Neurocognitive predictors of treatment completion and daytime activities at follow-up in multiproblem young adults.

Previous research has shown an association between cognitive control deficits and problematic behavior such as antisocial behavior and substance use, but little is known about the predictive value of cognitive control for treatment outcome. The current study tests whether selected markers of baseline cognitive control predict (1) treatment completion of a day treatment program involving a combination of approaches for multiproblem young adults and (2) daytime activities a year after the start of treatment, over and above psychological, social, and criminal characteristics. We assessed individual, neurobiological, and neurobehavioral measures, including functional brain activity during an inhibition task and two electroencephalographic measures of error processing in 127 male multiproblem young adults (age 18-27 years). We performed two hierarchical regression models to test the predictive power of cognitive control for treatment completion and daytime activities at follow-up. The overall models did not significantly predict treatment completion or daytime activities at follow-up. However, activity in the anterior cingulate cortex (ACC) during response inhibition, years of regular alcohol use, internalizing problems, and ethnicity were all significant individual predictors of daytime activity at follow-up. In conclusion, cognitive control could not predict treatment completion or daytime activities a year after the start of treatment over and above individual characteristics. However, results indicate a direct association between brain activity during response inhibition and participation in daytime activities, such as work or school, after treatment. As adequate baseline inhibitory control is associated with a positive outcome at follow-up, this suggests interventions targeting cognitive control might result in better outcomes at follow-up.

Error-related brain activity in relation to psychopathic traits in multi-problem young adults: An ERP study.

One of the most prominent issues in psychopathy is the inability to adequately monitor one's performance and learn from one's mistakes. We investigated the relationship between psychopathic traits, as measured with the Youth Psychopathy Inventory - Short Version, and both early and late error-related brain activity in an at-risk sample of male young adults. These multi-problem young adults (age 18-27) are severely dysfunctional in society and suffer from multiple problems including financial problems, delinquency, psychological problems, and drug use. Our final sample consisted of 115 multi-problem young adults and 26 controls. Participants performed an Eriksen-Flanker task during EEG measurements. We used the difference wave of the error-related negativity (ΔERN) as a measure of early error processing and the error positivity (Pe) as a measure of late error processing. Multi-problem young adults showed reduced ERN amplitudes compared to controls, but did not differ in Pe amplitude. We found no statistically significant relation between psychopathic traits and ERN and Pe amplitudes within the multi-problem group. Thus, we found evidence for dysfunctional error-processing in multi-problem young adults compared to controls. However, within the multi-problem sample we did not find evidence for a relationship between psychopathic traits and dysfunctional error-processing. One explanation may be that this is due to the specific developmental stage of our young adult participants in which a transition between error-processing deficits, as present in adolescents high in psychopathic traits, and error-processing overcompensation, as present in adults high in psychopathic traits, may occur.

Wound drains in non-complex lumbar surgery: a systematic review.

AIMS: Our aim was to perform a systematic review of the literature to assess the incidence of post-operative epidural haematomas and wound infections after one-, or two-level, non-complex, lumbar surgery for degenerative disease in patients with, or without post-operative wound drainage. PATIENTS AND METHODS: Studies were identified from PubMed and EMBASE, up to and including 27 August 2015, for papers describing one- or two-level lumbar discectomy and/or laminectomy for degenerative disease in adults which reported any form of subcutaneous or subfascial drainage. RESULTS: Eight papers describing 1333 patients were included. Clinically relevant post-operative epidural haematomas occurred in two (0.15%), and wound infections in ten (0.75%) patients. Epidural haematomas occurred in two (0.47%) patients who had wound drainage (n = 423) and in none of those without wound drainage (n = 910). Wound infections occurred in two (0.47%) patients with wound drainage and in eight (0.88%) patients without wound drainage. CONCLUSION: These data suggest that the routine use of a wound drain in non-complex lumbar surgery does not prevent post-operative epidural haematomas and that the absence of a drain does not lead to a significant change in the incidence of wound infection. Cite this article: Bone Joint J 2016;98-B:984-9.

