Alteration in surface muscle electrical anisotropy in the rat SOD1 model of amyotrophic lateral sclerosis

Objective

To evaluate the effects of progressive neurogenic change on surface-measured anisotropy via study in the rat superoxide dismutase 1 (SOD1) G93A amyotrophic lateral sclerosis (ALS) model.

Methods

Eight male ALS rats were studied over a period of 10 weeks. In each, the 20 kHz to 1 MHz electrical impedance of the gastrocnemius-soleus complex was measured with electrodes placed at 0° and at 90° relative to the major muscle fiber direction. The major outcome measure, the anisotropy difference (AD) for each of the resistance, reactance, and phase, was calculated as 90-0° values.

Results

All three parameters showed substantial alterations with disease progression. However, the phase AD demonstrated the most substantial change, increasing from 1.8 ± 1.58° to 10.2 ± 2.13° (mean ± standard error) comparing the first and last set of measurements (p = 0.028).

Conclusions

Anisotropy increases substantially with disease progression in the ALS rat.

Significance

Measurement of surface electrical anisotropy offers a non-invasive means for quantifying neurogenic change in muscle.     

Differential brain activation during facial emotion discrimination in first-episode schizophrenia

Background

Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms.

Methods

Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data.

Results

Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus.

Conclusions

First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.     

Normalization of horizontal pseudoneglect following right, but not left, upper limb amputation

Objectives

Subjects who have suffered limb amputations are known to have physiological alterations of their body's representation, or schema. Such changes of brain function might alter the right-left spatial allocation of attention. The goal of this study was to learn if, compared to normal subjects, limb amputees had alterations of right-left spatial attention.

Methods

The subjects were veterans with amputation of one upper or lower limb. All subjects performed horizontal line bisections in their left, middle and right body-centered space.

Results

Following right upper limb amputation, there appears to be a reduction of the normal left-sided bias (pseudoneglect) primarily for lines presented in the right body hemispace.

Conclusions

This amputation-induced alteration of attentional bias might be related to changes in the body schema, a compensatory strategy, or alterations of scanning patterns. Further studies are needed to reproduce these results and to learn the underlying brain mechanism.     

Anticoagulant effects of an antidiabetic drug on monocytes in vitro

Introduction

Monocyte- and microparticle (MP)-associated tissue factor (TF) is upregulated in diabetes. Lipopolysaccharide (LPS) induces expression of TF and alternatively spliced TF (asTF) and increases MP release from monocytes. Using LPS-stimulated TF-bearing human monocytes, we examined whether glibenclamide, a sulfonylurea used to treat diabetes type 2, might possess anticoagulant properties.

Methods

We studied the effects of glibenclamide on cell- and supernatant-associated procoagulant activity (Factor Xa-generating assay and clot formation assay), on expression of TF and asTF (flow cytometry, RT-qPCR, western blot) and on cell viability and MP release (flow cytometry).

Results

Glibenclamide dose-dependently decreased procoagulant activity of cells and supernatants. The reduction in cellular procoagulant activity coincided with reduced expression of TF and asTF in cells, whereas cell viability remained almost unchanged. The glibenclamide-induced reduction in procoagulant activity of supernatants appeared to be associated with a decreased number of released MPs.

Conclusions

Reduction of monocyte- and supernatant-associated procoagulant activity by glibenclamide is associated with decreased expression of TF and asTF and possibly with a reduced MP number. Our data indicate that glibenclamide reduces the prothrombotic state in LPS-stimulated monocytes in vitro. Glibenclamide might therefore also have an anticoagulant effect in vivo, but this needs to be further evaluated.     

Diplégie faciale au cours d’une neuropathie démyélinisante inflammatoire aiguë secondaire à une varicelle

Introduction

Primo-infection by varicella-zoster virus (VZV) may be associated with several neurologic complications. Bilateral facial palsy is a rather uncommon manifestation.

