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S Saba

Publications and source records attributed to S Saba.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac conduction abnormalities in a mouse model of Lyme borreliosis.

BACKGROUND: Borrelia Burgdorferi (BB) induces cardiac conduction abnormalities in infected humans. Mice models of Lyme disease have been developed, however their electrophysiologic (EP) properties of conduction are unknown. METHODS: Seventy-six C3H/J mice (BB infected and age- and gender-matched controls) underwent blinded in vivo EP studies. In a first phase of the study, 40 male C3H/J mice were divided into 2 groups: Group (A) mice were infected at age 3 (weeks) and studied at 5, and Group (B) mice were infected at 9 and studied at 11. In a second phase, 36 female mice were divided into 2 groups: Group (C) mice were infected at 3 weeks and studied at 5, and Group (D) mice were infected at 3 and studied at 11. RESULTS: Infected mice of group (A) and (C) had wider QRS complexes (21.0+/-1.6 versus 17.3+/-1.3ms, p< or =0.0001 and 20.3+/-2.1 versus 18.5+/-1.7, p = 0.05, respectively) compared to the healthy controls (HC). Infected mice of group (B) and group (D) were similar to the HC. In all groups, the presence of conduction abnormalities correlated very closely with the amount of inflammation on pathology. CONCLUSION: This study describes the first EP mouse model of Lyme carditis. C3H/J mice exhibit conduction abnormalities that are reversible 8 weeks after inoculation, closely paralleling the resolution of inflammation on pathology. This model can be a valuable tool in the developing and testing of new modalities for the prevention and treatment of Lyme carditis.

Animals↗
PubMed2001

Use of correlation waveform analysis in discrimination between anterograde and retrograde atrial electrograms during ventricular tachycardia.

INTRODUCTION: Discriminating between ventricular tachycardia (VT) with 1:1 ventriculoatrial association and sinus tachycardia can be difficult, even when assisted by intracardiac tracings. In this study, we used a new computer algorithm to perform correlation waveform analyses on intracardiac atrial electrograms to help distinguish between VT and sinus tachycardia. METHODS AND RESULTS: Electrophysiologic studies of 28 patients (22 men; age 66 +/- 14 years) with inducible VT and mean ejection fraction of 37% +/- 16% were analyzed. A template of an intracardiac high right atrial electrogram was obtained during sinus rhythm (SR). Atrial electrograms during SR and VT were compared with the template using the new algorithm, and correlation coefficients (rho) were generated. The correlation coefficient of SR beats with the template was 96.4% +/- 3.4%. During VT with AV dissociation and persistent SR, rho was 94.5% +/- 3.7% (P = NS). During VT with 1:1 retrograde conduction, rho was 70.6% +/- 11.3% (P < 0.0001). At a cutoff of 85%, rho had positive and negative predictive values of 99% and 96%, respectively. CONCLUSION: Our findings indicate that the new algorithm can reliably separate between anterograde and retrograde atrial activation during VT. It can, therefore, discriminate between sinus tachycardia and VT with 1:1 ventriculoatrial conduction and may be useful in preventing inappropriate shocks from dual chamber defibrillators.

Aged↗
PubMed2001

Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function.

Polymorphonuclear leukocyte-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease and may be associated with CF transmembrane conductance regulator (CFTR) dysfunction as well as infection. Mutant DeltaF508 CFTR is mistrafficked, accumulates in the endoplasmic reticulum (ER), and may cause "cell stress" and activation of nuclear factor (NF)-kappaB. G551D mutants also lack Cl- channel function, but CFTR is trafficked normally. We compared the effects of CFTR mutations on the endogenous activation of an NF-kappaB reporter construct. In transfected Chinese hamster ovary cells, the mistrafficked DeltaF508 allele caused a sevenfold activation of NF-kappaB compared with wild-type CFTR or the G551D mutant (P < 0.001). NF-kappaB was also activated in 9/HTEo-/pCep-R cells and in 16HBE/pcftr antisense cell lines, which lack CFTR Cl- channel function but do not accumulate mutant protein in the ER. This endogenous activation of NF-kappaB was associated with elevated interleukin-8 expression. Impaired CFTR Cl- channel activity as well as cell stress due to accumulation of mistrafficked CFTR in the ER contributes to the endogenous activation of NF-kappaB in cells with the CFTR mutation.

