The effects of eye movements on the content and characteristics of unpleasant autobiographical memories: an extended replication study.

Experimental studies show that vividness and emotionality of aversive memories decrease after recall with eye movements. We aimed at replicating this finding. Relatedly, consistent with Conway's view that memory retrieval is constructive, we examined changes in the content of the memories. If eye movements render a memory less aversive, it may be avoided less, stimulating recall and increasing the opportunity to infer (contextual) details. Two experiments (N = 97 and N = 250) examined whether eye movements affect the number of central and peripheral memory details and characteristics. Female undergraduate students were randomly allocated to either eye movements with recall (EM) or recall only (RO). Before and after the experimental task, participants rated the vividness and emotionality, provided a detailed description and evaluated other memory characteristics. We replicated earlier findings that vividness (both experiments) and emotionality (experiment 2) were reduced more after EM compared to RO. However, conditions did not statistically significantly differ with respect to content details and other memory characteristics. Overall, findings support the idea that eye movements decrease the experience of the memory as vivid and emotional. Results are inconclusive regarding the idea that eye movements alter the number of recalled central and peripheral memory details.

PET/CT prior to salvage surgery in recurrent head and neck squamous cell carcinoma.

PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival. RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

Otitis media with effusion after radiotherapy of the head and neck: a systematic review.

BACKGROUND: Otitis media (OM) and associated hearing problems may be side effects to radiotherapy of the head and neck region and affect patient quality of life. The condition is associated with the tumor location. OBJECTIVE: To perform a systematic review concerning the present knowledge of the risk of OM after radiotherapy of the head and neck. METHODS: A comprehensive search of PubMed and Embase was carried out between 1 October 2015 and 6 February 2017. The search strategy followed the PRISMA guideline for systematic reviews. RESULTS: Of 597 articles 11 fulfilled the inclusion criteria. Seven were retrospective and four prospective. There were no randomized controlled trials. Eight studies concerned nasopharyngeal cancer. One study concerned cancer of the parotid gland and two studies concerned other locations of head and neck cancer. Meta-analysis could not be done due to heterogeneity between the studies. The incidence of OM varied considerably (range 8-29%). CONCLUSIONS: The incidence of OM is high after radiotherapy of cancer of the upper head and neck area and the Eustachian tube (ET) irradiation dosage seems associated with development of OM, but the literature is poor. Research is needed to designate patients at risk of developing OM after radiotherapy. Preferably through analysis of dosage relationships between the ET and middle ear, and development of OM. Reporting of OM should be per ear and follow standardized protocols of middle ear assessment before and after radiotherapy. Furthermore, there is a need to find new ways to prevent and treat radiation-induced OME, preferably through randomized controlled trials.

Tumors of the sublingual gland: a national clinicopathologic study of 29 cases.

Tumors of the salivary glands are a heterogeneous group of diseases most often originating in the major salivary glands. Only a minor proportion of mainly malignant tumors arise in the sublingual gland. Due to the rarity of sublingual gland tumors (SGTs), little is known about the clinicopathologic characteristics, prognostic factors, and clinical course. We present a large national series of histopathologically revised SGTs from the past 35 years in Denmark with clinicopathologic correlation. Twenty nine cases were identified, of which 96.6 % were malignant and 16/28 (57.1 %) were adenoid cystic carcinomas (ACC). Patient demography was similar to salivary gland tumors in other locations. All fine needle aspiration cytologies (FNACs) interpreted as benign were from ACCs. Metastatic disease was found in 12.5 % of ACCs at diagnosis with one third of all ACC patients having metastases at the end of follow-up. Stage >II and T-stage >2 were significantly associated with shortened disease-specific survival (DSS) (p = 0.005 and <0.001, respectively), whereas perineural invasion and involved margins was not. No parameters were associated with disease-free survival. In conclusion, the majority of SGTs are malignant, most frequently ACC with a high rate of metastatic spread. The diagnostic value of FNAC in SGTs seems inferior to what is found for other major salivary glands. DSS is determined by stage and T-stage and not by histopathological parameters. International collaboration is warranted to confirm and elaborate these findings in larger materials.

