Defining the Role of Surgery for Primary Gastrointestinal Tract Melanoma

Objective The objective of the study was to determine the outcomes for primary gastrointestinal melanomas (PGIM). Material and methods The Surveillance, Epidemiology, and End Results database (1973–2004) was queried. Results Overall, 659 cases of PGIM were identified. The annual incidence of PGIM was approximately 0.47 cases per million in 2000. Overall median survival time was 17 months. Tumors were identified in the oral–nasopharynx (32.8%), anal canal (31.4%), rectum (22.2%), esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder (1.4%), and large bowel (0.9%). Univariate analysis demonstrated age, tumor location, stage, surgery, and lymph node status were significant predictors of improved survival. MST has not been reached for tumors located in the large bowel, while tumors located in the stomach demonstrated the shortest median survival (5 months). Improvement in MST was observed for those patients undergoing surgical resection. The presence of lymph node involvement conferred a poorer prognosis. Multivariate analysis of the cohort identified that location, advanced tumor stage, failure to undertake surgical resection, positive lymph node status, and age were all independent predictors of poorer outcome. Conclusion PGIM occurs most often in the oral–nasopharynx and anal canal. Surgical extirpation is the only identifiable treatment modality that significantly improves survival.     

Peptide-pulsed splenic dendritic cells prime long-lasting CD8(+) T cell memory in the absence of cross-priming by host APC.

Immunization with cells expressing endogenous antigens can stimulate long-lived CD8(+) T cell memory. In many cases, the response is also stimulated by host antigen-presenting cells (APC) that have processed antigen from internalized apoptotic cells or cell fragments. This study investigated whether immunization with peptide-pulsed dendritic cells (DC) could prime long-lasting, peptide-specific CD8(+) T cell immunity in the absence of cross-priming by host APC. C57BL / 6 female mice immunized with syngeneic male splenic DC pulsed with the H-2K(b)-restricted ovalbumin peptide OVA(257 - 264) made memory CD8(+) CD44(high) T cell responses to OVA(257 - 264) and the male antigen HY more than 1 year after immunization. Establishment and maintenance of peptide-specific CD8(+) T cell memory did not require antibody or B cells. Immunization of H-2(bxd) mice with OVA(257 - 264)-pulsed minor-incompatible H-2(b) or H-2(d) DC demonstrated that CD8(+) T cells were primed exclusively by the injected cells, and not by peptide transferred to host APC, even though there was very effective cross-priming for CD8(+) T cell responses to the minor antigens expressed by the DC. Thus peptide-pulsed DC can prime long-lasting CD8(+) memory responses without any requirement for cross-priming by other APC.     

A socioecological discourse of care or an economistic discourse: which fits better with transition?

Objective : To analyse a ‘socioecological’ health promotion discourse and its relationship to orthodox ‘economistic’ discourse in Australia. Method : In research on health promotion addressing equity and environmental sustainability, we identified a socioecological discourse, based on an ethic of care for people and ecosystems. Using Foucault's concept of discourse as a regime that produces and legitimises certain kinds of knowledge, and ecofeminist historical analysis, we analysed this discourse and its relationship to economism. Results : The socioecological discourse takes social and ecological wellbeing as primary values, while economism takes production and trade of goods and services, measured by money, as primary. Following British invasion, property‐owning white men in Australia had the right to control and profit from land, trade, and the work of women and subordinate peoples. A knowledge regime using money as a primary measure reflects this history. In contrast, a First Nations’ primary value expressed in the study was ‘look after the land and the children’. Conclusion and implications for public health : Public health often attempts to express value through economism, using monetary measures. However, socioecological discourse, expressed for example through direct measures of social and ecological wellbeing, appears more fit for purpose in promoting a fair and sustainable society.     

Radical Resection of Periampullary Tumors in the Elderly: Evaluation of Long-term Results

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65–87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 ± 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients ≥75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.     