Case report

We report the case of a 38-year-old woman who developed bilateral facial diplegia and paresthesia affecting all four limbs with subacute onset several days after varicella virus primoinfection. Ancillary tests showed hyperproteinorachia and signs of demyelinating polyneuropathy in nerve conduction tests. The diagnosis of Guillain-Barré syndrome was retained and a treatment with intravenous immunoglobulines was started, leading to progressive improvement.

Conclusion

Immunotherapy is a possible therapeutic approach in the context of neurologic postinfectious complications after VZV infection where an underlying mechanism is probable.     

Training primary care staff to deliver a computer-assisted cognitive-behavioral therapy program for anxiety disorders

Objectives

This paper describes the training approach used with primary care staff to deliver an evidence-based computer-assisted cognitive-behavioral therapy (CBT) program for anxiety disorders within a collaborative care treatment delivery model.

Methods

We describe the training and proficiency evaluation procedures utilized in the Coordinated Anxiety Learning and Management (CALM) study, a large multisite study of collaborative care for anxiety disorders in primary care. Training incorporated readings, didactic presentations, video demonstrations of CBT skills, role-plays, computer-assisted practice, CBT training cases and ongoing group supervision provided by study psychologists.

Results

Proficiency training case data from 15 clinicians are presented. The anxiety clinical specialists (ACSs) were highly proficient at delivering the CBT component of the CALM intervention. The ACSs also provided Likert-scale ratings and open-ended responses about their experiences with the training. Overall, the training was rated very positively and was described as very thorough, indicating a high level of acceptability to clinicians. Recommendations for future training are described.

Conclusions

Primary care staff with none or minimal prior CBT experience can be trained to deliver a computer-assisted, evidence-based treatment for anxiety disorders. The implications for dissemination and transportability of evidenced-based interventions are discussed.     

Axis I comorbidity and psychopathologic correlates of autodestructive syndromes

Objective

Nonsuicidal deliberate self-harm and factitious disorders have been proposed as subtypes within the autodestructive behavior spectrum, basically differing in the issue of concealment. Aims are to determine Axis I diagnoses and psychopathologic correlates of open self-harmers and patients diagnosed with factitious disorders.

Methods

One hundred ninety-four psychosomatic medicine inpatients participated. Assessment included the structured World Health Organization Composite International Diagnostic Interview (computerized version) and self-report questionnaires for anxiety, depression, perceived stress, and personal coping resources.

Results

Thirty-seven patients identified with self-destructive behavior were matched with 37 patients without such behavior. Overt self-harmers (n = 18) were more frequently diagnosed with anxiety, depressive, substance abuse/dependence, or eating disorders and reported more stress than factitious disorder patients (n = 19) or those without self-destructive behavior. Patients with factitious disorder exhibited lower Axis I comorbidity and less psychopathology than patients without self-harm behavior.

Conclusions

Regarding psychopathologic assessment, contrary to open self-harmers, factitious disorder patients appear strikingly inconspicuous.     

Safety of nerve conduction studies in patients with implantable cardioverter-defibrillators

Objective

A patient with an implantable cardioverter-defibrillator (ICD) may suffer from neuromuscular disorders and may need to undergo a nerve conduction study (NCS). However, a NCS may be a source of electromagnetic interference (EMI).The aim of the present study was to investigate whether the interference from NCS used in a standardised test protocol affects ICD function.

Methods

Twenty patients (19 males; mean age of 59.8 ± 9.9 years) with implantable ICDs (eight with integrated and 12 with true bipolar leads), treated with amiodarone and with symptoms suggesting neuropathy were included. NCS were conducted using repetitive stimulation with frequency of 2 Hz and single, rectangular pulses of intensity up to 100 mA. Stimulation was performed in standard sites including proximal sites in the arm.

Results

The impulses generated NCS were not detected by the ICD, irrespective of the site, rate or stimulus intensity.

Conclusions

Standardised test protocol for an NCS is safe in patients with an ICD regardless of the leads type.