Posttraumatic stress disorder following preeclampsia and PPROM: a prospective study with 15 months follow-up.

OBJECTIVE: A prospective longitudinal evaluation of the prevalence of and risk factors for posttraumatic stress disorder (PTSD) in women with preeclampsia (PE) or preterm premature rupture of membranes (PPROM) compared to uncomplicated pregnancies. METHODS: Participating women completed PTSD and depression questionnaires during pregnancy, 6 weeks, and 15 months postpartum. Data regarding psychiatric history and indices of obstetric care were collected from patient charts. RESULTS: We included 57 PE, 53 PPROM, and 65 healthy pregnant women, of whom 137 also participated in the 15-month follow-up (PE 70%, PPROM 48%, and controls 95%; P < .001). At 6 weeks postpartum, the prevalence of PTSD, but not depression, following childbirth was significantly higher in patients than in controls (14% vs 3%; P = .023). A history of depression, depressive symptoms during pregnancy, and infant death were significantly associated with symptoms of postpartum PTSD. The maternal condition seems to be of less decisive value, as there was no difference between the prevalence of PTSD after PE and PPROM (11% vs 17%; P = .324). At 15 months postpartum, 11% of women with PE had PTSD, some of which did not have PTSD 6 weeks postpartum. The low response rate in the PPROM group at 15 months postpartum does not allow for definite conclusions. CONCLUSION: Pregnancies complicated by PE or PPROM are associated with PTSD in a substantial number of women. Especially women with proven vulnerability for psychological problems are at risk of developing PTSD postpartum, as are women whose children died in the perinatal period.

Effects of retrieving childhood events on metamemory judgments depend on the questions you ask.

OBJECTIVE: The more people retrieve childhood memories, the less favourably they evaluate their own memory. It has been argued that this might play a role in self-reports of amnesia. However, a limitation of previous studies addressing this phenomenon is that participants' judgments about their memory were based on a single item. DESIGN: Students were randomly assigned to either of two conditions. In one condition, they were asked to retrieve nine negative childhood events, whereas in the other condition, participants were required to recall three events. METHOD: After recall, students completed measures on memory accessibility and 'repression'. RESULTS: Students who retrieved nine events rated their memories as less accessible, but also reported less repression than did students who retrieved three events. CONCLUSION: The direction of retrieval effects on metamemory judgments depends on the way in which questions are framed.

Correlates of autobiographical memory specificity: the role of depression, anxiety and childhood trauma.

The present study examined the role of childhood trauma, major depressive disorder (MDD), and anxiety disorder (AD) in overgeneral autobiographical memory. Ninety-three outpatients and 24 healthy controls completed a childhood trauma questionnaire and an autobiographical memory test (AMT). Results showed that MDD diagnosis rather than trauma history predicted AMT-performance. Memory specificity was not related to AD diagnosis, recovered MDD, or self-rated depression severity. The present findings cast doubts on theories that emphasize the role of childhood trauma in overgeneral autobiographical memory.

Linker length in podophyllotoxin-acridine conjugates determines potency in vivo and in vitro as well as specificity against MDR cell lines.

