Religious delusions in Dutch older adults in treatment for psychosis: a follow-up study.

OBJECTIVE: The course over time of religious delusions (RDs) in late-life schizophrenia and psychotic depression may be relevant to know how long certain aspects of RDs may affect treatment. The present study examines (1) the 1-year follow-up of RDs and other prevalent delusions, (2) the association between RDs and the clinical course of psychotic depression and schizophrenia compared to those without RDs, and (3) associations of RDs and other prevalent delusions with "indicators of complexity" (e.g., suicidality, refusing medication). DESIGN: Prospective study (half year and 1-year follow-up combined). SETTING: Outpatients and inpatients in Geriatric Psychiatry Institution of Yulius, South-Holland, the Netherlands. PARTICIPANTS: One hundred and thirty seven older adult patients, mean age 76.3 (s.d. 8.1). INTERVENTION: Natural follow-up study. MEASUREMENTS: Diagnostic interview measures included Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1), positive psychosis items of the Community Assessment of Psychic Experiences-42 (CAPE), and the 20-item measures from the Centre for Epidemiologic Studies Depression Scale (CES-D). RESULTS: Although RDs in older adults decline in the clinical course of psychotic depression, the course is unfavorable compared to psychotic depression without RDs with regard to depressive symptom severity as measured by CES-D. No significant differences were noted in relation to clinical course of positive psychotic symptoms for both psychotic depression and schizophrenia. In schizophrenia, RDs persist more frequently compared to the most prevalent delusions. No significant difference was observed between patients with RDs compared to patients without RDs regarding indicators of clinical complexity. CONCLUSIONS: RDs predicting a less favorable course over time in psychotic depression. In schizophrenia, RDs appears to be relatively pervasive.

Right versus left atrial pacing in patients with sick sinus syndrome and paroxysmal atrial fibrillation (Riverleft study): study protocol for randomized controlled trial.

BACKGROUND: The incidence of sick sinus syndrome will increase due to population ageing. Consequently, this will result in an increase in the number of pacemaker implantations. The atrial lead is usually implanted in the right atrial appendage, but this position may be ineffective for prevention of atrial fibrillation. It has been suggested that pacing distally in the coronary sinus might be more successful in preventing atrial fibrillation episodes. The aim of this trial is to study the efficacy of distal coronary sinus versus right atrial appendage pacing in preventing atrial fibrillation episodes in patients with sick sinus syndrome. METHODS/DESIGN: This study is designed as a multicenter, randomized controlled trial. Patients with sick sinus syndrome and at least one atrial fibrillation episode of 30 seconds or more in the six months before recruitment will be eligible for participation in this study.All participants will be randomized between pacing distally in the coronary sinus and right atrial appendage. Randomization is stratified for all participating centers. Conventional dual-chamber pacemakers with advanced home monitoring functionality will be implanted. The ventricular lead will be implanted in the right ventricular apex. The first three months of the 36-month follow-up period are considered as run-in time. During the pre-randomization visit and follow-up, an interview, electrocardiogram and pacemaker assessment will be performed, prescribed antiarrhythmic medication will be reviewed and patients will be asked to complete an SF-36 questionnaire. An echocardiographic examination will be conducted in the pre-randomization phase and at the end of each follow-up year. Home monitoring will be used to send daily reports in case of atrial fibrillation episodes. DISCUSSION: This randomized controlled trial is the first in which home monitoring will be used to compare atrial fibrillation recurrences between pacing in the distal coronary sinus or right atrial appendage. Home monitoring gives the opportunity to accurately detect atrial fibrillation episodes and to study characteristics of atrial fibrillation episodes. Should distal coronary sinus pacing significantly diminish atrial fibrillation recurrences, this study will redefine the preferential location of an atrial lead for preventive pacing. TRIAL REGISTRATION: Current Controlled Trials ISRCTN65911661, registered on 8 July 2013.

Clinical characteristics and acute results of catheter ablation for outflow tract ventricular tachycardia or premature beats.

