Vaccine-induced Th1-type responses are dominant over Th2-type responses in the short term whereas pre-existing Th2 responses are dominant in the longer term

The effect of adjuvant on induction of human papillomavirus type 16 E7 protein-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG)(2a) antibody was studied in C57BL/6 J mice immunized with various adjuvants and E7 protein. Quil-A adjuvant, but not complete Freund's adjuvant (CFA) or Algammulin, induced a T-helper 1 (Th1)-type response to E7, which was characterized by CTL activity against a tumour cell line transfected with E7 protein and by E7-specific IgG(2a). All tested adjuvants elicited comparable levels of E7-specific IgG(1). The longest duration and greatest magnitude of CTL response was seen following two immunizations with the highest dose of E7 and Quil-A. Simultaneous immunization with a Th1 and a T helper 2 (Th2)-promoting adjuvant gave a Th1-type response. However, E7 and Quil-A were unable to induce a Th1-type response (as measured by the inability to generate anti-E7 IgG(2a) antibody) in animals with a pre-existing Th2-type response to E7. These results suggest that saponin adjuvants may be suitable for immunotherapy in humans where a Th1-type response is sought, provided that there is no pre existing Th2-type response to the antigen.

Evidence of multiple transcription initiation and termination sites within the rDNA intergenic spacer and rRNA readthrough transcription in the urochordate Herdmania curvata

Analysis of the structure of the urochordate Herdmania curvata ribosomal DNA intergenic spacer (IGS) and its role in transcription initiation and termination suggests that rRNA gene regulation in this chordate differs from that in vertebrates. A cloned H, curvata IGS is 1881 bp and composed predominantly of two classes of similar repeat sequences that largely alternate in a tandem array. Southern blot hybridization demonstrates that the IGS length variation within an individual and population is largely the result of changes in internal repeat number. Nuclease S1 mapping and primer extension analyses suggest that there are two transcription initiation sites at the 3' end of the most 3' repetitive element; these sites are 6 nucleotides apart. Unlike mouse, Xenopus, and Drosophila, there is no evidence of transcription starting elsewhere in the IGS. Most sequence differences between the promoter repeat and the other internal repeats are in the vicinity of the putative initiation sites. As in Drosophila, nuclease S1 mapping of transcription termination sites suggest that there is not a definitive stop site and a majority of the pre-rRNAs read through a substantial portion of the IGS. Some transcription appears to proceed completely through the promoter repeat into the adjacent rDNA unit. Analysis of oocyte RNA by reverse transcription-polymerase chain reaction (RT-PCR) confirms that readthrough transcription into the adjacent rDNA unit is occurring in some small IGS length variants; there is no evidence of complete readthrough of IGSs larger than 1.0 kb.

Cannabis use and psychosis

This paper reviews evidence on two hypotheses about the relationship between cannabis use and psychosis. The first hypothesis is that heavy cannabis use may cause a cannabis psychosis-a psychosis that would not occur in the absence of cannabis use, the symptoms of which are preceded by heavy cannabis use and remit after abstinence. The second hypothesis is that cannabis use may precipitate schizophrenia, or exacerbate its symptoms. Evaluation of these hypotheses requires evidence of an association between cannabis use and psychosis, that is unlikely to be due to chance, in which cannabis use precedes psychosis, and in which we can exclude the hypothesis that the relationship is due to other factors, such as other drug use, or a personal vulnerability to psychosis. There is some clinical support for the first hypothesis. If these disorders exist they seem to be rare, because they require very high doses of THC, the prolonged use of highly potent forms of cannabis, or a pre-existing (but as yet unspecified) vulnerability. There is more support for the second hypothesis, in that a large prospective study has shown a linear relationship between the frequency with which cannabis has been used by age 18 and the risks over the subsequent 15 years of a diagnosis of schizophrenia. It is still unclear whether this means that cannabis use precipitates schizophrenia, whether it is a form of self-medication, or whether the association is due to the use of other drugs, such as amphetamines, which heavy cannabis users are more Likely to use. There is stronger evidence that cannabis use can exacerbate the symptoms of schizophrenia. Mental health services should identify patients with schizophrenia who use alcohol, cannabis and other drugs and advise them to abstain or to greatly reduce their drug use.