We have synthesized two podophyllotoxin-acridine conjugates-pACR6 and pACR8. In these compounds an 9-acridinyl moiety is beta linked to the C4 carbon of the four ring system in 4'-demethylepipodophyllotoxin (epiDPT) via eighter an N-6-aminohexanylamide linker (pACR6) or via an N-8-aminooctanylamide linker containing two more carbon atoms (pACR8). The acridine-linker moiety occupies the position where different glucoside moieties, dispensable for activity, are normally linked to epiDPT in the well known epipodophyllotoxins VP-16 and VM-26. As with VP-16 and VM-26, pACR6 and pACR8 show evidence of being topoisomerase II poisons as they stimulate topoisomerase II mediated DNA cleavage in vitro and induce DNA damage in vivo. This in vivo DNA damage, as well as pACR6/pACR8 mediated cytotoxicity, is antagonized by the catalytic topoisomerase II inhibitors ICRF-187 and aclarubicin, demonstrating that topoisomerase II is a functional biological target for these drugs. Despite their structural similarities, pACR6 was more potent than pACR8 in stimulating topoisomerase II mediated DNA cleavage in vitro as well as DNA damage in vivo and pACR6 was accordingly more cytotoxic towards various human and murine cell lines than pACR8. Further, marked cross-resistance to pACR6 was seen among a panel of multidrug-resistant (MDR) cell lines over-expressing the MDR1 (multidrug resistance protein 1) ABC drug transporter, while these cell lines remained sensitive towards pACR8. pACR8 was also capable of circumventing drug resistance among at-MDR (altered topoisomerase II MDR) cell lines not over-expressing drug transporters, while pACR6 was not. Two resistant cell lines, OC-NYH/pACR6 and OC-NYH/pACR8, were developed by exposure of small cell lung cancer (SCLC) OC-NYH cells to gradually increasing concentrations of pACR6 and pACR8, respectively. Here, OC-NYH/pACR6 cells were found to over-express MDR1 and, accordingly, displayed active transport of 3H-labeled vincristine, while OC-NYH/pACR8 cells did not, further suggesting that pACR6, but not pACR8, is a substrate for MDR1. Our results show that the spatial orientation of podophyllotoxin and acridine moieties in hybrid molecules determine target interaction as well as substrate specificity in active drug transport.

N-terminal and core-domain random mutations in human topoisomerase II alpha conferring bisdioxopiperazine resistance.

Random mutagenesis of human topoisomerase II alpha cDNA followed by functional expression in yeast cells lacking endogenous topoisomerase II activity in the presence of ICRF-187, identified five functional mutations conferring cellular bisdioxopiperazine resistance. The mutations L169F, G551S, P592L, D645N, and T996L confer > 37, 37, 18, 14, and 19 fold resistance towards ICRF-187 in a 24 h clonogenic assay, respectively. Purified recombinant L169F protein is highly resistant towards catalytic inhibition by ICRF-187 in vitro while G551S, D645N, and T996L proteins are not. This demonstrates that cellular bisdioxopiperazine resistance can result from at least two classes of mutations in topoisomerase II; one class renders the protein non-responsive to bisdioxopiperazine compounds, while an other class does not appear to affect the catalytic sensitivity towards these drugs. In addition, our results indicate that different protein domains are involved in mediating the effect of bisdioxopiperazine compounds.

Autobiographical memory and trauma in adolescents.

Several clinicians who work with traumatized children have noted that these children exhibit a poor autobiographical memory. The present study was a first attempt to subject this clinical impression to formal testing. Memory for autobiographical facts (i.e., semantic autobiographical memory) was assessed in 10 adolescents with an alleged history of trauma and 17 adolescents without such a background. Results suggest that traumatized adolescents, indeed, have more difficulty with semantic personal memory than non-traumatized adolescents. Implications of the present findings for future research on trauma and autobiographical memory in children and adolescents are discussed.

Differential recall of central and peripheral details of emotional slides is not a stable phenomenon.

A number of studies have reported that central information of an emotional scene is well retained, whereas peripheral details of such a scene are poorly recalled. Experiment 1 tested the hypothesis that attentional narrowing is responsible for this phenomenon. In addition, an attempt was made to increase the ecological validity of the experiment by giving extensive self-relevant instructions. Results showed that, although an emotional slide elicited eye-movements consistent with attentional narrowing, the corresponding recall patterns were absent. Experiments 2 and 3 explored some of the variables that might be responsible for the latter result. Experiment 2, relying on the original design of Christianson and E.F. Loftus (1991), found enhanced recall of central information of an emotional scene. Experiment 3 systematically varied stimulus exposure and interstimulus interval durations. However, the results of this experiment were rather complex and did not fully support the predicted differential recall patterns. Possible explanations for these findings are discussed. It is suggested that other methods (e.g. increasing levels of emotion rather than involvement) may be more suitable for testing the attentional narrowing hypothesis of emotional memory.

