bluuebunny/crossref_metadata_2025 huggingface dataset:
T5 spinal cord transection increases susceptibility to reperfusion-induced ventricular tachycardia by enhancing sympathetic activity in conscious rats
Authors: Lujan Heidi L. , DiCarlo Stephen E.
Published: October 2007

We recently documented that paraplegia (T5 spinal cord transection) alters cardiac electrophysiology and increases the susceptibility to ventricular tachyarrhythmias induced by programmed electrical stimulation. However, coronary artery occlusion is the leading cause of death in industrially developed countries and will be the major cause of death in the world by the year 2020. The majority of these deaths result from tachyarrhythmias that culminate in ventricular fibrillation. β-Adrenergic receptor antagonists have been shown to reduce the incidence of sudden cardiac death. Therefore, we tested the hypothesis that chronic T5 spinal cord transection increases the susceptibility to clinically relevant ischemia-reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity. Intact and chronic (4 wk after transection) T5 spinal cord-transected (T5X) male rats were instrumented to record arterial pressure, body temperature, and ECG. In addition, a snare was placed around the left main coronary artery. The susceptibility to sustained ventricular tachycardia produced by 2.5 min of occlusion and reperfusion of the left main coronary artery was determined in conscious rats by pulling on the snare. Reperfusion culminated in sustained ventricular tachycardia in 100% of T5X rats (susceptible T5X, 10 of 10) and 0% of intact rats [susceptible intact, 0 of 10 ( P < 0.05, T5X vs. intact)]. β-Adrenergic receptor blockade prevented reperfusion-induced sustained ventricular tachycardia in T5X rats [susceptible T5X 0 of 8, 0% ( P < 0.05)]. Thus paraplegia increases the susceptibility to reperfusion-induced sustained ventricular tachycardia due to enhanced sympathetic activity.
Chronic intermittent hypoxia increases the CO2 reserve in sleeping dogs
Authors: Katayama Keisho , Smith Curtis A. , Henderson Kathleen S. , Dempsey Jerome A.
Published: October 2007

We hypothesized that chronic intermittent hypoxia (CIH) would induce a predisposition to apnea in response to induced hypocapnia. To test this, we used pressure support ventilation to quantify the difference in end-tidal partial pressure of CO2 (PetCO2) between eupnea and the apneic threshold (“CO2 reserve”) as an index of the propensity for apnea and unstable breathing during sleep, both before and following up to 3-wk exposure to chronic intermittent hypoxia in dogs. CIH consisted of 25 s of PetO2 = 35–40 Torr followed by 35 s of normoxia, and this pattern was repeated 60 times/h, 7–8 h/day for 3 wk. The CO2 reserve was determined during non-rapid eye movement sleep in normoxia 14–16 h after the most recent hypoxic exposure. Contrary to our hypothesis, the slope of the ventilatory response to CO2 below eupnea progressively decreased during CIH (control, 1.36 ± 0.18; week 2, 0.94 ± 0.12; week 3, 0.73 ± 0.05 l·min−1·Torr−1, P < 0.05). This resulted in a significant increase in the CO2 reserve relative to control ( P < 0.05) following both 2 and 3 wk of CIH (control, 2.6 ± 0.6; week 2, 3.7 ± 0.8; week 3, 4.5 ± 0.9 Torr). CIH also 1) caused no change in eupneic, air breathing PaCO2; 2) increased the slope of the ventilatory response to hypercapnia after 2 wk but not after 3 wk compared with control; and 3) had no effect on the ventilatory response to hypoxia. We conclude that 3-wk CIH reduced the sensitivity of the ventilatory response to transient hypocapnia and thereby increased the CO2 reserve, i.e., the propensity for apnea was reduced.
Factors Regulating Trophoblast Invasion
Authors: Cohen Marie , Bischof Paul
Published: October 2007

Implantation in the human is unique. This uniqueness is characterized on the maternal side by a spontaneous and massive decidualization of the endometrium and on the embryonic side by an almost unlimited invasive potential. Human embryos express an intrinsic invasive potential, which allows them to implant almost anywhere except in the endometrium because it protects itself from implantation. Human implantation is thus only possible during a limited period of time known as the implantation window. This mini review stresses the importance of studying trophoblast invasion into the endometrium as a model for human implantation. Cytotrophoblastic cells (CTB) can easily be isolated from first-trimester legal abortions and retain their invasive behavior when cultured in vitro. This model shows that matrix metalloproteinases (MMPs) are produced by CTB and are instrumental to their invasive behavior. Embryo implantation and tumor invasion use these same biochemical mediators for invasion. However, in contrast to tumor invasion, trophoblast invasion is limited both in time and space: it occurs during the first trimester of pregnancy and invasion does not go beyond the proximal third of the myometrium. Factors regulating MMP expression are of maternal and fetal origin.
Histologic and Functional Aspects of the Endometrium in the Implantatory Phase
Authors: Bourgain Claire , Devroey Paul
Published: October 2007