Dose-response relationship for radiation-induced mutations at micro- and minisatellite loci in human somatic cells in culture

Purpose : The study was designed to determine the dose-response relationship for radiation induction of mutations at mini- and microsatellite loci in human somatic cells. Mutations induced by graded doses of gamma-irradiation were quantified by screening clones derived from single irradiated cells for micro- and minisatellite alterations following irradiation with 1, 2 or 3 Gy. Materials and methods : After irradiation, the moderately radioresistant glioma cell line UVW was seeded at low density into Petri dishes to allow formation of discrete colonies, 100 of which were examined at each dose. All the cells within a colony were presumed to have arisen from a single irradiated cell. Radiation-induced microsatellite alterations were determined at 16 different loci, by PCR amplification and visualization on polyacrylamide gels. Minisatellite alterations were identified at four different minisatellite loci by restriction enzyme digestion and Southern blotting. Results : A dose-response curve for mutation frequency was obtained by analysis of 100 clones, yielding a minisatellite mutation rate of 5.5 X 10 -3 mutations/locus/Gy/cell and a microsatellite mutation rate of 8.75 X 10 -4 mutations/locus/Gy/cell. At microsatellite loci, alterations were predominantly simple loss or gain of repeat units and loss of heterozygosity (LOH). The mutations in minisatellite loci resulted predominantly in LOH and variation in repeat number. The background instability at each locus was determined by analysis of non-irradiated clones. Only 2% and 1% of the micro- and minisatellite loci respectively showed altered bands. Conclusions : This is the first report of a dose-response relationship for radiation-induced micro- and minisatellite mutations in human somatic cells. Described is a sensitive method for analysis of low-dose radiation mutagenesis in somatic cells that may prove to be a useful tool for radiation protection and dosimetry.     

Measuring Intraoral Pressure: Adaptation of a Dental Appliance Allows Measurement During Function

This article introduces a new way of recording intraoral pressures from a range of locations within the oral cavity. To measure pressure flow dynamics during swallowing, we fitted eight miniature pressure transducers capable of measuring absolute pressures to a chrome-cobalt palatal appliance with a labial bow. Unlike previous devices, our design provides a rigid, custom-fitted platform for the simultaneous recording of pressures at eight locations within the oral cavity during function. We placed an anterior pair of gauges to measure lingual and labial contact against the left central incisor tooth, and two pairs of gauges to measure pressure contributions of the lateral tongue margin and cheeks on the canine and first molar teeth. Finally, lingual pressure on the midline of the palate was measured by two gauges, one at the position of the premolars and one on the posterior boundary of the hard palate. We then recorded intraoral pressures in five adult volunteers seated in an upright position and asked to swallow 10 ml of water. Labial pressures on the canine rose rapidly from a resting level of 10 kPa to 33 kPa, while pressure profiles from the labial aspects of the incisor and first molar teeth followed a negative pattern, peaking at -12 kPa for the incisor and -15 kPa for the molar sensor. Pressure profiles recorded from the palatal aspects of the first molar and the canine appeared to be similar, but the former fell to -13 kPa before rising to 9 kPa, and the canine pressure rapidly increased to 22 kPa before returning to its resting level of 4 kPa. The pressure profile of the palatal aspect of the central incisor was strikingly different; at the start of the swallow, pressure dropped precipitously to -20 kPa, before slowly rising to 10 kPa. It then followed the general pattern of the other two sensors, before peaking again at 10 kPa and then returning to a resting level of 4 kPa. We also showed that there were significant negative pressures in the mouth during function, and that pressure profiles varied markedly between individuals.     

Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians

Metabolic effects of cortisol may be critically modulated by glucocorticoid metabolism in tissues. Specifically, active cortisol is regenerated from inactive cortisone by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) in adipose and liver. We examined activity and mRNA levels of 11-HSD1 and tissue cortisol and cortisone levels in sc adipose tissue biopsies from 12 Caucasian (7 males and 5 females) and 19 Pima Indian (10 males and 9 females) nondiabetic subjects aged 28 +/- 7.6 yr (mean +/- SD; range, 18-45). Adipose 11-HSD1 activity and mRNA levels were highly correlated (r = 0.51, P = 0.003). Adipose 11-HSD1 activity was positively related to measures of total (body mass index, percentage body fat) and central (waist circumference) adiposity (P < 0.05 for all) and fasting glucose (r = 0.43, P = 0.02), insulin (r = 0.60, P = 0.0005), and insulin resistance by the homeostasis model (r = 0.70, P < 0.0001) but did not differ between sexes or ethnic groups. Intra-adipose cortisol was positively associated with fasting insulin (r = 0.37, P = 0.04) but was not significantly correlated with 11-HSD1 mRNA or activity or with other metabolic variables. In this cross-sectional study, higher adipose 11-HSD1 activity is associated with features of the metabolic syndrome. Our data support the hypothesis that increased regeneration of cortisol in adipose tissue influences metabolic sequelae of human obesity.