Spontaneous dissociation during functional MRI experiments

It is assumed that the procedures of functional magnetic resonance imaging (fMRI) are able to provoke significant dissociative responses. Trait and state dissociation of 32 healthy subjects undergoing fMRI have been recorded. At least one-third of the subjects showed dissociative responses of very large effect size (d=4.10). The contributing causal factors for that dissociative response could not yet identified clearly. Considering the impact of dissociation on mental functions, we recommend controlling subjects undergoing fMRI studies for dissociative responses. Further studies on the actual phenomenological experience of subjects undergoing fMRI procedures are warranted.     

Cytochrome P450 reductase dependent inhibition of cytochrome P450 2B1 activity: Implications for gene directed enzyme prodrug therapy

Cytochrome P450 (P450) enzymes are often used in suicide gene cancer therapy strategies to convert an inactive prodrug into its therapeutic active metabolites. However, P450 activity is dependent on electrons supplied by cytochrome P450 reductase (CPR). Since endogenous CPR activity may not be sufficient for optimal P450 activity, the overexpression of additional CPR has been considered to be a valuable approach in gene directed enzyme prodrug therapy (GDEPT). We have analysed a set of cell lines for the effects of CPR on cytochrome P450 isoform 2B1 (CYP2B1) activity. CPR transfected human embryonic kidney 293 (HEK293) cells showed both strong CPR expression in Western blot analysis and 30-fold higher activity in cytochrome c assays as compared to parental HEK293 cells. In contrast, resorufin and 4-hydroxy-ifosfamide assays revealed that CYP2B1 activity was up to 10-fold reduced in CPR/CYP2B1 cotransfected HEK293 cells as compared to cells transfected with the CYP2B1 expression plasmid alone. Determination of ifosfamide-mediated effects on cell viability allowed independent confirmation of the reduction in CYP2B1 activity upon CPR coexpression. Inhibition of CYP2B1 activity by CPR was also observed in CYP2B1/CPR transfected or infected pancreatic tumour cell lines Panc-1 and Pan02, the human breast tumour cell line T47D and the murine embryo fibroblast cell line NIH3T3. A CPR mediated increase in CYP2B1 activity was only observed in the human breast tumour cell line Hs578T. Thus, our data reveal an effect of CPR on CYP2B1 activity dependent on the cell type used and therefore demand a careful evaluation of the therapeutic benefit of combining cytochrome P450 and CPR in respective in vivo models in each individual target tissue to be treated.     

IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom

IntroductionSeizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom.Materials and methodsThis retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive.ResultsSeventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p = 0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p = 0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p = 0.0019).ConclusionIn WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.     

Involuntary hospitalization,stigma stress and suicidality: a longitudinal study

People with severe mental illness and a history of involuntary hospitalization may experience stigma-related stress and suffer negative consequences as a result. However, the long-term impact of stigma stress on suicidality in this population remains unknown. This longitudinal study therefore examined stigma stress, self-stigma, self-esteem and suicidal ideation among 186 individuals with mental illness and recent involuntary hospitalization. After adjusting for age, gender, diagnoses and symptoms, more stigma stress at baseline predicted suicidal ideation after 2 years, mediated by increased self-stigma and decreased self-esteem after 1 year. Anti-stigma interventions that reduce stigma stress and self-stigma could therefore support suicide prevention.     

Topiramate in add-on therapy: results from an open-label, observational study.

An open-label, observational prospective study assessed the effectiveness of topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above with a diagnosis of epilepsy and at least one epileptic seizure during the 12-week retrospective baseline were to be documented. After baseline evaluation, topiramate was added. Ninety-five percent of patients had at least one baseline AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started in monotherapy. Topiramate dose titration and target dose was determined by clinical response and side effect profile. Patients were intended to be followed for a total of 1 year which included 6 visits during which seizure frequency, adverse events, weight as well as clinical global impression were recorded. During the 12 weeks retrospective baseline, a median of 2.8 seizures per month were recorded which reduced significantly to 0.7 per month during the complete treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50% seizure reduction. Ten percent of patients were seizure free during the study. The most commonly reported adverse events were difficulties with memory (4.2%), somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated, and only 5% of patients discontinued treatment due to an adverse event. Retention in the study was higher than previously reported during randomized, dose controlled studies and is likely due to individualized doses as well as slower titration used.     

Platysma transverse myocutaneous flap: a 21 case series of an overlooked reconstructive method for facial skin defects

IntroductionSince the first report of a platysma transverse myocutaneous flap in 1977, few articles about this flap design have been added to the literature.ObjectiveOur aim is to describe our department’s experience with platysma transverse myocutaneous flap.MethodsA retrospective review of all patients undergoing platysma transverse myocutaneous flap reconstruction between 2011 and 2019.ResultsThere were 16 men and 5 women in this series. The mean patients’ age was 72.7 years old. In eight cases, we had wound complications, including four wound infections, one hematoma and three distal flap ischemia problems. Distal flap ischemia occurred only in cases that advanced beyond the midline and with length-to-width ratio equal to or over three to one. Neck dissection was performed in two of these three cases with ischemic complications.ConclusionSeveral factors may influence platysma transverse myocutaneous flap survival. Usually a long and narrow flap, especially crossing the neck midline and associated with neck dissection are more prone to poor outcomes.     

Preventing compulsory admission to psychiatric inpatient care through psycho-education and crisis focused monitoring

ABSTRACT: BACKGROUND: The high number of involuntary placements of people with mental disorders in Switzerland and other European countries constitutes a major public health issue. In view of the ethical and personal relevance of compulsory admission for the patients concerned and given the far-reaching effects in terms of health care costs, innovative interventions to improve the current situation are much needed. A number of promising approaches to prevent involuntary placements have been proposed that target continuity of care by increasing self-management skills of patients. However, the effectiveness of such interventions in terms of more robust criteria (e.g., admission rates) has not been sufficiently analysed in larger study samples.The current study aims to evaluate an intervention programme for patients at high risk of compulsory admission to psychiatric hospitals. Effectiveness will be assessed in terms of a reduced number of psychiatric hospitalisations and days of inpatient care in connection with involuntary psychiatric admissions as well as in terms of cost-containment in inpatient mental health care. The intervention furthermore intends to reduce the degree of patients' perceived coercion and to increase patient satisfaction, their quality of life and empowerment. METHODS: This paper describes the design of a randomised controlled intervention study conducted currently at four psychiatric hospitals in the Canton of Zurich. The intervention programme consists of individualised psycho-education focusing on behaviours prior to and during illness-related crisis, the distribution of a crisis card and, after inpatient admission, a 24-month preventive monitoring of individual risk factors for compulsory re-admission to hospital. All measures are provided by a mental health care worker who maintains permanent contact to the patient over the course of the study.In order to prove its effectiveness the intervention programme will be compared with standard care procedures (control group). 200 patients each will be assigned to the intervention group or to the control group. Detailed follow-up assessments of service use, psychopathology and patient perceptions are scheduled 12 and 24 months after discharge. DISCUSSION: Innovative interventions have to be established to prevent patients with mental disorders from undergoing the experience of compulsory admission and, with regard to society as a whole, to reduce the costs of health care (and detention). The current study will allow for a prospective analysis of the effectiveness of an intervention programme, providing insight into processes and factors that determine involuntary placement.Trial registrationCurrent Controlled Trials ISRCTN63162737.