Australian doctors' beliefs and practice regarding Helicobacter pylori

Objective: To determine beliefs and behaviours of Australian doctors regarding Helicobacter pylori. Design: Anonymous reply-paid postal survey mailed in December 1995 and again in March 1996. Subjects: All members on the mailing lists of the Gastroenterological Society of Australia Endoscopy Section (n = 397) and the Australian Society of Infectious Diseases (n = 264; those without medical qualifications were asked not to reply), and 400 general practitioners (GPs) randomly selected from the Royal Australian College of General Practitioners. Main outcome measures: Differences between specialist groups in belief in a causative association between H. pylori and peptic disease and in use of eradication therapy and pre- and post-treatment testing for H. pylori. Results: 92.6% of doctors believed H. pylori causes duodenal ulcer, with GPs significantly less likely to believe than gastroenterologists (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.00-0.81). In duodenal ulcer, 93.4% of doctors believed H. pylori eradication therapy should be given, but fewer (83.4%) claimed to give it always or mostly, with GPs less likely to report giving it than gastroenterologists (OR, 0.06; 95% CI, 0.02-0.19). For non-ulcer dyspepsia, gastrointestinal surgeons were more likely than gastroenterologists to believe in a causative link with H. pylori (OR, 5.6; 95% CI, 3.0-10.7) and in a need for eradication therapy (OR, 3.6; 95% CI, 1.7-7.7). Most doctors (79.3%) believed in confirming the presence of H. pylori before eradication therapy in duodenal ulcer. Only 51.6% believed post-eradication testing necessary (45.5%), yet 79.1% reported performing it. Conclusions: Significant differences exist between specialist groups in beliefs and self-reported behaviours regarding H. pylori.

The knowledge gap: A perspective on trade, industry, technology and policy from pre-war Australian music technology manufacturing (1903-30)

Australia struggles to achieve economic competitiveness, prevent expansion of the trade deficit and develop value-added production despite applications of policy strategies from protectionism to trade liberalisation. This article argues that these problems were emerging at the turn of the century, and that an investigation of music technology manufacturing in the first two decades of this century reveals fundamental problems in the conduct of relevant policy analysis. Analysis has focused on the trade or technology gap which is only symptomatic of an underlying knowledge gap. The article calls for a knowledge policy approach which can allow protection without the negative effects of isolation from global markets and without having to resort to unworkable utopian free-trade dogma. A shift of focus from a 'goods traded' view to a knowledge transaction (or diffusion) perspective is advocated.

Whole-body pre-cooling and heat storage during self-paced cycling performance in warm humid conditions

The aim of this study was to establish the effect that pre-cooling the skin without a concomitant reduction in core temperature has on subsequent self-paced cycling performance under warm humid (31 degrees C and 60% relative humidity) conditions. Seven moderately trained males performed a 30 min self-paced cycling trial on two separate occasions. The conditions were counterbalanced as control or whole-body pre-cooling by water immersion so that resting skin temperature was reduced by approximate to 5-6 degrees C. After pre-cooling, mean skin temperature was lower throughout exercise and rectal temperature was lower (P < 0.05) between 15 and 25 min of exercise. Consequently, heat storage increased (P < 0.003) from 84.0 +/- 8.8 W . m(-2) to 153 +/- 13.1 W . m(-2) (mean +/- s((x) over bar)) after pre-cooling, while total body sweat fell from 1.7 +/- 0.1 1 . h(-1) to 1.2 +/- 0.1 1 . h(-1) (P < 0.05). The distance cycled increased from 14.9 +/- 0.8 to 15.8 +/- 0.7 km (P < 0.05) after pre-cooling. The results indicate that skin pre-cooling in the absence of a reduced rectal temperature is effective in reducing thermal strain and increasing the distance cycled in 30 min under warm humid conditions.

Lessons from a comprehensive clinical audit of users of psychiatric services who committed suicide

Objective: Characteristics of patients who committed suicide were examined to provide a picture of the treatment they received before death and to determine whether and how the suicides could have been pre vented by the service system. Methods: The unnatural-deaths register was matched to the psychiatric case register in the state of Victoria in Australia to identify suicides by people with a history of public-sector psychiatric service use who committed suicide between July 1, 1989, and June 30, 1994. Data on patient and treatment characteristics were examined by three experienced clinicians, who made judgments about whether the suicide could have been prevented had the service system responded differently. Quantitative and qualitative data were descriptively analyzed. Results: A total of 629 psychiatric patients who had committed suicide were identified. Seventy-two percent of the patients were male, 62 percent were under 40 years old, and 51 percent were unmarried. They had a range of disorders, with the most common being schizophrenia or schizoaffective disorder (36 percent). Sixty-seven percent had previously attempted suicide. A total of 311 patients (49 percent) received care within four weeks of death. Twenty percent of the suicides were considered preventable. Key factors associated with preventability were poor staff-patient relationships, incomplete assessments, poor assessment and treatment of depression and psychological problems, and poor continuity of care. Conclusions: Opportunities exist for the psychiatric service system to alter practices at several levels and thereby reduce patient suicides.

