Screening for Pancreatic Cancer in a High-Risk Cohort: An Eight-Year Experience

Background

Pancreatic adenocarcinoma is the fourth leading cause of cancer death.

Methods

A prospective cohort study was undertaken between 2003 and 2011 at a tertiary care centre in Toronto, Canada. Two hundred and sixty-two subjects were enrolled based on an elevated estimated lifetime risk for pancreatic cancer due to known genetic mutations and/or cancer family history. Subjects underwent annual magnetic resonance imaging, followed by additional investigations if abnormal findings were detected. Evidence of malignancy or suspicious macroscopic abnormalities prompted referral for surgical intervention.

Results

Average length of follow-up was 4.2?years, during which 84/262 (32%) subjects demonstrated pancreatic abnormalities. Three participants developed pancreatic adenocarcinoma (one 1.5-cm tumor was resected but recurred, while the other two subjects developed metastatic cancer), and a fourth participant developed a pancreatic neuroendocrine tumor that was resected. Fifteen subjects had radiologic evidence of branch-duct intraductal papillary mucinous neoplasms, of which two underwent surgical resection. Sixty-five subjects had simple pancreatic cysts that have remained stable.

Conclusion

Magnetic resonance imaging can detect small pancreatic tumors and cystic lesions, but further improvement in sensitivity is needed. An understanding of the natural history of pre-invasive lesions in members of high-risk families is necessary for developing a more effective screening program.     

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle

Background

Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome.

Extreme sensory modulation behaviors in toddlers with autism spectrum disorders.

This study examined the incidence of extreme sensory modulation behaviors in toddlers with autism spectrum disorders (ASD) and investigated the consistency of sensory information across measures. Parent report of sensory behaviors in 101 toddlers with ASD was compared with 100 toddlers who were typically developing matched on chronological age and 99 additional infants or toddlers matched on mental age. Measures included the Infant/Toddler Sensory Profile, Infant-Toddler Social Emotional Assessment, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule-Generic. Toddlers with ASD were most distinct from typically developing groups in their high frequency of underresponsiveness and avoiding behaviors and their low frequency of seeking. Within the toddlers with ASD, there were significant associations across sensory parent report measures, but parent report was not correlated with clinical observation. Findings point to the early onset of an extreme sensory profile in ASD. Occupational therapists need to assess multiple domains of sensory behaviors to accurately identify the needs of toddlers with ASD.     

Interactive Decision Support for Risk Management: a Qualitative Evaluation in Cancer Genetic Counselling Sessions

Genetic counselling for inherited susceptibility to cancer involves communication of a significant amount of information about possible consequences of different interventions. This study explores counsellors' attitudes to computer software designed to aid this process. Eight genetic counsellors used the software with actors playing patients. Clinicians' rating of expected patient satisfaction, content, accuracy, timeliness, format, overall value, ease of use, effect on the patient–provider relationship and effect on clinician's performance were evaluated via qualitative and quantitative analysis of interviews, training tasks and questionnaires. Most counsellors found the software effective. Concerns related to possible impact on consultation dynamics and content. Participants suggested countering these through appropriate new counselling skills and selective use of the computer. The REACT software could provide effective support for genetic risk management counselling.     

Analgesia induced by electroconvulsive shock: brain enkephalins may mediate tolerance but not the induction of analgesia

Electroconvulsive shock (ECS) administered to rats produces potent analgesia. This analgesic effect displays opiate characteristics with tolerance to ECS analgesia seen with repeated induction and cross tolerance observed following the chronic administration of analgesic dose of morphine. Furthermore, tolerance development after repeated ECS application could be blocked by daily pretreatment with the long acting opiate antagonist naltrexone (5 mg/kg). In contrast to these opiate characteristics of ECS analgesia, naltroxone administration (0.5, 5 and 10 mg/kg) failed to attenuate the acute analgesic effect of ECS.

Measurement of brain enkephalin levels revealed an increase in enkephalin contents after 10 daily ECS applications, an effect which was not affected by naltrexone pretreatment. Acute administration of ECS did not affect brain enkephalin levels either immediately or 24 h after ECS administration. Significant increases in brain enkephalin following chronic ECS were observed in the hypothalamus and striatum but not in the mesencephalon or hindbrain. A gradual return of enkephalin levels to baseline values was seen with days when ECS was no longer administered. Parallel behavioral studies showed that ECS analgesia also showed a gradual recovery from tolerance after discontinuation of chronic ECS.

Based on these and previous studies we propose that different systems may mediated the acute analgesic effect of ECS on the one hand, and the tolerance to such an effect observed after repeated administration on the other. We further suggest that the acute action of ECS may be mediated by substances with only partial opiate characteristics, while the long term effects observed may be due to the increase in brain enkephalin contents after chronic ECS application.     

