Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block.

INTRODUCTION: We investigated changes in electrocardiographic spatial QRS and T vectors as markers of electrical remodeling before and after cardiac resynchronization therapy (CRT) and their association with altered outcome. METHODS AND RESULTS: In 41 patients with LBBB, ECGpost was recorded during intrinsic rhythm after interrupting CRT pacing and compared to the pre-implant ECGpre and the ECG during CRT (ECGCRT). Mean spatial angles between QRS and T vectors were determined with the Kors matrix conversion. Left ventricular ejection fraction (LVEF) was determined with nuclear isotope ventriculography before CRT implantation (LVEFpre) and at inclusion (LVEFpost). Following CRT, LVEF improved significantly from 26 ± 10 to 36 ± 14% (p=0.01). Duration of QRSpre (168 ± 15 ms) was not different from QRSpost (166 ± 15 ms). A smaller angle between QRSCRT and Tpost was related to a greater angle between Tpre and Tpost (Pearson's R -0.61 - p<0.001). During follow-up (30 ± 2 months) 9 patients (22%) died. Univariate Cox regression revealed higher mortality in the patients with lower LVEFpost (HR 1.10, p=0.01), a larger angle QRSCRTTpost (HR 1.03, p=0.03), a smaller angle QRSpreQRSpost (HR 0.97, p=0.03) and smaller angle TpreTpost (HR 0.95, p<0.01). After adjusting for LVEFpost, only smaller angle TpreTpost was associated with mortality (HR 0.96, p=0.03). CONCLUSIONS: Electrical remodeling can be quantified by measuring the angles between spatial QRS and T vectors before, during and after CRT. In absence of QRS duration changes, more extensive electrical remodeling is associated with a significantly better survival. QRS and T vector changes deserve further investigation to better understand the individual response to CRT.

[Rivaroxaban: Xarelto--recommendations for pharmacists]. / Le Rivaroxaban (Xarelto): guide de la pratique officinale.

Rivaroxaban is one of the new oral anticoagulants (NOACs). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis.

Traumatic rupture of splenic tissue 13 years after splenectomy. A case report.

After splenectomy, two types of splenic tissue can remain in the human body: one type is the congenital accessory spleen, with its own vasculature and capsule. The other type is the acquired splenosis, caused by the spread of splenic tissue following splenic injury. The aim of this paper is to briefly review the literature dealing with spontaneous bleeding of splenic tissue, apart from the primary spleen, and to report a case showing the clinical and surgical importance of remaining splenic tissue after splenectomy.

Functional and profiling studies prove that prostate cancer upregulated neuroblastoma thymosin beta is the true human homologue of rat thymosin beta15.

A peptide with a sequence identical to rat thymosin beta(Tb)15 was reported to be upregulated in human prostate cancer. However, in this report we provide evidence that TbNB, initially identified in human neuroblastoma, is the only Tb isoform upregulated in human prostate cancer and that the Tb15 sequence is not present herein. In addition, we demonstrate that human TbNB has a higher affinity for actin in comparison to Tb4 and promotes cell migration. In combination, this experimentally validates TbNB as functional homologue of rat Tb15 in the human organism and clarifies the current composition of the human Tb family.

EEG findings after a cerebral territorial infarct in patients who develop early- and late-onset seizures.

BACKGROUND: EEG findings are generally not considered to be very helpful for the diagnosis of poststroke seizures. PURPOSE: This retrospective study investigates the EEG characteristics in patients who develop seizures after a cerebral territorial infarct. PATIENTS AND METHODS: The study population consisted of 110 patients with seizures after a cerebral territorial infarct (12 with early- and 98 with late-onset seizures) and 275 without. All 110 patients had an interictal EEG after their first seizure. The EEG patterns after the stroke were compared between those available from 69 patients who developed seizures and those from 275 who did not. Also the EEG patterns after the seizure (n = 110) were compared to those in the poststroke group without subsequent seizures. RESULTS: Periodic lateralized epileptic discharges (PLEDs) on the EEG after stroke were only found in 5.8% of the patients with early- and late-onset seizures. They were absent in the stroke group without seizures. Frontal intermittent rhythmic delta activities (FIRDAs) were observed in 24.6% of the seizure group, compared to 1.1% in the control group. Diffuse slowing occurred also significantly more often in the former (21.7%) compared to the latter group (5.1%). Normal EEG findings were seen in 53.8% of the stroke patients without seizures, compared to 8.5% in those with seizures. The incidence of focal slowing was the same in both groups. Similar findings were observed when comparing the EEG patterns of the patients after the first poststroke seizure to those of the stroke group without subsequent seizures. In patients with early-onset seizures, PLEDs or FIRDAs were present in 25% each. FIRDAs and diffuse slowing were significantly more frequently observed on the poststroke EEGs of patients who developed late-onset seizures. CONCLUSIONS: FIRDAs, PLEDs and diffuse slowing are the most frequent EEG findings in patients with early-onset seizures. Patients with FIRDAs and diffuse slowing on the poststroke EEG have a high risk to develop late-onset seizures, while the chance is reduced in those with normal EEG findings.

