MELANOMA IN NEW SOUTH WALES 1970–76: SURGICAL THERAPY AND SURVIVAL

From a survey of melanoma cases in New South Wales, a random sample was selected for histopathological review and follow up concerning surgical therapy and survival. It was found that the principal factors influencing survival were tumour thickness, level of mitotic activity and the age of the patient. The form of treatment in many cases bore little relationship to the severity of the tumour, as determined by its thickness, or to survival. It is hypothesised that survival rates would be higher and unnecessarily extensive surgery avoided if treatment were chosen with greater regard to established prognostic indicators.     

Motor inhibition induced by aporphine derivatives in the mouse

The ability of some aporphine and benzylisoquinoline derivatives to inhibit mouse spontaneous locomotor activity at low doses, and at higher doses to have a reduced motor inhibitory effect, was used to determine whether motor inhibitory and facilitatory potentials could be dissociated, and the optimal structure required to cause these behavioural changes. Ability to displace [³H]2-amino-6,7-dihydroxy-1,2,3,4-tetrahydro-naphthalene [³H]ADTN from its binding sites in rat striatal tissue was used as a broad measure of the abilities of the test compounds to bind to the ‘dopamine receptor’. The order of potency for ‘low dose’ inhibition of mouse spontaneous locomotion was (1) (-)N-n-propylnorapomorphine>(2) apomorphine > (3) (-)2,10,11-trihydroxy-N-n-propylnoraporphine > (4) (-)2,10,11-trihydroxyaporphine > (5) f-10,11-dihydroxy-N-(hydroxy-ethyl)noraporphine > (6) norapomorphine > (7) (±)10-hydroxy-N-n-propylnoraporphine > (8) 1-(3,4-dihydroxybenzyl)-2-n-propyl-1,2,3,4-tetrahydroiso- quinoline. The latter two compounds were only weakly active and (±)8-hydroxy-N-n-propylnoraporphine and 1-(4-hydroxybenzyl)-2-n-propyl-1,2,3,4-tetrahydroisoquinoline were inactive. The reduction in motor inhibitory effect as dose of agonist was increased (indicative of facilitation of locomotion) was only observed with compounds 1 and 2, other compounds (3 and 4) caused non-specific changes which interfered with motor performance or the doses required were so large as to render testing impractical (5,6,7 and 8). The potent motor inhibitory actions of compounds 1–4 were antagonized by pretreatment with spiperone but not with prazosin or yohimbine. Specific binding of 2·0nM [³H]ADTN was displaced by nanomolar concentrations of (±)-ADTN and aporphine derivatives. Isoapomorphine and the two benzylisoquinoline derivatives were ineffective at 10^?6M. The optimal structure for those derivatives examined was shown in all tests to be (-)N-n-propylnorapomorphine.     

A pilot safety and immunogenicity study of the malaria vaccine SPf66 in Gambian infants

A pilot safety and immunogenicity trial of the malaria vaccine SPf66 has been undertaken in 150 Gambian infants. No significant systemic side effects were recorded but modest local reactions were seen after the administration of a third 1.0 mg dose. SPf66 produced in Colombia was more immunogenic than SPf66 produced in the USA and a 1.0 mg dose of each vaccine gave higher antibody levels than a 0.5 mg dose. However, antibody levels fell rapidly after administration of the third dose of vaccine and showed little change over the following malaria transmission season. The incidence of clinical malaria was higher among children who received SPf66 than among children who received inactivated polio vaccine, the effect being most marked among children who received 1.0 mg Colombian SPf66. As the trial was not designed to measure the effect of SPf66 on morbidity from malaria, the significance of this finding is uncertain.     

