Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials.

BACKGROUND: High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. PATIENTS AND METHODS: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. RESULTS: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CONCLUSIONS: CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

Factors affecting the species of Campylobacter colonizing chickens reared for meat.

AIM: To investigate factors influencing Campylobacter spp. colonization of broiler chickens. METHODS AND RESULTS: Campylobacters were isolated from caeca from 319 flocks of two different breeds (199 Cobb and 120 Hubbard), reared as standard (199), Freedom Food/corn fed (57), free-range (47) or organic (16). The standard category exclusively used Cobb birds slaughtered at 38-41 days. The Freedom Food/corn-fed and free-range Hubbard birds were slaughtered at 49-56 days and the organic flocks at 70 days. Campylobacters were picked at random from direct plates. Both breed of chicken (Hubbard) and age at slaughter were independently associated with increased likelihood of colonization by Campylobacter coli rather than Campylobacter jejuni, but breed could not be separated from other aspects of husbandry with the data available. CONCLUSIONS: Chickens are frequently colonized by C. jejuni and C. coli and most human infections originate from poultry. In most developed countries approximately 90% of human infections are caused by C. jejuni, but fewer than 10% by C. coli. This might be due to C. coli being less pathogenic than C. jejuni to humans, and/or to chicken meat carrying fewer C. coli than C. jejuni. More investigations are needed into these aspects before it can be concluded that slaughtering older birds from slower-growing breeds would reduce the risk of human Campylobacter disease. SIGNIFICANCE AND IMPACT OF THE STUDY: Meat from certain breeds of poultry are predominantly colonized by C. coli rather than C. jejuni. More research is needed to understand the impact this may have on the number and severity of human campylobacter infections.

Individualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy of curative intent: a descriptive pilot study.

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.

Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed. METHODS: We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes. RESULTS: Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43). CONCLUSIONS: p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.

Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer.

BACKGROUND: Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. PATIENTS AND METHODS: A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. RESULTS: The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. CONCLUSIONS: This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.

Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms.

OBJECTIVE: The World Mental Health Version of the Composite International Diagnostic Interview (WMH-CIDI) DSM-IV bipolar disorder diagnostic algorithms were recalibrated in about 2006 following evidence of over-diagnosis of bipolar I disorder. There have been no reports of the impact of this recalibration on epidemiological findings. METHOD: Data were taken from the 2007 Australian National Survey of Mental Health and Wellbeing. Findings for cases identified by the recalibrated bipolar disorder definition were contrasted against those identified by the un-recalibrated definition. RESULTS: The 12-month prevalence of recalibrated bipolar disorder and un-recalibrated bipolar disorder were 0.9% and 1.7% respectively. The un-recalibrated bipolar disorder group was younger and more likely to have never married than the recalibrated bipolar disorder group. They were also more likely to have a comorbid alcohol use disorder, substance use disorder and asthma or arthritis. While they were more likely to have at least severe interference in at least one of the Sheehan Scale domains of functioning, they were less likely to have made a suicide attempt. Similarly, they were less likely to have consulted a psychiatrist. CONCLUSION: It is not possible to be certain about the nature of these differences. Some may be artifactual (reflecting greater statistical power to detect differences with the larger un-recalibrated bipolar disorder defined sample), while others may be indicative of the inclusion of a clinically distinct subpopulation with the un-recalibrated bipolar disorder definition, thereby producing a more heterogeneous sample. These findings indicate the need for clarity in the diagnostic algorithm used in epidemiological reports on bipolar disorder using the World Mental Health Version of the Composite International Diagnostic Interview.

Freezing as an intervention to reduce the numbers of campylobacters isolated from chicken livers.

