A for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study

Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P = 0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P = 0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P = 0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P < 0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P < 0.05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Rapid opiate detoxification and naltrexone treatment: past, present and future

This Article does not have an abstract

Sterilization of girls and women with intellectual disabilities - Past and present justifications

This article describes findings from empirical research examining sterilization applications for miners made to the Family Court of Australia between 1992 and 1999. Original materials and written reports from experts,family members, and judicial officers are used to highlight the dominant discourse and themes. These are compared with historical characterizations of young women with disabilities used during the notorious eugenics period in the first half of the 20th century. The new ways of justifying sterilization use the sanitized language of best interests, silencing constructionist approaches to disability and gender issues. The new ways are reminiscent of the old ways of discrimination, prejudice, and violation.

Lucerne biology and genetic improvement - an analysis of past activities and future goals in Australia

Breeding methodologies for cultivated lucerne (Medicago sativa L.), an autotetraploid, have changed little over the last 50 years, with reliance on polycross methods and recurrent phenotypic selection. There has been, however, an increase in our understanding of lucerne biology, in particular the genetic relationships between members of the M. sativa complex, as deduced by DNA analysis. Also, the differences in breeding behaviour and vigour of diploids versus autotetraploids, and the underlying genetic causes, are discussed in relation to lucerne improvement. Medicago falcata, a member of the M. sativa complex, has contributed substantially to lucerne improvement in North America, and its diverse genetics would appear to have been under-utilised in Australian programs over the last two decades, despite the reduced need for tolerance to freezing injury in Australian environments. Breeding of lucerne in Australia only commenced on a large scale in 1977, driven by an urgent need to introgress aphid resistance into adapted backgrounds. The release in the early 1980s of lucernes with multiple pest and disease resistance (aphids, Phytophthora, Colletotrichum) had a significant effect on increasing lucerne productivity and persistence in eastern Australia, with yield increases under high disease pressure of up to 300% being recorded over the predominant Australian cultivar, up to 1977, Hunter River. Since that period, irrigated lucerne yields have plateaued, highlighting the need to identify breeding objectives, technologies, and the germplasm that will create new opportunities for increasing performance. This review discusses major goals for lucerne improvement programs in Australia, and provides indications of the germplasm sources and technologies that are likely to deliver the desired outcomes.

The walkeriana species-group of Euhesma Michener (Hymenoptera: Colletidae: Euryglossinae)

The walkeriana species-group of iridescent Euhesma bees is described with the following nine species considered new: E. allunga, E. banksia, E. bronzus, E. dongara, E. lobata, E. spinola, E. sybilae, E. viridescens and E. xana. Two new synonymies are proposed: E. mica (Cockerell) with E. neglectula (Cockerell), and E. halictoides (Rayment) with E. latissima (Cockerell). A key enables the separation of species, and distributions are mapped.

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: A phase II trial for the Trans-Tasman Radiation Oncology Group

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications. (C) 2001 Elsevier Science Inc.

Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations

Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Towards a blood-stage vaccine for malaria: Are we following all the leads?

Although the malaria parasite was discovered more than 120 years ago, it is only during the past 20 years, following the cloning of malaria genes, that we have been able to think rationally about vaccine design and development. Effective vaccines for malaria could interrupt the life cycle of the parasite at different stages in the human host or in the mosquito. The purpose of this review is to outline the challenges we face in developing a vaccine that will limit growth of the parasite during the stage within red blood cells - the stage responsible for all the symptoms and pathology of malaria. More than 15 vaccine trials have either been completed or are in progress, and many more are planned. Success in current trials could lead to a vaccine capable of saving more than 2 million lives per year.

Relationship of high energy expenditure and variation in dietary intake with reporting accuracy on 7 day food records and diet histories in a group of healthy adult volunteers

Objectives: To assess the accuracy of reporting from both a diet history and food record and identify some of the characteristics of more accurate reporters in a group of healthy adult volunteers for an energy balance study. Design: Prospective measurements in free-living people. Setting: Wollongong, Australia. Subjects: Fifteen healthy volunteers (seven male, eight female; aged 22 -59 y; body mass index (BMI) 19 - 33 kg/m(2)) from the local community in the city of Wollongong, Australia. Interventions: Measurement of energy intake via diet history interview and 7 day food records, total energy expenditure by the doubly labelled water technique over 14 days, physical activity by questionnaire, and body fat by dual-energy X-ray absorptiometry. Results: Increased misreporting of energy intake was associated with increased energy expenditure (r = 0.90, P < 0.0001, diet history; r(s)=0.79, P=0.0005, food records) but was not associated with age, sex, BMI or body fat. Range in number of recorded dinner foods correlated positively with energy expenditure (r(s)=0.63, P=0.01) and degree of misreporting (r(s)=0.71, P=0.003, diet history; r(s)=0.63, P=0.01, food records). Variation in energy intake at dinner and over the whole day identified by the food records correlated positively with energy expenditure (r=0.58, P = 0.02) and misreporting on the diet history (r=0.62, P=0.01). Conclusions: Subjects who are highly active or who have variable dietary and exercise behaviour may be less accurate in reporting dietary intake. Our findings indicate that it may be necessary to screen for these characteristics in studies where accuracy of reporting at an individual level is critical. Sponsorship: The study was supported in part by Australian Research Council funds made available through the University of Wollongong.

Emerging pathways in colorectal-cancer development

The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI). This feature arises through defective DNA mismatch repair, which is related either to a germline mutation (as in hereditary non-polyposis colorectal carcinoma) or to failure to express a mismatch-repair gene. CpG-island methylation has been linked to sporadic cancers with a high frequency of MSI. This type of methylation leads to loss of gene expression when it occurs in the promoter region of a gene. Tumours may have high or low type C (cancer-related) CpG-island methylation. When methylation affects hMLH1 (mismatch repair gene), the resultant cancer has high MSI.

Rapid diagnosis in pediatric infectious diseases: The past, the present and the future

The focus of rapid diagnosis of infectious diseases of children in the last decade has shifted from variations of the conventional laboratory techniques of antigen detection, microscopy and culture to that of molecular diagnosis of infectious agents. Pediatricians will need to be able to interpret the use, limitations and results of molecular diagnostic techniques as they are increasingly integrated into routine clinical microbiology laboratory protocols. PCR is the best known and most successfully implemented diagnostic molecular technology to date. It can detect specific infectious agents and determine their virulence and antimicrobial genotypes with greater speed, sensitivity and specificity than conventional microbiology methods. Inherent technical limitations of PCR are present, although they are reduced in laboratories that follow suitable validation and quality control procedures. Variations of PCR together with advances in nucleic acid amplification technology have broadened its diagnostic capabilities in clinical infectious disease to now rival and even surpass traditional methods in some situations. Automation of all components of PCR is now possible. The completion of the genome sequencing projects for significant microbial pathogens, in combination with PCR and DNA chip technology, will revolutionize the diagnosis and management of infectious diseases.