PURPOSE: Contemporary outcome data of catheter ablation for outflow tract tachycardia (OTT) and ventricular premature beats (VPBs) are rare. The aim of this study was to describe the clinical characteristics, the acute procedure success rate, and the long-term survival of patients who underwent an ablation procedure for OTT or VPBs. METHODS: The study was a single-center retrospective cohort study. All 82 consecutive OTT and VPB first ablation procedures between 1999 and 2009 were included. Patients with structural heart disease were excluded. RESULTS: Mean age was 46 ± 13 years. Forty-three percent of the patients were male. All patients were alive after a median follow-up duration of 31 months (interquartile range, 14-65 months). Eighty-nine percent suffered from palpitations and 12 % had a history of syncope. Ventricular tachycardia was documented in 73 % and monomorphic VPBs in 99 %. Seventy-three percent of the patients were ablated in the right ventricular outflow tract, 15 % in the left ventricular outflow tract, and 12 % in the coronary cusps. Radiofrequency energy was used in 95 % of the patients, cryo energy in 9 %. Acute success was achieved in 78 %. Six patients (7 %) experienced a complication (five pericardial effusions, one pseudo-aneurysm of the femoral artery). Three patients needed pericardiocentesis (4 %). CONCLUSION: Ablation for OTT and VPB is successful in the vast majority of cases, with a low but still existing complication rate. Long-term survival was excellent, underscoring the benign nature of this arrhythmia.

A complex double deletion in LMNA underlies progressive cardiac conduction disease, atrial arrhythmias, and sudden death.

BACKGROUND: Cardiac conduction disease is a clinically and genetically heterogeneous disorder characterized by defects in electrical impulse generation and conduction and is associated with sudden cardiac death. METHODS AND RESULTS: We studied a 4-generation family with autosomal dominant progressive cardiac conduction disease, including atrioventricular conduction block and sinus bradycardia, atrial arrhythmias, and sudden death. Genome-wide linkage analysis mapped the disease locus to chromosome 1p22-q21. Multiplex ligation-dependent probe amplification analysis of the LMNA gene, which encodes the nuclear-envelope protein lamin A/C, revealed a novel gene rearrangement involving a 24-bp inversion flanked by a 3.8-kb deletion upstream and a 7.8-kb deletion downstream. The presence of short inverted sequence homologies at the breakpoint junctions suggested a mutational event involving serial replication slippage in trans during DNA replication. CONCLUSIONS: We identified for the first time a complex LMNA gene rearrangement involving a double deletion in a 4-generation Dutch family with progressive conduction system disease. Our findings underscore the fact that if conventional polymerase chain reaction-based direct sequencing approaches for LMNA analysis are negative in suggestive pedigrees, mutation detection techniques capable of detecting gross genomic lesions involving deletions and insertions should be considered.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

INTRODUCTION: Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. METHODS: Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. RESULTS: In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). CONCLUSION: SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.

Usefulness of a pacing guidewire to facilitate left ventricular lead implantation in cardiac resynchronization therapy.

BACKGROUND: Intraoperative measurements of left ventricular (LV) pacing and sensing values were assessed using a novel 0.014-inch guidewire (Visionwire, Biotronik GmbH, Berlin, Germany) enabling pacing and sensing at the distal tip before final LV lead implantation. METHODS: Twenty-two consecutive patients selected for cardiac resynchronization therapy were studied. RESULTS: Significant correlation was found between the LV pacing threshold as assessed by the Visionwire and values after final LV lead implantation (r = 0.92, P < 0.001). Correlation for LV sensing was also significant (r = 0.72, P < 0.001). No significant correlation was present with respect to phrenic nerve stimulation. However, no phrenic nerve stimulation at 10 V/0.5 ms using the Visionwire identified 88% of patients without phrenic nerve stimulation at 10 V/0.5 ms with subsequent LV lead measurements. CONCLUSION: This technique may facilitate transvenous LV lead implantation by preventing implantation in a unsuitable target vessel with respect to pacing and sensing values or phrenic nerve stimulation, thereby reducing procedure and fluoroscopy time.

Analysis of 57,148 transmissions by remote monitoring of implantable cardioverter defibrillators.

INTRODUCTION: Remote monitoring of implantable cardioverter defibrillators (ICD) is designed to decrease the number of ambulatory visits and facilitate the early detection of adverse events. We examined the impact of remote monitoring on clinical workload by a comprehensive analysis of transmitted events. METHODS: The study population consisted of 146 recipients of ICD capable of remote monitoring. Data were transmitted daily or in case of pre-specified events (e.g., arrhythmia, out-of-range lead and/or shock impedance). Transmitted events were classified as clinical (disease-related) or system-related. Event rates/patient/month were calculated and compared according to events classification and clinical groups. RESULTS: During a mean follow-up of 22 +/- 16 months, a total of 57,148 remote transmissions were recorded. Of these transmissions, 1009 (1.8%) were triggered by a pre-specified event, including induced ventricular fibrillation (VF) episodes during defibrillation threshold testing. The median number of events/patient/month was 0.14. Event rates were similar in patients with primary and secondary prevention indications for ICD (0.15 vs. 0.11). After exclusion of the induced VF episodes, 5.6% of transmitted events were classified as system-related and 94.4% as clinical. The median number of clinical events/patient/month was 0.023. The clinical event-free rates were 62% and 45%, at 1 and 4 years, respectively. CONCLUSION: Remote monitoring of ICD patients is feasible. Despite the large number of data transmissions, remote monitoring imposed a minimal additional burden on the clinical workload. The rate of triggered data transmissions by critical events was, relatively, very low.