Animals↗
PubMed2000

Fibronectin influences cellular proliferation and apoptosis similarly in LNCaP and PC-3 prostate cancer cell lines.

The mechanisms responsible for the emergence of clinically advanced prostate cancer (PC) are incompletely understood. Recent studies suggest that altered tumoral apoptosis with disordered cell proliferation sustains advanced disease and may account for the phenomena of anti-androgen therapeutic resistance. Previous inquiry has focused primarily on faulty intracellular mechanisms with limited scrutiny of the extracellular matrix including fibronectin and collagen type 4. We evaluated cell proliferation with Ki-67 immunoassay/image analysis and apoptosis by TUNEL staining and Bcl-2 immunoassay/image analysis in LNCaP and PC-3 human PC cell lines at baseline and following propagation on fibronectin and collagen type 4-coated coverslip substrate. Cell cultures showed differing proliferative and apoptosis characteristics at baseline, with the LNCaP cell line showing relatively higher proliferation and apoptosis rates than the PC-3 cell line. Cell proliferation and apoptosis were statistically significantly decreased in both cell lines following propagation on fibronectin. Bcl-2 expression was significantly increased among both cell lines following propagation on fibronectin. In contrast, cell proliferation, apoptosis, and Bcl-2 expression showed insignificant changes in both cell lines following uncoated coverslip and collagen type 4 matrix propagation. Our findings showed that fibronectin influences cell proliferation, apoptosis, and Bcl-2 expression similarly among LNCaP and PC-3 PC cell lines. It is likely that the altered rates are independent of the androgen status of the cell line and are mediated through a nonhormonal mechanism.

Journal Article↗
PubMed2000

Invasive cardiac electrophysiology in the mouse: techniques and applications.

As the genetic nature of a wide spectrum of cardiovascular diseases is being elucidated, it is increasingly important to understand the functional role of specific genes on cardiac arrhythmia and conduction disturbances. The progress made in molecular genetics has allowed the creation of mice with targeted gene overexpression or elimination. These animals are valuable tools for researchers who have adapted their clinical and technical skills to the mouse, in order to extract information on the phenotypic consequences of the specific genetic disruption. In this review, we summarize the progress made in the field of invasive murine electrophysiology, focusing on the recent technical advances in in vivo electrophysiologic testing and its application to various genetically engineered mouse models. The authors' views on the future needs and trends in the field are also presented.

Animals↗
PubMed2000

Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities.

INTRODUCTION: Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Purkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of deficiencies in Cx40. METHODS AND RESULTS: Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40-/- mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6+/-6.4 msec vs 36.0+/-4.1 msec, P = 0.002). Not only the HV interval (14.0+/-3.0 msec vs 10.4+/-1.2 msec, P = 0.003) but also the AH interval (33.2+/-4.8 msec vs 27.1+/-3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice. CONCLUSION: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction.

Animals↗
PubMed1999

Assessment of atrioventricular nodal physiology in the mouse.