Significance

Current guidelines which limitate the NCS in patients with ICD may be the subject of revision.     

Periprocedural anticoagulation practices in warfarin-treated patients who require elective angiography with or without percutaneous coronary intervention: A retrospective chart review

Introduction

It may be possible to safely perform some procedures without interrupting warfarin therapy. Coronary angiography with or without percutaneous coronary intervention (PCI) is one such procedure. However, before further high quality research can be performed in this area, information such as current practice and associated event rates is required.

Materials and methods

We performed a retrospective chart review of 100 charts from a tertiary interventional cardiology referral centre. The primary outcome was access site bleeding. The perioperative anticoagulation strategy for each patient was also recorded.

Results and conclusions

All patients were managed with a strategy of warfarin interruption with or without bridging with a heparin. This was associated with an access site event rate of 2%. These results can be used to inform the design of high quality prospective studies, aimed at determining optimal anticoagulation management strategy in warfarin-treated patients who require coronary angiography or PCI.     

Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes

Background

Polyunsaturated fatty acids (PUFAs) are intrinsic cell membrane components and closely involved in neurotransmission and receptor function. Lower omega-3 levels are associated with increased risk of coronary artery disease (CAD), increases in cardiac events in CAD patients, and depression. We sought to examine relationships between depression and serum levels of omega-3 and omega-6 PUFAs in patients recovering from acute coronary syndromes (ACS).

Methods

We carried out a case-control study of serum PUFA levels and current major depression in 54 age- and sex-matched pairs approximately 2 months following ACS.

Results

Depressed patients had significantly lower concentrations of total omega-3 and docosahexaenoic acid (DHA), and higher ratios of arachidonic acid (AA) to DHA, AA to eicosapentaenoic acid (EPA), and n-3 to n-6 than controls. There were no baseline differences in any potential risk or protective factors for depression.

Conclusions

Results are consistent with previous reports in depressed patients without CAD, and with literature concerning omega-3 levels and risk of CAD events. Dietary, genetic, and hormonal factors may all play a role in both depression and CAD. Both prospective studies and randomized trials are needed to help clarify the interrelationships.     

Patient and general practitioner preferences for the treatment of depression in patients with cancer: How, who, and where?

Objective

The objective of this study was to determine and compare patient and general practitioner (GP) preferences for the treatment of depression in patients with cancer.

Methods

A treatment preference questionnaire was completed by 100 patients who had been diagnosed with both cancer and major depressive disorder and by 86 GPs who had had experience of at least 1 patient with cancer and depression. Participants were asked to rank options for how depression should be treated, who should deliver the treatment, and where treatment should occur.

Results

The top three preferences of patients and GPs for how depression should be treated differed (P<.001). Patients preferred talking treatment alone, whereas GPs preferred a combination of drug and talking treatment. Both patients and GPs preferred treatment to be given by the GP, with older patients having a stronger preference for this. Counselors and cancer nurses were also popular preferences; mental heath professionals were unpopular. The preferred place of treatment was primary care for both patients and GPs, although many patients preferred treatment in the cancer center.

Conclusion

Effective and acceptable services for depressed cancer patients need to take patients and GP preferences into account. A model of service that allows a choice of initial treatment modality and collaborative care between primary care and cancer center nurse would meet this requirement.     

Metacognitions and negative emotions as predictors of symptom severity in chronic fatigue syndrome

Objective

Chronic fatigue syndrome (CFS) describes a condition that is primarily characterized by fatigue and flu-like symptoms that are not alleviated by rest. This study investigated the relationship among metacognitions, negative emotions, and symptom severity in CFS.

Methods

A total of 96 patients who had received a diagnosis of CFS according to the Oxford Criteria completed a battery of self-report measures that consisted of the Depression Anxiety Stress Scales, the 30-Item Metacognitions Questionnaire, the Chalder Fatigue Questionnaire (CFQ), and the RAND 36-Item Short-Form Health Survey-Physical Functioning.

