Assessment of the post-implant final left ventricular lead position: a comparative study between radiographic and angiographic modalities

Purpose

Post-implant lateral and postero-anterior chest X-rays (CXR) are often utilized to determine the final LV lead tip position after cardiac resynchronization therapy (CRT). This study sought to compare post-implant standard CXRs with intra-procedural rotational coronary venous angiography (RCVA) to localize the final LV lead position.

Methods

Sixty-four patients undergoing CRT (69.2?±?11.4 years; males 68.7%; ischemic cardiomyopathy 59.4%; NYHA class 2.9?±?0.5 and LV ejection fraction 24%?±?9%) were included in the study. RCVA was done by recording a rapid 4-second isocentric cine-loop from RAO 55° to LAO 55° (120 frames). Conventional CXR method (CC) and a composite CXR strategy (CM) based on two-view CXR were separately compared with RCVA.

Results

The most common pacing site was lateral (64.1%), followed by postero-lateral (23.4%) and antero-lateral (10.9%). In 73.4% (47) cases, the LV lead position was misclassified by CC as compared to RCVA. Among the 47 (73.4%) cases misclassified by CC approach, 35 had lateral LV lead position misclassified by CC as postero-lateral (77%), posterior (20%) and antero-lateral (3%). On the other hand, CM strategy classified the LV lead position correctly in 46 (71.9%) of the patients (p?<?0.0001).

Conclusions

The composite CXR strategy is a useful method for post-procedure LV lead localization. Due to its simplicity, it can be widely applied in post-implant evaluation of LV lead position in CRT patients.     

Can genetics inform the management of cognitive deficits in schizophrenia?

There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.     

Diagnostic utility of skin biopsy in dystrophinopathies

Aims

Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy.

Methods

Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies.

Results

Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%).

Conclusion

Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy.     

A unique case of cortical myoclonus sensitive to visual stimuli in the peripersonal space

Multimodal representation of peripersonal or near space has been demonstrated in the brain of the nonhuman primate through invasive electrophysiological experiments. Representation of peripersonal space in the human brain has been inferred from extinction experiments and functional imaging studies. We present a unique case of lower limb myoclonus in a patient with common variable immunodeficiency which is sensitive to visual stimuli in the peripersonal space and light touch. This case provides further evidence for near space representation in the human brain. We hypothesize that somatopically organized multimodal areas exist in the human brain which code for peripersonal space. © 2008 Movement Disorder Society     

No gender differences in brain activation during the N‐back task: An fMRI study in healthy individuals

Gender differences have been well established in verbal and spatial abilities but few studies have examined if these differences also extend into the domain of working memory in terms of behavioural differences and brain activation. The conclusions that can be drawn from these studies are not clear cut but suggest that even though gender differences might not be apparent from behavioural measures, the underlying neural substrate associated with working memory might be different in men and women. Previous research suggests activation in a network of frontal and parietal regions during working memory tasks. This study aimed to investigate gender differences in patterns of brain activation during a verbal version of the N‐back working memory task, which incorporates the effects of increased demands on working memory. A total of 50 healthy subjects, aged 18 to 58 years, that were equally split by gender were recruited matched for age, levels of education and ethnicity. All subjects underwent functional magnetic resonance imaging. We found that men and women performed equally well in terms of accuracy and response times, while using similar brain regions to the same degree. Our observations indicate that verbal working memory is not affected by gender at the behavioural or neural level, and support the findings of a recent meta‐analysis by Hyde ([ 2005 ]: Sex Roles 53:717–725) that gender differences are generally smaller than intra‐gender differences in many cognitive domains. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Mechanisms of potentiation of Angiotensin II-induced contractile response of isolated rat aorta by hydrogen peroxide and tert-butyryl hydroperoxide

Objective:

To study the mechanism involved in hydrogen peroxide (H₂O₂) or tert-butyl hydroperoxide (t-BHP)-induced potentiation of the Ang II-mediated contraction of isolated rat thoracic aorta.

Materials and Methods:

Thoracic aorta was isolated from the Sprauge dawley rats (300–320 gm), cut spirally and response to Ang II (5 × 10⁻⁸M) was taken in the absence and presence of H₂O₂ (10⁻⁶M) and t-BHP (10⁻⁵M). To explore the probable mechanism of H₂O₂ and t-BHP-induced potentiation of Ang II-mediated contractile response, different blockers such as losartan (AT₁ receptor blocker; 1 μM), catalase (H₂O₂ scavenger; 500 U/ml), lercanidipine (L-type calcium channel blocker; 1 μM), geinistein (tyrosine kinase inhibitor; 100 μM), and indomethacin (cyclo-oxygenase inhibitor; 10 μM) were used.

Results:

In spiral preparation of rat thoracic aorta, H₂O₂ (10⁻⁶M) and t-BHP (10⁻⁵M) did not produce the contraction as such. However, when they are added simultaneously with Ang II (5 × 10⁻⁸ M), they potentiated the contractile response of the Ang II. Catalase (500 U/ml) partially antagonized the Ang-II-induced contraction, as well as antagonized the potentiation induced by H₂O₂. Losartan (1 μM) and lercanidipine (1 μM) antagonized the Ang II-induced contractile response without affecting H₂O₂ (10⁻⁶M)-mediated potentiation. Geinistein (100 μM) antagonized H₂O₂ (10⁻⁶M)-mediated potentiation, but it slightly decreased the Ang II response. Losartan (1 μM) and lercanidipine (1 μM) and Geinistein (100 μM) antagonized the Ang II-induced contractile response but not t-BHP-mediated potentiation. Indomethacin antagonized t-BHP-mediated potentiation without affecting much of Ang II response.

Conclusion:

From the above-mentioned results, we can reasonably conclude that H₂O₂ and t-BHP potentiated the contraction induced by the Ang II. H₂O₂-induced potentiation of Ang II response may be mediated through tyrosine kinase activation and t-BHP through the activation of cyclo-oxygenase enzyme.     

Regional cortical thinning in subjects with violent antisocial personality disorder or schizophrenia

Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.     

Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP)

The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (E_Man) was examined. While the C4BP concentration for inhibiting 50% (IC₅₀) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05 nM), 3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81 nM) and E_Man (42.66 nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000–431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79 ± 0.60) when the C4b density on E_Man was increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a 7- to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions.     

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

Objective  

To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.