Performance of Dedicated Versus Integrated Bipolar Defibrillator Leads with CRT-Defibrillators: Results from a Prospective Multicenter Study

Introduction: Right ventricular (RV) anodal stimulation may occur in cardiac resynchronization therapy defibrillators (CRT-D) when left ventricular (LV) pacing is configured between the LV lead and an electrode on the RV defibrillator lead. RV defibrillator leads can have a dedicated proximal pacing ring electrode (dedicated bipolar) or utilize the distal shocking coil as the proximal pacing electrode (integrated bipolar). This study compares the performance of integrated versus dedicated leads with respect to anodal stimulation incidence, sensing, and inappropriate ventricular tachyarrhythmia detection in patients implanted with CRT-D.
Methods: Two hundred ninety-two patients were randomly assigned to receive dedicated or integrated bipolar RV leads at the time of CRT-D implantation. Patients were followed for 6 months.
Results: Patients with dedicated bipolar RV leads exhibited markedly higher rates of anodal stimulation than did patients with integrated leads. The incidence of anodal stimulation was 64% at implant for dedicated bipolar RV leads compared to 1% for integrated bipolar RV leads. The likelihood of anodal stimulation in patients with dedicated leads fell progressively during the 6-month follow-up (51.5%), but always exceeded the incidence of anodal stimulation in patients with integrated leads (5%). Clinically detectable undersensing and oversensing were very unusual and did not differ significantly between lead designs. There were no inappropriate ventricular tachyarrhythmia detections for either lead type.
Conclusion: Integrated bipolar RV defibrillator leads had a significantly lower incidence of RV anodal stimulation when compared to dedicated bipolar RV defibrillation leads, with no clinically detectable oversensing or undersensing, and with no inappropriate ventricular tachyarrhythmia detections for either lead type.     

Drugs and Psychosis Project: A multi‐centre European study on comorbidity

Introduction and Aims. This paper describes the sociodemographic characteristics of 196 psychotic patients admitted to acute psychiatric wards in the UK, Denmark, Germany and Italy, with the aim of comparing comorbid with non‐comorbid patients. Design and Methods. It is a prospective field study with repeated measures at 1, 6 and 12 months. Patients were recruited from acute psychiatric wards in four European centres. They were grouped as comorbid or not on the basis of urine analysis. The Schedules for Clinical Assessment in Neuropsychiatry was used to provide a psychiatric diagnosis, and the Positive and Negative Symptom Severity Scale for further information on specific symptoms with results from the Fragerstrom test for nicotine dependence also reported. Results. Comorbid patients were younger than those who were not but did not differ significantly in the other sociodemographic measures. Differences in sociodemographic characteristics of patients between centres were apparent. Comorbid patients had higher levels of positive and lower levels of negative symptoms than those who were non‐comorbid. Differences were found in the patterns of drug use between comorbid patients who were using cannabis compared with those who were not. Discussion and Conclusions. Cross‐cultural differences in the sociodemographic characteristics of the comorbid patient population give us a better insight into this heterogenous group.[Baldacchino A, Blair H, Scherbaum N, Grosse‐Vehne E, Riglietta M, Tidone L, Criaco C, Marelli MC, Sommer B, Tan L, Little H, Ghodse H. Drugs and Psychosis Project: A multi‐centre European study on comorbidity. Drug Alcohol Rev 2009;28:379–389]     

Determinants of endotoxin levels in living environments of farmers'' children and their peers from rural areas

BACKGROUND: Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non-farming households. OBJECTIVE: The aim of the present study was to investigate which home and lifestyle characteristics of farm and non-farm families contribute to endotoxin levels measured in different indoor home environments. METHODS: In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non-farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus-Amebocyte-Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires. RESULTS: Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose-dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non-farm children. In non-farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure. CONCLUSION: These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non-farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels.     