The endometrium is receptive to an intrusive blastocyst during a limited time span, defined as the implantation window. No definite clinically applicable receptivity marker has been discovered yet. Current approaches of the endometrium are focusing on factors emerging in the implantation window or retrieved from animal or in-vitro studies. These data fail to correlate endometrial parameters with ongoing pregnancy. Morphological tools are limited by difficulties in interpretation and inter-observer variability. In recent studies, extremely deviant endometrial morphology on the day of oocyte retrieval in IVF cycles with embryo transfer has been associated with a deleterious effect on clinical pregnancy. Gene expression data have identified clusters of genes involved in the regulation of the implantation window. Ideally, future studies should link endometrial morphology and function in precisely timed biopsies, analyzing functional biological pathways in a selected endometrial target area.
Uterine Receptivity and Cytokines: New Concepts and New Applications
Authors: Lédée Nathalie , Dubanchet Sylvie , Oger Pierre , Meynant Céline , Lombroso Raoul , Ville Yves , Chaouat Gérard
Published: October 2007

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.
Role of T-Cell Cytokines in Decidua and in Cumulus Oophorus during Pregnancy
Authors: Piccinni Marie-Pierre
Published: October 2007

We focus on the roles of decidual and cumulus oophorus T cells. It was suggested that Th1-type cytokines (IFN-γ and TNF-β), which promote allograft rejection, may compromise pregnancy, whereas the Th2-type cytokines (IL-4, IL-5, IL-10) inhibiting the Th1 responses promote allograft tolerance and therefore may improve fetal survival. We found that T cells’ leukemia inhibitory factor (LIF), M-CSF, IL-4 and IL-10 production at the fetomaternal interface could contribute to the maintenance of pregnancy. Interestingly, we did not find an increased production of IFN-γ by decidual T cells during spontaneous abortion, as expected. We detected T cells in the cumulus oophorus, which surrounds the oocyte during ovulation and the egg before implantation. Cumulus oophorus T cells produce higher levels of IL-4 and LIF than the T cells of peripheral blood or the ovary. We can only speculate what the factors present in the microenvironment of the T cells are that could be responsible for the cytokine profile of decidual and cumulus oophorus T cells. Hormones present in the decidua and in the cumulus oophorus could be the first candidates. In particular, progesterone is a potent inducer of production of Th2-type cytokines, LIF and M-CSF. Other candidates could be molecules produced by the trophoblast or the embryo.
The Baboon as a Research Model for the Study of Endometrial Biology, Uterine Receptivity and Embryo Implantation
Authors: Nyachieo Atunga , Chai Daniel C. , Deprest Jan , Mwenda Jason M. , D’Hooghe Thomas M.
Published: October 2007

The process of embryo implantation includes attachment of the embryo to the endometrium and penetration through the epithelial layer, decidualization of the basement membrane, invasion of the uterine stroma and access to blood supply. This implantation process is very different in humans when compared to pigs, cattle or rodents. The process of invasion in humans where the embryo gets embedded in decidual tissue and in spiral arteries is more aggressive, but otherwise similar to the process of implantation and invasion in non-human primates such as rhesus monkeys and baboons. For ethical reasons, it is unacceptable to study directly the process of embryo implantation in women, and to this day, this remains one of the ‘black boxes’ of reproductive science. Indeed for many clinicians practicing reproductive medicine, in fertility centers, the most difficult question and of concern asked by patients is: ‘Why do my healthy appearing embryos not implant: is there a problem with my endometrium or uterus?’ The olive baboon (Papio anubis anubis) is an excellent animal model for reproductive research. In contrast with smaller non-human primates like rhesus monkeys or cynomolgus monkeys, it is possible in baboons to use transcervical uterine probes (curettes, catheters and hysteroscopic equipment) to perform endometrial biopsy, embryo flushing or transfer and hysteroscopy in a non-invasive way. This can be done easily in multiparous baboons during menstruation, but may be more difficult at the end of the follicular phase (maximal perineal swelling impedes vaginal/cervical access) or during the luteal phase (narrow cervix), in nulliparous baboons and in animals with abnormal internal genitals. In this paper we present an overview regarding the potential of the baboon model to study in vivo uterine receptivity and embryo implantation using invasive and non-invasive approaches.
Dialogue between Blastocyst hCG and Endometrial LH/hCG Receptor: Which Role in Implantation?
Authors: Perrier d’Hauterive S. , Berndt S. , Tsampalas M. , Charlet-Renard C. , Dubois M. , Bourgain C. , Hazout A. , Foidart J.-M. , Geenen V.
Published: October 2007

The specific interaction of blastocyst-derived human chorionic gonadotropin (hCG) and endometrial LH/hCG-R constitutes a fundamental component of the molecular dialogue at the materno-fetal interface. From our observations and studies from other groups, hCG was indeed shown to play a significant role in implantation and tolerance of the embryo, decidual differentiation and remodeling, as well as in placentation. The profile pattern of LH/hCG-R expression by endometrial epithelium correlates with the theoretical timing of the implantation window. Studies are currently being conducted in assisted medical procreation and in an animal model of implantation to establish the index of LH/hCG-R expression as a new biomarker of uterine receptivity for embryo implantation.
Role of Aneuploidy on Embryo Implantation
Authors: Farfalli V.I. , Magli M.C. , Ferraretti A.P. , Gianaroli L.
Published: October 2007

