Mon2-monocytes and increased CD-11b expression before transcatheter aortic valve implantation are associated with earlier death.

BACKGROUND: In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation. METHODS: Flow-cytometric quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-expression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests. RESULTS: Elevated Mon2 (CD14++CD16+) - monocytes (38 vs. 62 cells/µl, p < 0.001) and a high expression of CD11b prior to TAVI (MFI 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death. CONCLUSIONS: Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI.

Students' perceptions of a near-peer Objective Structured Clinical Examination (OSCE) in medical imaging.

INTRODUCTION: Near-peer learning, where peers from more senior year levels teach more junior peers is a popular teaching strategy in healthcare education. There is an emerging trend to utilise this teaching strategy in preparing students for Objective Structured Clinical Examinations (OSCEs) in the form of near-peer led formative OSCEs (NP-OSCE). However, there is little exploration of this teaching strategy in medical imaging education, nor how students perceive NP-OSCEs as beneficial to their learning. This study addresses this gap. METHODS: Using a students as partners inquiry approach, 47 near-peer learners' (NPLs) and 6 near-peer teachers' (NPTs) perceptions of participating in a NP-OSCE were examined using an anonymous self-report questionnaire. RESULTS: NPLs reported that participating in the immersive NP-OSCE helped their performance in the summative OSCE by helping with their preparedness; including understanding expectations, experiencing emotions and being able to identify gaps in their knowledge and skills, which they then used to direct their revision in a manner that demonstrated the development of skills in evaluative judgement. There were mixed findings regarding the impact the NP-OSCE had on NPLs' levels of anxiety. NPTs also found the NP-OSCE beneficial for identifying gaps in their own knowledge and skills, yet found taking on the role of an examiner challenging. CONCLUSION: Students perceive NP-OSCEs as a valuable learning activity that helps them prepare for their OSCEs by providing a student perspective of an authentic immersive learning experience. NP-OSCEs enable students to focus their revision and develop skills in evaluative judgement. IMPLICATIONS FOR PRACTICE: Educators should consider including NP-OSCEs in their medical imaging curriculum as students perceive it as a valuable learning experience that assists them to prepare for their OSCE.

Elevated cardiac troponin T indicating myocardial infarction or myocarditis-urgent cardiac catheter examination-or do we have to consider other reasons?

Alveolar rhabdomyosarcoma is an aggressive tumour in adulthood, in which cardiac troponin T seems to be a tumour marker and course parameter. We present the clinical course of a young man suffering from this rare disease and the development of troponin T during therapy. Noninvasive cardiac imaging was used to exclude cardiac involvement, myocardial infarction or inflammation processes.

Evaluation and classification of right ventricular wall motion abnormalities in healthy subjects by 3-tesla cardiovascular magnetic resonance imaging.

BACKGROUND: Right ventricular (RV) shape and function serves as an indicator in several types of heart disease such as arrhythmogenic right ventricular dysplasia (ARVD). However, there is no in-depth knowledge of RV motion, even in healthy subjects. The aim of our study was to provide a quantitative analysis of normal variations in RV wall motion in healthy subjects by cardiac magnetic resonance imaging (CMRI). MATERIAL AND METHODS: The study population consisted of 65 consecutive patients referred for the evaluation of cardiac function by 3 Tesla CMR. Balanced steady-state free-precession images were obtained and areas of disordered RV wall motion were evaluated and classified based on a standardised segmental model for the right ventricle. RESULTS: In 59 patients (90.8 %) wall motion abnormalities (WMA) of the right ventricle were evident. WMA were predominately detected in the apicolateral segments (72 %) compared with mediolateral (24 %, P < 0.001) and inferolateral segments (4 %, P < 0.001). Dyskinesia was the most frequent wall motion disorder (62.4 %), followed by hypokinesia (20.8 %) and bulging (16.8 %). The mean WMA diameter in the transverse plane (6.4 ± 1.9 mm) was significantly shorter compared with the diameter in the horizontal long-axis (8.1 ± 3.6 mm, P = 0.002) and short-axis plane (10.7 ± 4.6 mm). CONCLUSION: WMA of the right ventricle are common. Therefore, one should be aware that these nonpathological wall motion disorders can easily be mistaken for a pathological regional wall motion contraction, particularly in ARVD where to date, clear wall motion criteria are lacking.

High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest.