[Relapsing paraneoplastic cerebellar syndrome and limbic encephalitis in a patient with breast cancer]. / Rezidivierende paraneoplastische Zerebellopathie und limbische Enzephalitis. Fallbericht bei einer Patientin mit Mammakarzinom.

Paraneoplastic neurological syndromes are rare diseases that occur in relation to cancer. Supporting the hypothesis of an autoimmune mechanism, specific antineuronal antibodies have sometimes been detected. The current possibilities for treatment are limited. A female patient, aged 57, suffering from a breast cancer, developed a severe paraneoplastic cerebellar syndrome and limbic encephalitis within a few weeks. It is possible that the impressive partial remission that occurred during the ensuing 6 months was not due to therapy. Although the patient was still bound to a wheelchair, discharge from hospital was possible because she was still able to perform daily tasks by herself. A recurrence of the cerebellar symptoms with mild alterations of mental status occurred 2 months later but again showed a good remission.

Self-mutilating behaviour of psychiatric inpatients.

In the present study two broad hypotheses about the origins of self-mutilation in psychiatric patients were evaluated. The first hypothesis states that self-mutilation originates from child abuse and experiences of neglect and is connected to dissociation in later life. The second hypothesis views self-mutilation as the consequence of impulse control problems. To test these two hypotheses, data concerning traumatic childhood experiences and dissociative symptoms (hypothesis 1), as well as data concerning aggressiveness, obsessive-compulsiveness and sensation seeking (hypothesis 2) were collected in a sample of 54 psychiatric inpatients. Twenty-four out of 54 patients (44%) reported having engaged in self-mutilation. Mean age of onset of this behaviour was 23 years. Self-report measures of self-mutilators were more in line with the first than with the second hypothesis. That is, patients who engaged in self-mutilation reported more traumatic childhood experiences and dissociative symptoms than did control patients. The two groups did not differ in terms of aggressiveness, obsessive-compulsiveness, and sensation seeking. In line with earlier studies, the current results indicate that self-mutilating behaviour is linked to a history of abuse and neglect.

Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform.

Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity. This is in contrast to topoisomerase II poisons as etoposide and amsacrine (m-AMSA), which act by stabilizing enzyme-DNA-drug complexes at a stage in which the DNA gate strand is cleaved and the protein is covalently attached to DNA. Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change in expression of the beta isoform. Sequencing of the entire topoisomerase IIalpha cDNA from NYH/187 cells demonstrated a homozygous G-->A point mutation at nucleotide 485, leading to a R162Q conversion in the Walker A consensus ATP binding site (residues 161-165 in the alpha isoform), this being the first drug-selected mutation described at this site. Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines. Alkaline elution assay demonstrated a lack of inhibition of etoposide-induced DNA single-stranded breaks in NYH/187 cells, whereas this inhibition was readily apparent in NYH cells. Site-directed mutagenesis in human topoisomerase IIalpha introduced into a yeast Saccharomyces cerevisiae strain with a temperature-conditional yeast TOP2 mutant demonstrated that R162Q conferred resistance to the bisdioxopiperazines ICRF-187 and -193 but not to etoposide or m-AMSA. Both etoposide and m-AMSA induced more DNA cleavage with purified R162Q enzyme than with the wt. The R162Q enzyme has a 20-25% decreased catalytic capacity compared to the wt and was almost inactive at <0.25 mM ATP compared to the wt. Kinetoplast DNA decatenation by the R162Q enzyme at 1 mM ATP was not resistant to ICRF-187 compared to wt, whereas it was clearly less sensitive than wt to ICRF-187 at low ATP concentrations. This suggests that it is a shift in the equilibrium to an open-clamp state in the enzyme's catalytic cycle caused by a decreased ATP binding by the mutated enzyme that is responsible for bisdioxopiperazine resistance.

Psychopathological correlates of self-reported behavioural inhibition in normal children.