Adherence to cardiovascular prevention strategies in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular disease (CVD). Recent national and international guidelines suggest strict treatment of CVD risk factors in RA. The aim of this study was to evaluate the self-reported adherence to CV prevention strategies in patients with RA. METHOD: RA patients visiting an outpatient clinic for strict CVD risk management received a validated questionnaire to evaluate adherence to CV prevention strategies. Strict treatment targets were defined and lifestyle recommendations were given following a prespecified protocol. CVD risk was assessed using the SCORE algorithm. RESULTS: In total, 111 questionnaires were returned (response rate of 82%). A high 10-year CVD risk (≥ 20%) was present in 53%, but only 3% thought they had an increased CVD risk. A total of 53% of patients reported that they 'follow the doctors' suggestions exactly' and 75% reported finding it 'easy to follow the suggestions'. Of the 69% of patients who were prescribed lipid- and/or blood pressure-lowering drugs, 90% reported taking all prescribed tablets. The advice to follow a diet was given to 42%, of whom 68% said they followed the advised diet. Physical exercise was advised to 67%, of whom 62% said they performed specific physical exercise on at least 3 days a week. The adherence to lifestyle recommendations was not significantly different across the CVD risk groups. CONCLUSIONS: RA patients tend to underestimate their CVD risk. The self-reported adherence of RA patients to CVD risk management was high concerning pharmaceutical interventions and moderate in the case of lifestyle interventions.

Extramedullary relapses after allogeneic non-myeloablative stem cell transplantation in multiple myeloma patients do not negatively affect treatment outcome.

Recent literature suggests that after non-myeloablative allogeneic (NMA) stem cell transplantation (SCT), the incidence of extramedullary (EM) relapse in multiple myeloma (MM) patients is increased and that these relapses have a poor prognosis. However, numbers on incidence and treatment outcome are scarce. We collected data from 54 relapsed MM patients from a total group of 172 treated with sequential autologous and allogeneic NMA SCT at seven transplantation centres. There were 43 (79.6%) systemic relapses, including 6 with concurrent EM localisation. Five patients had a local EM relapse only. Six patients relapsed with only bone involvement. Patients with deletion of chromosome 13 had a higher incidence of EM relapse (30.8 versus 5.6%, P=0.06). EM relapses were treated with donor lymphocyte infusion, radiotherapy, or chemotherapy, especially with novel agents. The response rate was 45.5%, which was not different when compared to patients without EM disease (54.1%). Overall survival and progression-free survival were not significantly different in patients with EM disease, when compared to those without EM disease. In conclusion, the incidence of relapse with EM disease following allogeneic NMA SCT was 20.4%. There was no negative impact of EM relapse on response rate, overall survival and progression-free survival.

First case of ataxia with isolated vitamin E deficiency in the Netherlands.

We present a 36-year-old Dutch woman who suffered from a progressive form of cerebellar ataxia since school age. In her childhood she was diagnosed with Friedreich's ataxia. Genetic analysis of the frataxin gene at 34 years of age, however, had revealed no abnormal GAA triplet expansion. We identified two point mutations in the alpha-tocopherol transport protein (alpha-TTP) gene on chromosome 8q13, and the diagnosis ataxia with isolated vitamin E deficiency (AVED) was made. This report illustrates the diagnosis AVED and its relation to vitamin E metabolism. It is important to evaluate previously made diagnoses when newly developed tests can be performed for confirmation.

The effect of rhythmic somatosensory cueing on gait in patients with Parkinson's disease.

