The anthracycline doxorubicin has little activity against colorectal cancers. It is hypothesized that this is attributable to a multifactorial resistance mechanism in which the glutathione S-transferases (GST) may play a role. We studied the relationship between GST expression and doxorubicin resistance in four human colon adenocarcinoma cell lines (HT-29, LoVo, SW620, and Caco-2), with the goal of modulating GST activity to overcome resistance. Caco-2 cells were the most resistant to doxorubicin, showing an IC50 value approximately 80- to 90-fold higher than HT-29 or LoVo and 600-fold higher than SW620. Total GST catalytic activity was significantly higher in Caco-2 cells compared with the other lines. All four cell lines expressed GST-pi at the catalytic activity, protein, and mRNA levels; however, no significant differences were observed among the cell lines. GST-mu expression was not detectable at the protein and mRNA levels, and the four cell lines displayed very low catalytic activity toward a GST-mu-selective substrate. Caco-2 cells showed a unique, highly expressed GST-alpha-immunoreactive band that was not detected in the other lines; however, the glutathione peroxidase activity of Caco-2 cells was the lowest among the four cell lines. Neither ethacrynic acid nor glutathione analogues that function as GST class-selective inhibitors were able to potentiate the cytotoxic effects of doxorubicin in these colon cancer cell lines, as demonstrated in both microplate colorimetric and clonogenic assays. The multidrug resistance-associated protein and P-glycoprotein were either not detectable or expressed at such low levels that they are not likely to contribute to the differences in doxorubicin sensitivity observed among these cell lines.
Background: Use of drugs such as 3,4-methylenedioxy-N-methylamphetamine hydrochloride, γ‐hydroxybutyric acid, and cocaine at music and outdoor festivals is common. There are no published studies on drug toxicity at festival events celebrating the lesbian, gay, bisexual, and trans (LGBT) community nor the beneficial effects of physicians in reducing transfer to secondary healthcare facilities.Methods: Data were collected on presentations to "on-site" St John Ambulance facilities during an outdoor LGBT event where physicians were present (outdoor day event) and then at the subsequent outdoor after party where physicians were not present (outdoor after party).Results: Of 227 presentations, 204 were during the outdoor day event and 23 during the outdoor after party; Of those during the outdoor day event 27.9% related to drugs and/or ethanol, compared to 47.8% at outdoor after party; 10.6% of presentations were transferred to a secondary healthcare facility; rates were significantly higher during the outdoor after party (39.1%) than the outdoor day event (7.4%).Conclusion: There appears to be fewer transfers to secondary healthcare facilities during an LGBT outdoor day event where physicians were present. Further studies are needed to determine if other factors contribute to the rates of transfer to secondary healthcare facilities during similar events.
Background: The published ambulance referral criteria (ARC) for assessing individuals with acute recreational drug toxicity in the prehospital setting consist of nine domains. The ARC recommend that an ambulance is called to transfer those with a score ≥1 to hospital.Methods: Individuals presenting to a physician-led medical facility with acute drug and/or ethanol toxicity during an outdoor festival were assessed to determine whether the ARC recommended hospital transfer. Final disposition following management in the facility was compared with ARC assessment to determine if physician-led management reduced the need for hospital transfer.Results: A total of 28 patients were presented during the study period; 16 (57.1%) had an initial ARC ≥1 (range 1–5). Twelve (75%) of these were discharged after management in the facility. Four were transferred to hospital: two for severe acute recreational drug toxicity and two due to closure of the facility at the end of the event.Conclusions: Physicians present at this festival event significantly reduced the need for hospital transfer of individuals with acute recreational drug toxicity. Organisers of similar festivals should consider whether it would be appropriate to arrange for appropriate physician-level support to reduce the use of local health-care resources during the event for individuals with acute recreational drug/ethanol toxicity.
FFP3 (filtering face piece 3) respirators are recommended for health care workers caring for patients with probable or confirmed flu-like illness where aerosol generating procedures are being undertaken.1 2
We recently admitted our first patient with suspected swine flu to intensive care on a weekend night shift. …
The UK Health Protection Agency advises that health care workers caring for patients with probable or confirmed flu-like illnesses, where aerosol generating procedures are being undertaken, to use filtering face piece-3 (FFP3) respirators.
Background: Most people would rather die at home than in hospital but only 18% of patients do so. Palliative care focuses on the physical, spiritual and psychosocial wellbeing of patients and their families, which should include facilitating transfers home when possible. Patients can have more autonomy over their care and be surrounded by loved ones which can have a significant impact on their quality of life. In this article we describe two cases of home repatriation for palliation. Case 1 describes the transfer of a patient with difficulties and gaps in planning, but with a safe transfer ultimately. Case 2 recounts a more comprehensive planning process emphasising collaboration between teams. Benefits and difficulties of palliative critical care transfers: Facilitating home-based care aligns with patients’ desires for familiar surroundings and emotional support. A secondary benefit is that releasing a bed space allows another patient to receive critical care treatment. Challenges of palliative critical care transfers include needing a highly trained team and thorough planning. Early discussion with the family and community palliative care teams makes this a more feasible option for patients. Conclusion: A multidisciplinary team of hospital and community healthcare professionals working with the patient and their family can facilitate the transfer from intensive care to allow them to die at a place of their choosing. We should aim to fulfil these wishes at the end of life as it can greatly improve the patient’s and their family’s physical and emotional wellbeing during this difficult time.
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