INTRODUCTION: After cardiac arrest due to acute coronary syndromes (ACS) therapeutic hypothermia (HT) is the standard care to reduce neurologic damage. Additionally, the concomitant medical treatment with aspirin and a P2Y12 receptor inhibitor like clopidogrel (Cl), prasugrel (Pr) or ticagrelor (Ti) is mandatory. The platelet inhibitory effect of these drugs under hypothermia remains unclear. METHODS: 164 patients with ACS were prospectively enrolled in this study. 84 patients were treated with HT, 80 patients were under normothermia (NT). All patients were treated with aspirin and one of the P2Y12 receptor inhibitors Cl, Pr or Ti. 24h after the initial loading dose the platelet reactivity index (PRI/VASP-index) was determined to achieve the platelet inhibitory effect. RESULTS: In the HT-group the PRI/VASP-index was significantly higher compared to the NT-group (54.86%±25.1 vs. 28.98%±22.8; p<0.001). In patients under HT receiving Cl, the platelet inhibition was most markedly reduced (HT vs. NT: 66.39%±19.1 vs. 33.36%±22.1; p<0.001) compared to Pr (HT vs. NT: 37.6%±25.0 vs. 27.04%±25.5; p=0.143) and Ti (HT vs. NT: 41.5%±21.0 vs. 17.83%±14.5; p=0.009). The rate of non-responder defined as PRI/VASP-index>50% was increased in HT compared to NT (60.7% vs. 22.5%; p<0.001) with the highest rates in the group receiving Cl (CL: 82% vs. 26%, p<0.001; Pr: 32% vs. 23%; n.s.; Ti: 30% vs. 8%, n.s.). CONCLUSION: The platelet inhibitory effect in patients treated with HT after cardiac arrest is significantly reduced. This effect was most marked with the use of Cl. The new P2Y12-inhibitors Pr and Ti improved platelet inhibition in HT, but could not completely prevent non-responsiveness.

[Time-resolved autofluorescence in retinal vascular occlusions]. / Zeitaufgelöste Autofluoreszenz bei retinalen Gefäßverschlüssen.

BACKGROUND: Cellular metabolism can be evaluated using time-resolved autofluorescence. Because the fluorescence of ocular tissue is an accumulation of the fluorescence of several endogenous fluorophores, it is hard to determine the influence of a single fluorophore. In branch retinal artery occlusion, metabolic changes can be compared with normal tissue. METHOD: Time-resolved autofluorescence was measured in two patients in two spectral channels, K1 (490-560 nm) and K2 (560-700 nm), and was 3-exponentially approximated and compared with representative results of a healthy eye. RESULTS: In K1, lifetime τ1 in the undersupplied tissue was weak, but τ2 was strongly elongated compared with the healthy tissue. In K2, the distribution of τ2 was identical in both tissues. In the healthy eye, there was an equal distribution of all lifetimes in corresponding fundus regions. CONCLUSIONS: The elongation of τ1 in undersupplied tissue is probably caused by a reduced contribution of protein-bound FAD. The elongation of τ2 (about 500 ps) in healthy tissue, compared to about 1.5 ns in undersupplied tissue, is probably caused by protein-bound NADH, which is formed in glycolysis.

[Comparison of parameters of time-resolved autofluorescence between healthy subjects and patients suffering from early AMD]. / Vergleich von Parametern der zeitaufgelösten Autofluoreszenz bei Gesunden und Patienten mit früher AMD.

BACKGROUND: A fluorescence lifetime mapper (FLM) was tested for quantitative estimation of early alterations in age-related macular degeneration (AMD) which are assumed to be in cellular metabolism. METHOD: In FLM time-resolved autofluorescence of the fundus is excited by picosecond (ps) laser impulses at 448 nm and detected in 2 spectral ranges (K1=490-560 nm and K2=560-700 nm) by time-correlated single photon counting. The time-dependent decrease in fluorescence intensity was approximated using 3 decay rates. The calculated lifetimes allow a comparison with endogenous fluorophores of cellular metabolism. RESULTS: Initially mean lifetimes were determined for 8 healthy subjects (K1: tau1=118 ps, tau2=584 ps, tau3=2826 ps, K2: tau1=104 ps, tau2=477 ps, tau3=1623 ps). In 15 AMD patients (AREDS categories I and II) the lifetimes were longer (K1: tau1=166 ps, tau2=986 ps, tau3=3309 ps, K2: tau1=137 ps, tau2=583 ps, tau3=1924 ps). The best separation between healthy subjects and patients with early AMD was possible by parameters 1 and 2 in the short-wave channel. Fluorophore-specific alterations in the macula could be demonstrated in isolated cases with advanced AMD. CONCLUSION: Measurements in the 30 degrees fundus field demonstrated that specific alterations were already present even in early AMD and also outside the macula. These act in the neuronal retina, because parameter tau2 is related to this layer. Increases in the lifetime of parameter tau2 in the short wave channel could at least partially be determined by an increase of protein bound NADH, the content of which increases with reduced cellular respiration.