Approximately 30% of oocytes in the human species carry a chromosomal imbalance. This condition has severe clinical consequences as approximately one-third of spontaneous abortions are aneuploid. The most obvious link to the increase of aneuploidy in oocytes is maternal age. This has been directly confirmed by the analysis of polar bodies. Their analysis permits to give confirmation of the high predisposition of oocytes to meiotic errors. Also, the study of chromosomes on sperm has revealed a frequency of 6–7% aneuploidy in normal sperm samples, and is significantly increased in cases of severe oligoasthenoteratospermia or azoospermia due to testicular failure. During the preimplantation period there is a progressive loss of abnormal embryos at specific stages in early development, through growth arrest and degeneration of abnormal embryos. The frequency of chromosomal abnormalities is strictly related to the category of patients (advanced maternal age, repeated cycles, altered karyotype, repeated miscarriages, TESE). Based on these considerations, preimplantation genetic diagnosis for aneuploidy is proposed in reproductive medicine with the finality of improving the clinical outcome after IVF. Substantial evidence has been accumulated on the positive impact of the technique, reporting increased implantation rates and a concomitant decrease of spontaneous abortions and trisomic pregnancies.
Simultaneous Onset of Ulcerative Colitis and Disseminated Pyoderma Gangrenosum
Authors: Neesse Albrecht , Michl Patrick , Kunsch Steffen , Ellenrieder Volker , Gress Thomas M. , Steinkamp Martin
Published: October 2007

Pyoderma gangrenosum (PG) is an immune-mediated inflammatory skin condition representing one of the most distinct extraintestinal manifestations of inflammatory bowel disease (IBD). PG occurs independently from intestinal disease activity in about 1–2% of patients suffering from ulcerative colitis or Crohn’s disease and is characterized by chronic deep skin ulcers whose exact pathogenesis is still unknown. So far, patients with ulcerative colitis have only been reported to develop PG during the course of IBD but not at the initial manifestation of bowel symptoms. This is the first report demonstrating the simultaneous onset of ulcerative colitis and severe multifocal PG. In addition, we provide first evidence that infliximab may have a particularly powerful effect in early disseminated PG compared to late-onset PG, advocating an early application of this drug.
Radio-Frequency Ablation of Atrial Flutter: Long-Term Results and Predictive Value of Cavo-Tricuspid Isthmus Bidirectional Block as Determined by a Simplified Technique
Authors: Maury Philippe , Raczka Frank , Gaty Denis , Duparc Alexandre , Couderc Philippe , Hollington Lucy , Celse Dominique , Delay Marc , Fauvel Jean-Marie , Puel Jacques , Davy Jean-Marc
Published: October 2007

Objectives: Complete bidirectional cavo-tricuspid isthmus (CTI) block is mandatory for radio-frequency (RF) ablation of typical atrial flutter (AF). CTI block can be assessed by a simplified method using two catheters and the technique of differential pacing, but long-term results in large series are poorly known. Methods: CTI RF ablation was performed in 255 consecutive patients with typical AF, using one quadripolar catheter, and the ablation catheter, in association with the technique of differential pacing. Results: Procedural success, as defined by documentation of complete bidirectional CTI block using limited activation mapping, positive differential pacing together with termination of ongoing AF, was achieved in 80% of patients. AF recurred in 37 patients (14%) over a mean follow-up period of 15 ± 9 months. Two hundred and forty-one patients (94%) were finally cured, with 1.1 procedures/patient. The recurrence rate was related to the achievement of complete CTI bidirectional block (12% vs. 29%, p = 0.01). Conclusions: Long-term results of CTI ablation, employing a simplified method using the differential pacing technique, are similar to those for the standard methods using multipolar catheters. Therefore, this technique compares favorably to other established methods for such common RF procedures, especially due to its lower cost.
Eclipsed Mitral Regurgitation: A New Form of Functional Mitral Regurgitation for an Unusual Cause of Heart Failure with Normal Ejection Fraction
Authors: Avierinos Jean-François , Thuny Franck , Tafanelli Laurence , Renard Sebastien , Chalvignac Virginie , Guedj Eric , Lambert Marc , Quilici Jacques , Bonnet Jean-Louis , Enriquez-Sarano Maurice , Habib Gilbert
Published: October 2007

Background: Transient functional mitral regurgitation (MR) has never been reported as a cause of heart failure (HF) with normal ejection fraction (EF) in the absence of epicardial coronary artery stenosis. Results: Performance of echocardiography in patients with acute HF before initiation of HF medical treatment allowed identification of three patients with normal EF but transient massive functional MR during the HF episode. In all patients, massive MR occurred as a consequence of sudden extreme apical tenting of both leaflets with total lack of coaptation, despite normal EF and absence of detectable left ventricular (LV) remodeling, and despite absence of significant stenosis on coronary arteries. In all patients MR was triggered by methylergonovine injection and was reversible either spontaneously or after nitroglycerine administration, leaving patients with normal echocardiogram between HF episodes. In two patients, long-term administration of calcium channel blockers prevented recurrences of MR and HF, whereas in one, mitral valve was eventually replaced. Conclusion: Sudden reversible apical tenting of mitral leaflets with subsequent torrential MR and acute HF can occur despite normal EF, absence of pre-existing LV remodeling and absence of coronary artery stenosis. This atypical type of functional MR is an unusual mechanism of HF in patients with normal LVEF.
Induction of Atrial Depolarization Abnormality during Dipyridamole Stress Imaging: A Cautionary Note
Authors: Prajapat Laxman , Ariyarajah Vignendra , Spodick David H.
Published: October 2007