LV lead fixation in a coronary vein may be the cause and result of thrombosis.

A recently implanted left ventricular lead was fixated in the coronary sinus due to thrombosis while attempting to reposition the lead because of phrenic nerve stimulation.

The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study.

AIMS: The BRIGHT study evaluated bifocal right ventricular (RV) (apex and outflow tract) pacing in a single, blind, randomized crossover study in patients eligible for cardiac resynchronization therapy (CRT). Forty-two patients were enrolled with the following characteristics: chronic drug refractory heart failure New York Heart Association (NYHA) class III-IV; ejection fraction (EF)<35%; QRS width >or= 120 ms; and a left bundle branch block. The aim of the study was to assess an improvement in left ventricular (LV) EF, 6 min walk test, Minnesota quality-of-life score, and NYHA classification. Methods and result Patients were randomized to receive either bifocal pacing or the control mode, each for a period of 3 months. Parameters were measured prior to randomization and after 3 months of control or bifocal pacing. Eight patients failed to make the 7 month follow-up, three patients died (one prior to randomization at the first month), five patients dropped out, and three patients refused further participation. One patient had a persistent lead problem, which was subsequently replaced with an LV lead, and one patient suffered with persistent atrial fibrillation. Compared with baseline, bifocal pacing improved EF from 26 +/- 12% to 36 +/- 11% (P < 0.0008), NYHA classification decreased from 2.8 +/- 0.4 to 2.3 +/- 0.7 (P < 0.007). Furthermore, the 6 min walk test improved from 372 +/- 129 m to 453 +/- 122 m (P < 0.05), and the Minnesota Living with Heart Failure scores decreased from 33 +/- 20 to 24 +/- 21 (P < 0.006). In the control group, no significant changes in any parameters were observed. Eight patients did not tolerate reprogramming from DDD BRIGHT to control pacing, with symptoms disappearing in all patients after reprogramming to bifocal pacing. CONCLUSION: Bifocal RV pacing in patients with a classic indication for CRT shows improvement in all parameters.

Reversible left bundle branch block induced congestive heart failure. A case report.

Intraventricular conduction delay in the form of left bundle branch block plays an important role in the genesis and the progression of congestive hart failure. We report on the clinical course of a patient and the improvement in functional status after the disappearance of left bundle branch block, despite withholding cardiac resynchronization therapy.

Acute subclavian or axillary vein occlusion during biventricular pacemaker implantation.

During biventricular pacemaker implantation, multiple punctures of the subclavian vein were performed and venous occlusion was apparent during the procedure, which in one case was stopped before lead insertion and in the other patient new access has to be forced through the occlusion by removing one of the already implanted leads. For implanting physicians, it is important to know that acute venous occlusion may occur during lead implantation.

Characteristics of bifocal pacing: right ventricular apex versus outflow tract. An interim analysis.

Bifocal RIGHT ventricular stimulation (BRIGHT) is an ongoing, randomized, single-blind, crossover study of atrial synchronized bi-right ventricular (RV) pacing in patients in New York Heart Association heart failure functional class III, a left ventricular ejection fraction <35%, left bundle branch block and QRS complexes >/=120 ms. This analysis compared the electrical and handling characteristics, and the complications of pacing at the RV apex (Ap) with passive, versus RV outflow tract (OT) with active fixation leads. A mean of 1.6 +/- 0.9 and 2.2 +/- 2.0 attempts were needed to position the Ap and OT leads, respectively (ns). R-wave amplitudes at Ap versus OT were 23 +/- 13 mV versus 14 +/- 8 mV (n = 36, P < 0.001). R-wave amplitudes at the Ap remained stable between implant and M7. R-wave amplitudes at the OT could not be measured after implantation. In two patients, atrioventricular block occurred during active fixation at the OT. Conduction recovered spontaneously within 4 months. Ventricular fibrillation was induced in one patient during manipulation of an Ap lead in the RV. Marked differences were found between leads positioned in the OT versus Ap, partly related to the difference in lead design. Mean R-wave amplitude was higher at the Ap that at the OT. Ease and success rate of lead implant was similar in both positions.

