Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals.

BACKGROUND AND PURPOSE: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

Real-time transmission of 16 Tb/s over 1020km using 200Gb/s CFP2-DCO.

We demonstrate real-time transmission of 16 Tb/s (80x200Gb/s) over 1020km TeraWave ULL fiber with 170km span length using the world's first 200Gb/s CFP2-DCO module with a record low power consumption less than 0.1W/Gbps.

Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

800Gb/s (8x128Gb/s) unrepeatered transmission over 515-km large-area ultra-low-loss fiber using 2nd-order Raman pumping.

We demonstrate unrepeatered transmission of 8x128Gb/s PDM-QPSK signals over a 515k-m fiber link. This ultra-long distance of 800 Gb/s unrepeatered transmission in a single fiber configuration is achieved by employing enabling techniques such as large-effective-area ultra-low-attenuation fibers, co-propagating and counter-propagating 2nd-order-pumped distributed Raman amplification, and remote optically pumped amplifier (ROPA). The ROPA itself is also counter-propagating 2nd-order Raman pumped. The designs and characteristics of the ROPA and 2nd-order pumped distributed Raman amplification are described, and optimization of the transmission performance of this ultra-long reach 800Gb/s unrepeatered transmission fiber link is discussed in this paper.

Utilization of Health Research Recommendation in Policy and Planning in Nepal.

BACKGROUND: Over the past decade in Nepal, a large number of studies have been carried in a variety of health areas; however whether evidence derived from these studies has been used to inform health policy has not been explored. This study aims to assess the utilization of recommendations from health research in health policy and plans, and to identify the factors that influence utilization of research findings by policy makers' in Nepal. METHODS: Qualitative study incorporating literature review and semi-structured interviews was used. Research reports and health related policies were collected from governmental and non-governmental bodies. Documents were reviewed to identify the utilization of research-based recommendations in health policy and plan formulation. In-depth interviews were conducted with key policy makers and researchers to identify factors that hinder the utilization of research recommendations. RESULTS: A total of 83 health related research reports were identified, of which 48 had recommendations. Four policies and three plans, from total 21 identified plans and policies, were found to have incorporated recommendations from research. Of the 48 studies that had recommendations, 35 were found to be used in the policy making process. Lack of appropriate communication mechanisms, and concerns related to the quality of research conducted, were the main factors hindering the translation of evidence into policy. CONCLUSIONS: Communication gaps exist between researchers and policy makers, which seem to have impeded the utilization of research-based information and recommendations in decision-making process. Establishing a unit responsible for synthesizing evidences and producing actionable messages for policy makers can improve utilization of research findings.

Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration.

BACKGROUND AND PURPOSE: A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS: The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS: One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS: Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images.

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. SUBJECTS: Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). RESULTS: In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. CONCLUSION: Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

Longitudinal assessment of oxaliplatin-induced neuropathy.

OBJECTIVES: To characterize the natural history of oxaliplatin-associated neuropathy (ON) and determine whether intraepidermal nerve fiber density (IENFD) is a sensitive measure of neuropathy progression. In addition, we sought to assess the potential of ON as a neuroprotection model and gain insight into the relationship between axon loss and neuropathic symptoms. METHODS: Eight subjects receiving oxaliplatin for advanced colorectal cancer were prospectively followed prior to starting chemotherapy and at 30, 90, 180, and 360 days (180 days after completing treatment). Electrophysiology, punch biopsies, symptom assessment, and examinations with calculation of a reduced total neuropathy score (rTNS) were performed at each time point. Changes over time were assessed through Poisson regression for IENFD and a mixed effects model for rTNS and electrophysiology measures. RESULTS: The distal leg IENFD, rTNS, peroneal, and sural amplitudes were all significantly reduced over time, while conduction velocity (peroneal and sural) and distal thigh IENFD were not. Measures of axon loss continued to worsen following discontinuation of oxaliplatin. Five of 8 subjects reported prominent symptoms associated with oxaliplatin administration. CONCLUSIONS: This study demonstrates that oxaliplatin is associated with mild, sensory, and motor axon loss that may not be reversible. Axonal loss was detected by electrophysiology, rTNS, and distal leg IENFD. Several subjects reported prominent sensory symptoms that were not associated with axon loss, and that may or may not represent neuropathy. ON is an attractive paradigm for neuroprotection studies and the distal leg IENFD is an objective measure that requires minimal subject participation or study site expertise.

Association of endothelial and oxidative stress with metabolic syndrome and subclinical atherosclerosis: multi-ethnic study of atherosclerosis.