P-wave widening on the 12-lead electrocardiogram denotes abnormal atrial depolarization and has been shown to be associated with myocardial ischemia during treadmill exercise tolerance testing. However, its true significance during dipyridamole (Persantine) stress imaging remains questionable given the potential direct as well as indirect effects of dipyridamole on the atria. We present a novel series of 5 comparable cases of dipyridamole stress imaging where serial P-wave duration increase occurred during administration of dipyridamole. We observed that such P-wave widening occurred even in the absence of evidence of myocardial ischemia on subsequent myocardial perfusion imaging. Clinicians should therefore be aware of this potential association where, unlike that observed with graded exercise treadmill testing, P-wave widening during dipyridamole infusion could perhaps be a pharmacological effect on the atria instead of an indication of underlying myocardial ischemia.
Simvastatin May Improve Myocardial Perfusion Abnormality in Slow Coronary Flow
Authors: Cakmak Mahmut , Tanriverdi Halil , Cakmak Nazmiye , Evrengul Harun , Cetemen Sebnem , Kuru Omur
Published: October 2007

Background: The slow coronary flow (SCF) phenomenon is a coronary microvascular disorder characterized by the delayed passage of contrast in the absence of obstructive epicardial coronary disease. Recent studies showed the possible role of endothelial dysfunction, diffuse atherosclerosis and inflammation in the pathogenesis of this phenomenon. We aimed to investigate the effect of statin on myocardial perfusion in patients with SCF. Methods and Results: The study population consisted of 97 patients with SCF. Coronary flow patterns of the cases are determined by thrombolysis in myocardial infarction (TIMI) frame count method. Single-photon emission computed tomographic myocardial perfusion imaging studies and lipid parameters of the patients were obtained before and after 6 months of simvastatin treatment period. During the study, daily single dose of 40 mg simvastatin has been given to each subject. We found a significant positive correlation between mean TIMI frame count and basal reversibility score (r = 0.84, p = 0.0001). In addition, analysis of the reversibility scores demonstrates that simvastatin treatment has significantly improved the myocardial perfusion abnormality at the end of the follow-up period. Conclusion: Present findings allow us to conclude that simvastatin improved myocardial perfusion in patients with SCF.
Association of Met439Thr Substitution in Heat Shock Protein 70 Gene with Postoperative Atrial Fibrillation and Serum HSP70 Protein Levels
Authors: Afzal Ali R. , Mandal Kaushik , Nyamweya Samuel , Foteinos Georgios , Poloniecki Jan , Camm A. John , Jahangiri Marjan , Xu Qingbo
Published: October 2007

Background: Atrial fibrillation (AF) is a common arrhythmia encountered following cardiac surgery. Previously, we have shown that higher expression of heat shock protein (HSP) 70 was associated with decreased incidence of postoperative AF (PoAF), suggestive of an antiarrhythmic role. Objective: We have hypothesised that Met493Thr substitution of one of the important hsp70 genes may cause loss of these protective antiarrhythmic effects. We therefore set out to examine the influence of hsp70 genotype on the incidence of PoAF. Methods and Results: We prospectively recruited 244 Caucasian patients undergoing elective coronary artery bypass surgery. The median age was 65 years (40–80 years). PoAF was defined as the characteristic arrhythmia lasting for at least 15 min, occurring within first week following surgery and requiring treatment. This occurred in 48 patients (19.7%). Validated Met493Thr substitution in hsp70-Hom was determined using established techniques. Of 244 patients, genotype was determined for 242 cases. The three genotypes (MM, MT, and TT) were present at frequencies of 0.66, 0.31, and 0.03, respectively, and were in Hardy-Weinberg equilibrium. In unifactorial analysis patients carrier or homozygous for 493Thr mutation had significantly higher incidence of PoAF (Pearson χ2 = 4.3, p = 0.037). Multivariate analysis confirmed the positive association of hsp70-Hom with PoAF (OR, 2.43; p = 0.016) independent of age, sex, previous myocardial infarction, number of distal anastomoses, and duration of ventilation, respectively. Serum HSP70 was ranging from 0.74 to 31.91 ng/ml (median, 2.89) and was not correlated with PoAF. Presence of 493Thr mutation was also significantly correlated with higher levels of serum HSP70 (p = 0.009). Conclusions: Our data show that a mutation in hsp70-Hom gene is associated with higher incidence of PoAF. These findings are consistent with our previous results and may suggest that patients harbouring this substitution will have less endogenous myocardial protection against AF in stressful situations.
Phenotypic Spectrum and Clinical Characteristics of Apical Hypertrophic Cardiomyopathy: Multicenter Echo-Doppler Study
Authors: Choi Eui-Young , Rim Se-Joong , Ha Jong-Won , Kim Yong-Jin , Lee Sang-Chol , Kang Duk-Hyun , Park Seung Woo , Song Jae-Kwan , Sohn Dae-Won , Chung Namsik
Published: October 2007