Disruption of Drosophila Rad50 causes pupal lethality, the accumulation of DNA double-strand breaks and the induction of apoptosis in third instar larvae.

The Rad50/Mre11/Nbs1 protein complex has a crucial role in DNA metabolism, in particular in double-strand break (DSB) repair through homologous recombination (HR). To elucidate the role of the Rad50 protein complex in DSB repair in a multicellular eukaryote, we generated a Rad50 deficient Drosophila strain by P-element mediated mutagenesis. Disruption of Rad50 causes retarded development and pupal lethality. To investigate the mechanism of pupal death, brains and wing imaginal discs from third instar larvae were studied in more detail. Wing imaginal discs from Rad50 mutant larvae displayed a 3.5-fold increase in the induction of spontaneous apoptotic cells in comparison to their heterozygous siblings. This finding correlates with increased levels of phosphorylated histone H2Av, indicating an accumulation of DSBs in Rad50 mutant larvae. A 45-fold increase in the frequency of anaphase bridges was detected in the brains of Rad50 deficient larvae, consistent with a role for Rad50 in telomere maintenance and/or replication of DNA. The induction of DSBs and defects in chromosome segregation are in agreement with a role of Drosophila Rad50 in repairing the DSBs that arise during replication.

Ice mapping during cryothermal ablation of accessory pathways in WPW: the role of the temperature time constant.

AIM: Cryothermal energy has the ability reversibly to demonstrate loss of function with cooling, ice mapping, at less deep temperatures. The purpose of this study was to investigate the time course of the temperature during ice mapping of accessory pathways. METHODS AND RESULTS: Thirteen patients with the Wolff-Parkinson-White (WPW) syndrome underwent cryoablation. After identification of a prospective ablation site, ice mapping was performed by cooling the tip to a minimum of -30 degrees C. Successful ice mapping was defined by loss of accessory pathway (AP) conduction. A total of 104 ice maps were analyzed. Successful ice mapping was demonstrated in 17 attempts. There was no significant difference in mapping temperature between successful and unsuccessful ice mapping (-29.4+/-3.2 degrees Celsius vs -30.4+/-1.7 degrees Celsius). The temperature time constant tau during successful ice mapping was significantly shorter compared with unsuccessful ice mapping (7.0+/-1.1 s vs 10.1+/-1.3 s; P<0.0001). The response time (RT) to mapping temperature of -30 degrees C was significantly prolonged in unsuccessful ice mapping attempts (35.8+/-4.5 s vs 53.5+/-11.0 s; P<0.0001). Significant correlations were found between successful ice mapping and the temperature time constant, and between RT and the temperature time constant (P<0.001). CONCLUSION: The ability to identify prospective ablation sites by ice mapping was demonstrated. Successful ice mapping attempts were characterized by a short temperature time constant and a short response time to mapping temperature with a sudden disappearance of pathway conduction.

The Drosophila melanogaster DNA Ligase IV gene plays a crucial role in the repair of radiation-induced DNA double-strand breaks and acts synergistically with Rad54.

DNA Ligase IV has a crucial role in double-strand break (DSB) repair through nonhomologous end joining (NHEJ). Most notably, its inactivation leads to embryonic lethality in mammals. To elucidate the role of DNA Ligase IV (Lig4) in DSB repair in a multicellular lower eukaryote, we generated viable Lig4-deficient Drosophila strains by P-element-mediated mutagenesis. Embryos and larvae of mutant lines are hypersensitive to ionizing radiation but hardly so to methyl methanesulfonate (MMS) or the crosslinking agent cis-diamminedichloroplatinum (cisDDP). To determine the relative contribution of NHEJ and homologous recombination (HR) in Drosophila, Lig4; Rad54 double-mutant flies were generated. Survival studies demonstrated that both HR and NHEJ have a major role in DSB repair. The synergistic increase in sensitivity seen in the double mutant, in comparison with both single mutants, indicates that both pathways partially overlap. However, during the very first hours after fertilization NHEJ has a minor role in DSB repair after exposure to ionizing radiation. Throughout the first stages of embryogenesis of the fly, HR is the predominant pathway in DSB repair. At late stages of development NHEJ also becomes less important. The residual survival of double mutants after irradiation strongly suggests the existence of a third pathway for the repair of DSBs in Drosophila.

Induction of epithelial tumors in Drosophila melanogaster heterozygous for the tumor suppressor gene wts.

