Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival.

BACKGROUND: Collagen and calcium-binding EGF domains 1 (CCBE1) is an uncharacterised gene that has down-regulated expression in breast cancer. As CCBE1 maps to 18q21.32, a region frequently exhibiting loss of heterozygosity in ovarian cancer, the aim of this study was to determine the expression and function of CCBE1 in ovarian cancer. METHODS: Expression and methylation patterns of CCBE1 were determined in ovarian cancer cell lines and primary tumours. CCBE1 contains collagen repeats and an aspartic acid/asparagine hydroxylation/EGF-like domain, suggesting a function in extracellular matrix remodelling and migration, which was determined using small-interfering RNA (siRNA)-mediated knockdown and over-expression of CCBE1 in cell lines. RESULTS: CCBE1 is expressed in normal ovary, but is reduced in ovarian cancer cell lines and primary carcinomas. Pharmacological demethylation/deacetylation in ovarian cancer cell lines re-induced CCBE1 expression, indicating that epigenetic mechanisms contribute to its silencing in cancer. CCBE1 promoter hypermethylation was detected in 6/11 (55%) ovarian cancer cell lines and 38/81 (41%) ovarian carcinomas. siRNA-mediated knockdown of CCBE1 in ovarian cancer cell lines enhanced their migration; conversely, re-expression of CCBE1 reduced migration and survival. Hence, loss of CCBE1 expression may promote ovarian carcinogenesis by enhancing migration and cell survival. CONCLUSIONS: These data suggest that CCBE1 is a new candidate tumour suppressor in ovarian cancer.

The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro.

Despite a high initial response rate to first-line platinum/paclitaxel chemotherapy, most women with epithelial ovarian cancer relapse with recurrent disease that becomes refractory to further cytotoxic treatment. We have previously shown that the E3 ubiquitin ligase, EDD, a regulator of DNA damage responses, is amplified and overexpressed in serous ovarian carcinoma. Given that DNA damage pathways are linked to platinum resistance, the aim of this study was to determine if EDD expression was associated with disease recurrence and platinum sensitivity in serous ovarian cancer. High nuclear EDD expression, as determined by immunohistochemistry in a cohort of 151 women with serous ovarian carcinoma, was associated with an approximately two-fold increased risk of disease recurrence and death in patients who initially responded to first-line chemotherapy, independently of disease stage and suboptimal debulking. Although EDD expression was not directly correlated with relative cisplatin sensitivity of ovarian cancer cell lines, sensitivity to cisplatin was partially restored in platinum-resistant A2780-cp70 ovarian cancer cells following siRNA-mediated knockdown of EDD expression. These results identify EDD as a new independent prognostic marker for outcome in serous ovarian cancer, and suggest that pathways involving EDD, including DNA damage responses, may represent new therapeutic targets for chemoresistant ovarian cancer.

Caregivers' use of, and attitudes towards, written asthma action plans in North-West Melbourne.

We investigated the attitudes of caregivers towards written asthma action plans (WAAPs). A small number of caregivers participating in a larger randomised controlled trial (RCT) participated in qualitative interviews. 'Ownership and use of WAAPs' and 'Schools and WAAPs' were the main themes to emerge. The new school year is an opportunity to review and update WAAPs.

Factors associated with ownership and use of written asthma action plans in North-West Melbourne.

PURPOSE: Written asthma action plans (WAAPs) have become a core component of asthma management in Australia. We investigated ownership, utilisation and factors associated with ownership of asthma action plans by caregivers. METHODS: 443/776 (57%) caregivers of children aged 2-14 years with asthma were identified from 32 GP clinics as part of a randomised controlled trial (RCT), and completed self-administered questionnaires. RESULTS: Only 29% of participants owned a WAAP, while 13% possessed verbal instructions, and 56% had no plan. An asthma action plan for children, which was developed by a general practitioner (GP) was more likely to comprise verbal instructions (p = 0.001), while action plans developed by paediatricians were more likely to be written (p < 0.001). Just over one half of caregivers (59%) reported discussing their child's action plan the last time they visited their doctor for asthma. Factors associated with WAAP ownership included nights waking (p = 0.013), self reported severity (p = 0.001), and days lost from school (p = 0.037). Children who had seen a GP in the last 3 months for asthma, or who had been to the Emergency Department (ED) or hospital were more likely to possess a WAAP (p < 0.001). Caregivers who were less satisfied with their child's asthma control were more likely to own a WAAP (p = 0.037). Caregivers with any action plan found it useful and 82% reported using their action plan for management of an acute attack. However, caregivers with a WAAP were more likely to adhere to the plan for an acute attack compared to caregivers with verbal instructions (OR = 4.5, p < 0.05). Caregivers with a WAAP were more knowledgeable about asthma (p = 0.002), better able to recognise the difference between preventer and reliever medications (p = 0.01), and better able to recognise an asthma attack (p = 0.006). CONCLUSIONS: Ownership of WAAPs in this group was still too low. Importantly, caregivers with written instructions were more knowledgeable about asthma and more likely to report following the action plan during an asthma attack.

Reliability of home observation for victims of mild closed-head injury.

Victims of mild closed-head injury who do not require hospitalization frequently are observed at home. The efficacy of home observation for such cases and the extent to which after-care management plans are executed in this setting, however, are unknown. We studied 47 consecutive victims of mild closed-head injury discharged from the emergency department for home observation under the care of a responsible individual with a set of written after-care instructions for management. The instructions were reinforced verbally by ED staff before discharge. Followup was performed within 24 hours by telephone, and a questionnaire was sent. Three patterns emerged. Nine patients (19%), Group A, denied having received written after-care instructions despite documentation to the contrary in the medical record. Seventeen patients (36%), Group B, received the instructions alone and were told to convey them to the individual responsible for performing the home management. In the remaining 21 cases (45%), Group C, the instructions were given directly to the individual responsible for providing the home management. Although the after-care management plan specified observing or awakening the patient every two hours, this was done in only two patients (22%) in Group A and in four patients (24%) in Group B (NS). Fourteen patients (67%) in Group C, by comparison, were observed correctly as specified by the after-care instructions (P less than .02). No one in Group A could recall more than two of the eight items in the after-care management plan, and only three individuals (18%) in Group B (NS), could recall more than two items.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration of intravenous alcohol for prevention of withdrawal in alcoholic burn patients.

We studied the effects of intravenous alcohol infusions on 22 alcoholic burn patients admitted to our burn center. The relationship of infusion rates to blood alcohol levels was studied over a 3 to 8 day period of administration, and daily blood test results in liver function were followed. No patients had signs of withdrawal either during the infusion period or after the discontinuation of alcohol therapy. Our data suggest that the intravenous infusion of ethanol at rates of 0.02 to 0.06 g/kg per hour provides low but measurable blood alcohol levels (2 to 8 mg/100 ml), avoids sedation and toxic effects, and prevents the appearance of withdrawal symptoms in severely alcoholic burn patients.