The present study examined the relationship between self-reported behavioural inhibition and psychopathological symptoms in a sample of 152 children aged 12-14 years. Children were provided with a definition of behavioural inhibition and then asked to classify themselves as low, middle or high on behavioural inhibition. Furthermore, children completed questionnaires of worry, depression and anxiety symptoms. Results showed that children who endorsed the high behavioural inhibition category had elevated levels of anxiety, worry and depression compared to children who endorsed the low or middle behavioural inhibition categories. Moreover, children high on behavioural inhibition more frequently reported anxiety disorders symptoms in the subclinical range. These findings fit well with those of previous studies on behavioural inhibition.

Assumptions of students and psychotherapists about memory.

The present study explored assumptions about memory in a Dutch sample consisting of 27 psychotherapists and 50 undergraduate students. Participants completed a questionnaire about memory and repression. Analysis indicated that a substantial proportion of the participants held assumptions about memory that are unrealistic in the sense that they do not meet a generally accepted standard among memory scientists. Although most respondents said that memory is not an accurate reflection of reality, metaphors provided by students and psychotherapists suggest that the reconstructive nature of memory was less well acknowledged.

Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor ICRF-159: a Tyr49Phe mutation confers high-level resistance to bisdioxopiperazines.

Anticancer drugs targeted to the nuclear enzyme DNA topoisomerase II are classified as poisons that lead to DNA breaks or catalytic inhibitors that appear to completely block enzyme activity. To examine the effects of the bisdioxopiperazine class of catalytic inhibitors to topoisomerase II, we investigated a Chinese hamster ovary (CHO) subline selected for resistance to ICRF-159 (CHO/159-1). Topoisomerase IIalpha content in CHO/159-1 cells was reduced by 40-50%, compared to wild-type CHO cells, whereas the beta isoform was increased by 10-20% in CHO/159-1 cells. However, the catalytic activity of topoisomerase II in nuclear extracts from CHO/159-1 cells was unchanged, as was its inhibition by the topoisomerase II poison etoposide (VP-16). No inhibition of topoisomerase II catalytic activity by ICRF-187 was seen in CHO/159-1 cells up to 500 microM, whereas inhibition was evident at 50 microM in wild-type CHO cells. VP-16-mediated DNA single-strand breaks and cytotoxicity were similar in the two sublines. ICRF-187 could abrogate these VP-16 effects in the wild-type line but had no effect in CHO/159-1 cells. Western blots of topoisomerase IIalpha after incubation of CHO cells with ICRF-187 demonstrated a marked band depletion, whereas this effect was completely lacking in CHO/159-1 cells, and an equal effect of VP-16 was observed in both lines. These data imply that the CHO/159-1 topoisomerase IIalpha lacks sensitivity to bisdioxopiperazines and that the mechanism of resistance in this cell line does not confer cross-resistance to topoisomerase II poisons, suggesting that mutations conferring resistance to bisdioxopiperazines can occur at sites distinct from those responsible for resistance to complex stabilizing agents. Accordingly, CHO/159-1 cDNA showed two heterozygous mutations in the proximal NH2-terminal part of topoisomerase IIalpha (Tyr49Phe and delta 309Gln-Gln-Ile-Ser-Phe313), which is in contrast to those induced by topoisomerase II poisons, which cluster further downstream. Site-directed mutagenesis and transformation of the homologous Tyr50Phe coding mutation in human topoisomerase IIalpha in a temperature-conditional yeast system demonstrated a high-level resistance to ICRF-193, compared to cells expressing wild-type cDNA, but none toward the poisons VP-16 or amsacrine, thus confirming that the Tyr50Phe mutation confers specific resistance to bisdioxopiperazines. Thus, these results indicate that the region of the protein involved in ATP-binding also plays a critical role in sensitivity to bisdioxopiperazines, a result consistent with the known requirement for the formation of an ATP-bound closed clamp for bisdioxopiperazine activity. These results may enable a more precise understanding of the interaction of topoisomerase II-directed drugs with their target enzyme.