Programmed Cell Death of Peripheral Blood B Cells Determined by Laser Scanning Cytometry in Sjögren’s Syndrome with a Special Emphasis on BAFF

Functionally impaired B cells play an important role in the pathogenesis of Sjögrens syndrome (SS). The aim of the study was to investigate the apoptosis susceptibility of peripheral blood B cells from patients with SS and the impact of B cell activating factor (BAFF) on the apoptosis capability of these cells in correlation with IgG production. Peripheral blood B cells were isolated and stained for apoptosis markers (Bax, Bcl-2) and members of the TNF-R superfamily, CD95 and CD40. The apoptosis frequency of cells bearing these markers were assessed. Also, the apoptosis capability of cultured B-lymphocytes was investigated in medium alone, with anti-CD95 or with soluble BAFF. Quantitative ELISA was performed to detect plasma levels of sBAFF. Furthermore, the level of circulating B-cell cytokines was measured. BAFF levels were compared between patients with normal and elevated IgG levels. In SS, Bcl-2 positive B cell counts were significantly higher then in controls, also in this population the apoptosis frequency was reduced. Apoptosis within Bax+ and CD40+ B cells were significantly decreased in patients. BAFF induced a significant antiapoptotic effect in SS; also this effect was clearly evident in B cells from SS with hypergammaglobulinaemia. Plasma BAFF levels were significantly higher in SS, mostly in patients with hypergammaglobulinaemia. Plasma B-cell cytokines were raised in SS. In Sjögrens syndrome B cells, a general antiapoptotic tendency might lead to prolonged B-cell survival driven at least partly by elevated levels of BAFF and supposedly by B-cell cytokines. Also, the exaggerated BAFF stimulation might lead to excessive immunoglobulin production. The B-cell apoptosis defects, the increased BAFF levels—correlating with hypergammaglobulinaemia—together with the raised B-cell cytokine levels indicates the disturbed B-cell biology in the disease.     

Iodine-125 Irradiation of Choroidal Melanoma: Clinical Experience from the Prince of Wales and Sydney Eye Hospitals

We examined the records of 53 patients treated for choroidal melanoma between 1985 and 1989. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females, aged 20 to 77 years (median 61 years), treated for single tumours with a median diameter of 9mm (range 5 to 15mm) and with a median thickness of 4mm (range 2 to 10mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10mm (16 patients); 15mm (36 patients); 20mm (one patient). All patients are alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients): retinitis (19), optic neuropathy (7); cataract (41, rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. Iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision.     

The Incidence of Retrograde Conduction in Children

With the increasing use of "physiological" pacemakers in the pediatric age group, retrograde conduction in children has become of clinical importance. Pacemakers which sense atrial depolarization may sense "retrograde" P waves. The pacemaker may then act as the antegrade limb of a reciprocating tachycardia circuit, while the patient's own conduction system acts as the retrograde limb. We reviewed the data of 127 patients who underwent antegrade and retrograde electrophysiologic study at Texas Children's Hospital, with regard to retrograde conduction. Sixty percent of the patients had ventriculo-atrial conduction through the A-V node; the incidence of retrograde conduction in patients after surgical correction of a tetralogy of Fallot was significantly lower (33%). None of the patients with third-degree A-V block had retrograde conduction. The mean retrograde conduction time was 162 ms (range 70-335 ms) at the slowest pacing rate and 257 ms (range 80-475 ms) at the fastest pacing rate. This high incidence of retrograde conduction and the variability of conduction times must be taken into account when "physiological" pacemakers are to be implanted.     

NMR structure of neuromedin C,a neurotransmitter with an amino terminal CuII-, NiII-binding (ATCUN) motif

The structure of neuromedin C, a 10-residue bombesin-like neuropeptide with the sequence Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH₂, has been investigated. Like human serum albumin, neuromedin C contains the amino-terminal Cu^II-, Ni^II-binding (ATCUN) motif which has high affinity for Cu^II and Ni^II. The solution structure of the Ni^II-peptide complex has been calculated based on 2D ROESY data obtained at 25°C, using a hybrid distance geometry-simulated annealing approach. Comparison of H, ¹³C and ¹⁵N chemical shifts and ROESY data in the presence and absence of Ni^II demonstrates that the metal binds at the N-terminus of the peptide, leading to a conformational change. The metal complex adopts a conformation comprising two connected turns including residues Gly to ³His and ⁵Ala to ⁸His. The first turn corresponds to the Ni^II coordination ligands in a square planar conformation, and the second reflects the interaction between ⁴Trp and ⁸His. The results may have important physiological implications in the phenomenon of neurotransmission. © Munksgaard 1997.