Age effects on trail making test during acute depressive and manic episode

Impairment of executive functions and attention has been found in patients with acute depressive episodes but has rarely been investigated in manic patients to date. At the same time, executive functions decline with age. Thus, it is currently a matter of debate how to best measure decreased executive performance in elderly patients with affective disorders. In our study, we examined 30 depressed patients, 28 manic patients, and 30 healthy subjects of all age groups, using the Trail Making Test (TMT). Both depressed and manic patients needed twice as long as healthy subjects to perform the TMT Part A. In addition to this reduced performance due to affective disorders, we were also able to detect a decline in performance due to age. One could thus postulate that age and affective disorders each influence a different neuropsychological function, age affecting executive performance and affective disorders affecting attention, as measured in both cases by the TMT.     

Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli

Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[(18)F]fluoro-l-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes elicited by standardized affectively positive, negative and neutral visual stimuli. The magnitude of in the ventral striatum was positively correlated with BOLD signal increases in the left anterior cingulate cortex and right insular operculum elicited by positive vs. neutral stimuli, but not negative vs. neutral stimuli. In the dorsal striatum, the magnitude of was positively correlated with processing of positive and negative stimuli in the left dorsolateral prefrontal cortex. These findings suggest that dopamine synthesis capacity in the ventral striatum correlates with the attentional processing of rewarding positive stimuli in the anterior cingulate cortex of healthy subjects. Dopaminergic neurotransmission in the associative dorsal striatum has been associated previously with habit learning. The observed correlation between dopamine synthesis capacity in the dorsal striatum and BOLD signal changes in the dorsolateral prefrontal cortex suggests dopaminergic modulation of processing of emotional stimuli in brain areas associated with motor planning and executive behaviour control.     

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics

Rational Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia.Objective We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation.Methods Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence.Results Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms.Conclusions Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.Georg Juckel and Florian Schlagenhauf contributed equally to this work.     

Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group.

PURPOSE: To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction. RESULTS: After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively. CONCLUSION: Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.     

Factors affecting the efficacy of peripheral blood progenitor cells collections by large-volume leukaphereses with standardized processing volumes

BACKGROUND: Peripheral blood progenitor cell (PBPC) collections should be safe and efficient. Therefore, the influence and risk factors in large-volume leukaphereses (LVL) with standardized blood volumes was investigated. STUDY DESIGN AND METHODS: In a total of 724 autologous LVL performed at our center, either 4x or 6x the patient's blood volume (PBV) was processed. The group with processing 4x the PBV showed a median of 31 circulating CD34+ cells per microL, and the group with processing 6x the PBV had a median of 13 CD34+ cells per microL before LVL. Individual clinical factors, laboratory factors, and apheresis run variables influencing the yields of PBPCs were retrospectively analyzed. Furthermore, the changes of laboratory variables and adverse effects during LVL were investigated. RESULTS: Multivariate analysis identified "age,"circulating CD34+ cells," and "percentage of mononuclear cells" as only factors influencing the yields of PBPCs. Altogether, processing 6x versus 4x the PBV did not result in significantly higher yields of CD34+ cells for the total group, but requested PBPC yields were achieved more often after processing 6x the PBV in patients below 20 CD34+ cells per microL blood. Processing 6x versus 4x the PBV showed a significant difference for the decrease of platelets, but not for any other laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without accumulation in one group. CONCLUSION: In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.     

111In-DOTA- dPhe1-Tyr3-octreotide, 111In-DOTA-lanreotide and 67Ga citrate scintigraphy for visualisation of extranodal marginal zone B-cell lymphoma of the MALT type: a comparative study

