Opioid overdose mortality in Australia, 1964-1997: birth-cohort trends

Objective: To examine trends in rates of opioid overdose deaths from 1964 to 1997 in different birth cohorts. Design: Age-period-cohort analysis of national data from the Australian Bureau of Statistics. Main outcome measures: Annual population rates of death attributed to opioid dependence or accidental opioid poisoning in people aged 15-44 years, by sex and birth cohort tin five-year intervals, 1940-1944 to 1975-1979). Results: The rate of opioid overdose deaths increased 55-fold between 1964 and 1997, from 1.3 to 71.5 per million population aged 15-44 years. The rate of opioid overdose deaths also increased substantially over the eight birth cohorts, with an incidence rate ratio of 20.70 (95% confidence interval, 13.60-31.46) in the 1975-1979 cohort compared with the 1940-1944 cohort. The age at which the cumulative rate of opioid overdose deaths reached 300 per million fell in successive cohorts (for men, from 28 years among those born 1955-1959 to 22 years among those born 1965-1974; for women, from 33 years among those born 1955-1959 to 27 years among those born 1965-1969). Conclusions: Heroin use in Australia largely began in the early 1970s and rates of heroin use have markedly increased in birth cohorts born since 1950.

HIV risk behaviour and prevention in prison: a bleach programme for inmates in NSW

One hundred and eighty-one inmates in AIDS education courses were surveyed about their risk behaviour and access to disinfectants for syringe cleaning in 1993, Overall, 40% of respondents reported HIV risk behaviour in prison. One-quarter of respondents reported injecting, of whom three-quarters reported sharing syringes in prison. Most respondents who shared syringes reported cleaning them with disinfectants (96%), even though only one-third reported having easy access to disinfectants. One-sixth of respondents reported sharing tattooing equipment, of whom two-thirds reported using a disinfectant to clean the tattoo needle. Few respondents reported fellatio (8%) or anal intercourse (4%) in prison. Although some respondents faced difficulty in obtaining disinfectants, almost all respondents cleaned syringes with bleach when sharing. High levels of risk behaviour in prison might be reduced by methadone maintenance and condom programmes. A trial of strict one-for-one syringe exchange warrants consideration.

Reducing the toll of opioid overdose deaths in Australia

Opioid overdose mortality among young adults in Australia has increased consistently over the past several decades. Among Australian adults aged 15-44 years, the number of these deaths has increased from six in 1964 to 600 in 1997. The rate (per million adults in this age group) increased 55-fold, from 1.3 in 1964 to 71.5 in 1997, The proportion of all deaths in adults in this age group caused by opioid overdose increased from 0.1% in 1964 to 7.3% in 1997, The magnitude of the increase makes it unlikely to be an artefact of changes in diagnosis, especially as similar increases have also been observed in other countries. These trends are also consistent,vith historical information which indicates that illicit heroin use first came to police attention in Sydney and Melbourne in the late 1960s, There is an urgent need to implement and evaluate a variety of measures to reduce the unacceptable toll of opioid overdose deaths among young Australians. These include: peer education about the risks of polydrug use and overdose after resuming opioid use after periods of abstinence, and attracting more dependent users into opioid maintenance treatment. Measures are also needed to improve responses to overdose by encouraging witnesses to call ambulances, training drug users in CPR, and trialling distribution of the opiate antagonist naloxone to users at high risk of overdose.

Integrable Kondo impurities in the one-dimensional supersymmetric extended Hubbard model

An integrable Kondo problem in the one-dimensional supersymmetric extended Hubbard model is studied by means of the boundary graded quantum inverse scattering method. The boundary K-matrices depending on the local moments of the impurities are presented as a non-trivial realization of the graded reflection equation algebras in a two-dimensional impurity Hilbert space. Further, the model is solved by using the algebraic Bethe ansatz method and the Bethe ansatz equations are obtained.

Novel solitons in parametric amplifiers and atom lasers

We review recent developments in quantum and classical soliton theory, leading to the possibility of observing both classical and quantum parametric solitons in higher-dimensional environments. In particular, we consider the theory of three bosonic fields interacting via both parametric (cubic) and quartic couplings. In the case of photonic fields in a nonlinear optical medium this corresponds to the process of sum frequency generation (via chi((2)) nonlinearity) modified by the chi((3)) nonlinearity. Potential applications include an ultrafast photonic AND-gate. The simplest quantum solitons or energy eigenstates (bound-state solutions) of the interacting field Hamiltonian are obtained exactly in three space dimensions. They have a point-like structure-even though the corresponding classical theory is nonsingular. We show that the solutions can be regularized with the imposition of a momentum cut-off on the nonlinear couplings. The case of three-dimensional matter-wave solitons in coupled atomic/molecular Bose-Einstein condensates is discussed.

