Evaluation of the 'Jumping to conclusions' bias in different subgroups of the at-risk mental state: from cognitive basic symptoms to UHR criteria.

BACKGROUND: Patients with psychosis display the so-called 'Jumping to Conclusions' bias (JTC) - a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in 'at-risk mental state' (ARMS) patients, specifically in ARMS samples fulfilling 'ultra-high risk' (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups. METHOD: In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument - Adult Version (SPI-A). RESULTS: The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement. CONCLUSIONS: Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.

Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects.

BACKGROUND: Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects of MST and the influence of MST on regional brain glucose metabolism. METHOD: Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients underwent a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed. RESULTS: A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic increase in the frontal cortex bilaterally and a decrease in the left striatum. CONCLUSIONS: Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effective, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression.

Differential expression of THELPER 1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation.

INTRODUCTION: Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)-specific T cells are essential for the control of viral infections. However, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult. METHODS: We analyzed Ag-specific T-cell populations, subdivided according to the expression of different THELPER- 1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-γ, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-α) secretion of T cells after ex vivo stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes. RESULTS: Isolation based on IFN-γ production provides a T-cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag-specific expression of IL-2 or TNF-α, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion. CONCLUSION: We conclude that the exclusive secretion of IFN-γ in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF-α secreting T-cell populations.

Bilateral bispectral index monitoring during and after electroconvulsive therapy compared with magnetic seizure therapy for treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective and established treatment for depression. Magnetic seizure therapy (MST) has recently been developed and seems equally effective while associated with fewer side-effects. Both require general anaesthesia, which could be quantified using the bispectral index (BIS). We compared ECT and MST with respect to recovery times, left-sided BIS, and left-right differences in BIS. METHODS: In this prospective, observational study, we enrolled 10 successive patients receiving ECT and 10 patients undergoing MST. Anaesthesia was performed with propofol and monitored with a bilateral BIS sensor. The seizure was elicited when the BIS was within a range from 50 to 60. The time to eye opening was measured and bilateral BIS were recorded for 10 min after seizure induction. RESULTS: A comparable anaesthetic depth was observed in the ECT and MST groups at baseline [mean (standard deviation, sd) BIS values of 94.1 (4.1) and 95.5 (3.0), respectively] and before seizure induction [mean (sd) BIS values of 52.3 (9.6) and 55.2 (10.3), respectively]. Post-ictally, MST patients opened their eyes significantly earlier than ECT patients [3.0 (1.0) vs 6.7 (1.3) min, P<0.001]. They showed a significantly higher BIS at 2 min after seizure induction [69.2 (10.1) vs 50.9 (15.9), P=0.003], and this difference was still present at 10 min after seizure induction [BIS 81.5 (6.5) vs 68.0 (16.4), P<0.001]. Significant differences between the left and right BIS were observed in neither the ECT nor the MST group. CONCLUSIONS: At a comparable anaesthetic depth, MST is superior to ECT in terms of post-ictal recovery, which is correctly reflected by higher post-ictal BIS values. Unilateral BIS monitoring is sufficient to monitor anaesthetic depth in ECT and MST patients. TRIAL REGISTRY NUMBER: NCT 01318018.

[Brain stimulation procedures. Transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation]. / Hirnstimulationsverfahren. Transkranielle Magnetstimulation, Magnetkrampftherapie und tiefe Hirnstimulation.

Brain stimulation methods are promising treatment options in severe treatment-resistant psychiatric disorders. A safe and noninvasive method is transcranial magnetic stimulation, but the clinical application is not clear. Magnetic seizure therapy is a further development of transcranial magnetic stimulation, by which generalized seizures are induced under anaesthesia. Previous results with regard to the antidepressant effects and the fewer cognitive side effects were significant. Deep brain stimulation is an invasive procedure in which electrodes are stereotactically implanted in special brain areas. The effects in severe therapy-resistant obsessive-compulsive disorders and depressions are promising. However, the evaluation of ethical issues remains an important task.