The aims of this study were (i) to determine the prevalence and numbers of campylobacters in 63 samples of raw livers purchased at retail across the UK and (ii) to investigate whether the freezing of chicken livers contaminated with Campylobacter was a reliable method for decontamination. Chicken livers naturally contaminated with campylobacters were subjected to freezing at -15 and -25°C for one day and 7 days. Numbers of campylobacters on the livers were determined immediately before and after a 24-h or 7-days freeze treatment and daily during 3 days post-thaw refrigerated storage. Freezing for 24 h at -25°C can reduce numbers of Campylobacter by up to 2 log10 CFU g(-1). Freezing the livers for 24 h at -25°C, thawing overnight in a fridge set to 4°C and refreezing for another 24 h at -25°C reduced the numbers of campylobacters by up to three logs. Reduction in the numbers of campylobacters was significantly greater following a second freeze treatment compared with a single freeze treatment.

Quantitative Determination of Campylobacter on Broilers along 22 United Kingdom Processing Lines To Identify Potential Process Control Points and Cross-Contamination from Colonized to Uncolonized Flocks.

ABSTRACT: As part of a program to reduce numbers of the human pathogen Campylobacter on retail chickens, 22 broiler processing lines, representing more than 90% of UK production, were characterized by enumerating Campylobacter on pooled neck skins after exsanguination, scalding, defeathering, evisceration, crop removal, inside-outside washing, and air-chilling stages of processing. Sixteen of the processing lines investigated showed significant (P < 0.05) reductions in Campylobacter numbers because of carcass scalding. However, in all of these lines, the following defeathering stage caused a significant increase in Campylobacter contamination that effectively negated the reductions caused by scalding. On four processing lines, primary chilling also caused a significant reduction in numbers of Campylobacter. On three lines, there was a significant microbiological benefit from inside-outside washing. The stages where Campylobacter numbers were reduced require further investigation to determine the specific mechanisms responsible so that the observed pathogen reductions can be optimized and then more widely implemented. The transfer of up to 4 log CFU Campylobacter per g of neck skin from a colonized flock to a following uncolonized flock was observed. Cross-contamination was substantial and still detectable after 5,000 carcasses from an uncolonized flock had been processed. Numbers of Campylobacter recovered from the uncolonized flocks were highest on the first of the uncolonized birds to pass along the line, and in general, the numbers declined as more uncolonized birds were processed. Air sampling recovered low numbers at the processing stages monitored, indicating that airborne transmission was unlikely to be the primary transfer mechanism operating for cross-contamination between flocks.

Rupture mechanism of a liquid film.

The rupture mechanism of edge-supported liquid films appears to involve the viscous and drag energies as well as previously postulated kinetic and surface energies. Although details are obscure, the mechanism appears to involve a liquid-gathering process at the free edge, followed by fragmentation of this thickened edge into drops whose radii are approximately 50 times the film's original thickness.

Consequences of Using Two Types of Skin Samples from Chilled Chicken Broiler Carcasses To Measure the Degree of Contamination by Campylobacter spp.

HIGHLIGHTS: Campylobacter levels on chicken neck and breast skin were compared. Neck skin was significantly more contaminated (P < 0.05) than breast skin. No relationship between the two skin types was found for Campylobacter levels. A UK government reduction target for highly contaminated chicken was not achieved.

Campylobacter spp. contamination of chicken carcasses during processing in relation to flock colonisation.