Increasing serum levels of non-DDT-derivative organochlorine pesticides in the younger population of the Canary Islands (Spain).

Organochlorine pesticides are a lipophilic class of chemicals that persist in the environment and tend to accumulate in human tissues for years. They came into widespread use in the late 1940s. Because of their capacity to bioaccumulate and biomagnify in food chains and their toxic effects, most of them were banned in industrialized countries, among them Spain, in the late 1970s and 1980s. In 1998 organochlorine pesticides were determined in a representative sample of a Spanish population (around 690 serum samples from people 6 to 75years old from the Canary Islands). Serum levels of lindane aldrin, dieldrin and endrin, were determined. Our results showed that a high percentage of samples presented detectable levels of some of the organochlorines measured, endrin being the most frequently detected (72%) and at highest concentration (mean 136.7ng/g fat). Mean concentrations of the main cyclodiene evaluated, dieldrin, was lower to those found in other Western populations. However, serum levels of lindane were higher than those described in North European populations. Influence of geographical and sociodemographic factors was evaluated. Urban populations showed the highest levels of dieldrin, while non-urban population showed the highest serum values of lindane, aldrin and endrin. Unexpectedly, serum values of lindane, aldrin and dieldrin were higher in younger than in older people. Subjects under 18years showed almost twice as high serum levels of lindane, aldrin and dieldrin than subjects of 65-75years. These results may well suggest that people living in the Canary Islands have been and are currently exposed to non-DDT-organochlorine pesticides. The type and source of exposure could vary between islands and type of habitat. Contaminated food and/or the environment could be related with this situation.

Clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease.

BACKGROUND: Seizures and epilepsy are harmful and worsen the disability of stroke patients. There are currently no good clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease (CVD). PATIENTS AND METHODS: 110 patients with delayed seizures after an ischaemic or a haemorrhagic stroke, a transient ischaemic attack or a subarachnoid haemorrhage (60 with a single seizure and 50 with epilepsy) and 366 without seizures were included in this retrospective study. The clinical syndrome, the stroke aetiology and the vascular risk factors were compared. The groups with a single seizure and with epilepsy were also analysed separately. RESULTS: There were no differences in age, gender, aetiology and vascular risk factors between the groups with and without seizures. When comparing the incidence of the clinical syndromes, ischaemic partial anterior circulation syndrome (PACS) was significantly more and transient ischaemic attack less frequent in the group with seizures compared to the control group. The severity of the neurological impairment on admission and the degree of disability on discharge after a PACS was similar in those who developed late-onset seizures compared with those who did not. Also on the Cox proportional hazards analysis, PACS appeared to be the only clinical risk factor for development of seizures and epilepsy in patients with CVD. No differences were observed in clinical predictors between patients with a single seizure and those with epilepsy. CONCLUSION: PACS is the only independent predictor for the occurrence of late-onset seizures in patients with CVD.

Preservation of renal function after heart transplantation: initial single-center experience with sirolimus.

BACKGROUND: Long-term survivors of heart transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin-inhibitors. Sirolimus is increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity. METHODS: Between November 2002 and November 2003, 9 adult heart transplant candidates with moderate to severe chronic renal disease were switched from cyclosporine to sirolimus. The conversion scheme consisted of an immediate stop of cyclosporine and an 8-mg loading dose of sirolimus, followed by 3 mg/d; after 1 week, the sirolimus dose was adjusted to maintain trough levels between 5 and 15 microg/L. The majority of patients were on corticosteroids, and on either azathioprine or mycophenolate mofetil. At conversion, the mean serum creatinine level was 2.11 (+/-0.4) mg/dL and the mean glomerular filtration rate (GFR) was 32 (+/-7) mL/min/1.73 m(2). Prior to conversion, the renal dysfunction was predominantly stable. RESULTS: After conversion, there were 7 dropouts (75%) due to several side effects related to sirolimus: edema (n = 2), general discomfort (n = 2), delayed wound healing (n = 1), cardiac thrombus (n = 1), and diarrhea (n = 1). The median treatment time with Sirolimus, therefore, was only 4.0 months. While on sirolimus, the renal function of all patients remained unchanged or showed even some improvement. Retrospective nephrological review revealed severe renal artery stenoses in 2 patients and serious generalized abdominal and renal atheromatosis in 7 patients. No cardiac dysfunction was seen. CONCLUSION: Conversion from cyclosporine to sirolimus was problematic due to sirolimus side effects, occurring at any time after the switch. One should also question whether chronic kidney disease after heart transplantation is routinely caused by the administration of calcineurin-inhibitors, in view of the generalized renal and abdominal atheromatosis.

