Declining incidence of keratinocyte carcinoma in organ transplant recipients.

BACKGROUND: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC). OBJECTIVES: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. METHODS: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population. RESULTS: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades. CONCLUSIONS: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.

Donation after circulatory death.

Donation after circulatory death (DCD) describes the retrieval of organs for the purposes of transplantation that follows death confirmed using circulatory criteria. The persisting shortfall in the availability of organs for transplantation has prompted many countries to re-introduce DCD schemes not only for kidney retrieval but increasingly for other organs with a lower tolerance for warm ischaemia such as the liver, pancreas, and lungs. DCD contrasts in many important respects to the current standard model for deceased donation, namely donation after brain death. The challenge in the practice of DCD includes how to identify patients as suitable potential DCD donors, how to support and maintain the trust of bereaved families, and how to manage the consequences of warm ischaemia in a fashion that is professionally, ethically, and legally acceptable. Many of the concerns about the practice of both controlled and uncontrolled DCD are being addressed by increasing professional consensus on the ethical and legal justification for many of the interventions necessary to facilitate DCD. In some countries, DCD after the withdrawal of active treatment accounts for a substantial proportion of deceased organ donors overall. Where this occurs, there is an increased acceptance that organ and tissue donation should be considered a routine part of end-of-life care in both intensive care unit and emergency department.

Public at risk: a survey of sunbed parlour operating practices in Northern Ireland.

BACKGROUND: The International Agency for Research on Cancer has identified artificial ultraviolet (UV) radiation as a class 1 carcinogen. The contribution of sunbeds to malignant melanoma has been estimated at 100 deaths per year in the U.K. The sunbed industry is growing and claims self-regulation. OBJECTIVES: To explore the standards of operation and client protection for sunbed users. METHODS: An observational study of tanning parlour practices was conducted by Environmental Health Practitioners who made unannounced visits to the majority of known commercial tanning parlours in Northern Ireland (population 1.77 million) during July/August 2007. Descriptive statistics were produced and comparisons between groups were made using chi(2) analysis. RESULTS: All 332 premises visited cooperated with the survey. The UV type in machines was unknown in 71.2% of premises while 15.6% reported using type 4, high-dose UV devices; 36.2% of premises did not regularly service sunbeds or were unsure. Unsupervised use of sunbeds was reported in 8.6% of parlours and 3.4% provided a home sunbed service. Eye protection was available in 97.6% of premises but 34.6% charged for the service and only 79.6% sanitized these between use. Of the responders 15.9% were members of the Sunbed Association. These were more likely to have maintenance records and operating manuals but were also more likely to provide a home sunbed service. CONCLUSIONS: This study highlights the need for improved standards of regulation of the sunbed industry to protect clients from excessive and dangerous levels of UV radiation in a population where the numbers of melanomas continue to rise.

Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.

Fas ligand (FasL/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).

Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?

Elevated expression of COX-2 and increased levels of PGE2 are found in numerous cancers and are associated with tumour development and progression. Although epidemiological, clinical and preclinical studies have shown that the inhibition of PGE2 synthesis through the use of either non-steroidal anti-inflammatory drugs (NSAIDs) or specific COX-2 inhibitors (COXibs) has the potential to prevent and treat malignant disease, toxicities due to inhibition of COX-2 have limited their use. Thus, there is an urgent need for the development of strategies whereby COX-2 activity may be reduced without inducing any side effects. The biological effects of PGE2 are mediated by signalling through four distinct E-type prostanoid (EP) receptors - EP1 , EP2 , EP3 and EP4 . In recent years, extensive effort has gone into elucidating the function of PGE2 and the EP receptors in health and disease, with the goal of creating selective inhibitors as a means of therapy. In this review, we focus on PGE2 , and in particular on the role of the individual EP receptors and their signalling pathways in neoplastic disease. As knowledge concerning the role of the EP receptors in cancer grows, so does the potential for exploiting the EP receptors as therapeutic targets for the treatment of cancer and metastatic disease.

Language in dreaming and regional EEG alpha power.

In an intensive single-subject design, electroencephalographic (EEG) alpha power and receptive and expressive language in dreaming were studied in 12 dreams during rapid eye movement (REM) sleep on 12 separate nights. Bilateral EEG was recorded continuously from 21 sites and digitized. We used the Fast Fourier transformation (FFT) for power spectral analysis to measure EEG power in the alpha frequency range (8-12 Hz) at each of the EEG sites. The subject was awakened after about 14 minutes into the second REM period, and dream reports were collected. We scored the dream reports for expressive and receptive language. The lower the alpha power on the left sides of those homologous pairs that roughly correspond to Broca's (C3) or Wernicke's area (P3), the more expressive or receptive language in dream reports. The largest difference between the correlation of the left and that of the right homologous pair of regions was found in the central (C3, C4) area for expressive language and in the parietal (P3, P4) area for receptive language. Our finding suggests lateralized and localized cortical activation in relation to language in dreaming.

Epistemological barriers to radical behaviorism.