The presence and numbers of campylobacters on chicken carcasses from 26 slaughter groups, originating from 22 single-house flocks and processed in four UK plants, were studied in relation to the level of flock colonisation determined by examining the caecal contents of at least ten birds per group. The prevalence of campylobacters on carcasses from five campylobacter-negative flocks processed just after other negative flocks was low (8.0 log(10) cfu) than carcasses originating from low prevalence flocks (average of 2.3 log(10) cfu; range: <1.1 to 4.1 log(10) cfu). There was a reduction in the numbers of campylobacters on carcasses between plucking and chilling in eight of ten fully colonised flocks. In another eight flocks, a significant (P<0.001) decrease (0.8 log(10) cfu) in the number of campylobacters on carcasses from just before to after chilling was detected. Campylobacter spp. could be isolated from aerosols, particles and droplets in considerable numbers in the hanging-on, defeathering and evisceration areas but not in the chillers. This was the case even when campylobacters were not isolated from the target flock. Campylobacters on carcasses from two partly colonised flocks were either the same subtype, as determined by speciation, Multi-Locus Sequence Typing (MLST) and flaA Restricted Fragment Length Polymorphism (RFLP) typing, as those in the fully colonised flocks processed previously, although not necessarily the most prevalent ones; or were the same subtypes as those found in the caeca of the flock itself. The prevalences of the different campylobacter subtypes found on carcasses from two fully colonised flocks did not closely reflect those found in the caeca. MLST combined with flaA RFLP provided a good method for ascertaining the relatedness of strains isolated from carcasses and caecal contents. This study showed that carcass contamination is related to the within-flock prevalence of campylobacter colonisation, but that contamination from previously processed flocks was also significant, especially on carcasses from low prevalence flocks. Forced dry air cooling of carcasses reduced contamination levels.

Mantle irradiation alone for clinical stage I-II Hodgkin's disease: long-term follow-up and analysis of prognostic factors in 261 patients.

PURPOSE: To evaluate mantle radiotherapy (MRT) alone as the initial therapy of patients with clinical stage (CS) I-II Hodgkin's disease (HD). PATIENTS AND METHODS: We performed a retrospective study of patients treated with MRT alone for CS I-II supradiaphragmatic HD between 1969 and 1994. Prognostic factor analysis was performed for progression-free survival (PFS) and overall survival (OS). Outcome was also assessed in favorable cohorts defined in the literature. RESULTS: There were 261 eligible patients. The median follow-up period for surviving patients was 8.4 years (range, 1.8 to 27.4 years). The 10-year OS rate was 73%. Multifactor analysis for OS showed that age was the only important prognostic factor. The 10-year PFS rate was 58%. On multifactor analysis for PFS, the most important prognostic factors were clinical stage, B symptoms, histology, number of sites, and tumor bulk. The 10-year PFS rate for lymphocyte-predominant disease was 81% for stage I and 78% for stage II. In favorable patient cohorts defined in the literature, the 10-year PFS rate ranged from 70% to 73% for the whole group and from 71% to 90% in patients with favorable stage I disease, but only from 48% to 57% in patients with favorable stage II disease. On competing-risks analysis, the cumulative 10-year incidence of first site of failure in the para-aortic/splenic region alone was 10.5%. Sixty percent of relapsed patients remain progression-free at 10 years after chemotherapy salvage. CONCLUSION: These results support the use of MRT alone in patients with favorable CS I HD and CS I-II HD with lymphocyte-predominant histology. The remainder of patients with CS I-II HD require more intensive treatment.

Parotid-sparing radiotherapy: does it really reduce xerostomia?

AIMS: Parotid-sparing radiotherapy (PSRT) was introduced for patients with selected head and neck cancer requiring bilateral upper-neck irradiation at our centre in 2000. The aim of this study was to compare the subjective degree of xerostomia in patients treated with PSRT between January 2000 and June 2003 with patients treated using conventional techniques (radiotherapy) over the same period. MATERIALS AND METHODS: Eligible patients were required to have completed treatment 6 months previously and be recurrence-free at the time of interview. PSRT was defined as conformal radiotherapy, in which the mean dose to at least one parotid gland was 33 Gy or less, as determined by the dose-volume histogram. Patients receiving radiotherapy were treated with standard parallel-opposed fields, such that both parotids received a minimum of 40 Gy. Xerostomia was assessed using a validated questionnaire containing six questions with a rating between 0 and 10. Lower scores indicated less difficulty with xerostomia. RESULTS: Thirty-eight eligible patients treated with PSRT were identified: 25 with oropharyngeal cancer and 13 with nasopharyngeal cancer (NPC). The mean overall questionnaire score (Q1-5) for this group was 4.20 (standard error = 0.33). Forty-four patients (24 oropharyngeal, 21 NPC) treated with radiotherapy over the same period were eligible. The mean overall questionnaire score (Q1-5) for this group was 5.86 (standard error = 0.35). The difference in mean overall scores between the two groups of patients was statistically significant (P < 0.001), as were the scores for four of the six individual questions. CONCLUSION: These results suggest that PSRT offers improved long-term xerostomia-related quality of life compared with conventional radiotherapy.

