A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245)

Chromogranin A (CgA), a major protein of chromaffin granules, has been described as a potential marker for neuroendocrine tumours. Because of an extensive proteolysis which leads to a large heterogeneity of circulating fragments, its presence in blood has been assessed in most cases either by competitive immunoassays or with polyclonal antibodies. In the present study, 24 monoclonal antibodies were raised against native or recombinant human CgA. Their mapping with proteolytic peptides showed that they defined eight distinct epitopic groups which spanned two-thirds of the C-terminal part of human CgA. All monoclonal antibodies were tested by pair and compared with a reference radioimmunoassay (RIA) involving CGS06, one of the monoclonal antibodies against the 198–245 sequence. It appears that CgA C-terminal end seems to be highly affected by proteolysis and the association of C-terminal and median-part monoclonal antibodies is inadequate for total CgA assessment. Our new immunoradiometric assay involves two monoclonal antibodies, whose contiguous epitopes lie within the median 145–245 sequence. This assay allows a sensitive detection of total human CgA and correlates well with RIA because dibasic cleavage sites present in the central domain do not seem to be affected by degradation. It has been proved to be efficient in measuring CgA levels in patients with neuroendocrine tumours. © 1999 Cancer Research Campaig

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.

Background: Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy.Case presentation: A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal.Conclusion: Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea. © 2013 Gennatas et al.; licensee BioMed Central Ltd

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

Pre-divorce problems in 3-year-olds: a prospective study in boys and girls

Objective: We examined to what extent internalizing and externalizing problems at age 3 preceded and predicted parental divorce, and if divorce and the time lapse since divorce were related to internalizing and externalizing problems at age 12. Methods: Parental ratings of internalizing and externalizing problems were collected with the Child Behavior Checklist (CBCL) in a large sample (N = 6,426) of 3-yearold children. All these children were followed through the age of 12 years, at which parents completed the CBCL again, while teachers completed the Teacher's Report Form. Children whose parents divorced between age 3 and age 12 were compared with children whose families remained intact. Results: Girls whose parents divorced between ages 3 and 12 already showed more externalizing problems at age 3 than girls whose parents stayed married. Higher levels of externalizing problems in girls at age 3 predicted later parental divorce. Parental reports indicated that 12-year-olds with divorced parents showed more internalizing and externalizing problems than children with married parents. Levels of teacher-reported problems were not different between children with married versus divorced parents. However, children whose parents divorced between ages 3 and 12 showed more teacher-rated internalizing problems at age 12 when the divorce was more recent than when the divorce was less recent. Parental ratings of both internalizing and externalizing problems at age 12 were not associated with the time lapse since divorce. Conclusion: Externalizing problems in girls precede and predict later parental divorce. Post-divorce problems in children vary by raters, and may depend on the time lapse since divorce

Comparisons of the factor structure and measurement invariance of the Spence children’s anxiety scale - parent version in children with autism spectrum disorder and typically developing anxious children

The Spence Children’s Anxiety Scale - Parent version (SCAS-P) is often used to assess anxiety in children with autism spectrum disorder (ASD), however, little is known about the validity of the tool in this population. The aim of this study was to determine whether the SCAS-P has the same factorial validity in a sample of young people with ASD (n=285), compared to a sample of typically developing young people with anxiety disorders (n=224). Poor model fit with all of the six hypothesised models precluded invariance testing. Exploratory factor analysis indicated that different anxiety phenomenology characterises the two samples. The findings suggest that cross-group comparisons between ASD and anxious samples based on the SCAS-P scores may not always be appropriat

Expression of p21WAF1 in Astler–Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy

In several, but not all, previous studies, positive p21WAF1 expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21WAF1 expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler–Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21WAF1 was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21WAF1 was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21WAF1 expression but not in the subgroup of 61 stage B2 patients with negative p21WAF1 expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21WAF1 expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21WAF1 in colorectal tumor cells identifies a subgroup of Astler–Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy

A study protocol to investigate the management of depression and challenging behaviors associated with dementia in aged care settings

Background:&nbsp;The high occurrence and under-treatment of clinical depression and behavioral and psychological symptoms of dementia (BPSD) within aged care settings is concerning, yet training programs aimed at improving the detection and management of these problems have generally been ineffective. This article presents a study protocol to evaluate a training intervention for facility managers/registered nurses working in aged care facilities that focuses on organisational processes and culture as well as knowledge, skills and self-efficacy. Methods. A Randomised Control Trial (RCT) will be implemented across 18 aged care facilities (divided into three conditions). Participants will be senior registered nurses and personal care attendants employed in the aged care facility. The first condition will receive the training program (Staff as Change Agents - Enhancing and Sustaining Mental Health in Aged Care), the second condition will receive the training program and clinical support, and the third condition will receive no intervention. Results: Pre-, post-, 6-month and 12-month follow-up measures of staff and residents will be used to demonstrate how upskilling clinical leaders using our transformational training approach, as well as the use of a structured screening, referral and monitoring protocol, can address the mental health needs of older people in residential care. Conclusions: The expected outcome of this study is the validation of an evidence-based training program to improve the management of depression and BPSD among older people in residential care settings by establishing routine practices related to mental health. This relatively brief but highly focussed training package will be readily rolled out to a larger number of residential care facilities at a relatively low cost.</div