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus.

OBJECTIVE: To define the phenotype and function of CD4+,CD25+ regulatory T cells (Treg) in patients with cutaneous lupus erythematosus (CLE), a heterogeneous autoimmune disease characterized primarily by inflammatory skin lesions. METHODS: The number of Treg in skin specimens obtained from patients with various subtypes of CLE was investigated by immunohistochemical analysis, using anti-Foxp3 and anti-CD4 monoclonal antibodies. Furthermore, characterization of peripheral blood CD4+,CD25+ Treg from normal healthy donors and patients with CLE was carried out by flow cytometry, analyzing the expression of Foxp3 and Treg subpopulations. We also purified CD4+,CD25(high) Treg obtained from patients with CLE and tested the sensitivity of these cells to CD95L-mediated apoptosis. RESULTS: Quantitative analysis of CD4+ T cells in skin lesions from patients with CLE revealed that the number was similar to that in lesions from patients with other chronic inflammatory diseases, but the number of Foxp3+ Treg in CLE was significantly reduced. There was no correlation between disease subtype and the frequency of Foxp3+ Treg in the skin of patients with CLE. In peripheral blood, no significant differences were observed in the number and phenotype of CD4+,CD25+ Treg or in the sensitivity to apoptosis of CD4+,CD25(high) Treg derived from patients with CLE and those derived from normal healthy donors. CONCLUSION: These data suggest that an organ-specific abnormality of Treg in the skin underscores the importance of analyzing Treg in the affected tissue. Such a local process might give insight into the pathogenic mechanisms of CLE and differs from a global peripheral dysfunction as reported for patients with a systemic manifestation of the disease.

Arbovirus infection increases with group size.

Buggy Creek (BCR) virus is an arthropod-borne alphavirus that is naturally transmitted to its vertebrate host the cliff swallow (Petrochelidon pyrrhonota) by an invertebrate vector, namely the cimicid swallow bug (Oeciacus vicarius). We examined how the prevalence of the virus varied with the group size of both its vector and host. The study was conducted in southwestern Nebraska where cliff swallows breed in colonies ranging from one to 3700 nests and the bug populations at a site vary directly with the cliff swallow colony size. The percentage of cliff swallow nests containing bugs infected with BCR virus increased significantly with colony size at a site in the current year and at the site in the previous year. This result could not be explained by differences in the bug sampling methods, date of sampling, sample size of the bugs, age structure of the bugs or the presence of an alternate host, the house sparrow (Passer domesticus). Colony sites that were reused by cliff swallows showed a positive autocorrelation in the percentage of nests with infected bugs between year t and year t+1, but the spatial autocorrelation broke down for year t+2. The increased prevalence of BCR virus at larger cliff swallow colonies probably reflects the larger bug populations there, which are less likely to decline in size and lead to virus extinction. To the authors' knowledge this is the first demonstration of arbovirus infection increasing with group size and one of the few known predictive ecological relationships between an arbovirus and its vectors/hosts. The results have implications for both understanding the fitness consequences of coloniality for cliff swallows and understanding the temporal and spatial variation in arboviral epidemics.

Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. Hertfordshire Neuroscience Research Group.

Several case reports have engendered concern about the safety of coadministering lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and there are theoretical reasons to suppose that lithium and serotonergic antidepressants may be associated with dangerous interactions. Systematic reports regarding combination therapy with lithium and SSRI antidepressants were assimilated for the purpose of this review. Although there are many publications, few are directly informative as to safety and tolerability. A total of 503 patients are considered in systematic reports and, among these, no serious or life-threatening adverse events can be identified. Such data as there are demonstrate little potential for toxic interactions between lithium and SSRIs, although new, non-serious, adverse events do frequently arise. The evidence for the efficacy of addition of lithium to SSRIs in treatment refractory depression is only provisional.

A protocol for the pharmacologic treatment of major depression. A field test of a potential prototype.