The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers.

The importance of the principle of clinical significance-defining significant to whom and for what purpose: a response to tingey, lambert, burlingame, and hansen.

Tingey, Lambert, Burlingame, and Hansen (1996) argue that although there are benefits and utility of clinical significance, extensions to the concept proposed a decade ago (Jacobson, Follette, & Revenstorf, 1984a) are necessary. The criticisms of the original paper and subsequent extensions are problematic and fail to appreciate the underlying principle of clinical significance, namely defining for whom and for what purpose significant change would be identified. This paper responds to several of the criticisms outlined in Tingey et al. with regard to operationalizing a comparison group, the perceived limitations of using two distributions, and the problems with their approach of specifying a method for determining whether groups are distinct. We then propose that there is a principle that underlies the concept of clinical significance that should be appreciated. We conclude by describing under what conditions "functional" distributions may be supplemented by including information to allow comparisons of outcomes with the current best available treatment alternative, but offer a cautionary statement about the potential risks run by extensions such as Tingey et al.'s that can obscure the concept of clinical significance to the point that researchers are no longer discussing change in terms meaningful to the client.

MDMA toxicity presenting with severe hyperpyrexia: a case report.

Ingestion of even small amounts of MDMA ('ecstasy') by a small subset of the population may result in a potentially fatal clinical syndrome of severe hyperpyrexia, cardiovascular collapse, coagulopathy, rhabdomyolysis and multiple organ failure. Rapid and aggressive temperature control is of utmost importance in the management of these patients. We report a case of MDMA toxicity presenting with severe hyperpyrexia (43 degrees C) who survived after a rapid reduction in temperature to 36 degrees C within 60 minutes following active surface cooling, cooled (approximately 4 degrees C) intravenous solutions, urinary and gastric lavage solutions and replacement fluids for continuous veno-venous diafiltration.

The role of immune-enhancing diets in the management of perioperative patients.

OBJECTIVE: To review the effects of immunonutrients in the perioperative patient. DATA SOURCES: Articles and published peer-review abstracts of studies reported on immune enhancing diets in patients during the perioperative period. SUMMARY OF REVIEW: Enteral nutrition is the method of choice for substrate supplementation in patients with a normal gastrointestinal tract but who are otherWise unable to eat normally. It is also a safer, more practical and less expensive alternative to the parenteral route and is now being used successfully in previously contraindicated conditions including pancreatitis and major abdominal trauma. Advances in enteral nutrition include the development of immunonutrients which have been used to attenuate the adverse effects of starvation, illness and surgery on the architecture and function of the gastrointestinal tract, implicated in the development of multiple organ dysfunction syndrome. These agents stimulate immune function and are potentially an effective strategy in improving the outcome in the peri-operative period by reducing post-operative infections and length of hospital stay. CONCLUSIONS: Immunonutrition confers an additive benefit when compared with standard enteral and parenteral nutrient preparations in the management of perioperative malnourished patients. What is less clear is at what severity of illness this benefit begins, whether there is a significant reduction in mortality and at what point the cost benefit in the reduction in complications no longer occurs.

REM sleep eye movement counts correlate with visual imagery in dreaming: a pilot study.

Based on the findings of our previously published positron emission tomography study, we proposed that recorded eye movements during REM sleep are visually targeted saccades. In the present study, we examined the correlation between the number of eye movements in REM sleep (EM) and visual imagery in dreaming (V) and provided further support for our proposal. All the observations (N = 11) were made with one individual to eliminate interindividual variation and were made during the second REM sleep period to control for a time-of-night effect. V, with or without dream report length partialled out, was strongly associated with EM only in the 1-min interval immediately preceding awakening. The time course of the association suggests that the strong EM-V association reflects a phasic, localized activation of the eye-movement-control system in association with REM sleep eye movements.

Reactive oxygen species inducible by low-intensity laser irradiation alter DNA synthesis in the haemopoietic cell line U937.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the possible role of reactive oxygen species (ROS) in mediating previously recorded alterations in DNA synthesis, inducible by low-intensity laser irradiation (LILI), in the haemopoietic cell line U937. STUDY DESIGN/MATERIALS AND METHODS: The ability of LILI (660 nm, 12 mW, 5 kHz) to induce ROS from U937 cells was assessed spectrophotometrically at energy densities (E.D.) from 1.0 to 11.5 J/cm2. In order to assess whether laser-induced ROS could alter cellular proliferation DNA synthesis was measured post-irradiation, by the incorporation of tritiated thymidine (3H-TdR) into the cells in both the presence and absence of the antioxidant catalase (CAT). RESULTS: Detectable ROS were produced post-irradiation only from the differentiated form of the cell line. Analysis by Student's t-test for unrelated groups showed a significant difference, at E.D.s 2.9 and 8.6 J/cm2, in the extent of DNA synthesis occurring in cells irradiated in the presence of CAT or in its absence. CONCLUSION: These findings demonstrate that laser-inducible ROS can mediate laser's effects on this cell line.