Salvage radiotherapy for Hodgkin's disease following chemotherapy failure.

PURPOSE: This study aims to: 1) assess failure-free survival (FFS), overall survival (OS), and failure pattern after salvage radiotherapy (SRT) for patients with Hodgkin's disease (HD) who fail chemotherapy (CT); 2) identify patients suitable for SRT as an alternative to more aggressive salvage regimens. METHODS AND MATERIALS: Between 1978 and 1992, 52 patients with relapsed/refractory HD following 26 CT received SRT at the Peter MacCallum Cancer Institute. Patient characteristics at diagnosis were: median age (range 12-63); male-31, female-21; Stage I-4, II-16, III-25, or IV-7. Prior to SRT 27 patients had received the equivalent of both MOPP and ABV(D). The duration of initial complete response (CR) from CT was greater than 12 months in 22 patients. SRT (dose 34-42 Gy) was given to active disease sites. RESULTS: Five-year FFS and OS rates following SRT were 26 and 57%, respectively. Five-year FFS and OS rates of 36 and 75%, respectively, were achieved in patients who relapsed in supradiaphragmatic nodal sites without B symptoms; in a subset of patients with initial Stage I-II disease the FFS and OS rates were 50 and 86%, respectively. On multivariate analysis significant factors for FFS were B symptoms at the time of SRT (p = 0.003), extranodal involvement (p = 0.011) and histology (p = 0.018). For OS significant factors were B symptoms (p = 0.0007), age (p = 0.014) and number of prior CT regimens (p = 0.03). CONCLUSION: The relatively poor results of SRT in terms of FFS justify the use of alternative salvage strategies for most patients with Hodgkin's disease who fail CT. However, SRT offers a low morbidity, potentially curative option for a subset of patients. Our data suggest that patients most suitable for SRT are those with relapse in supradiaphragmatic nodal sites and no B symptoms.

Nodal radiation therapy for metastatic melanoma.

PURPOSE: The aim of this retrospective study was to review our experience of radiation therapy to regional nodes in patients with proven nodal metastases, with respect to regional control, late toxicity, and overall survival. METHODS AND MATERIALS: All patients with a histological diagnosis of malignant melanoma, with involvement of the regional nodes but without distant metastases, who commenced nodal irradiation between January 1985 and July 1995 at Peter MacCallum Cancer Institute were studied. The study population of 113 patients was divided into two categories: those with no residual macroscopic disease following nodal surgery (adjuvant group, 42 patients) and those who had no surgery (8) or had macroscopic residual disease following nodal surgery (63) (palliative group, 71 patients). RESULTS: In the adjuvant group at 5 years following commencement of nodal irradiation 26% were estimated to be failure-free. Of the 74% who had experienced treatment failure by 5 years, an estimated 20% failed first with nodal relapse, 52% with distant metastases, and 2% with both nodal relapse and distant metastases. The estimated 5-year overall survival for this group was 33%. In the palliative group 16 patients (23%) had an objective complete response. Altogether 48 patients (68%) had a symptomatic response. At 5 years the overall survival in this group was 8% and an estimated 4% were failure-free. Of the 96% who had failed by 5 years, 68% failed first in the regional nodes, 25% had distant metastases as the first failure, and 3% had both nodal relapse and distant metastases. CONCLUSION: We recommend adjuvant postoperative radiation therapy for patients with proven nodal metastases and high risk of regional recurrence (multiple nodes, extracapsular extension, or recurrent nodal disease) in addition to adjuvant interferon.