[The development of deep brain stimulation as a putative treatment for resistant psychiatric disorders]. / Die Entwicklung der tiefen Hirnstimulation bei der Behandlung therapieresistenter psychiatrischer Erkrankungen.

Since approximately 10 years investigations have been carried out on the impact of deep brain stimulation (DBS) of treatment-resistant obsessive-compulsive disorders and depression. New fields of application are for Tourette's syndrome, substance abuse, dementia and anxiety. New functional, structural and molecular data have led to a new conceptualization of these disorders as dysfunctions of networks which process motivational and affective stimuli. DBS permits the selective and basically reversible modulation of such networks. So far adverse effects have been graded as marginal. In the field of treatment-resistant obsessive-compulsive disorders and depressive disorders uncontrolled studies have been published with initial satisfactory and concordant indications of the therapeutic effect of DBS in a variety of target areas of the brain. It is most important to provide a consistent interdisciplinary and durable development of concepts for a responsible use of DBS in patients with psychiatric disorders. Only in this way can the potentially most interesting therapeutic development of clinical psychiatry of the last 20 years be continued uninterrupted.

Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide.

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.

Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues.

The primary function of telomerase is the synthesis of telomeric DNA, which is the main pathway by which telomere length is maintained in the human germline and stem cells. Activation of telomerase is associated with elongation of telomeres and cell immortalization. Recently, telomerase activity has been detected in tissues from many human cancers but not in the majority of normal tissues, suggesting that telomere stabilization and telomerase activation may play a role in tumorigenesis. To explore telomerase activity in head and neck neoplastic and preneoplastic tissues, we studied 16 head and neck squamous cell carcinoma (HNSCC) cell lines and 60 specimens from 29 patients with HNSCC for telomerase activity. We precisely compared telomerase activity with histological features in adjacent tissue sections. We detected telomerase activity in 16 of 16 (100%) HNSCC cell lines, 26 of 29 (90%) invasive tumors, 7 of 7 (100%) dysplastic lesions, and 5 of 5 (100%) hyperplastic lesions, whereas 0 of 17 normal tissues or 2 hyperkeratotic lesions had detectable telomerase activity. Our data indicate that activation of telomerase activity is frequent in HNSCC and may occur early in the tumorigenesis process. The reactivation of telomerase may be a useful marker for cancer risk assessment in the oral cavity.

A MAGE-A1 HLA-A A*0201 epitope identified by mass spectrometry.

Peptides presented by HLA-A*0201 molecules on the surface of the human breast carcinoma cell line KS24.22 after IFN-gamma induction were analyzed by the "Predict-Calibrate-Detect" approach, which combines epitope prediction and high-performance liquid chromatography mass spectrometry. One of the predicted epitopes, MAGE-A1(278-286) (KVLEYVIKV), was found to be presented by HLA-A*0201, with an estimated copy number of 18 molecules/cell. HLA-A*0201 transgenic mice (HHD mice) were used to generate CTL lines that stained positive with an HLA-A*0201 tetramer folded around the KVLEYVIKV peptide and killed peptide-loaded mouse target cells expressing HLA-A*0201. IFN-gamma-treated or -nontreated HLA-A*0201 expressing HeLa cells transiently transfected with a plasmid expressing the MAGE-A1 gene stimulated in vitro cytokine production by the CTL lines. Moreover, IFN-gamma-treated KS24.22 cells, but not IFN-gamma-treated HLA-A*0201(+) MAGE-A1(-) cells or IFN-gamma-treated HLA-A*0201(-) MAGE-A1(+) cells, were killed by these CTLS: Thus, the combination of HLA epitope prediction, peptide analysis, and immunological methods is a powerful approach for the identification of tumor-associated epitopes.

Individuals with inherited chromosomally integrated human herpes virus 6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity.