Reduction of the pace polarization artefact for capture detection applications by a tri-phasic stimulation pulse.

This study investigated the ability to minimize pace polarization artefacts (PPA) by adjusting the post-stimulus pulse duration of a tri-phasic stimulation pulse. Adjustment of the stimulation pulse was enabled by downloading special study software into an already implanted pacemaker. Tests were performed in a total of 296 atrial leads and 311 ventricular leads. Both chronic and acute leads were included in the study. Statistically significant differences were found in the initial PPA (without any adjustment of the stimulus pulse) between atrial and ventricular leads. In addition, significant differences were observed among various lead models with respect to changes over time in the initial ventricular PPA. Successful PPA reduction was defined as a reduction of the PPA below 0.5 mV for atrial leads and below 1 mV for ventricular leads. Results show a success rate for ventricular and atrial PPA reduction of 97.8% and 98.7%, respectively. Threshold tests showed that after reduction of the PPA loss of ventricular capture can be reliably detected. However, atrial threshold tests showed many false positive evoked response detections. In addition, unexpectedly high evoked response amplitudes were observed in the atrium after reduction of the PPA. Results from additional measurements suggest that these high atrial evoked response amplitudes come from the influence of the input filter of the pacemaker.

Screening for glaucoma in a general population with the non-mydriatic fundus camera and the frequency doubling perimeter.

PURPOSE: To evaluate the usefulness of non-mydriatic fundus camera (NMFu-camera) and frequency doubling perimeter (FDP) for detecting glaucoma in a general population. METHODS: This prospective observational multicenter study consisted in screening for glaucoma in the populations of three Belgian cities. Intraocular pressure (IOP) was measured with non-contact pneumo-tonometer (NCT) and applanation tonometry (AT) if NCT IOP was > or = 17 mmHg. Visual field was screened with FDP (C-20-5) and digitized optic disc photographs (ODPs) were taken with NMFu-camera. FDP was considered abnormal if at least one defective point was found. ODPs were graded as normal or glaucomatous by consensus of three glaucoma specialists. Optic disc and visual field results were matched per eye. Subjects with known ocular hypertension and/or treated primary open angle glaucoma were excluded from the analysis. RESULTS: A total of 1620 subjects were included in the study. Their mean age was 63.2 years. AT IOP was > 21 mmHg in 8.2%. A total of 98.1% of ODPs could be interpreted. Glaucomatous optic discs were detected in 3.5% of the subjects. In this group only 24% had an AT IOP > or = 22 mmHg. FDP was abnormal in 44.5%. The sensitivity and specificity of FDP to identify patients with an optic disc graded as glaucomatous were 58.6% and 64.3% respectively. CONCLUSIONS: The combined use of the NMFu-camera and the FDP is a feasible method for an initial glaucoma mass screening. NMFu-camera may be a useful and quick method to screen for glaucomatous damage in a community. FDP in screening strategy was revealed to be not sensitive enough when setting the cut-off value at one defective test location. IOP measurements were confirmed to be a poor tool to detect glaucomatous damage.

The prognostic significance of changes in lesion size of established cerebral infarcts on computed tomography of the brain.