Primary central nervous system lymphoma: age and performance status are more important than treatment modality.

PURPOSE: To assess prognostic factors and treatment modalities of patients with primary central nervous system lymphoma (PCNSL) in terms of response rates, patterns of failure and overall survival. METHODS AND MATERIALS: Sixty-two patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer Institute with no evidence of human immunodeficiency virus infection were included in the study. Their median age was 60 years; World Health Organisation (WHO) performance status was > or = 2 in 85%. All patients were planned to receive whole brain irradiation; 7 also received spinal irradiation. The median planned dose to the target volume was 50.4 Gy. Twenty patients were planned to receive chemotherapy as well. Patients were followed up to June 20, 1995, giving a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2 years. RESULTS: The clinical response rate to treatment was 77% [95% confidence interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months (CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO performance status < or = 1, treatment to the target volume > or = 45 Gy, and treatment with additional chemotherapy, were associated with a significantly better overall survival (p < 0.05). On multivariate analysis only age and performance status remained significant prognostic variables. Relapse involved the central nervous system or cerebrospinal fluid (CSF) in all patients with known sites of relapse except three who had ocular relapse only. There was a low incidence of relapse in the initial brain site (23% of known cases) and a high incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to initial or subsequent treatment. CONCLUSIONS: Patient outcome is strongly influenced by age and performance status. Studies suggesting better survival for patients treated with chemoradiation may reflect patient selection rather than treatment variables. Optimal management remains to be defined. The high CSF/spinal relapse rate deserves particular attention.

Radiation with concurrent late chemotherapy intensification ('chemoboost') for locally advanced head and neck cancer.

The aim of this study was to review our experience with a treatment regimen that combined conventionally fractionated radiation therapy (70 Gy over 7 weeks) with chemotherapy (cisplatin and fluorouracil), given concurrently in the last 2 weeks of radiation therapy in patients with previously untreated advanced squamous cell cancer of the head and neck region.Twenty-eight patients, all but two having UICC stage IV disease, were treated at the Peter MacCallum Cancer Institute between November 1995 and April 1998. Planned chemotherapy consisted initially of continuous infusion at 10 mg/m(2) per day of cisplatin and 400 mg/m(2) per day of fluorouracil on days 1-5 of weeks 6 and 7 of a conventionally fractionated course of radiotherapy. After the first 14 patients, the dose of fluorouracil was reduced to 360 mg/m(2) per day because of acute toxicity.36.8 months), with an estimated 50% surviving at 2 years (CI, 29-71%). Sixteen patients (57%) developed confluent mucositis and 11 (39%) developed patchy mucositis. The median duration of mucositis for these 27 patients was 1.5 months. Seventeen patients (61%) required nutritional support for a median duration of 1.4 months. Fourteen patients (50%) had grade three skin reactions, and 12 (43%) had one or more other significant (Grade 3) toxicities, predominantly infective. Grade 3 late toxicity has been observed in three patients to date (three xerostomia, including one with severe depression), and one patient had chronic ulceration of the oral tongue (grade 4). This chemoradiation regimen achieved an excellent complete response rate and good locoregional control at 2 years in patients with a poor initial prognosis. Acute toxicity was significant but manageable. The regimen offers an alternative to surgery and postoperative radiation therapy in locally advanced head and neck cancer.

Proenkephalin gene expression in the brainstem regulates post-exercise hypotension.

