ASO Visual Abstract: Margin Management and Adjuvant Therapy for Phyllodes Tumors—Practice Patterns of the American Society of Breast Surgeons Members

Annals of Surgical Oncology -     

Chronic pain in adults with an intellectual disability: prevalence, impact, and health service use based on caregiver report

This study examined chronic pain in adults with an intellectual disability (ID), in terms of its prevalence, impact on physical and psychological functioning, and treatments used. Questionnaires were distributed to 2378 primary caregivers (caregivers) of community-dwelling adults with an ID. The questionnaires were used to gather data on demographics, general health, nature of pain, impact of pain, treatment, and health-related decision making. Responses were received from 753 caregivers (31.6% response rate). Caregivers reported that 15.4% of this sample was experiencing chronic pain, for an average of 6.3 years. Significantly more females than males were reported to experience chronic pain, although age, communication ability, and level of ID were not found to be associated with the presence of pain. However, the presence of pain was associated with cerebral palsy, physical disability, and reports of challenging behaviour. A significant proportion of individuals with chronic pain also experienced limitations in several aspects of daily living, and more than 78% of caregivers reported that the service user had become upset or distressed by pain. More than 80% of service users were receiving some form of treatment for their pain, with most seeing a family physician and using analgesics as the primary form of pain treatment. Results indicate that chronic pain is a significant problem for persons with an ID, with a proportion of service users living with daily pain for many years and experiencing limitations in daily functioning, emotional well-being, and quality of life.     

Nurses' needs for education on cancer and end-of-life care

BACKGROUND: Changes in cancer and end-of-life care require frequent assessment of educational needs of nurses. METHODS: The Nurse Oncology Education Program surveyed a random sample of Texas registered nurses about their continuing education practices, level of knowledge, and educational needs. RESULTS: The 352 nurses responding to the survey primarily obtained continuing education from workshops, inservice education, and independent studies citing cost, location, content, and length of course as influencing factors. Their cancer educational needs included clinical trials, genetics, complementary therapies, and pain management. Nurses' perceptions of end-of-life needs were for physical needs, "what to expect" concerns, and transition to palliative care. CONCLUSION: These findings provide specific direction for future continuing education programs about cancer and end-of-life issues for nurses.     

Effects of the flavoprotein inhibitor, diphenyleneiodonium sulfate, on ex vivo organic nitrate tolerance in the rat

The flavoprotein inhibitor, diphenyleneiodonium (DPI), inhibits the action of glyceryl trinitrate (GTN) and the D-enantiomer of isoidide dinitrate (IIDN), but not the L-enantiomer (L-IIDN), in isolated rat aorta via inhibition of the bioactivation of these prodrugs. Paradoxically, a vascular NAD(P)H oxidase, which also is inhibited by DPI, has been proposed to generate superoxide that quenches nitric oxide (NO) produced during GTN biotransformation, and increased oxidase levels are proposed to contribute to the phenomenon of organic nitrate tolerance. We examined the effect of DPI on isolated rat aorta using an in vivo model of organic nitrate tolerance. The EC(50) values for GTN-, D-IIDN-, and L-IIDN-induced relaxation of aorta from GTN-tolerant rats were increased 4.5- to 7.5-fold. Treatment of blood vessels with DPI (0.3 microM) increased the EC(50) values for GTN and D-IIDN by the same magnitude in control and tolerant aortae, a result that would not be predicted if DPI and GTN tolerance affected common targets. The expression of NADPH-cytochrome P450 reductase (CPR) during in vivo tolerance was assessed by NADPH-dependent cytochrome c reductase activity of aortic microsomes, immunoblotting, and Northern analysis. By all three determinants, CPR expression was unchanged in aorta from GTN-tolerant rats. Superoxide dismutase-inhibitable NADPH-dependent cytochrome c reductase activity (a measure of superoxide generation) of tolerant rat aortic microsomes was not different from that of controls. Superoxide dismutase-inhibitable NADH-dependent cytochrome c reductase activity was detected only in microsomes from tolerant animals. DPI caused a modest increase in the sensitivity for relaxation by the NO donor DEA NONOate to an equal extent in tolerant and nontolerant tissues, whereas the superoxide scavenger, 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), had no effect on the sensitivity for relaxation by GTN. These results would not be expected if tolerance-induced increases in superoxide were a causative factor for the reduced relaxation response in tolerance. We conclude that neither reduced flavoprotein-dependent metabolic activation of organic nitrates, such as that mediated by CPR, nor increased superoxide due to increased NAD(P)H oxidase activity can account for the development of in vivo tolerance to GTN.     

Neural and Behavioral Correlates of Aberrant Salience in Individuals at Risk for Psychosis

The “aberrant salience” model proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to the attribution of significance to stimuli that would normally be considered irrelevant. This is thought to occur during the prodromal phase of psychotic disorders, but this prediction has not been tested previously. In the present study, we tested this model in 18 healthy volunteers and 18 unmedicated individuals at ultra-high risk of psychosis. Subjects performed the Salience Attribution Test, which provides behavioral measures of adaptive and aberrant motivational salience, during functional magnetic resonance imaging to assess neural responses to relevant and irrelevant stimulus features. On a separate occasion, the same subjects were also studied with [¹⁸F]fluorodopa positron emission tomography to measure dopamine synthesis capacity. Individuals at ultra-high risk of psychosis were more likely to attribute motivational salience to irrelevant stimulus features (t(26.7) = 2.8, P = .008), and this bias was related to the severity of their delusion-like symptoms (r = .62, P = .008). Ventral striatal responses to irrelevant stimulus features were also correlated with delusion-like symptoms in the ultra-high risk group (r = .59, P = .017). Striatal dopamine synthesis capacity correlated negatively with hippocampal responses to irrelevant stimulus features in ultra-high risk individuals, but this relationship was positive in controls. These data are consistent with the hypothesis that aberrant salience processing underlies psychotic symptoms and involves functional alterations in the striatum, hippocampus, and the subcortical dopamine system.Key words: psychosis, aberrant salience, salience attribution test, functional magnetic resonance imaging, positron emission tomography, dopamine     

Production of collagenase and inhibitor (TIMP) by normal, rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin

1. The amounts of latent and active collagenase and of collagenase inhibitor (TIMP) produced by two normal, three rheumatoid and two osteoarthritic synovial specimens in culture were compared. Normal synovia produced TIMP, but little latent enzyme. Rheumatoid synovia produced higher levels of total collagenase activity than normal, of which up to 50% in one sample was present in the medium in an active form, whereas no specific inhibitory activity due to TIMP was detectable. The amounts of collagenase and TIMP produced by osteoarthritic synovia were more variable and appeared to reflect the degree of inflammation in the tissue at the time of initiating the cultures. 2. Concentrations of TIMP were usually higher in the culture media of normal, rheumatoid and osteoarthritic synovia when hydrocortisone was present. Correspondingly, amounts of total collagenase were reduced. Production of prostaglandin E (PGE) were inhibited in a dose-dependent manner by hydrocortisone. 3. Indomethacin had no consistent effect on the production of TIMP by rheumatoid and osteoarthritic synovia, although it tended to depress production of collagenase. The production of TIMP by normal synovia was depressed by indomethacin. No PGE was detectable in the media when indomethacin was present. 4. These results are consistent with those from previous animal studies, and we conclude that the balance between production of collagenase and TIMP may be critical in determining the extent of the destructive processes in arthritis. The ability of hydrocortisone to suppress production of collagenase and to increase free TIMP concentration, as well as to inhibit synthesis of prostaglandin, may explain in part how the drug exerts its therapeutic effects in patients with rheumatoid arthritis.