The imaginal disk cells of Drosophila have a cell cycle that is very similar to that of mammalian cells. Data concerning factors inducing tumors in these cells may directly relate to the risk of these factors for inducing cancer in humans. One of the genes involved in the regulation of cell cycle control is wts (warts), the Drosophila homolog of the mammalian tumor suppressor gene LATS1. The Drosophila wts mutations are recessive lethal. However, homozygous clones that arise in heterozygous flies in the imaginal disk cells lead to epithelial tumors, spectacular outgrowths visible on the cuticle of the adult. We have treated Drosophila larvae, heterozygous for wts, with the chemical mutagen MMS (methyl methanesulfonate) or with X-rays and measured the appearance of epithelial tumors in the eclosing adult flies. This test is a variation of the well-known Drosophila somatic mutation and recombination test (SMART), where mostly recessive markers have been used leading to visible phenotypes in the eyes and wings of the fly. We show that the sensitivity of this test is far greater than the comparable test system using the recessive eye marker white.

Involvement of mouse Rev3 in tolerance of endogenous and exogenous DNA damage.

The Rev3 gene of Saccharomyces cerevisiae encodes the catalytic subunit of DNA polymerase zeta that is implicated in mutagenic translesion synthesis of damaged DNA. To investigate the function of its mouse homologue, we have generated mouse embryonic stem cells and mice carrying a targeted disruption of Rev3. Although some strain-dependent variation was observed, Rev3(-/-) embryos died around midgestation, displaying retarded growth in the absence of consistent developmental abnormalities. Rev3(-/-) cell lines could not be established, indicating a cell-autonomous requirement of Rev3 for long-term viability. Histochemical analysis of Rev3(-/-) embryos did not reveal aberrant replication or cellular proliferation but demonstrated massive apoptosis in all embryonic lineages. Although increased levels of p53 are detected in Rev3(-/-) embryos, the embryonic phenotype was not rescued by the absence of p53. A significant increase in double-stranded DNA breaks as well as chromatid and chromosome aberrations was observed in cells from Rev3(-/-) embryos. The inner cell mass of cultured Rev3(-/-) blastocysts dies of a delayed apoptotic response after exposure to a low dose of N-acetoxy-2-acetylaminofluorene. These combined data are compatible with a model in which, in the absence of polymerase zeta, double-stranded DNA breaks accumulate at sites of unreplicated DNA damage, eliciting a p53-independent apoptotic response. Together, these data are consistent with involvement of polymerase zeta in translesion synthesis of endogenously and exogenously induced DNA lesions.

Hallux valgus: soft tissue procedure versus bony procedure.

Hallux valgus is one of the most common fore-foot problem in civilized populations. 49 feet of 33 cases, 8 males and 25 females with an average age of 50 years old, were treated surgically from 1987 to 1992 for hallux valgus and followed up for an average of 47.8 months, comprising 20 feet with McBride's soft tissue procedure and 29 feet of Mitchell metatarsal osteotomy. The clinical criteria for follow up included pain relief, cosmetic out look, shoe wearing comfort, metatarsophalangeal motion etc. 87.5% of the cases in the McBride's group and 95% of the cases in the Mitchell group were satisfied with the clinical results. The immediate post-operative metatarsophalangeal (MP) angle and intermetatarsal (IM) angle were both well corrected, but there was a significantly higher recurrence rate of hallux valgus in the group with the McBride's procedure (P < 0.05). One case in the McBride's group had the complication of hallux varus and one case from the Mitchell group had delayed union. The Mitchell bony procedure has a more stable result compared to the McBride's soft tissue procedure for the correction of moderate hallux valgus, and the modified Mitchell osteotomy is less invasive, easier to perform, easier to care for, and has more satisfactory long-term results.

Tuberous sclerosis with cardiac rhabdomyoma manifested by fetal bradycardia: report of a case.

This is a case of neonatal tuberous sclerosis associated with cardiac rhabdomyoma and manifested by fetal cardiac arrhythmia-bradycardia. The prenatal echocardiography showed multiple cardiac tumors which occupied the left and right ventricles. The largest one measured 5.2 cm in diameter. It was found to be 4.5 x 4.1 x 3.5 cm in size at autopsy. A postnatal cranial echogram showed multiple subependymal nodules. The patient expired after 7 hours of life. The autopsy findings confirmed the diagnosis. The mother of the patient had adenoma seb'aceum on the face and an ungual fibroma on the left little finger. Cranial computerized tomography revealed a small calcified tubercle.