Family-based intervention to enhance infant-parent relationships in the neonatal intensive care unit

OBJECTIVE: To examine how family-based interventions in the neonatal intensive care unit (NICU) may change parental knowledge and behaviors and decrease stress. METHODS: Eighty-four high-risk mother-infant dyads were randomly assigned to two intervention and one control groups. Group 1 (n = 28) participated in a demonstration of infant reflexes, attention, motor skills, and sleep-wake states. Group 2 (n = 31) viewed educational materials. Group 3 (n = 25), controls, participated in an informal discussion. Parent-infant interactions (Nursing Child Assessment Feeding Scale) were videotaped. Mothers completed measures of stress (Parenting Stress Index) and knowledge of infant cues (Knowledge of Preterm Infant Behavior Scale). RESULTS: Mothers in both intervention groups evidenced greater knowledge and more contingent and sensitive interactions with their infants than did the control group. Stress also differed across groups, and all mothers reported scores above norms. CONCLUSIONS: In a high-risk sample, short-term, family-based NICU interventions may enhance mothers' knowledge, sensitivity, contingency, and stress.     

The effect of the distance between post and residual gutta-percha on the clinical outcome of endodontic treatment

To determine whether the distance between the post and the residual gutta-percha influences the clinical outcome of endodontic treatment, 94 endodontically treated teeth following post and core restoration were evaluated radiographically. The teeth were divided into three groups: (I) no gap between the gutta-percha and the post; (II) a gap of >0 to 2 mm; (III) a gap of >2 mm. Treatment outcome was evaluated in follow-up radiographs, taken 1 yr after treatment and up to 5 yr posttreatment. In group I, 83.3% of the teeth were evaluated normal, 53.6% of group II, and only 29.4% of group III. A gap between the gutta-percha and the post was related to an increased rate of emerged disease in endodontically treated teeth restored with a post and core.     

'The multiple-sit-to-stand' field test for older adults: what does it measure?

BACKGROUND: The need to predict decline in functional status in a large number of older adults has brought researchers and clinicians to develop easy-to-administer field tests. One of them is the 'multiple-sit-to-stand' (MSTS), which claims to measure leg strength. OBJECTIVE: To assess the extent to which the MSTS is a leg strength, leg endurance or general endurance test. METHODS: 49 independently functioning women (72.2 +/- 6.4 years) were assessed on the MSTS, on a submaximal stress test, and on strength and endurance of knee extensors measured by isokinetics. The knee extensors were selected, more than in other muscle groups responsible for movement of the lower extremity, as the largest range of motion, and the largest torques required while performing activities of daily living (ADL) is found in this group. RESULTS: The correlation of the MSTS with the stress test was moderate and significant but very low and nonsignificant with the isokinetic measurements. CONCLUSIONS: The MTST is not able to predict strength of knee extensors, the leading group of leg muscles in ADL. If at all, it predicts general endurance rather than any measure--muscle strength or muscle endurance--of lower extremities. Longitudinal studies assessing the potential of the MSTS to predict deterioration in ADL in older adults are recommended, as well as studies assessing other factors related to both MSTS and ADL, such as muscle-nerve coordination affecting multiple joint activities.     

Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells

Studies in both animal models and humans have shown a subset of B cells behaving as immuno-regulatory cells, being a source of inhibitory cytokines such as IL-10 and TGF-β. Our aims were to establish the presence of human B regulatory (Breg) cells and to assess their ability to suppress proliferation of CD4(+) T cells and to mediate T regulatory (Treg) cells' properties. For this purpose, human Breg, CD4(+) T and Treg cells were purified using magnetic microbeads. CFSE-labeled CD4(+) T cells were stimulated and cultured alone or with Breg cells. Their proliferative response was determined 72 hours later based on the CFSE staining. In parallel, Treg cells were cultured alone or with Breg cells in different conditions for 24 hours, and then stained and analyzed for Foxp3 and CTLA-4 expression. We found that, the co-culture of Breg cells (defined as CD25(high) CD27(high) CD86(high) CD1d(high) IL-10(high) TGF-β(high)) with autologous stimulated CD4(+) T cells decreased significantly (in a dose-dependent way) the proliferative capacity of CD4(+) T cells. Furthermore, Foxp3 and CTLA-4 expression in Treg cells were enhanced by non-stimulated and further by ODN-CD40L stimulated Breg cells. The regulatory function of Breg cells on Treg cells was mainly dependent on a direct contact between Breg and Treg cells, but was also TGF-β but not IL-10 dependent. In conclusion, human Breg cells decrease the proliferation of CD4(+) T cells and also enhance the expression of Foxp3 and CTLA-4 in Treg cells by cell-to-cell contact.