Gene transfer and expression of a non-viral polycation-based vector in CD4(+) cells

CD4-selective targeting of an antibody-polycation-DNA complex was investigated The complex was synthesized with the anti-CD4 monoclonal antibody B-F5, polylysine(268) (pLL) and either the pGL3 control vector containing the luciferase reporter gene or the pGeneGrip vector containing the green fluorescent protein (GFP) gene. B-F5-pLL-DNA complexes inhibited the binding of I-125-B-F5 to CD4(+) Jurkat cells, while complexes synthesised either without B-F5 or using a non-specific mouse IgG1 antibody had little or no effect Expression of the luciferase reporter gene was achieved in Jurkat cells using the B-F5-pLL-pGL3 complex and was enhanced in the presence of PMA. Negligible luciferase activity was defected with the non-specific antibody complex in Jurkat cells or with the B-F5-pLL-pGL3 complex in the CD4(-) K-562 cells. Using complexes synthesised with the pGeneGrip vector, the transfection efficiency in Jurkat and K-562 cells was examined using confocal microscopy. More than 95% of Jurkat cells expressed GFP and the level of this expression was markedly enhanced by PMA. Negligible GFP expression was seen in K-562 cells or when B-F5 was replaced by a nonspecific antibody. Using flow cytometry, fluorescein-labelled complex showed specific targeting to CD4(+) cells in a mixed cell population from human peripheral blood. These studies demonstrate the selective transfection of CD4(+) T-lymphoid cells using a polycation-based gene delivery system. The complex may provide a means of delivering anti-HIV gene therapies to CD4(+) cells in vivo.

Sensitivity of multiple frequency bioelectrical impedance analysis to changes in ion status

Bioelectrical impedance analysis has found extensive application as a simple noninvasive method for the assessment of body fluid volumes, The measured impedance is, however, not only related to the volume of fluid but also to its inherent resistivity. The primary determinant of the resistivities of body fluids is the concentration of ions. The aim of this study was to investigate the sensitivity of bioelectrical impedance analysis to bodily ion status. Whole body impedance over a range of frequencies (4-1012 kHz) of rats was measured during infusion of various concentrations of saline into rats concomitant with measurement of total body and intracellular water by tracer dilution techniques. Extracellular resistance (R-o), intracellular resistance (R-i) and impedance at the characteristic frequency (Z(c)) were calculated. R-o and Z(c) were used to predict extracellular and total body water respectively using previously published formulae. The results showed that whilst R-o and Z(c) decreased proportionately to the amount of NaCl infused, R-i increased only slightly. Impedances at the end of infusion predicted increases iu TBW and ECW of approximately 4-6% despite a volume increase of less than 0.5% in TBW due to the volume of fluid infused. These data are discussed in relation to the assumption of constant resistivity in the prediction of fluid volumes from impedance data.

Role of chemical cues from cotton in mediating host selection and oviposition behaviour in Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

We investigated the role of chemoreception in the host selection and oviposition behaviour of Helicoverpa armigera in the laboratory using five cotton genotypes and synthetic volatile terpenes. Female moths oviposited on substrates treated with methanol, ethanol, acetone and pentane extracts of leaves, squares and flowers of the cotton genotypes. Phytochemicals soluble in pentane were the most efficient in eliciting oviposition behaviour. In a two-way bioassay, pentane extracts of leaves or squares of a Multiple Host-plant Resistance genotype (MHR11), Deltapine commercial (DP90), and Smith Red Leaf (SRL) received significantly more eggs than solvent-treated controls. Extracts of squares of the native genotype Gossypium nelsonii did not receive more eggs. Females preferred DP90 and MHR11 to SRL and G. nelsonii. Female moths also laid more eggs on pentane extracts of MHR11 flowers than MHR11 leaves from preflowering, early flowering and peak-flowering plants. In a flight chamber, female moths used olfactory cues at short range to mediate oviposition and discrimination between host plants. Egg-laying, mated females were attracted at a distance (1.5 m) to volatile compounds released by whole plants and odours emanating from filter papers treated with synthetic volatile terpenes. Individually, the terpenes did not stimulate any significant oviposition response. However, there was a significant oviposition response to a mixture of equal volumes of the terpenes (trans-beta-caryophyllene, alpha-pinene, beta-pinene, myrcene, beta-bisabolol, and alpha-humulene). Conversely, antennectomised (moths with transected antennae), egg-laying, mated females did not stimulate any significant oviposition response. The significance of these findings in relation to H. armigera hostplant selection are discussed.

First record in Australia of Myriogenospora atramentosa on lemongrass and sugarcane

Myriogenospora atramentosa has been found on lemongrass (Cymbopogon citratus) and sugarcane (Saccharum interspecific hybrids) in Queensland. These are the first records of this fungus outside of the Americas.

