Dose-intense weekly cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFP) in advanced breast cancer.

Weekly chemotherapy with cyclophosphamide 80 mg m-2 day-1 p.o. continuously, methotrexate 35 mg m-2 week-1 i.v., 5-fluorouracil 500 mg m-2 week-1 i.v., vincristine 1.4 mg m-2 i.v. every two weeks and prednisolone 20 mg m-2 day-1 p.o. continuously (CMFVP) was prospectively studied in 45 previously untreated outpatients with advanced breast cancer to determine the feasibility of delivering a dose-intense regimen. Of 40 evaluable patients, complete response (CR) occurred in one patient, partial response (PR) in 20 (CR + PR 53%), stable in eight, progression in 11 and five were unevaluable for response. The median relapse-free survival for responders was 25 weeks and median survival for all patients was 31 weeks. The mean dose intensity relative to the Cooper regimen fell from 1.02 to 0.6 within the first 4 weeks of treatment and the median dose intensity achieved for all patients on study was only 0.52. Eighty-seven per cent of patients had treatment delays with a mean of 3.9 delays per patient and 71% had dose reductions. Neutropenia was the major toxicity with WHO grade 3 or 4 neutropenia (less than 1.0 x 10(9) l-1) in 62% of patients and three septic deaths while neutropenic. Dose-intense weekly CMFVP in this schedule cannot be delivered to previously untreated outpatients with advanced breast cancer

Transdermal fentanyl for the treatment of pain caused by osteoarthritis of the knee or hip: an open, multicentre study

BACKGROUND: This study was designed to evaluate the utility of transdermal fentanyl (TDF, Durogesic(®)) for the treatment of pain due to osteoarthritis (OA) of the knee or hip, which was not adequately controlled by non-opioid analgesics or weak opioids. The second part of the trial, investigating TDF in patients with rheumatoid arthritis (RA) is reported separately. METHODS: Current analgesia was optimised during a 1-week run-in. Patients then received 28 days treatment with TDF starting at 25 μg/hr, with the option to increase the dose until adequate pain control was achieved. Metoclopramide was taken during the first week and then as needed. RESULTS: Of the 159 patients recruited, 75 with OA knee and 44 with OA hip completed the treatment phase, 30 knee and 18 hip patients entered the one-week taper-off phase. The most frequently used maximum dose of TDF was 25 μg/hr. The number of patients with adequate pain control increased during the run-in period from 4% to 27%, and further increased during TDF treatment to 88% on day 28. From baseline to endpoint, there were significant reductions in pain (p < 0.001) and improvements in functioning (p < 0.001) and physical (p < 0.001) and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of patients would recommend it for OA-related pain. Nausea and vomiting were the most common adverse events (reported by 32% and 26% of patients respectively), despite prophylaxis with metoclopramide, which showed limited efficacy in this setting. CONCLUSION: TDF significantly increased pain control, and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting; more effective anti-emetic treatment may enable more people to benefit from strong opioids such as TDF. This study suggests that four weeks is a reasonable period to test the benefit of adding TDF to improve pain control in OA patients and that discontinuing therapy in cases of limited benefit creates no major obstacles

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-α and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation between absolute number of peripheral blood lymphocytes (P=0.028), CD3 (P=0.017), CD57 (P=0.041) and objective response was demonstrated. There was no correlation between any peripheral blood leukocyte subsets and survival. Cytotoxicity of peripheral blood mononuclear cells was not correlated to objective response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0.015), CD57 (P=0.009) and objective response was demonstrated. A significant positive correlation between intratumoral baseline CD4 (P=0.047), baseline CD57 (P=0.035), CD3 at one month (P=0.049) and survival was demonstrated. These data provide novel in vivo evidence of the possible contribution of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients

Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

Rat-specific IgG and IgG 4

OBJECTIVES: The relationship between exposure to rodent allergens and laboratory animal allergy is complex; at highest allergen exposures there is an attenuation of sensitisation and symptoms which are associated with increased levels of rat-specific immunoglobulin (Ig)G and IgG4 antibodies. We set out to examine whether the increased levels of rat-specific IgG and IgG4 antibodies that we have previously observed at high allergen exposure in our cohort of laboratory animal workers play a functional role through blockage of the binding of IgE-allergen complex binding to CD23 receptors on B cells.METHODS: Cross-sectional survey of laboratory animal workers (n=776) in six UK pharmaceutical companies were surveyed. IgE-allergen complex binding to B cells was measured in 703 (97.9%) eligible employees; their exposure was categorised by either job group or number of rats handled daily.RESULTS: We observed a significant decrease in IgE-allergen complex binding to B cells with increasing quartiles of both rat-specific IgG and IgG4 antibodies (p&lt;0.001). IgE-allergen complex binding to B cells was lower in workers with high allergen exposure, and significantly so (p=0.033) in the subgroup with highest exposures but no work-related chest symptoms.CONCLUSIONS: These findings demonstrate a functional role for rat-specific IgG/G4 antibodies in laboratory animal workers, similar to that observed in patients treated with high dose immunotherapy who become clinically tolerant, suggesting a potential explanation for the attenuation of risk at highest allergen exposures.</p

Commercial sexual practices before and after legalization in Australia

The nature of sex work changes over time for many reasons. In recent decades around the world, there has been movement toward legalization and control of sex economies. Studies of the possible impact of legalization mainly have focused on sexually transmitted infections and violence, with little attention to change in the diversity of sexual services provided. This study examined the practices of sex workers before and after legalization of prostitution. Cross-sectional surveys of comparable samples of female sex workers were conducted in 1991 (N = 200, aged 16–46 years) and 2003 (N = 247, aged 18–57 years) in Queensland, Australia, spanning a period of major change in regulation of the local industry. In 2003, male clients at brothels and private sole operators (N = 161; aged 19–72 years) were also interviewed. Over time, there was a clear increase in the provision of “exotic” sexual services, including bondage and discipline, submission, fantasy, use of sex toys, golden showers, fisting, and lesbian double acts, while “traditional” services mostly remained at similar levels (with substantial decrease in oral sex without a condom). Based on comparisons of self-reports of clients and workers, the demand for anal intercourse, anal play, and urination during sex apparently exceeded supply, especially in licensed brothels. Within this population, legalization of sex work coincided with a substantial increase in diversity of services, but it appears that in the regulated working environments, clients who prefer high risk practices might not dictate what is available to them