Objectives: The aim of this study was to define the phenotypic spectrum of apical hypertrophic cardiomyopathy (ApHCM) and clinical characteristics pertaining to identified subtypes. Methods: In 182 consecutive ApHCM patients (58.9 ± 11.2 years; 142 men) with left ventricular ejection fraction ≧50%, we measured end-diastolic wall thickness of all 16 left ventricular segments to determine patterns of hypertrophy. Echo-Doppler parameters, electrocardiography patterns, and clinical findings were analyzed. Results: ApHCM was classified into three types as pure focal (n = 81), pure diffuse (n = 70) and mixed type (n = 31) according to patterns of hypertrophy. Incidence of atrial fibrillation (5% for pure focal vs. 11% for pure diffuse vs. 23% for mixed type, p < 0.05) and left atrial volume index (30.9 ± 11.8, 35.7 ± 14.8, and 41.3 ± 15.9 ml/m2, respectively, p < 0.001) were significantly different among subtypes. Peak systolic (6.6 ± 1.0 vs. 6.3 ± 1.2 vs. 5.9 ± 1.1 cm/s, respectively, p < 0.05), diastolic (5.1 ± 1.8 vs. 5.0 ± 1.2 vs. 4.1 ± 1.3 cm/s, respectively, p < 0.05) mitral annular velocity, E/E′ (13.3 ± 4.2 vs. 13.7 ± 5.4 vs. 16.1 ± 6.1, respectively, p < 0.05) were also significantly different. Conclusions: ApHCM contains three morphologically distinct phenotypes and detailed subtyping is important in the prediction of development of atrial fibrillation, left atrial volume index and left ventricular longitudinal function.
Prevalence, Characteristics and Outcomes of People Aged 65 Years and Over with an Incidental Rise in Cardiac Troponin I
Authors: Myint Phyo K. , Al-Jawad Muna , Chacko Sanoj M. , Chu Gavin S. , Vowler Sarah L. , May Helen M.
Published: October 2007

Background: Cardiac troponin I (cTnI) is a sensitive and specific marker of acute cardiac damage. We examined the prevalence, characteristics and outcome of incidental cTnI rises in older patients. Methods: One hundred and eighty-seven consecutive patients aged 65 years or over with a raised cTnI on admission at least 8 h after symptom onset were categorised into: (1) ST-elevation myocardial infarction, (2) other acute coronary syndromes (ACS), (3) other recognised non-ACS causes of cTnI rise and (4) non-ACS with no other identifiable cause (an incidental finding). The number of readmissions and deaths for each group was measured at 30 and 90 days. Results: Age range = 65–98 years. Male = 55.6%. Fifty-four percent had a raised cTnI due to non-ACS illnesses, whilst in 18% it was an incidental finding. The latter group was relatively older and had a significantly lower degree of cTnI rise (U = 1718.5, p = 0.002), but a higher readmission and mortality rate compared to the other groups (categories 1–3) for both follow-up periods. Conclusions: Incidental cTnI rise is common in older patients and is associated with a poorer prognosis compared to ACS or a recognised non-ACS condition. Future research should attempt to evaluate the significance of such incidental rises in elderly patients.
Intermittent Advanced Atrial Depolarization Abnormality?
Authors: Ariyarajah Vignendra , Ali Massud , Spodick David H.
Published: October 2007

Abnormal atrial depolarization, characterized by P waves ≧110 ms on the electrocardiogram, can manifest as partial or advanced interatrial block (IAB). Advanced IAB, denoted by biphasic P waves in leads II, II and aVF, is considered to confer increased severity in interatrial conduction delay, and is now perceived to be a result of continued deterioration in interatrial impulse propagation between the atria. While progression from partial to advanced IAB has been described, the converse, resolution of advanced IAB, which has often been touted as ‘complete block’ to its partial, ‘incomplete’ type, i.e. the occurrence of intermittent advanced IAB, has escaped observations so far. We present the first known report of such a scenario.
Significantly Better Prognosis for Patients with Primary Plasma Cell Leukemia than for Patients with Secondary Plasma Cell Leukemia
Authors: Cha Choong Hwan , Park Chan Jeoung , Huh Joo Ryung , Chi Hyun Sook , Suh Cheol Won , Kang Yoon Koo
Published: October 2007

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of PCL (7 cases of primary PCL and 3 cases of secondary PCL) and 20 sex- and age-matched cases of MM were compared. The patients with primary PCL showed significantly lower platelet and neutrophil counts in peripheral blood and higher cellularity in bone marrow than patients with MM (p = 0.002, < 0.001 and 0.027, respectively). Immunophenotypic studies showed a different expression of HLA-DR and CD117 antigens among the 3 groups. There was a significant difference in survival between the 3 groups (median survival of primary PCL, secondary PCL and MM = 22.2, 1.3 and 36.4 months, respectively; p = 0.048). The patients with primary PCL showed better prognosis than those with secondary PCL. Primary PCL might be a differently developed disease from MM. In diagnosing PCL, it is important to differentiate primary PCL from secondary PCL for the prediction of prognosis.
Subcortical Hyperintensities in Alzheimer’s Disease: No Clear Relationship with Executive Function and Frontal Perfusion on SPECT
Authors: Levy-Cooperman Naama , Lobaugh Nancy J. , Caldwell Curtis , Gao FuQiang , Black Sandra E.
Published: October 2007

