include parents boosting both rewards for and opportunities to participate in prosocial activities, and the importance of expressing clear disapproval of antisocial behavior and drug use. Family management practices and family conflict influence adolescents' views about school and home and need to be addressed. There is evidence of the validity of ecological approaches to development, which underscores the inter-relationships between young people's developmental contexts.

Herb-drug interactions: a literature review

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations.
Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.
Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).
In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.

Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs

Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of CYP3A4 is characterised by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-, time- and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYP isoenzymes to reactive metabolites capable of irreversibly binding covalently to CYP3A4. Approaches using in vitro, in silico and in vivo models can be used to study CYP3A4 inactivation by drugs. Human liver microsomes are always used to estimate inactivation kinetic parameters including the concentration required for half-maximal inactivation (K(I)) and the maximal rate of inactivation at saturation (k(inact)).Clinically important mechanism-based CYP3A4 inhibitors include antibacterials (e.g. clarithromycin, erythromycin and isoniazid), anticancer agents (e.g. tamoxifen and irinotecan), anti-HIV agents (e.g. ritonavir and delavirdine), antihypertensives (e.g. dihydralazine, verapamil and diltiazem), sex steroids and their receptor modulators (e.g. gestodene and raloxifene), and several herbal constituents (e.g. bergamottin and glabridin). Drugs inactivating CYP3A4 often possess several common moieties such as a tertiary amine function, furan ring, and acetylene function. It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.Compared with reversible inhibition of CYP3A4, mechanism-based inhibition of CYP3A4 more frequently cause pharmacokinetic-pharmacodynamic drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesised CYP3A4 protein. The resultant drug interactions may lead to adverse drug effects, including some fatal events. For example, when aforementioned CYP3A4 inhibitors are coadministered with terfenadine, cisapride or astemizole (all CYP3A4 substrates), torsades de pointes (a life-threatening ventricular arrhythmia associated with QT prolongation) may occur.However, predicting drug-drug interactions involving CYP3A4 inactivation is difficult, since the clinical outcomes depend on a number of factors that are associated with drugs and patients. The apparent pharmacokinetic effect of a mechanism-based inhibitor of CYP3A4 would be a function of its K(I), k(inact) and partition ratio and the zero-order synthesis rate of new or replacement enzyme. The inactivators for CYP3A4 can be inducers and P-gp substrates/inhibitors, confounding in vitro-in vivo extrapolation. The clinical significance of CYP3A inhibition for drug safety and efficacy warrants closer understanding of the mechanisms for each inhibitor. Furthermore, such inactivation may be exploited for therapeutic gain in certain circumstances.

Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2

Somatostatin, originally identified as a peptide involved in neurotransmission, functions as an inhibitor of multiple cellular responses, including hormonal secretion and proliferation. Somatostatin acts through activation of G-protein-coupled receptors of which five subtypes have been identified. We have recently established that human CD34/c-kit expressing hematopoietic progenitors and acute myeloid leukemia (AML) cells exclusively express SSTR2. A major mechanism implicated in the antiproliferative action of somatostatin involves activation of the SH2 domain-containing protein tyrosine phosphatase SHP-1. While 0.1-1 x 10(-9) M of somatostatin, or its synthetic stable analog octreotide, can inhibit G-CSF-induced proliferation of AML cells, little or no effects are seen on GM-CSF- or IL-3-induced responses.
MATERIALS AND METHODS: To study the mechanisms underlying the antiproliferative responses of myeloblasts to somatostatin, clones of the IL-3-dependent murine cell line 32D that stably express SSTR2 and G-CSF receptors were generated. RESULTS: Similar to AML cells, octreotide inhibited G-CSF-induced but not IL-3-induced proliferative responses of 32D[G-CSF-R/SSTR2] cells. Somatostatin induced SHP-1 activity and inhibited G-CSF-induced, but not IL-3-induced, activation of the signal transducer and activator of transcription proteins STAT3 and STAT5.
CONCLUSION: Based on these data and previous results, we propose a model in which recruitment and activation of the tyrosine phosphatase SHP-1 by SSTR2 is involved in the selective negative action of somatostatin on G-CSF-R signaling.

