Benefits of Intranasal Administration of Diamorphine and Midazolam in the Management of Patients Receiving Palliative Care in the Community: A Case Series.

Opioids and benzodiazepines are cornerstones of the pharmacological management of pain and agitation in palliative medicine. Oral drug delivery is the most popular route of administration, with the subcutaneous route typically utilized where oral medications are not tolerated or are ineffective. Intranasal drug delivery offers an important alternative administration route, with benefits including ease of administration, tolerability and avoidance of needle use, and is particularly useful in the community, where medications may be administered by lay carers or by patients themselves. Intranasal diamorphine and intranasal midazolam both have demonstrated efficacy and safety in adult and pediatric cohorts, however there is limited research into their use in managing pain and agitation in palliative care. We describe the management of three patients under the community palliative care team who received intranasal diamorphine, two of whom also received intranasal midazolam, to manage breakthrough symptoms of pain and agitation at home. In each case, the patient or their relative was taught how to prepare and administer the relevant intranasal medication. This case series demonstrates that for selected patients, diamorphine and midazolam administered intranasally by patients or lay carers at home is efficacious, acceptable and generally well tolerated.

Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression.

BACKGROUND: The purpose of this study was to investigate the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in the treatment of prostate cancer by monitoring blood cytokine levels. PATIENTS AND METHODS: Participants were stage I-II prostate cancer patients receiving xRT alone (n=18) or TAS+xRT (n=19) under the procedures outlined in RTOG protocols #94-08 and #94-13. Peripheral blood samples were collected immediately prior to TAS (xRT+TAS group), immediately prior to xRT, 24 hours after initiation of xRT, and weekly during xRT. Samples were monitored for the immunoregulatory cytokines interleukin (IL)-1beta, IL-6 and transforming growth factor (TGF)beta using ELISA procedures. RESULTS: Following initiation of xRT, both patient groups demonstrated an immediate elevation of the proinflammatory cytokines IL-1beta and IL-6 in their plasma. These cytokine levels appeared to peak after 1-2 weeks of xRT before returning toward pre xRT levels. In contrast, the profibrotic cytokine TGFbeta appeared to decrease immediately following initiation of xRT, but, subsequently, underwent two distinct waves of elevation, occurring at 1-2 weeks and 5-6 weeks into the xRT. Surprisingly, while the temporal pattern of plasma cytokine response was similar in both treatment groups, the magnitude of cytokine expression was noticeably different, appearing to be significantly affected by the addition of TAS. Indeed, administration of neoadjuvant TAS appeared to bring about a marked elevation of IL-1beta and IL-6 and a significant reduction in TGFbeta when compared to patients receiving xRT alone. CONCLUSION: The precise mechanisms underlying this TAS-related increase of the proinflammatory cytokines IL-1beta and IL-6 and decrease of the profibrotic cytokine TGFbeta remain unclear. However, previous reports have documented that androgens tend to be immunosuppressive in nature. It is conceivable, therefore, that administration of TAS shifts the ratio of proinflammatory and profibrotic cytokines toward a more immunostimulatory state.

Radioprotection of murine gastrointestinal epithelium by interleukin-1alpha involves down-regulation of the apoptotic response.

BACKGROUND: Interleukin-1alpha (IL-1) is known to radioprotect the gastrointestinal tract, but the mechanism by which this protection occurs remains unclear. These studies were undertaken to investigate whether the radioprotective potential of IL-1 may be linked to an ability to reduce apoptosis within the gastrointestinal crypts. MATERIALS AND METHODS: IL-1 was administered to C57Bl/6 mice 24 hours prior to receiving 8 Gy abdominal X-irradiation (xRT). At designated times, experimental mice were sacrificed, jejunal tissue removed, and paraffin-embedded sections analyzed for apoptosis indices (AI) and immunohistochemical determination of active caspase-3, -8 and -9. RESULTS: AI data demonstrated that 8 Gy irradiation resulted in a marked jejunal apoptotic response, but IL-1 pretreatment significantly attenuated this response. Concomitant with this attenuation, reduced levels of caspase-3 and 9, but not caspase-8, activation were observed, particularly within goblet cells. CONCLUSION: The results outlined herein suggest that radioprotection by IL-1 is mediated, at least in part, through a reduction in the apoptotic response which appears to involve down-regulation of the intrinsic apoptotic pathway.