BACKGROUND/OBJECTIVES: A cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress. SUBJECTS/METHODS: Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of 45- to 84-year-old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand factor, soluble intercellular adhesion molecule-1 (sICAM-1), CD40 ligand (CD40L), soluble thrombomodulin, E-selectin and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal-medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods. RESULTS: MetS was associated with higher levels of each of the biomarkers (P<0.001, CD40L-suggestive association P=0.004), with greater IMT (P<0.001), and with greater extent of CAC in those in whom CAC was detectable (P=0.01). The association of MetS with measures of subclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (P=0.005) and thicker internal carotid IMT (P=0.002), whereas sICAM-1 was significantly associated with greater prevalence of detectable CAC (P=0.001). CONCLUSIONS: The association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms.

Heterogeneous expression of Gap junction channels in the heart leads to conduction defects and ventricular dysfunction.

BACKGROUND: - Heterogeneous remodeling of gap junctions is observed in many forms of heart disease. The consequent loss of synchronous ventricular activation has been hypothesized to result in diminished cardiac performance. To directly test this hypothesis, we designed a murine model of heterogeneous gap junction channel expression. Methods and Results-- We generated chimeric mice formed from connexin43 (Cx43)-deficient embryonic stem cells and wild-type or genetically marked ROSA26 recipient blastocysts. Chimeric mice developed normally, without histological evidence of myocardial fibrosis or hypertrophy. Heterogeneous Cx43 expression resulted in conduction defects, however, as well as markedly depressed contractile function. Optical mapping of chimeric hearts by use of voltage-sensitive dyes revealed highly irregular epicardial conduction patterns, quantified as significantly greater negative curvature of the activation wave front (-1.86+/-0.40 mm in chimeric mice versus -0.86+/-0.098 mm in controls; P<0.01; n=6 for each group). Echocardiographic studies demonstrated significantly reduced fractional shortening in chimeric mice (26.6+/-2.3% versus 36.5+/-1.6% in age-matched 129/SvxC57BL/6F1 wild-type controls; P<0.05). CONCLUSIONS: - These data suggest that heterogeneous Cx43 expression, by perturbing the normal pattern of coordinated myocardial excitation, may directly depress cardiac performance.

Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development.

Connexin43 (Cx43) is the principal connexin isoform in the mouse ventricle, where it is thought to provide electrical coupling between cells. Knocking out this gene results in anatomic malformations that nevertheless allow for survival through early neonatal life. We examined electrical wave propagation in the left (LV) and right (RV) ventricles of isolated Cx43 null mutated (Cx43(-/-)), heterozygous (Cx43(+/)(-)), and wild-type (WT) embryos using high-resolution mapping of voltage-sensitive dye fluorescence. Consistent with the compensating presence of the other connexins, no reduction in propagation velocity was seen in Cx43(-/-) ventricles at postcoital day (dpc) 12.5 compared with WT or Cx43(+/)(-) ventricles. A gross reduction in conduction velocity was seen in the RV at 15.5 dpc (in cm/second, mean [1 SE confidence interval], WT 9.9 [8.7 to 11.2], Cx43(+/)(-) 9.9 [9.0 to 10.9], and Cx43(-/-) 2.2 [1.8 to 2.7; P<0.005]) and in both ventricles at 17.5 dpc (in RV, WT 8.4 [7.6 to 9.3], Cx43(+/)(-) 8.7 [8.1 to 9.3], and Cx43(-/-) 1.1 [0.1 to 1.3; P<0.005]; in LV, WT 10.1 [9.4 to 10.7], Cx43(+/)(-) 8.3 [7.8 to 8.9], and Cx43(-/-) 1.7 [1.3 to 2.1; P<0.005]) corresponding with the downregulation of Cx40. Cx40 and Cx45 mRNAs were detectable in ventricular homogenates even at 17.5 dpc, probably accounting for the residual conduction function. Neonatal knockout hearts were arrhythmic in vivo as well as ex vivo. This study demonstrates the contribution of Cx43 to the electrical function of the developing mouse heart and the essential role of this gene in maintaining heart rhythm in postnatal life.

Visualization and functional characterization of the developing murine cardiac conduction system.