Transgenic mice are increasingly being utilized for understanding cardiac electrophysiologic abnormalities. However, little is known about the normal atrioventricular nodal and infraHisian physiology in the mouse because of the prior inability to record a His-bundle deflection. We present the first comprehensive examination of the murine atrioventricular nodal and His-Purkinje systems employing His-bundle recordings. Normal, healthy, male C57BL/6J mice (n = 48) underwent an in vivo electrophysiology study using a 2 F octapolar electrode catheter. Effective refractory periods were determined during premature atrial and ventricular stimulation. The PR interval measured 44 +/- 6 ms with a mean sinus cycle length of 185 +/- 42 ms. Baseline AH intervals were 36 +/- 5 ms and HV intervals were 10 +/- 2 ms. At a pacing cycle length of 140 ms the atrioventricular nodal effective refractory period (AVNERP) and atrial effective refractory period (AERP) were 86 +/- 19 ms and 57 +/- 17 ms, respectively. The mean AV Wenckebach and 2:1 paced cycle length were 103 +/- 14 ms and 84 +/- 13 ms, respectively. Premature atrial stimulation curves were asymptotic without discontinuity. A subset of nine mice was studied after administration of isoproterenol. The sinus cycle length, AVNERP and AERP decreased significantly from baseline measurements. This method establishes a practical and feasible technique to record in vivo His-bundle electrograms in the mouse to assess atrioventricular nodal and infraHisian physiology. Use of this model will allow for the examination of abnormalities of atrioventricular nodal and infraHisian conduction in transgenic murine models.

Adrenergic beta-Agonists↗
PubMed1999

Localization of the sites of conduction abnormalities in a mouse model of myotonic dystrophy.

INTRODUCTION: A mouse strain lacking functional myotonic dystrophy protein kinase (DMPK) has recently been developed. DMPK-/- mice exhibit muscular and conduction abnormalities consistent with the disease; however, the site of abnormal cardiac conduction is unknown. METHODS AND RESULTS: Nine homozygous DMPK-/- mice and seven age matched wild-type (WT) controls underwent in vivo electrophysiologic studies using an endocardial 2-French catheter. Baseline intervals as well as Wenckebach and 2:1 cycle lengths were measured to assess AV and ventriculoatrial (VA) conduction. Effective refractory periods (ERP) and functional refractory periods were determined during atrial and ventricular premature stimulation. His-bundle recordings were obtained on all the studied animals (16/16). DMPK-/- mice had significantly prolonged PR (48.1 +/- 5.5 vs 40.9 +/- 3.9 msec, P = 0.010) and AH (36.7 +/- 4.0 vs 31.6 +/- 4.8 msec, P = 0.037) intervals compared to WT controls. HV intervals were very significantly prolonged as well (14.7 +/- 2.0 vs 10.3 +/- 0.8 msec; P < 0.0001). Three of 9 DMPK-/- and 1 of 7 WT mice exhibited VA block. Atrial ERP was reached before AV node ERP in 2 (22%) of 9 of the knockout mice and 5 (71%) of 7 of the controls (P = 0.06). Only one mouse (DMPK-/-) exhibited infra-Hisian block on premature atrial stimulation. CONCLUSION: In this mouse model of myotonic dystrophy, AV conduction abnormalities were localized to the supra-Hisian and infra-Hisian conduction tissues, with a higher predilection to the latter, a finding similar to the human form of the disease.

Animals↗
PubMed1999

Design of a cast bar reinforced provisional restoration for the management of the interim phase in implant dentistry.

Implant therapy is becoming the treatment of choice for the replacement of teeth in partially edentulous arches. The interim phase of implant treatment often presents particular problems because of the position of the remaining teeth, their periodontal status, and the loss of vertical dimension of occlusion. This case report will discuss the design and fabrication of a cast bar reinforced long-span provisional restoration based on a diagnostic wax-up to simplify the management of the interim phase.

Dental Implantation, Endosseous↗
PubMed1999

Aorto-right ventricular fistula: a late complication of aortic valve replacement.

We report the case of a patient who was found to have an aorto-right ventricular fistula 17 years after receiving a Björk-Shiley prosthetic aortic valve. A pseudoaneurysm had formed at the aortotomy suture line, and it had extended into the interventricular septum and had eventually opened into the right ventricle. Using transesophageal echocardiography, we identified the defect in the ascending aorta, and a left-to-right shunt. Aortography was used to confirm these findings. The pseudoaneurysm was successfully resected and the ascending aorta was replaced with a Dacron graft. To the best of our knowledge, no similar late complication of aortic valve replacement has been reported in the medical literature.

Aged↗