BACKGROUND AND AIMS: Gait and gait related activities in patients with Parkinson's disease (PD) can be improved with rhythmic auditory cueing (e.g. a metronome). In the context of a large European study, a portable prototype cueing device was developed to provide an alternative for rhythmic auditory cueing: rhythmic somatosensory cueing (RSC, a miniature vibrating cylinder attached to the wrist). We investigated whether PD patients could adapt their walking pattern using RSC under conditions of changing walking speed and the presence of potentially distracting visual flow while walking on a treadmill. METHODS: A total of 17 patients with PD participated (mean age 63.4+/-10.3 years; Hoehn-Yahr score 2.5+/-0.9, mean Unified Parkinson's Disease Rating Scale score 49.8+/-13.7, mean disease duration 7.7+/-5.1 years). They performed systematic walking speed manipulations under 4 conditions in a random order: (1) no cue, no visual flow, (2) no cue, visual flow, (3) cue, no visual flow and (4) cue, visual flow. Visual flow in the form of a virtual corridor that moved at the current walking speed was projected on a 2 x 2 m rear-projection screen. The cueing rhythm was set at -10% of preferred stride frequency at each speed. Stride frequency was assessed using peaks in the trajectories of thigh sagittal plane segmental angles. RESULTS: Walking with RSC resulted in lower stride frequencies, and thus larger step lengths (p-values <0.05), regardless of walking speed. The presence of visual flow did not impair the use of RSC, as evidenced by the lack of differences between conditions 3 and 4 (p>0.05). CONCLUSION: Rhythmic somatosensory cueing may be a viable alternative for auditory cueing and is robust to changes in walking speed and visual distractors.

Relationship between impulsive sensation seeking traits, smoking, alcohol and caffeine intake, and Parkinson's disease.

BACKGROUND: An inverse relation exists between smoking and coffee intake and Parkinson's disease (PD). The present study explored whether this is explained by low sensation seeking, a personality trait believed to characterise PD. METHODS: A total of 106 non-demented patients with PD and 106 age and sex matched healthy controls completed a short version of Zuckerman's Sensation Seeking Scale (SSS), the Geriatric Depression Scale, and the Trait Anxiety Inventory. Data were collected on past and current cigarette smoking, and participants also completed food frequency questionnaires to estimate current caffeine and alcohol intake. RESULTS: Patients with PD had lower sensation seeking and higher depression and anxiety scores. They were also less likely to have ever smoked, and had lower caffeine and alcohol intakes. Analysis of the data using conditional logistic regression suggested that the inverse association of PD risk with sensation seeking was independent of smoking, and caffeine and alcohol intake. Moreover, low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on PD. However, the effect of smoking was weakened only slightly when SSS was included in the regression model. CONCLUSION: This study raises the possibility that there is a neurobiological link between low sensation seeking traits--which might underlie the parkinsonian personality--and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD.

The effects of visual rhythms and optic flow on stride patterns of patients with Parkinson's disease.

This study was aimed at determining the effects of rhythmic visual cueing under changing visual conditions on stride frequency in patients with Parkinson's disease (PD; n = 21) and healthy age matched controls (n = 7) while walking at different speeds on a treadmill. Stride frequency and stride length in patients with PD as well as controls were not rigidly coupled to walking speed and could be manipulated with walking speed as well as by using spatial and temporal rhythmic visual cues.

Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes.

Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes against end-to-end fusion. Previous in vitro studies in human fibroblast models indicated that telomere dysfunction results in chromosome instability. Loss of telomere function can result either from critical shortening of telomeric DNA or from loss of distinct telomere-capping proteins. It is less clear whether telomere dysfunction has an important role in human cancer development in vivo. Acute myeloid leukemia (AML) is a good model to study mechanisms that generate chromosome instability in human cancer development because distinct groups of AML are characterized either by aberrations that theoretically could result from telomere dysfunction (terminal deletions, gains/losses of chromosome parts, nonreciprocal translocations), or aberrations that are unlikely to result from telomere dysfunction (e.g., reciprocal translocations or inversions). Here we demonstrate that AML with multiple chromosome aberrations that theoretically could result from telomere dysfunction is invariably characterized by critically short telomeres. Short telomeres in this group are not associated with low telomerase activity or decreased expression of essential telomeric capping proteins TRF2 and POT1. In contrast, telomerase activity levels are significantly higher in AML with short telomeres. Notably, short telomeres in the presence of high telomerase may relate to significantly higher expression of TRF1, a negative regulator of telomere length. Our observations suggest that, consistent with previous in vitro fibroblast models, age-related critical telomere shortening may have a role in generating chromosome instability in human AML development.

Carcinomatous meningitis in cancer of the uterine cervix.