Induction of propranolol metabolism by Ginkgo biloba extract EGb 761 in rats

Ginkgo biloba is one of the most popular herbal medicines in the world, due to its purported pharmacological effects, including memory-enhancing, cognition-improving, and antiplatelet effects. When used in the elderly, Ginkgo has a high potential for interactions with cardiovascular drugs. This study aimed to investigate the effects of the standard Ginkgo biloba extract (EGB 761) treatment on the pharmacokinetics of propranolol and its metabolism to form Ndesisopropylpropranolol (NDP) in rats. We also examined the activity and expression of cytochrome P450 (CYP) 1A and other CYPs in rats treated with EGb 761 at 10 and 100 mg/kg/day for 10 days. A single oral dose of propranolol (10 mg/kg) was administered on day 11 and the concentrations of both propranolol and NDP were determined using validated liquid chromatography-mass spectrometry (LC-MS) methods. The levels of mRNA and protein of various CYPs were determined by RT-PCR and Western blotting analysis, respectively. Pretreatment of EGb 761 at 100 mg/kg, but not 10 mg/kg, for 10 days significantly reduced the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max) of propranolol, whereas those values of NDP were significantly increased. CYP1A1, 1A2, 2B1/2, and 3A1 activities and gene expression in the rat liver were significantly increased in a dose-dependent manner by pretreatment with EGb 761. The ex-vivo formation of NDP in liver microsomes from rats pretreated with EGb 761 was markedly enhanced. The formation of NDP from propranolol in liver microsomes was significantly inhibited by α- naphthoflavone (ANF, a selective CYP1A2 inhibitor), but not by quinidine (a CYP2D inhibitor). These results indicated that EGb 761 pretreatment decreased the plasma concentrations of propranolol by accelerated conversion of parental drug to NDP due to induction of CYP1A2. EGb 761 pretreatment also significantly induced CYP2B1/2 and CYP3A1, suggesting potential interactions with substrate drugs for these two enzymes. Further study is needed to explore the potential for gingko-drug interactions and the clinical impact.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

Pathology of chronic achilles-tendon injuries in athletes

Overuse tendon conditions have traditionally been considered to result from an inflammatory process and were treated as such. Microscopic examination of abnormal Achilles-tendon tissues, however, reveals a non-inflammatory degenerative process. The histopathology found in surgical specimens in patients with chronic overuse Achilles tendinopathy and those with Achilles-tendon rupture are reviewed. Seminal studies suggest that so-called tendinitis is a rare condition that might occur occasionally in the Achilles tendon in association with a primary tendinosis. These data have clinical implications and require a review of the traditional classification of pathologies seen in tendon conditions, The authors recommend that nomenclature be based on histopathological findings rather than traditional hypothesis.

Lean meat and heart health

The general health message to the public about meat consumption is both confusing and misleading. It is stated that meat is not good for health because meat is rich in fat and cholesterol and high intakes are associated with increased blood cholesterol levels and coronary heart disease (CHD). This paper reviewed 54 studies from the literature in relation to red meat consumption and CHD risk factors. Substantial evidence from recent studies shows that lean red meat trimmed of visible fat does not raise total blood cholesterol and LDL-cholesterol levels. Dietary intake of total and saturated fat mainly comes from fast foods, snack foods, oils, spreads, other processed foods and the visible fat of meat, rather than lean meat. In fact, lean red meat is low in saturated fat, and if consumed in a diet low in SFA is associated with reductions in LDL-cholesterol in both healthy and hypercholesterolemia subjects. Lean red meat consumption has no effect on in vivo and ex vivo production of thromboxane and prostacyclin or the activity of haemostatic factors. Lean red meat is also a good source of protein, omega-3 fatty acids, vitamin B12, niacin, zinc and iron. In conclusion, lean red meat, trimmed of visible fat, which is consumed in a diet low in saturated fat does not increase cardiovascular risk factors (plasma cholesterol levels or thrombotic risk factors).