Background/Aims: To investigate relationships between subcortical hyperintensities (SH), frontal perfusion and executive function (EF) in a sample of Alzheimer’s disease (AD) patients with varying severities of SH. Methods: A sample of 63 AD patients underwent brain imaging with magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) scans. Severity of SH was assessed using a standardized visual rating scale on MRI. Patients were classified into severe (n = 20), moderate (n = 23) or no SH (n = 20) groups. Four frontal SPECT regions of interest (anterior cingulate cortex, dorsolateral prefrontal cortex) and neuropsychological assessment of EF were analyzed. Results: Overall, no significant relationships were found between severity of SH and measures of SPECT perfusion or EF, except for one subsection of the Dementia Rating Scale, with severe SH scoring slightly worse than the other two groups. Conclusion: These findings support previous studies which suggest minimal adverse effects of SH on brain function and cognition. Global severity of SH on MRI in AD was not associated with decline in frontal perfusion and only mildly related to a decline in a specific EF task. More accurate measures of SH volume, not just global severity of SH, may be necessary to capture such complex brain behavior relationships; if they do indeed exist.
Wernicke-Korsakoff Encephalopathy
Authors: Pearce J.M.S.
Published: October 2007

Wernicke described the clinical features of three patients, including two alcoholics, suffering from confusion, ataxia and ophthalmoplegia in whom pathologically he found ‘polioencephalitis haemorrhagica superioris’. Korsakoff’s doctoral thesis related similar findings but expanded the confabulation and amnesic elements, relating them to alcoholism. This paper, which summarises the salient aspects of the syndrome, discusses their work and shows important earlier descriptions by James Jackson, (1822) Samuel Wilks (1868) and Charles Gayet (1875).
Cajal on Solar Eclipse
Authors: Triarhou Lazaros C. , del Cerro Manuel
Published: October 2007

An impression that sculpted a lasting memory on the mind of the great neuroanatomist Santiago Ramón y Cajal, an 8-year-old boy at the time, was the total solar eclipse of 18 July 1860. This short article provides a translation of the relevant passage, found in a 1933 Buenos Aires schoolbook, and places the celestial event at the crossroads of neuroscience, astronomy and literature.
In vivo and in vitro Skin Permeation of Butyl Methoxydibenzoylmethane from Lipospheres
Authors: Iannuccelli V. , Coppi G. , Sergi S. , Mezzena M. , Scalia S.
Published: October 2007

Lipid microparticles (lipospheres) loaded with butyl methoxydibenzoylmethane (BMDBM), a widely used UV-A sunscreen agent, were prepared by melt technique and evaluated for skin permeation both in vivo, by tape stripping method, and in vitro, by a flow-through diffusion chamber. Following in vivo human skin application of an O/W emulsion containing 2% of BMDBM loaded in lipospheres, 15% of the applied sunscreen accumulated in the uppermost layers of the stratum corneum without remarkably modifying the skin permeation of the unencapsulated sunscreen. These results were found to be predicted by an in vitro methodology involving the diffusion of BMDBM through a lipophilized synthetic membrane into a hydrophilic receptor phase, simulating the viable epidermis better than an ethanolic receptor phase.
Prioritized Subset Analysis: Improving Power in Genome-wide Association Studies
Authors: Li Chun , Li Mingyao , Lange Ethan M. , Watanabe Richard M.
Published: October 2007

Background: Genome-wide association studies (GWAS) are now feasible for studying the genetics underlying complex diseases. For many diseases, a list of candidate genes or regions exists and incorporation of such information into data analyses can potentially improve the power to detect disease variants. Traditional approaches for assessing the overall statistical significance of GWAS results ignore such information by inherently treating all markers equally. Methods: We propose the prioritized subset analysis (PSA), in which a prioritized subset of markers is pre-selected from candidate regions, and the false discovery rate (FDR) procedure is carried out in the prioritized subset and its complementary subset, respectively. Results: The PSA is more powerful than the whole-genome single-step FDR adjustment for a range of alternative models. The degree of power improvement depends on the fraction of associated SNPs in the prioritized subset and their nominal power, with higher fraction of associated SNPs and higher nominal power leading to more power improvement. The power improvement can be substantial; for disease loci not included in the prioritized subset, the power loss is almost negligible. Conclusion: The PSA has the flexibility of allowing investigators to combine prior information from a variety of sources, and will be a useful tool for GWAS.
Multilocus Lod Scores in Large Pedigrees: Combination of Exact and Approximate Calculations
Authors: Tong Liping , Thompson Elizabeth
Published: October 2007