Community care and criminal offending in schizophrenia

Background The introduction of community care in psychiatry is widely thought to have resulted in more offending among the seriously mentally ill. This view affects public policy towards and public perceptions of such people. We investigated the association between the introduction of community care and the pattern of offending in patients with schizophrenia in Victoria, Australia. Methods We established patterns of offending from criminal records in two groups of patients with schizophrenia over their lifetime to date and in the 10 years after their first hospital admission. One group was first admitted in 1975 before major deinstitutionalisation in Victoria, the second group in 1985 when community care was becoming the norm. Each patient was matched to a control, by age, sex, and place of residence to allow for changing patterns of offending over time in the wider community. Findings Compared with controls, significantly more of those with schizophrenia were convicted at least once for ail categories of criminal offending except sexual offences (relative risk of offending in 1975=3.5 [95% CI 2.0-5.5), p=0.001, in 1985=3.0 [1.9-4.9], p=0.001). Among men, more offences were committed in the 1985 group than the 1975 group, but this was matched by a similar increase in convictions among the community controls. Those with schizophrenia who had also received treatment for substance abuse accounted for a disproportionate amount of offending. Analysis of admission data for the patients and the total population of admissions with schizophrenia showed that although there had been an increase of 74 days per annum spent in the community for each of the study population as a whole, first admissions spent only 1 more day in the community in 1985 compared with 1975. Interpretation Increased rates in criminal conviction for those with schizophrenia over the last 20 years are consistent with change in the pattern of offending in the general community. Deinstitutionalisation does not adequately explain such change. Mental-health services should aim to reduce the raised rates of criminal offending associated with schizophrenia, but turning the clock back on community care is unlikely to contribute towards any positive outcome.

Contribution of beta-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wild-type and beta(3)-adrenoceptor knockout mice

1 The smooth muscle relaxant responses to the mixed beta(3)-, putative beta(4)-adrenoceptor agonist, (-)-CGP 12177 in rat colon are partially resistant to blockade by the beta(3)-adrenoceptor antagonist SR59230A suggesting involvement of beta(3)- and putative beta(4)-adrenoceptors. We now investigated the function of the putative beta(4)-adrenoceptor and other beta-adrenoceptor subtypes in the colon, oesophagus and ureter of wild-type (WT) and beta(3)-adrenoceptor knockout (beta(3)KO) mice. 2 (-)-Noradrenaline and (-)-adrenaline relaxed KCl (30 mM)-precontracted colon mostly through beta(1)-and beta(3)-adrenoceptors to a similar extent and to a minor extent through beta(2)-adrenoceptors. In colon from beta(3)KO mice, (-)-noradrenaline was as potent as in WT mice but the effects were mediated entirely through beta(1)-adrenoceptors. (-)-CGP 12177 relaxed colon from beta(3)KO mice with 2 fold greater potency than in WT mice. The maintenance of potency for (-)-noradrenaline and increase for (-)-CGP 12177 indicate compensatory increases in beta(1)- and putative beta(4)-adrenoceptor function in beta(3)KO mice. 3 In oesophagi precontracted with 1 mu M carbachol, (-)-noradrenaline caused relaxation mainly through beta(1)-and beta(3)-adrenoceptors. (-)-CGP 12177 (2 mu M) relaxed oesophagi from WT by 61.4+/-5.1% and beta(3)KO by 67.3+/-10.1% of the (-)-isoprenaline-evoked relaxation, consistent with mediation through putative beta(4)-adrenoceptors. 4 In ureter, (-)-CGP 12177 (2 mu M) reduced pacemaker activity by 31.1+/-2.3% in WT and 31.3+/-7.5% in beta(3)KO, consistent with mediation through putative beta(4)-adrenoceptors. 5 Relaxation of mouse colon and oesophagus by catecholamines are mediated through beta(1)- and beta(3)- adrenoceptors in WT. The putative beta(4)-adrenoceptor, which presumably is an atypical state of the beta(1)-adrenoceptor, mediates the effects of(-)-CGP 12177 in colon, oesophagus and ureter.

Concentration-effect relationship of hydroxychloroquine in patients with rheumatoid arthritis - A prospective, dose ranging study

Objective. A 6 month prospective randomized double blind study was conducted to investigate hydroxychloroquine dose concentration-effect relationships in people with rheumatoid arthritis. Methods. Patients were randomized in 2 groups: one group received 200 mg hydroxychloroquine sulfate daily (A) and one group received 400 mg daily (B). Each month, 8 disease variables were assessed, adverse events recorded, and hydroxychloroquine blood concentrations determined. Results. Twenty-three patients were included: 10 in group A and 13 in group B. After 6 months of therapy, a significant improvement in disease activity was noted for 6 criteria with no statistical differences between groups: pain (assessed by a visual analog scale), joint scores (swelling and tenderness), impairment in daily Living activity (18 activities graded 0 to 8), patient assessment of disease state, and erythrocyte sedimentation rate. Hydroxychloroquine steady-state blood concentrations (Month 6) were significantly different between groups (mean +/- SD): 450.6 +/- 285.3 ng/ml (A) vs 870.3 +/- 329.3 ng/ml(B) (p = 0.0001). Steady-state concentrations were correlated with the daily dose (r = 0.63, p = 0.005), the improvement in activity of daily living (r = 0.49, p = 0.03), and the improvement in joint tenderness score (r = 0.47, p = 0.038). Conclusion. The data indicate that hydroxychloroquine is an effective therapy, but there were no further improvements observed in the group receiving 400 mg daily compared to those receiving 200 mg. There were some correlations between hydroxychloroquine steady-state blood concentrations and effects.