Cross-national compartability of burden of disease estimates:the European disability weights project

Objective: To investigate the sources of cross-national variation in disability-adjusted life-years (DALYs) in the European Disability
Weights Project.

Methods: Disability weights for 15 disease stages were derived empirically in five countries by means of a standardized procedure and the cross-national differences in visual analogue scale (VAS) scores were analysed. For each country the burden of dementia in women, used as an illustrative example, was estimated in DALYs. An analysis was performed of the relative effects of cross-national variations in demography, epidemiology and disability weights on DALY estimates.

Findings: Cross-national comparison of VAS scores showed almost identical ranking orders. After standardization for population size and age structure of the populations, the DALY rates per 100 000 women ranged from 1050 in France to 1404 in the Netherlands. Because of uncertainties in the epidemiological data, the extent to which these differences reflected true variation between countries was difficult to estimate. The use of European rather than country-specific disability weights did not lead to a significant change in the burden of disease estimates for dementia.

Conclusions: Sound epidemiological data are the first requirement for burden of disease estimation and relevant between-countries comparisons. DALY estimates for dementia were relatively insensitive to differences in disability weights between European countries.

Growth and product quality of European eel (Anguilla anguilla) as affected by dietary protein and lipid sources

A 12-week feeding trial was undertaken to evaluate the effects of partial replacement of marine raw materials in the diet with soybean meal and beef tallow on growth and product quality of European eel (Anguilla anguilla ). Based on growth, feed efficiency and chemical composition, soybean meal was found to be an unsuitable ingredient for eel diets as a substitute for fishmeal (25% on a protein basis), probably because of the low digestibility of its carbohydrate content. However, beef tallow can be used to replace 50% of fish oil without reduction in growth, provided that digestible carbohydrates are present in the diet. No major effects of protein and lipid sources in the diet were found on fillet chemical composition. Sensory analysis revealed no significant differences between fish fed the control and the experimental diets, with the exception of salty taste which was significantly higher in fish fed combined soybean meal and beef tallow compared with fish fed the control diet.

Modelling linkages between Australian financial futures markets

This paper investigates the dynamic interdependence of the Australian financial futures markets. A multivariate EGARCH model is developed to investigate linkages and stochastic volatility interactions between the 10-year Treasury bond, 90-day bank-accepted bill, and the All Ordinaries share price index futures markets. In this analysis, the empirical results strongly suggest that significant volatility interactions are evident across the 3 markets.

The overt behaviour scale (OBS): a tool for measuring challenging behaviours following ABI in community settings

OBJECTIVES: The Overt Behaviour Scale (OBS) was designed as a comprehensive measure of common challenging behaviours observed after acquired brain injury (ABI) in community settings. The OBS comprises 34 items in nine categories that measure aggression, inappropriate sexual behaviour, perseveration, wandering, inappropriate social behaviour and lack of initiation. The aim of the current study was to determine the reliability, validity and responsiveness of the OBS. METHOD: Two adult community-based samples of people with ABI were recruited. Sample 1 (n= 30) were concurrently evaluated on the OBS by two raters and again 1 week later to test stability. Other validating scales were also administered. Sample 2 (n= 28) were clients of the ABI Behaviour Consultancy who were treated for challenging behaviours and were administered the OBS before treatment commenced and then again 4 months later. RESULTS: Inter-rater reliability and stability coefficients for the OBS total score was strong (0.97 and 0.77, respectively). Initial evidence of convergent and divergent validity was shown by the differential pattern of correlations with other measures. Moderate-to-strong coefficients (range 0.37-0.66) were observed between the OBS and other measures that had behavioural content (i.e. Mayo-Portland Adaptability Inventory, Current Behaviour Scale, Neurobehavioural Rating Scale-Revised). Divergent validity was shown by the lack of correlation between the OBS and the sub-scales of these tools that do not measure challenging behaviour. Finally, responsiveness was demonstrated with a significant decrease in OBS scores in the expected direction over the 4-month period. This improvement was confirmed by corroborating evidence from key informants. CONCLUSION: The OBS shows promise as a reliable, valid and responsive measure that can be used for the systematic assessment of challenging behaviours in community settings.