Results

Correlation analyses showed that negative emotions and metacognitions were positively correlated with measures of symptom severity and that metacognitions were a better predictor of symptom severity than anxiety and depression. Hierarchical regression analyses indicated that (1) lack of cognitive confidence predicted both mental and physical factors of the CFQ and physical functioning independently of negative emotions and (2) beliefs about the need to control thoughts predicted the mental factor of the CFQ independently of negative emotions and lack of cognitive confidence.

Conclusion

The data support the potential application of the metacognitive model of psychological disorder to understanding CFS.     

Platelet-induced inhibition of tumor cell growth

Background

Previous studies have suggested that platelets play a role in hematogenous metastasis of cancer cells by enhancing their survival in and extravasation from the bloodstream. We initiated studies to determine the effect of platelets on the proliferation of tumor cells.

Methods

Intact platelets or platelet subfractions were prepared and used for co-culture with various tumor cell lines of different major histocompatibility complex (MHC) backgrounds. Proliferation of tumor cells was monitored using a colorigenic method; flow cytometry was used to measure apoptosis or the cell cycle in L1210 cells.

Results

Co-culture of platelets with tumor cells inhibited proliferation of tumor cells in an MHC-independent manner; soluble factors released from platelets as well as physical contact between platelets and tumor cells were involved. Cell-cycle analysis showed that platelets inhibited proliferation mainly through arrest of the cell cycle and inhibition of DNA synthesis. Neither cytotoxicity nor apoptosis mechanisms dominate in the platelet-induced inhibition of tumor cell proliferation.

Conclusion

We observed that murine platelets inhibit growth of tumor cells in vitro in an MHC-I-independent way, and this inhibition is not limited to specific tumor types, nor is it dependent on cytotoxicity or apoptotic pathways; rather it relies on impairment of the cell cycle.     

The platelet hyporeactivity of extremely low birth weight neonates is age-dependent

Introduction

We have previously demonstrated that, as compared to adults, the platelets of extremely low birth weight (ELBW) neonates are markedly hyporeactive on day 0 - 1 of life. The purpose of this study was to examine the age dependency of this hyporeactivity.

Materials and Methods

On days 0 - 1, 3 - 4, and 10 - 14, peripheral blood was collected from 14 stable ELBW neonates and compared to peripheral blood from normal adults run in parallel. Whole blood flow cytometry was used to examine the activation-dependent increase in platelet surface P-selectin (reflecting degranulation) and platelet surface binding of factor V/Va (reflecting platelet surface procoagulant activity) and decrease in platelet surface glycoprotein (GP) Ib (the von Willebrand factor receptor).

Results

In the physiologic milieu of whole blood, ELBW neonatal platelets on days 0 - 1 and 3 - 4 were markedly less reactive than adult platelets. However, by day 10 - 14, the platelet function of ELBW neonates improved significantly, although not completely to adult levels.

Conclusions

The age-dependent platelet hyporeactivity of ELBW neonates demonstrated in this study may be a contributing factor to the similar age-dependent propensity of ELBW neonates to intraventricular hemorrhage.     

Venlafaxine-induced acute eosinophilic pneumonia

Introduction

Acute Eosinophilic Pneumonia (AEP) is a severe syndrome which can be potentially induced by many reasons, including drugs. It is characterized by pulmonary infiltrates, peripheral blood eosinophilia and respiratory failure. AEP has rarely been associated with antidepressant treatment.

Case report

We report a case of an 80-year-old woman who presented with fever, lung infiltrates, peripheral blood eosinophilia and acute respiratory failure. All evidence charge venlafaxine as the only possible causal factor. The syndrome rapidly resolved after discontinuation of the drug and upon reception of corticosteroids in low doses. The patient had a past medical history of AEP induced by sertraline and a recent medical history of Acute Lung Injury on the context of acute pancreatitis during treatment with venlafaxine.