BACKGROUND: Much attention is being given to developing clinical practice guidelines for management of mental health disorders. The aim of this study was to field test a prototype protocol for the pharmacologic treatment of Major Depression. METHOD: The protocol consisted of four, six week, treatment phases with critical choices in therapy defined by scores on the MADRS (Montgomery Asberg Depression Rating Scale). Observational data as collected on the behaviour of the protocol in terms of relevance, acceptability, ease of use and effectiveness. RESULTS: Effectiveness of the protocol was good for those patients who were retained within it, with three quarters of them attaining remission. However more than half of all patients dropped out-non attendance and adverse events being the most common reasons for this. CONCLUSION: The protocol for the treatment of Major Depression appeared relevant, easy to use and potentially effective. LIMITATION: Problems with non-adherence by both doctors and patients posed major challenges to the protocol's design. Such difficulties demonstrate the need to field test any proposed design as preconceptions about a protocol's performance may be misplaced. CLINICAL RELEVANCE: The protocol tested represents progress towards the goal of developing optimal strategies for the use of pharmacotherapeutic agents in the treatment of depression.

A preliminary study to examine the adequacy of long-term treatment of depression and the extent of recovery in general practice.

About 1% of patients in general practice take antidepressants for long periods. Many receive repeat prescriptions, without review. It might be assumed that these patients are well and are on adequate maintenance treatment. Our findings refute this assumption; of 78 patients on long-term repeats, only a third were in remission and a fifth had Beck Depression Inventory scores suggesting persisting syndromal major depression. Subtherapeutic dosing of classic tricyclics was the norm rather than the exception. Patients on long term antidepressant treatment need regular review and adequate treatment to ensure remission is maintained.

A review of the psychomotor effects of paroxetine.

All 10 placebo-controlled studies of the psychomotor effects of paroxetine are reviewed. The total number of subjects is 195. The majority of studies show little or no effect of paroxetine on psychomotor function. No adverse effects are apparent at the dose of 20 mg/day, although minor impairments can be identified at 40 mg/day. An overview of the data indicates that at the standard therapeutic dose of 20 mg/day, paroxetine has no psychomotor or behavioural toxicity.

Safety and tolerability of combined treatment with moclobemide and SSRIs: a systematic study of 50 patients.

Fifty major depressed patients, resistant to multiple pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess tolerability. There were 188 adverse events: insomnia, dizziness, headache, nausea, dry mouth and myoclonic jerks were the most common. Many events were rated as severe. The high rate of adverse events suggest that there are clinically significant pharmacodynamic interactions between moclobemide and SSRIs. However the uncontrolled data on effectiveness is encouraging and the combination deserves further consideration as a strategy for treating intractable depression.

Fetal alcohol syndrome: the nurse practitioner perspective.

Fetal alcohol syndrome is the leading cause of mental retardation in the United States. The tragedy is that while FAS is irreversible, it is 100% preventable. FAS is caused by maternal consumption of alcohol during pregnancy. Alcohol is a teratogen and acts in different ways to produce physical and central nervous system malformations and defects in the developing embryo and fetus. FAS is characterized by a history of maternal alcohol ingestion, central nervous system dysfunction, growth deficiencies, and specific physical anomalies. Adolescents and adults with FAS have behavioral problems that differentiate them from other mentally disabled individuals. Nurse practitioners can have an impact on the prevalence of FAS by educating clients about FAS and its relationship to alcohol consumption. NPs need to carefully identify high-risk women and their partners before a pregnancy occurs and assist with interventions to stop active alcoholism or alcohol use during pregnancy. NPs have the capability to decrease the severity of alcohol's effects during pregnancy through education, counseling, and intervention. NPs have the skills to work with case-finding and early identification of infants and children who display signs and symptoms of FAS. With such case-finding, early identification, and prompt referral to the appropriate diagnostic and/or supportive community agencies, individuals with FAS can receive timely intervention to minimize the effects of FAS. Adults with behavioral problems can be assessed for FAS and referred for appropriate assistance as well. Finally, NPs can facilitate public awareness of FAS through educational efforts with individuals, families, and communities.

Safety and tolerability of combined treatment with moclobemide and SSRIs: a preliminary study of 19 patients.

Nineteen major depressed patients, resistant to previous pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess the adverse events and tolerability. There were 77 emergent events, insomnia, headache, nausea and dizziness being the most common. Many events were rated as severe. The high rate of adverse events suggests that there may be clinically significant interactions between moclobemide and SSRIs. However, the uncontrolled data on effectiveness is encouraging and the combination deserves further attention as a strategy for treating intractable major depression.