Alcohol consumption and sickness absence: from the Whitehall II study

Previous studies suggest that problem drinkers have markedly increased sickness absence. However, it is not dear how more moderate alcohol consumption and abstinence relate to sickness absence. As part of the Whitehall II study the relationship between different drinking patterns and, sickness absence is examined. A total of 10314 male and female civil servants completed a baseline questionnaire about their drinking habits—the amount of alcohol consumed over the past 7 days and the frequency of drinking over the past 12 months. All sickness absence has been recorded prospectively. Drinking patterns and sickness absence are examined for short spells (7 days) and long spells (> 7 days) adjusting for other causes of sickness absence: age, grade of employment, smoking, work characteristics and baseline health. Alcohol consumption was strongly related to employment grade, the lower the grade the higher proportion of men and women reporting no alcohol consumption. For men the relation of alcohol intake to short spelts of sickness absence (> 7 days) appeared to be U-shaped, for long spells (> 7 days) increased rates of absence were found only in frequent drinkers. There was no clear relationship for women, however higher rates of sickness absence were found in non-drinkers.     

Characterization of the Block Structure and Molecular Weight of Sodium Alginates

Sodium alginates are widely used within the pharmaceutical sciences, yet the molecular characteristics of these materials are frequently not stated. In this study, a range of characterization techniques is applied to five sodium alginate samples and the data compared, both between techniques and with the information obtained from the manufacturer. The mannuronic acid to guluronic acid (MG) ratio and the distribution of uronic acid residues of five sodium alginate samples have been measured using circular dichroism and NMR, with circular dichroism yielding MG ratios between 42.1 and 63.6%, depending on the grade of alginate used. The MG ratios obtained from NMR studies were in broad agreement with these values, and the technique also yielded information on the distribution of uronic acid residues within each batch; this was again found to vary considerably (NG > 1 values ranging from 6.9 to 17.5). It was noted that samples with similar MG ratios could have markedly different chain-distribution characteristics. The uronic acid ratio ranges obtained from the manufacturers were found to be in good agreement with those found experimentally. Intrinsic viscosity measurements were used to compare the molecular weights of the samples; values between approximately 12000 and 180000 were obtained for the different batches. The study has enabled comparison of different methods for characterization of sodium alginate samples, highlighting their relative merits and the possible protocols that might be adopted. A critical discussion is given of the individual and combined use of these techniques and the relevance of such studies to the rational design and quality control of alginate-based pharmaceutical systems.     

Treatment outcomes for methamphetamine users receiving outpatient counselling from the Stimulant Treatment Program in Australia

Introduction and Aims. The purpose of this study was to document treatment outcomes for methamphetamine users receiving outpatient counselling from the Stimulant Treatment Program (STP) in Australia. Design and Methods. Clients attending the STP for methamphetamine use (n = 105) were assessed on entry to the service and at 3 (n = 86) and 6 months (n = 83) after starting treatment. At each interview methamphetamine use (days of use, severity of dependence), other drug use and health and social functioning (HIV risk behaviour, crime, disability, psychotic symptoms and hostility) were assessed for the past month. Results. Participants received a median of six counselling sessions (interquartile range 1–11) over a period of 89 days (interquartile range 41–148 days). Past month methamphetamine use fell from 79% at treatment entry to 53% at the 3‐month follow‐up (P < 0.001) and 55% at the 6‐month follow‐up (P < 0.001). There were statistically significant reductions in psychotic symptoms, hostility and disability associated with poor mental health. There was no change in other drug use, crime or HIV risk behaviour. Reductions in methamphetamine were more common among younger participants, those who had no history of drug treatment and those without concurrent heroin use. Discussion and Conclusions. Methamphetamine users entering the STP showed reductions in methamphetamine use and improvements in their mental health after treatment. Improved treatment responses are needed to address polydrug use and other harms within in this population.[McKetin R, Dunlop AJ, Holland RM, Sutherland RA, Baker AL, Salmon AM, Hudson SL. Treatment outcomes for methamphetamine users receiving outpatient counselling from the Stimulant Treatment Program in Australia. Drug Alcohol Rev 2013;32:80–87]