To evaluate the human herpes virus 6 (HHV-6) -specific immune response in individuals with chromosomally integrated HHV-6 (ciHHV-6), we measured HHV-6-antigen-specific cytokine responses (interferon-γ, interleukin-2, tumour necrosis factor-α) in T cells by flow cytometry in 12 and 16 individuals with and without ciHHV-6, respectively. All individuals with ciHHV-6 showed HHV-6-specific T cells with higher frequencies of HHV-6-specific CD8(+) cells (0.03-14.93, median 2.15% of CD8(+) cells) compared with non-ciHHV-6 (0.0-10.67, median 0.36%, p 0.026). The observed increased HHV-6-specific functionally active responses in individuals with ciHHV-6 clearly disprove speculations on immune tolerance in ciHHV-6 and indicate clinical and immunological implications of ciHHV-6.

Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89%; P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD.

Enalaprilat, a new parenteral angiotensin-converting enzyme inhibitor: rapid changes in systemic and coronary hemodynamics and humoral profile in chronic heart failure.

Systemic and coronary hemodynamic, metabolic and humoral effects of a new intravenous angiotensin-converting enzyme inhibitor, enalaprilat, were evaluated in 14 patients with chronic heart failure. Onset of hemodynamic action occurred within 15 minutes and persisted for 6 hours. At the time of peak effect, there was a significant reduction in mean arterial pressure (-21%) and pulmonary capillary wedge pressure (-33%). Systemic vascular resistance decreased by 32% and stroke volume index increased by 20%. These systemic hemodynamic changes indicate improved left ventricular function. There was a substantial sustained reduction in rate-pressure product initially without a change in coronary sinus blood flow or myocardial oxygen consumption. There was also reduced myocardial oxygen extraction and augmented coronary sinus oxygen saturation at 30 minutes and 1 hour. In three patients, abnormal myocardial lactate extraction, present before enalaprilat, changed to uptake after enalaprilat, indicating amelioration of myocardial ischemia that was not clinically manifest. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma renin activity increased and plasma aldosterone decreased. These findings suggest that enalaprilat produces inhibition of the angiotensin-converting enzyme and consequent beneficial systemic hemodynamic changes in heart failure. In some patients with heart failure, silent myocardial ischemia at rest can occur and can be alleviated with enalaprilat. Decreased myocardial oxygen extraction, increased coronary sinus oxygen saturation and lack of expected decrease in coronary sinus blood flow despite reduced rate-pressure product suggest transient coronary vasodilation by enalaprilat.

Involvement of a Gardos-type potassium channel in head activator-induced mitosis of BON cells.

The human neuroendocrine cell line BON was used to study second messengers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entry into mitosis. HA-induced mitosis is mediated by an inhibitory G protein, the action of which is blocked by pertussis toxin. HA signaling requires inhibition of the cAMP pathway, calcium influx, and hyperpolarization of cells. The latter is a very important and sensitive step involving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with specific inhibitors of this potassium channel. Pharmacology and RNA analysis suggest identity with the recently cloned Gardos-type potassium channel.

Potential interaction between ritonavir and carbamazepine.

Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an anticonvulsant, were administered concurrently to a patient who had human immunodeficiency virus infection and epilepsy. The combination resulted in elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and transient liver dysfunction. After discontinuing RTV and reducing the dosage of CBZ, the serum concentration of CBZ returned to the optimal range, symptoms subsided, and liver function returned to baseline. Carbamazepine is metabolized in the liver to a large extent by the cytochrome P450 (CYP) system, especially CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a potent inhibitor of this enzyme. Careful clinical monitoring may help prevent adverse drug interactions when these drugs are administered concurrently.

Angiographic results after minimally invasive coronary bypass grafting using the minimally invasive direct coronary bypass grafting (MIDCAB) approach.