BACKGROUND: As a second part of our prospective study, we assessed the size of the infarct lesion on computed tomography (CT) of the brain at two fixed time points after stroke in order to investigate its influence on the clinical outcome. METHODS: From 220 consecutive stroke patients, admitted within 24 h after onset with symptoms lasting more than 24 h, we selected 150 displaying an anterior circulation infarct or syndrome. All included patients had CT scans without contrast enhancement on day 3 (+/- 8 h) and on day 10 (+/- 8 h) after stroke onset. The size of the X-ray hypoattenuation zone was determined by superimposing the CT slices on digital cerebral vascular maps, on which the contours of the infarct area were delineated. The lesion size was expressed as the fraction of the total surface area of these digital cerebral maps. The patients were divided into four groups according to their degree of disability at 3 months on the modified Rankin (R) scale as follows : R 0-1, R 2-3, R 4-5, R 6. RESULTS: There was a clear association between lesion size on CT, on day 3 and on day 10, and the clinical outcome. Lesion size decreased between day 3 and day 10 in the groups R 0-1 and R 2-3, remained unchanged in the group R 4-5 and further increased in group R 6. CONCLUSION: Lesion size on CT is a significant predictor of stroke outcome. It decreases from day 3 to day 10 in patients with no or low disability at 3 months, but increases in those who do not survive their stroke.

Mode switching failure during atrial flutter: the '2:1 lock-in' phenomenon.

AIMS: To evaluate incidence and mechanism of a special form of automatic mode switching (MS) failure in patients with atrial flutter. METHODS AND RESULTS: Retrospectively the charts of 134 patients implanted with dual chamber pacemakers with MS algorithms were reviewed. Seven patients (5.2%) were identified that presented with sustained rapid ventricular pacing resulting from atrial flutter with failure of automatic MS. Since this form of MS failure implies 2:1 tracking of atrial flutter, it was coined '2:1 lock-in'. A theoretical timing model was developed to clarify the mechanism of this special form of MS failure. Prerequisites for the '2:1 lock-in' phenomenon are: (1). the sum of the AV delay and the post ventricular blanking (PVAB) must be longer than the cycle length of the atrial flutter, (2). the tachycardia detection rate must be higher than half the atrial flutter rate and (3). the maximum tracking rate (MTR) must be higher than half the atrial flutter rate. Recommendations for programming in order to avoid this specific form of MS failure are made accordingly and parallel algorithms for flutter detection are discussed. CONCLUSION: '2:1 lock-in' is a typical form of MS failure in patients with atrial flutter and the mechanism is closely linked to the typical atrial sensing windows.

Prefoldin recognition motifs in the nonhomologous proteins of the actin and tubulin families.

Nascent actin and tubulin molecules undergo a series of complex interactions with chaperones and are thereby guided to their native conformation. These cytoskeletal proteins have the initial part of the pathway in common: both interact with prefoldin and with the cytosolic chaperonin containing tailless complex polypeptide 1. Little is understood with regard to how these chaperones and, in particular, prefoldin recognize the non-native forms of these target proteins. Using mutagenesis, we provide evidence that beta-actin and alpha-tubulin each have two prefoldin interaction sites. The most amino-terminally located site of both proteins shows striking sequence similarity, although these proteins are nonhomologous. Very similar motifs are present in beta- and gamma-tubulin and in the newly identified prefoldin target protein actin-related protein 1. Actin-related proteins 2 and 3 have related motifs, but these have altered charge properties. The latter two proteins do not bind prefoldin, although we identify them here as target proteins for the cytosolic chaperonin. Actin fragments containing the two prefoldin interaction regions compete efficiently with actin for prefoldin binding. In addition, they also compete with tubulins, suggesting that these target proteins contact similar prefoldin subunits.

Posterior cortical atrophy. Two case reports and a review of the literature.

We present two cases of progressive early-onset dementia with apraxia and visuospatial disability as initial manifestations. In the later stages of the illness Gerstmann's and Balint's syndromes developed. Structural neuroimaging demonstrated parieto-occipital atrophy and functional imaging revealed bilateral hypometabolism and hypoperfusion in these areas. These cases fulfil the diagnostic criteria of posterior cortical atrophy (PCA). Frontal lobe involvement became evident as the disease progressed. Alzheimer's disease also typically features this anterior spread and possibly this is the underlying pathological substrate for this clinical syndrome, although definite pathology is lacking. In this report, we describe longitudinal evolution in these two cases of PCA.

Isolated non-compaction of the left ventricle: a rare indication for transplantation.

This report describes the diagnostic difficulty encountered in a young female patient presenting with neurologic symptoms, atrial fibrillation and severe left ventricular systolic dysfunction, eventually leading to cardiac transplantation. The scrutiny used in the evaluation of the particular aspect of the left ventricle, and the integration of the information obtained from echocardiography, angiography and magnetic resonance imaging, led to the diagnosis of a rare and mostly unknown cause of cardiac failure. The correct identification of this entity is mandatory because enhanced risk of thromboembolism and malignant arrhythmia should be anticipated. A review of the literature revealed only 6 patients in whom isolated non-compaction of the left ventricle was treated by heart transplantation.