Carcinomatous meningitis is extremely rare in cervical cancer. The diagnosis of carcinomatous meningitis is a difficult one when clinical symptoms are limited and radiographic imaging is normal. Demonstration of malignant cells in the cerebrospinal fluid remains the gold standard to establish the diagnosis. For patients without bulky disease who can be treated with radiotherapy, standard treatment for carcinomatous meningitis is chemotherapy, which may be administered intrathecally. Despite the poor prognosis, treatment may result in effective palliation. We describe a 54-year-old patient who was diagnosed with carcinomatous meningitis in the course of metastatic cervical cancer and who responded to administration of intrathecal methotrexate.

Olfactory function distinguishes vascular parkinsonism from Parkinson's disease.

OBJECTIVE: To compare olfactory function in vascular parkinsonism and Parkinson's disease diagnosed according to published clinical diagnostic criteria. METHODS: The University of Pennsylvania smell identification test (UPSIT) was carried out in 14 patients with vascular parkinsonism, 18 with Parkinson's disease, and 27 normal controls matched for age, sex, and smoking status. RESULTS: UPSIT scores in vascular parkinsonism (mean 26.1, 95% confidence interval, 23.1 to 29.0) were significantly better than in Parkinson's disease (mean 17.1 (14.5 to 19.7)) (p<0.0001), and did not differ from the healthy controls (mean 27.6 (25.8 to 29.4)) (p = 0.32). CONCLUSIONS: Testing olfactory function may be helpful in differentiating vascular parkinsonism from Parkinson's disease.

Post-stroke movement disorders: report of 56 patients.

BACKGROUND: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke. METHODS: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs. RESULTS: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case-control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6). CONCLUSIONS: Chorea is the commonest movement disorder following stroke and appears in older patients. Involuntary movements tend to persist despite the functional recovery of motor deficit. Deep vascular lesions are more frequent in patients with movement disorders.

Dynamics of protein binding to telomeres in living cells: implications for telomere structure and function.

Telomeric proteins have an essential role in the regulation of the length of the telomeric DNA tract and in protection against end-to-end chromosome fusion. Telomere organization and how individual proteins are involved in different telomere functions in living cells is largely unknown. By using green fluorescent protein tagging and photobleaching, we investigated in vivo interactions of human telomeric DNA-binding proteins with telomeric DNA. Our results show that telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2, which has a dual role in chromosome end protection and telomere length homeostasis, resides at telomeres in two distinct pools. One fraction ( approximately 73%) has binding dynamics similar to TRF1 (residence time of approximately 44 s). Interestingly, the other fraction of TRF2 binds with similar dynamics as the putative end-protecting factor hPOT1 (residence time of approximately 11 min). Our data support a dynamic model of telomeres in which chromosome end-protection and telomere length homeostasis are governed by differential binding of telomeric proteins to telomeric DNA.

Telomerase activity level, but not hTERT mRNA and hTR level, regulates telomere length in telomerase-reconstituted primary fibroblasts.

The critical factors in the regulation of telomere length are not yet clearly defined. Telomerase is a key player in telomere elongation, although previous studies have shown that telomeres are differentially elongated after telomerase reconstitution. Moreover, a clear relation between the level of telomerase activity and telomere length was not observed. To investigate which factors are critical in telomere length regulation, we generated 24 telomerase-reconstituted primary human fibroblast clones. In these clones, in vitro telomerase activity level is clearly related to telomere length. High levels of telomerase activity are associated with longer telomeres and better telomere maintenance over time. The correlation coefficient, however, indicates that the level of telomerase activity is not the only factor in the regulation of telomere length. Clearly, factors that are not measured in an in vitro telomerase activity assay are involved in telomere length regulation in vivo. To investigate which telomerase components are critical in regulating telomerase activity levels, we studied expression levels of hTERT mRNA and hTR. Expression is highly variable between individual clones, but not related to the level of telomerase activity or telomere length. Our results indicate that expression levels of hTERT mRNA and hTR do not regulate the activity level of the telomerase complex, suggesting posttranscriptional modification of hTERT or the presence of additional proteins that modulate telomerase enzyme activity.

The L-dopa response in vascular parkinsonism.