To detect the positions of disease loci, lod scores are calculated at multiple chromosomal positions given trait and marker data on members of pedigrees. Exact lod score calculations are often impossible when the size of the pedigree and the number of markers are both large. In this case, a Markov Chain Monte Carlo (MCMC) approach provides an approximation. However, to provide accurate results, mixing performance is always a key issue in these MCMC methods. In this paper, we propose two methods to improve MCMC sampling and hence obtain more accurate lod score estimates in shorter computation time. The first improvement generalizes the block-Gibbs meiosis (M) sampler to multiple meiosis (MM) sampler in which multiple meioses are updated jointly, across all loci. The second one divides the computations on a large pedigree into several parts by conditioning on the haplotypes of some ‘key’ individuals. We perform exact calculations for the descendant parts where more data are often available, and combine this information with sampling of the hidden variables in the ancestral parts. Our approaches are expected to be most useful for data on a large pedigree with a lot of missing data.
Increased Efficiency of Case-Control Association Analysis by Using Allele-Sharing and Covariate Information
Authors: Schmidt Silke , Schmidt Michael A. , Qin Xuejun , Martin Eden R. , Hauser Elizabeth R.
Published: October 2007

Objective: We compared the efficiency of case selection strategies for following up a genome-wide linkage screen of multiplex families. We simulated datasets under three models by which continuous environmental or clinical covariates may contribute to disease risk or linkage heterogeneity: (i) a quantitative trait locus (QTL) underlying a continuous disease risk factor, (ii) a gene-environment interaction model, (iii) a heterogeneity model defined by distinct covariate distributions in linked and unlinked families. Methods: Marker genotypes and covariate values were generated for affected sibling pair (ASP) families, according to the three models above. We evaluated two case selection strategies relative to a reference design, which compared all family probands to a sample of unrelated controls (‘all’). The first strategy ignored covariates and selected probands from families with NPL scores ≧0 (‘linked best’). The second strategy selected probands from families identified by an ordered subset analysis (OSA), which utilizes family-specific linkage and covariate information. Results: The ‘linked best’ design provided power very similar to the ‘all’ design under all three models. Under some QTL and heterogeneity models, the OSA design was both most powerful and most efficient. Conclusions: Incorporating allele sharing and covariate information from ASP families into a case-control study design can increase power and reduce genotyping cost.
Estimates of Genetic and Environmental Contribution to 43 Quantitative Traits Support Sharing of a Homogeneous Environment in an Isolated Population from South Tyrol, Italy
Authors: Marroni Fabio , Grazio Daniela , Pattaro Cristian , Devoto Marcella , Pramstaller Peter
Published: October 2007

As part of the genomic health care program ‘GenNova’, we measured 43 quantitative traits in 1,136 subjects living in three isolated villages in South Tyrol (Italy), for which extended genealogical information was available. Thirty-seven of the studied traits had been previously investigated in other populations, while six of them are, to the best of our knowledge, studied here for the first time. For all 43 traits we estimated narrow-sense heritability, individual-specific environmental effects, and shared environmental effects. Estimates of narrow-sense heritability were in good agreement with previous findings. We found significant heritability for all traits; after correcting for multiple testing, all traits except serum concentration of glutamic oxaloacetic transaminase (GOT) and potassium still showed significant heritability. In contrast, the effect of living in the same sibship or village (the so-called sibship and household effects, respectively) was significant for a few traits only, and after correcting for multiple testing no trait showed significant shared environment effect. We suggest that the sharing of a highly similar environment by the subjects included in this study explains the low contribution of the household effects to the overall trait variation. This peculiarity should provide an advantage in gene-mapping projects by reducing environmental bias.
Longitudinal Study of Amnesic Patients at High Risk for Alzheimer’s Disease: Clinical, Neuropsychological and Magnetic Resonance Spectroscopy Features
Authors: Rami Lorena , Gómez-Anson Beatriz , Sanchez-Valle Raquel , Bosch Beatriz , Monte Gemma C. , Lladó Albert , Molinuevo José L.
Published: October 2007

Background/Aims: To prospectively follow up a group of amnesic patients at risk for Alzheimer’s disease (AD), to characterize a group of patients whose features were intermediate between amnesic mild cognitive impairment (aMCI) and probable AD, prodromal AD (Prd-AD), and to investigate if these patients were at higher risk for AD conversion. Methods: A total of 109 subjects were assessed by neuropsychological evaluation and by 1H magnetic resonance spectroscopy (1H-MRS): 27 controls, and 16 aMCI, 34 probable AD and 32 Prd-AD patients. Results: Episodic memory and frontal test scores resulted lower in Prd-AD compared to aMCI patients. Prd-AD patients obtained significantly higher scores than AD ones in language, perception, praxis and frontal functions. Although Prd-AD and AD patients had distinct 1H-MRS features from aMCI ones, there were no 1H-MRS differences between Prd-AD and AD patients. The AD annual conversion rate after 1 year of follow-up for Prd-AD (57.1%) was higher than in aMCI patients (20%; p < 0.01). A logistic regression, in which all amnesic patients were treated as a single group, showed that the Visual Memory Test was a significant neuropsychological predictor for AD conversion. Conclusions: Prd-AD patients are a clinically distinguishable group, with distinct neuropsychological and 1H-MRS features and a higher conversion rate to probable AD than aMCI patients.
Molecular Epidemiology and Antibiotic Resistance Patterns of Salmonella enterica from Southwestern Greece
Authors: Spiliopoulou Iris , Zografou Sofia , Goula Amalia , Dimitracopoulos George , Christofidou Myrto
Published: October 2007