Impact of increasing the re-supply interval on the seasonality of subsidised prescription use in Australia

Objective: To evaluate the impact of increasing the minimum resupply period for prescriptions on the Pharmaceutical Benefits Scheme (PBS) in November 1994. The intervention was designed to reduce the stockpiling of medicines used for chronic medical conditions under the PBS safety net. Methods: Interrupted times series regression analyses were performed on 114 months of PBS drug utilisation data from January 1991 to June 2000. These analyses assessed whether there had been a significant interaction between the onset of the intervention in November 1994 and the extreme levels of drug utilisation in the months of December (peak utilisation) and January (lowest utilisation) respectively. Both serial and 12-month lag autocorrelations were controlled for. Results: The onset of the intervention was associated with a significant reduction in the December peak in drug utilisation; after the introduction of the policy there were 1,150,196 fewer proscriptions on average or that month (95% Cl 708,333-1,592,059). There was, however, no significant change in the low level of utilisation in January. The effect of the policy appears to be decreasing across successive postintervention years. though the odds of a prescription being dispensed in December remained significantly lower in 1999 compared to each of the pre-intervention years (11% vs. 14%) Conclusion: Analysis of the impact of increasing the re-supply period for PBS prescriptions showed that the magnitude of peak utilisation in December had been markedly reduced by the policy, though this effect appears to be decreasing over time. Continued monitoring and policy review is warranted in order to ensure that the initial effect of the intervention be maintained.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease

Objective: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. Methods: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. Results and conclusions: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Allowing the medical use of cannabis

Cannabis has been advocated as a treatment for nausea, vomiting, wasting, pain and muscle spasm in cancer, HIV/AIDS, and neurological disorders. Such uses are prohibited by law; cannabinoid drugs are not registered for medical use in Australia and a smoked plant product is unlikely to be registered. A New South Wales Working Party has recommended granting exemption from prosecution to patients who are medically certified to have specified medical conditions. This proposal deserves to be considered by other State and Territory governments.

The preparation and execution of self-initiated and externally-triggered movement: A study of event-related fMRI

Studies of functional brain imaging in humans and single cell recordings in monkeys have generally shown preferential involvement of the medially located supplementary motor area (SMA) in self-initiated movement and the lateral premotor cortex in externally cued movement. Studies of event-related cortical potentials recorded during movement preparation, however, generally show increased cortical activity prior to self-initiated movements but little activity at early stages prior to movements that are externally cued at unpredictable times. In this study, the spatial location and relative timing of activation for self-initiated and externally triggered movements were examined using rapid event-related functional MRI. Twelve healthy right-handed subjects were imaged while performing a brief finger sequence movement (three rapid alternating button presses: index-middle-index finger) made either in response to an unpredictably timed auditory cue (between 8 to 24 s after the previous movement) or at self-paced irregular intervals. Both movement conditions involved similar strong activation of medial motor areas including the pre-SMA, SMA proper, and rostral cingulate cortex, as well as activation within contralateral primary motor, superior parietal, and insula cortex. Activation within the basal ganglia was found for self-initiated movements only, while externally triggered movements involved additional bilateral activation of primary auditory cortex. Although the level of SMA and cingulate cortex activation did not differ significantly between movement conditions, the timing of the hemodynamic response within the pre-SMA was significantly earlier for self-initiated compared with externally triggered movements. This clearly reflects involvement of the pre-SMA in early processes associated with the preparation for voluntary movement. (C) 2002 Elsevier Science.

The demise of a planned randomised controlled trial in an urban Aboriginal medical service

To fill a gap in knowledge about the effectiveness of brief intervention for hazardous alcohol use among Indigenous Australians, we attempted to implement a randomised controlled trial in an urban Aboriginal Medical Service (AMS) as a joint AMS-university partnership. Because of low numbers of potential participants being screened, the RCT was abandoned in favour of a two-part demonstration project. Only 16 clients were recruited for follow-up in six-months, and the trial was terminated. Clinic, patient, Aboriginal health worker, and GP factors, interacting with study design factors, all contributed to our inability to implement the trial as designed. The key points to emerge from the study are that alcohol misuse is a difficult issue to manage in an Indigenous primary health care setting; RCTs involving inevitably complex study protocols may not be acceptable or sufficiently adaptable to make them viable in busy, Indigenous primary health care settings; and gold-standard RCT-derived evidence for the effectiveness of many public health interventions in Indigenous primary health care settings may never be available, and decisions about appropriate interventions will often have to be based on qualitative assessment of appropriateness and evidence from other populations and other settings.