Discussion

Pathophysiological mechanisms implicated in the development of AEP in our patient seems to be associated with eotaxin and serotonin eosinophilic-specific chemoattracting action.

Conclusion

This is a case report with clinical adverse reaction of AEP in two antidepressant agents (venlafaxine and sertraline) with a similar neurochemical mechanism of action via the serotoninergic system.     

A new scale for assessing the quality of randomized clinical trials of psychotherapy

Context

In 2004, the American Psychiatric Association's Committee on Research on Psychiatric Treatments appointed a subcommittee to investigate the status of empirical evidence with regard to psychodynamic psychotherapy.

Objective

As a part of this effort, the committee developed a rating scale designed to assess the quality of randomized controlled trials (RCTs) of psychotherapy.

Data Sources

A 25-item RCT of Psychotherapy Quality Rating Scale was generated by expert consensus. Interrater reliability, internal consistency, and validity testing were undertaken using 7 trained raters.

Study Selection

A PubMed search was conducted to locate all RCTs of psychotherapies identified by their authors as being “psychodynamic” or “psychoanalytic” in origin and implementation.

Data Extraction

A total of 69 RCTs were independently rated by 2 raters.

Data Synthesis

The scale was found to have good interrater reliability (total score intraclass correlation = 0.76), internal consistency (Cronbach α = .87), and external validity.

Conclusions

This scale establishes a new standard for the design and execution of psychotherapy RCTs and provides a systematic empirical method for evaluating the quality of published RCTs.     

Short duration repetitive transcranial magnetic stimulation for tinnitus treatment: a prospective Asian study

Background

Tinnitus is a subjective auditory perception of sounds or noise not triggered by external auditory stimuli. To date, treatment in severe cases is generally unsatisfactory. Characteristic functional brain imaging changes associated with tinnitus include hyperactivity encompassing both the primary auditory cortex (AC) and the secondary or associative cortex. Brief repetitive transcranial magnetic stimulation (rTMS) trains applied to the scalp overlying the hyperactive left AC is known to produce moderate tinnitus attenuation.

Objective

Although Western studies have documented the value of rTMS in tinnitus treatment, we evaluate the efficacy of a short duration rTMS protocol for the first time in the Asian setting.

Method

Consecutive patients were recruited at our tinnitus clinic. Detailed history, examination, audiogram and baseline tinnitus scales were recorded. RTMS consisted of 1000 pulses/day at 1 Hz and 110% of the motor threshold, for five consecutive days over the left temporoparietal cortex. Tinnitus ratings were determined weekly for 4 weeks after rTMS.

Result

Fifteen patients completed the trial; none experienced significant side effects. Repeated measures ANOVA showed significant linear decrease in Tinnitus Handicap Inventory (THI) scores over the time period (F_(1,14) = 4.7, p = 0.04). However, none of the other parameters (severity, annoyance, effect on lifestyle and overall impression: visual analogue scale) showed beneficial outcomes.

Conclusions

Our findings point to a positive effect of short duration rTMS in tinnitus treatment using the THI. However, no significant benefits were demonstrated for other subjective patient ratings. Although well tolerated and convenient, short duration rTMS may prove inadequate for modulating maladaptive plastic changes at the cortical level, and our results suggest the need for delivery of more stimuli. Future studies will utilize at least 2000 pulses/day, in line with previous experience in Western settings.     

Spontaneous K-complexes in chronic psychophysiological insomnia

Objective

Spontaneous K-complexes are electroencephalographic features unique to non-rapid eye movement sleep. It has been suggested that this phasic event is a sleep-protective mechanism. Because insomnia sufferers report poor sleep quantity and quality, the objective of this study was to document the occurrence of spontaneous K-complexes in Stage 2 sleep of individuals with chronic insomnia. Specifically, the number and density of spontaneous K-complexes were studied in psychophysiological insomnia sufferers.

Setting

This study took place in a sleep and event-related potentials laboratory.