The opioid receptor antagonist naloxone reverses the reduction in blood pressure following exercise. We have previously demonstrated that compared to genetically matched controls, spontaneously hypertensive rats (SHR) have decreased proenkephalin mRNA levels in the nucleus tractus solitarius (NTS), the caudal (CVLM) and rostral ventrolateral medulla (RVLM) of the brainstem. We hypothesized that in SHR an acute bout of exercise would increase proenkephalin mRNA in the NTS and RVLM. Female 12-week-old SHR (n = 4/group) were randomly assigned to exercise and control groups. Mean arterial pressure (MAP) and heart rate were recorded at rest and every 5 min for 30 min following: (1) 40 min of treadmill running at 30 m/min, 10% grade; or (2) 40 min of rest on the treadmill. Rats were sacrificed 30 min post-exercise or post-rest. Exercise induced increases in MAP and heart rate, approximately 18 mmHg and approximately 140 beats/min, respectively, P < 0.001. There were no differences in pre-exercise/rest MAP between groups, or in control rats following rest on the treadmill, 162.5 +/- 3 vs. 163.1 +/- 4 mmHg, control and control after treadmill rest, respectively; NS P > 0.05. The pre- to post-exercise reduction in MAP after 40 min of treadmill running was from 164 +/- 5.1 to 146 +/- 2.0 mmHg (P < 0.001) as recorded 30 min post-exercise. At 30 min post-exercise proenkephalin mRNA levels in the NTS, CVLM and RVLM were increased: 97, 198 and 227%, respectively, P < 0.01. These data reconfirm the existence of post-exercise hypotension in SHR and suggest that increases in enkephalin synthesis and release in the NTS, CVLM, and RVLM may be involved in regulating post-exercise hypotension.

Systemic therapy in breast cancer: efficacy and cost utility.

Cancer treatment accounts for a large proportion of healthcare costs. Often, new treatment modalities provide benefits, but at high costs. The impression that cancer treatment is expensive is enhanced by publicity surrounding treatments like bone marrow transplantation. There is a need to evaluate costs of different treatment approaches and to address the cost utility of cancer treatment in general compared with therapies for other conditions. Breast cancer can serve as a good model for economic evaluation of cancer treatment because of the broad range of treatment options and objectives it encompasses, and also because well defined benefits can be achieved. The cost utility of contemporary adjuvant therapy strategies, specifically chemotherapy in premenopausal women and hormonal treatment in estrogen-receptor (ER) positive pre- as well as postmenopausal women, seems favourable. Cost-utility ratios {cost per quality-adjusted life-year (QALY) gained} range from $US4000 to $US10 000. However, hormonal treatment in ER-negative women may be associated with cost-per-QALY ratios of $US50 000 to $US200 000. So far there are no published cost-utility analyses of neo-adjuvant therapy or adjuvant bone marrow transplantation as the long term effects of these treatment options are undefined. Few data exist on cost utilities of systemic drug treatment in advanced breast cancer, although drugs may account for only a moderate part of the total treatment and caring costs. Bone marrow transplantation in patients with metastatic breast cancer costs about $US100 000 per QALY, which is expensive.

Effect of polymyxin B nonapeptide and polymyxin B sulphate on trichothecene mycotoxin sensitivity of yeasts using a conductimetric instrument.

The addition of polymyxin B sulphate (PBS), or an inactive by-product, polymyxin B nonapeptide (PBN) to a yeast bioassay system, increased its sensitivity to various toxic agents. The nil effect level (NEL) of T-2 toxin was reduced from 0.1 to 0.01 microgram/ml for Kluyveromyces fragilis GK 1005 in the presence of these agents when using a Malthus AT 192 conductimetric instrument. Other synergistic agents (DMSO, ethanol, cetyl trimethyl ammonium bromide and Triton X-100) gave poor results in the conductimetric system. PBN also increased sensitivity of K. fragilis GK 1005 towards cycloheximide in the Malthus system, and PBS reduced the NEL of T-2 toxin for K. fragilis GK 1005 in a disc diffusion assay from 0.2 to 0.04 microgram per disc. No yeasts were found sensitive to the trichothecene deoxynivalenol (DON) even at a DON concentration of 10 micrograms/ml, except in the presence of PBN and PBS. The minimal inhibitory concentration (mic) of DON in the presence of PBS was 2 micrograms/ml for K. fragilis GK 1005.