Background: A study was conducted at the University Hospital of Patras between January 2002 and December 2003 to investigate antibiotic resistance patterns and clonality of Salmonella enterica in southwestern Greece. Methods: Ninety-five isolates recovered from different outpatients were characterized by specific antisera and were tested for their susceptibility to various antimicrobial agents. Clones were identified by pulsed-field gel electrophoresis (PFGE) of XbaI chromosomal DNA digests. Results: Five serotypes were characterized among 95 isolates, recovered mainly from children, with the predominance of Salmonellaenteritidis followed by Salmonellatyphimurium. The strains were further distinguished by PFGE to 16 clones. The majority of S.enteritidis (61 strains) belonged to clone A, already characterized in Greece, while S.typhimurium (18 isolates) belonged to 3 clones, exhibiting multiresistant phenotypes. Conclusions: One clone S.enteritidis, type A, circulates in southwestern Greece, mainly during summer, while clonality was also observed among S.typhimurium.
Importance of the Efflux Pump Systems in the Resistance of Mycobacterium tuberculosis to Fluoroquinolones and Linezolid
Authors: Escribano I. , Rodríguez J.C. , Llorca B. , García-Pachon E. , Ruiz M. , Royo G.
Published: October 2007

Objective: Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid. Methods: We studied the mutations in gyrA and gyrB genes and the influence of efflux pump systems with 2 inhibitors (reserpine and MC 207.110). Results: The effect of the active efflux system on the decrease in sensitivity to ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin, gatifloxacin and linezolid was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. These inhibitors exhibit activity both in strains that are resistant and in strains that are susceptible to these antibiotics. However, they are seen to be most active in resistant strains, since the minimum inhibitory concentration of the antibiotics studied in these strains was reduced between 2- and 6-fold. Conclusions: Therefore, these mechanisms are involved in the resistance to both compounds. It would be of interest to carry out further studies to determine to what extent these active efflux systems influence resistance to the different groups of drugs used in the treatment of tuberculosis, with a view to the possibility of using the inhibitors of these systems in future therapeutic applications.
Response to Interferon-Alpha in Chronic Hepatitis B Patients with and without Precore Mutant Strain and Effects on HBsAg Titers
Authors: Akhan Sila Cetin , Yulugkural Zerrin , Vahaboglu Haluk
Published: October 2007

Background: Chronic hepatitis B (CHB) affects 400 million people worldwide and is a major cause of morbidity and mortality. It is known that HBV DNA sequences were detected after the clearance of serum hepatitis B surface antigen (HBsAg) often in serum, liver and peripheral blood mononuclear cells. The objectives of our study were to evaluate the previous measurements of HBsAg titers versus. quantitative hepatitis B virus (HBV) DNA and ALT measurements in order to predict the nonresponse and response in interferon-alpha (IFN-α)-treated HBeAg-positive and HBeAg-negative chronic HBV patients. Methods: We investigate whether the presence of precore mutant affects the response to IFN-α therapy and on the titer of HBsAg or not. Twenty-one HBeAg-positive (group1), 38 HBeAg-negative (group 2), and 47 healthy inactive carriers (group 3) made up this study. Liver biopsy showed chronic hepatitis, there was no cirrhosis and none of the patients had IFN-α therapy before. Results: The decrease in HBsAg titers was found as statistically not significant in groups 1 (p = 0.192) and 3 (p = 0.236) and statistically significant in group 2 (p = 0.0001) within a 6-month interval. Conclusion: HBsAg titer may be a factor to predict the primary responders and nonresponders specially in HBeAg-negative patients.
Expression of HIF-1α in Injured Arteries Controls SDF-1α–Mediated Neointima Formation in Apolipoprotein E–Deficient Mice
Authors: Karshovska Ela , Zernecke Alma , Sevilmis Gueler , Millet Andrea , Hristov Mihail , Cohen Clemens D. , Schmid Holger , Krotz Florian , Sohn Hae-Young , Klauss Volker , Weber Christian , Schober Andreas
Published: October 2007

Objective—

Hypoxia-inducible factor (HIF)-1α is the regulatory subunit of a transcriptional complex, which controls the recruitment of multipotent progenitor cells and tissue repair in ischemic tissue by inducing stromal cell-derived factor (SDF)-1α expression. Because HIF-1α can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1α in SDF-1α–mediated neointima formation after vascular injury.

Methods and Results—

Wire-induced injury of the left carotid artery was performed in apolipoprotein E–deficient mice. HIF-1α expression was increased in the media as early as 1 day after injury, predominantly in SMCs. Nuclear translocation of HIF-1α and colocalization with SDF-1α was detected in neointimal cells after 2 weeks. HIF-1α mRNA expression was induced at 6 hours after injury as determined by real-time RT-PCR. Inhibition of HIF-1α expression by local application of HIF-1α-siRNA reduced the neointimal area by 49% and significantly decreased the neointimal SMCs content compared with control-siRNA. HIF-1α and SDF-1α expression were clearly diminished in neointimal cells of HIF-1α-siRNA treated arteries.

Conclusions—

HIF-1α expression is directly involved in neointimal formation after vascular injury and mediates the upregulation of SDF-1α, which may affect the stem cell–based repair of injured arteries.