Design

Spontaneous K-complexes were scored during Stage 2 sleep on the second and third nights of a four-consecutive-nights protocol of polysomnographic recordings.

Participants

The sample included 14 participants suffering from psychophysiological insomnia (INS group; mean age=44.1 years) and 14 good sleepers (mean age=38.1 years). Participants underwent sleep and psychological evaluations. INS group participants met the diagnostic criteria for primary psychophysiological insomnia (mean duration of insomnia=9.6 years).

Intervention

Not applicable.

Results

The total number of spontaneous K-complexes and the density according to the total time spent in Stage 2 sleep (spontaneous K-complexes per minute) were compiled. Repeated-measures analyses of variance showed no significant difference in the number and density of spontaneous K-complexes between the INS group (313.98 and 2.66) and the GS group (361.10 and 2.88), respectively.

Conclusion

These results suggest no deficiency in the sleep-protective mechanism of psychophysiological insomnia sufferers in comparison with good sleepers, as measured by the spontaneous K-complexes' number and density.     

Poor creativity in frontotemporal dementia: A window into the neural bases of the creative mind

Background

The prefrontal cortex (PFC) supports functions critical for creative thinking. Damage to the PFC is expected to impair creativity. Yet, previous works suggested the emergence of artistic talent in patients with frontotemporal lobar degeneration (FTLD), which was interpreted as increased creativity.

Objective

We designed a study in patients with frontal variant (fv) of FTLD in order to verify whether: (1) creativity is impaired after frontal degeneration, (2) poor creativity is associated with frontal dysfunctions, and (3) poor creativity is related to hypoperfusion in specific PFC regions.

Materials and methods

Three groups of subjects were enrolled in the study: fvFTLD patients (n = 17), non-demented Parkinson's disease (PD) patients (n = 12) and healthy controls (n = 17). Participants performed a standardized test of creativity, the Torrance Test of Creative Thinking (TTCT) and tests assessing frontal functions. Brain perfusion was correlated to fvFTLD patients’ performance in the TTCT.

Results

Patients with fvFTLD were strongly impaired in all dimensions of the TTCT, compared to PD patients and controls. Disinhibited and perseverative responses were observed only in fvFTLD patients, leading to “pseudo-creative” responses. Poor creativity was positively correlated with several frontal tests. Poor creativity was also correlated with prefrontal hypoperfusion, particularly in the frontal pole.

Conclusions

Poor creativity is associated with fvFTLD. The results also suggest that the integrity of the PFC (in particular frontopolar) is strongly associated with creative thinking. The emergence of artistic talent in patients with fvFTLD is explained by the release of involuntary behaviors, rather than by the development of creative thinking.     

Which electrophysiological measure is appropriate in predicting prognosis of facial paralysis?

Objective

The prognostic value of electrophysiology and its significance in the prediction facial function outcome in facial palsy patients remains unclear because of the different methodologies used in previous studies. We aimed to establish the prognostic value of electrophysiological testing in a group of patients with facial palsy.

Methods

We prospectively analyzed facial nerve electrophysiology results and compared them with the House–Brackmann scale in 65 patients. The treatment consisted of a standard corticosteroid plus antiviral regimen. Clinical evaluation comprised the House–Brackmann grading system and electrophysiological tests (nerve excitability, nerve conduction study (NCS), needle electromyography (EMG), and blink reflex) conducted on the 5th, 20th, and 90th days after paralysis onset.

Results

In predicting the prognosis, the nerve excitability test in the acute phase, NCS in the subacute phase, blink reflex in the acute and subacute phases and needle EMG in the subacute phase provided statistically significant results.

Conclusion

Prognosis can be determined, and excessive tests can be eliminated with proper timing and electrophysiological testing.

Significance

In determining the prognosis of facial paralysis, the nerve excitability test should be used in the acute phase, and NCS and needle EMG should be used in the subacute phase. Blink reflex studies are helpful in both the acute and subacute phases.