OBJECTIVE: To determine whether a positive L-dopa response in vascular parkinsonism (VP) is correlated with the presence of nigrostriatal pathology due to either vascular damage or neuronal cell loss. METHODS: Seventeen patients with pathologically confirmed VP were selected from the pathological collection of the Queen Square Brain Bank for Neurological Disorders, and their L-dopa response during life was compared with the presence of macroscopic vascular damage in the nigrostriatal pathway and microscopic substantia nigra cell loss. RESULTS: Ten of the twelve patients with a good or excellent response had macroscopic infarcts or lacunae caused by enlarged perivascular spaces in the basal ganglia or microscopic neuronal cell loss in the substantia nigra. In contrast, only one of the five patients with a moderate or no response had lacunae in the putamen, and none had lacunar infarcts or substantia nigra cell loss. CONCLUSION: These results suggest that a substantial number of patients with clinically suspected VP may respond with benefit to dopaminergic therapy, especially those with lesions in or close to the nigrostriatal pathway.

Molecular remission of Philadelphia/bcr-abl-positive acute myeloid leukaemia after treatment with anti-CD33 calicheamicin conjugate (gemtuzumab ozogamicin, CMA-676).

The anti-CD33 monoclonal antibody linked to NAc-gamma calicheamicin gemtuzumab ozogamicin (CMA-676) was used to treat a patient with Philadelphia/bcr-abl-positive acute myeloid leukaemia. We report a morphological and cytogenetic complete remission after treatment with two doses of gemtuzumab ozogamicin as a single agent. Using real-time polymerase chain reaction (PCR), gemtuzumab ozogamicin treatment resulted in a 3-log tumour mass reduction in bone marrow.

Analysis of gene expression in subpopulations of murine hematopoietic stem and progenitor cells.

OBJECTIVE: The aim of the present work was to study how functional differences between subsets of the murine hematopoietic stem/progenitor cell compartment are manifested on the level of different patterns of gene expression in these subsets. MATERIALS AND METHODS: Amplified 3' terminal total cDNA fragment populations from four stem and progenitor cell fractions sorted using differential staining with Rhodamine 123 were prepared, and gene expression patterns were analyzed by Southern hybridization with a panel of gene markers. RESULTS: For the vast majority of lineage-specific markers, no expression was detected in the long-term repopulating stem cell fraction. Expression of a number of key genes positively regulating entry and progression through the cell cycle was down-regulated in long-term repopulating cells, in accordance with the quiescent state of the latter. In contrast, certain but not all cell division kinase inhibitors were significantly up-regulated in long- and short-term repopulating stem cell fractions. Expression of several genes important for entry into the apoptotic pathway was moderately reduced in long-term repopulating cells. Messenger RNA levels of the transcription factors GATA-1, GATA-2, c-Myb and SCL were down-regulated in long-term repopulating cells, as compared to more mature stem/progenitor cells. Finally, expression of the MDR1a gene encoding the Pgp efflux pump was highest in long-term repopulating cells, and progressively decreased with maturation. CONCLUSION: The patterns of gene expression in the stem/progenitor cell fractions are in good correlation with the known properties of adult hematopoietic stem/progenitor cells and may provide insight into molecular mechanisms underlying stem cell physiology.

EEG findings in patients with vascular parkinsonism.

OBJECTIVES: To investigate whether the conventional and quantitative EEGs of patients with vascular parkinsonism (VP) differ from those of idiopathic Parkinson's disease (PD) patients. MATERIAL AND METHODS: The EEGs of 13 patients with vascular parkinsonism and 14 patients with idiopathic Parkinson's disease were scored on a simple scale regarding aspects of conventional EEG variables. Alpha band power asymmetry and EEG slowing (increased delta and theta power) were calculated by the neurometrics method of quantitative EEG data evaluation. RESULTS: Analysis of both conventional and quantitative EEG data shows that VP patients had significantly less EEG slowing than PD patients. CONCLUSION: This study shows that the EEG in a group of patients with vascular parkinsonism differ from a patient group with idiopathic Parkinson's disease. Our results indicate that VP patients are not PD patients with subcortical vascular lesions, because then they would have had at least as much EEG slowing as PD patients.