Somatostatin receptor (SSTR) scintigraphy and gallium-67 citrate ((67)Ga) scintigraphy have been used for visualisation of Hodgkin's lymphoma and non-Hodgkin's lymphoma. However, experience with B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type is very limited. The aim of this study was to prospectively compare the (67)Ga scintigraphy results with those obtained by (111)In-DOTA- dPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOCT) and (111)In-DOTA-lanreotide ((111)In-DOTA-LAN) scintigraphy in patients with proven MALT-type lymphoma. Comparative scintigraphic examinations using (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN were performed in 18 patients (11 female and 7 male, median age 64+/-15 years) with histologically verified MALT-type lymphomas of various origin. Planar and single-photon emission tomography imaging acquisitions were performed after injection of a mean dose of 185+/-26 MBq (67)Ga and 165+/-20 MBq (111)In-DOTA-TOCT or (111)In-DOTA-LAN. All scintigraphic results were correlated with other conventional examinations including gastroscopy, colonoscopy, endosonoscopy, ophthalmologic investigation, CT of the thorax and abdomen and bone marrow biopsy. This comparative study showed that (67)Ga scintigraphy found abnormalities in 10 of 16 patients (63%) and detected 18 of 31 clinically involved sites (58%), but was false positive in three patients. (111)In-DOTA-TOCT found abnormalities in 9 of 15 patients (60%) and detected 15 of 27 clinical lesions (56%); it was false positive in two patients. (111)In-DOTA-LAN scintigraphy showed abnormalities in 7 of 11 patients (64%) and found 12 of 22 clinical lesions (55%). False-positive (111)In-DOTA-LAN scan results were found in two patients. For supra-diaphragmatic lesions, (67)Ga scintigraphy detected 12 of 16 sites (75%). (111)In-DOTA-TOCT scintigraphy revealed 7 of 15 lesions (47%). (111)In-DOTA-LAN showed 6 of 12 positive sites (50%). For infra-diaphragmatic involvement, the sensitivities of (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN were 40%, 67% and 60%, respectively. It is concluded that MALT-type lymphoma can be visualised by (67)Ga, (111)In-DOTA-TOCT and (111)In-DOTA-LAN scintigraphy. Although there were no statistically significant differences in patient-related and site-related sensitivities when using (67)Ga compared with (111)In-DOTA-TOCT and (111)In-DOTA-LAN, the sensitivity of (67)Ga tended to be superior to that of (111)In-DOTA-TOCT and (111)In-DOTA-LAN for supra-diaphragmatic lesions but inferior for infra-diaphragmatic involvement. In selected cases, the combination of (67)Ga and (111)In-DOTA-LAN or (111)In-DOTA-TOCT may increase the diagnostic efficiency in patients with MALT-type lymphoma.     

Evidence for predictive validity of blood assays to evaluate individual radiosensitivity

PURPOSE: An escalation in standard irradiation dose ensuring improved local tumor control is estimated, but this strategy would require the exclusion of the most sensitive individuals from treatment. Therefore, fast and reliable assays for prediction of the individual radiosensitivity are urgently required. METHODS AND MATERIALS: Seven parameters in lymphocytes of 40 patients with leukemia were analyzed before, during, and after total body irradiation (TBI) and in vitro X-ray irradiation. These were: cell proliferation, nuclear damage, activation of cytokines, and numbers of total leukocytes of CD34+ hematopoietic blood stem cells and of CD4+ and CD8+ lymphocytes. Additionally, antioxidative capacity of blood plasma, uric acid, and hemoglobin levels were measured. Blood samples of 67 healthy donors were used as controls. RESULTS: In vivo and in vitro irradiations showed comparable results. A dose-response relationship was found for most parameters. Three parameters were associated with severe acute oral mucositis (Grade 3 or 4 vs. Grade 0 to 2): leukocytes fewer than 6200/microL after 4 Gy TBI, a rate of >19% lymphocytes with reduced DNA and protein content ("necroses") after 4 Gy in vitro irradiation, and a small antioxidative capacity in blood plasma (<0.68 mMol) after 8 Gy TBI. CONCLUSION: Three simple blood assays were associated with oral mucositis that are posed here hypothetically as an early symptom of enhanced radiosensitivity in leukemic patients: leukocyte count, damaged lymphocyte score, and the antioxidative capacity after exposure.     

Sexual Problems After Total or Partial Laryngectomy

Objectives: To investigate sexual problems that can occur after laryngeal and hypopharyngeal cancer surgery and to specify possible influencing factors. Study Design: Multi‐institutional cross‐sectional study. Methods: Two hundred six patients were interviewed in person using the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ‐H&N35), the Hospital Anxiety and Depression Scale, and a structured interview assessing alcohol and tobacco consumption, sociodemographic data, and specific sexual problems. Type of surgery, tumor site, and tumor stage were documented according to the participants' medical records. Multivariate analysis of variance was used to assess the independent impact of each factor. Results: More than half of the patients in our study reported having reduced libido and sexual enjoyment after treatment. Sixty percent considered it an important issue for their contentment with life. Sexual difficulties were found to be unrelated with gender, formal education, alcohol and tobacco consumption, type of surgery (partial vs. total laryngectomy), radiotherapy, and tumor site. Psychological distress (F = 46.27, P < .001) was seen to have a strong independent impact on the occurrence of sexual difficulties and stage of disease (F = 4.50, P < .05) and age (F = 4.79, P < .05), a moderate independent impact. Conclusions: Reduced libido and sexual enjoyment is a common problem after laryngeal and hypopharyngeal cancer surgery. However, it is not caused by the oncological treatment but rather by the cancer itself. Depression is often associated with sexual problems. Both should be discussed in medical consultations with head and neck cancer patients when appropriate to provide adequate treatment.