OBJECTIVE: The aim of the study was to evaluate the early and mid-term angiographic results after minimally invasive coronary bypass grafting using an 'off-pump' technique via a lateral minithoracotomy. METHODS: In 221 out of 271 patients (81.5%) who underwent minimally invasive direct coronary bypass grafting (MIDCAB) the quality of the internal thoracic artery (ITA)-graft and the anastomosis was evaluated by conventional coronary angiography between the 2nd and 6th postoperative day (POD). A subgroup of 130 patients (47.9%) of the initial cohort were repeatedly controlled by angiography 6 months later. RESULTS: The early postoperatively patency rate of the grafts was (96.8%). Moderate anastomotic stenosis between 50 and 75% was found in 13/221 (5.8%) patients, whereas severe stenosis of more than 75% was seen in 10/221 (4.5%) and occlusion of the graft in 3/221 (1.3%) patients. A stress-ECG was performed in patients with a severe stenosis to provoke ST-segment changes or clinical findings of myocardial ischemia. A positive stress test was found in 4/221 patients (1,8%). Early re-intervention was required in 7/221 (3.1%) patients. After 6 months, angiographic follow-up revealed a patency rate of (95.4%). Of 130 patients 5 (3.8%) presented with moderate anastomotic stenosis, whereas 3/130 (2.0%) patients showed a severe stenosis with one patient (0.7%) having myocardial ischemia during stress test. Occlusion of the graft was seen in 3/130 patients (2.3%). During follow-up, 4/130 (3.0%) patients underwent re-intervention. A comparison between early postoperative and 6-months angiogram revealed a decrease or a disappearance of the severity of the stenosis in 4/15 patients (26.6%). CONCLUSION: Since stenosis of the anastomosis may occur after minimally invasive, beating heart coronary bypass grafting, postoperative angiography should be performed to provide quality control and to guide appropriate further treatment. The latter is necessary if the stenosis is accompanied by reduced run-off and evidence of myocardial ischemia during stress test. An improvement of early stenosis at the anastomosis may be expected in more than 25%.

[Aortic regurgitation caused by quadri-cuspid aortic valve]. / Négyhegyü aortabillentyü okozta regurgitatio.

Authors report the surgical treatment of a rare malformation of the aortic valve associated with coronary artery stenosis. The aortic valve had a supernumerary cusp which was revealed intraoperatively. The supernumerary cusp appeared to be similar in size to the three other. Surveying the literature it is stated, that the number of similar entities are about 50 in number. Autopsy findings note, that the prevalence is about 0.008-0.012%. During the past 25 years, in aortic valve replacement cases such entity could have not been explored. The possible significance of the entity lays in--that without rheumatic or degenerative origin-in the life span (above 40 years of age) it may lead to severe regurgitation leading to functional deterioration.

[Incidence of perioperative myocardial necrosis in the course of coronary bypass surgery]. / Perioperatív myocardium necrosis gyakorisága coronaria mütéteink során.

Authors report an analysis of 101 patients' perioperative data in the view of myocardial necrosis development. Perioperative myocardial infarction is defined as simultaneous detection of new Q wave, and myocardial specific enzyme release with concomitant, transient pump failure. They conclude by the data of patients operated upon, that the quoted criteria were detected simultaneously in 9 patients. Other 7 patients had CK-MB levels of pathological level, but without evidences of any other myocardial infarction criteria. Minimal myocardial mass loss as a sort of terminology is introduced, which is obviously not considered as equal to true myocardial infarction.

[Simultaneous surgery for trivalvular and ischemic heart disease as well as calcification of the ascending aorta]. / Trivalvularis és iszkémiás szívbetegség, valamint aorta ascendens calcificatio egyidejü sebészi kezelése.

Authors present a case report about the surgical management of trivalvular and ischemic heart disease. The strategy of surgery: venous, arterial revascularisation, valve replacements, valvular plasty is discussed in conjunction with the management of the calcified ascending aorta. The details of the procedure and data of the early follow up period (6 months) are presented.

[Headache, hypertension]. / Kopfschmerzen, Hypertonie.

Headache and hypertension were the main clinical symptoms in this slim 77-year-old lady. Because the hypertension presented as paroxysmal and was combined with palpitations, dizziness, and sweating the suspicion of a phaeochromocytoma arouse. The vanillyl mandelic acid in the urine was elevated. As further investigation revealed that this elevation was due to medication with L-dopa because of Parkinson-syndrome. A proper history of the patients' medication or alternative laboratory tests prevent false conclusions.