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. The molecular mechanisms regulating the specification and patterning of cells that form this conductive network are largely unknown. Studies in avian models have suggested that components of the cardiac conduction system arise from progressive recruitment of cardiomyogenic progenitors, potentially influenced by inductive effects from the neighboring coronary vasculature. However, relatively little is known about the process of conduction system development in mammalian species, especially in the mouse, where even the histological identification of the conductive network remains problematic. We have identified a line of transgenic mice where lacZ reporter gene expression delineates the developing and mature murine cardiac conduction system, extending proximally from the sinoatrial node to the distal Purkinje fibers. Optical mapping of cardiac electrical activity using a voltage-sensitive dye confirms that cells identified by the lacZ reporter gene are indeed components of the specialized conduction system. Analysis of lacZ expression during sequential stages of cardiogenesis provides a detailed view of the maturation of the conductive network and demonstrates that patterning occurs surprisingly early in embryogenesis. Moreover, optical mapping studies of embryonic hearts demonstrate that a murine His-Purkinje system is functioning well before septation has completed. Thus, these studies describe a novel marker of the murine cardiac conduction system that identifies this specialized network of cells throughout cardiac development. Analysis of lacZ expression and optical mapping data highlight important differences between murine and avian conduction system development. Finally, this line of transgenic mice provides a novel tool for exploring the molecular circuitry controlling mammalian conduction system development and should be invaluable in studies of developmental mutants with potential structural or functional conduction system defects.

Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43.

Cardiac arrhythmia is a common and often lethal manifestation of many forms of heart disease. Gap junction remodeling has been postulated to contribute to the increased propensity for arrhythmogenesis in diseased myocardium, although a causative role in vivo remains speculative. By generating mice with cardiac-restricted knockout of connexin43 (Cx43), we have circumvented the perinatal lethal developmental defect associated with germline inactivation of this gap junction channel gene and uncovered an essential role for Cx43 in the maintenance of electrical stability. Mice with cardiac-specific loss of Cx43 have normal heart structure and contractile function, and yet they uniformly (28 of 28 conditional Cx43 knockout mice observed) develop sudden cardiac death from spontaneous ventricular arrhythmias by 2 months of age. Optical mapping of the epicardial electrical activation pattern in Cx43 conditional knockout mice revealed that ventricular conduction velocity was significantly slowed by up to 55% in the transverse direction and 42% in the longitudinal direction, resulting in an increase in anisotropic ratio compared with control littermates (2.1+/-0.13 versus 1.66+/-0.06; P:<0.01). This novel genetic murine model of primary sudden cardiac death defines gap junctional abnormalities as a key molecular feature of the arrhythmogenic substrate.

Understanding conduction of electrical impulses in the mouse heart using high-resolution video imaging technology.

The conduction of electrical impulses in the heart depends on the ability to efficiently transfer excitatory current between individual myocytes. Several recent studies have focused on the use of optical mapping techniques to determine the electrophysiological consequences and the proarrhythmic effects of reducing intercellular coupling in newly developed connexin knockout mice. This work has begun to unravel important questions regarding the role of connexins in intercellular coupling and propagation of electrical impulses in the heart. The purpose of this review is to discuss the techniques and unique issues involved in imaging electrical wave propagation in the heart. In addition, we will review recent experimental studies that address the role of intercellular communication in the development of cardiac arrhythmias.

High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system.

Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained using a high-speed CCD camera while simultaneously recording volume-conducted ECGs. In Cx40(-/-) mice, the PR interval was prolonged (47.4+/-1.4 in wild-type [WT] [n=6] and 57.5+/-2.8 in Cx40(-/-) [n=6]; P<0.01). WT ventricular epicardial activation was characterized by focused breakthroughs that originated first on the right ventricle (RV) and then the left ventricle (LV). In Cx40(-/-) hearts, the RV breakthrough occurred after the LV breakthrough. Additionally, Cx40(-/-) mice showed RV breakthrough times that were significantly delayed with respect to QRS complex onset (3.7+/-0.7 ms in WT [n=6] and 6.5+/-0.7 ms in Cx40(-/-) [n=6]; P<0.01), whereas LV breakthrough times did not change. Conduction velocity measurements from optical mapping of the RBB revealed slow conduction in Cx40(-/-) mice (74.5+/-3 cm/s in WT [n=7] and 43.7+/-6 cm/s in Cx40(-/-) [n=7]; P<0.01). In addition, simultaneous ECG records demonstrated significant delays in Cx40(-/-) RBB activation time with respect to P time (P-RBB time; 41.6+/-1.9 ms in WT [n=7] and 55.1+/-1.3 ms in [n=7]; P<0.01). These data represent the first direct demonstration of conduction defects in the specialized conduction system of Cx40(-/-) mice and provide new insight into the role of gap junctions in cardiac impulse propagation.

Temporal organization of atrial activity and irregular ventricular rhythm during spontaneous atrial fibrillation: an in vivo study in the horse.

INTRODUCTION: Atrial fibrillation (AF) is common in healthy horses. We studied the temporal organization of AF to test the hypothesis that the arrhythmia is governed by a high degree of periodicity and therefore is not random in the horse. Further, we surmised that concealed conduction of AF impulses in the AV node results in an inverse relationship between AF frequency and ventricular frequency. METHODS AND RESULTS: Fast Fourier transform (FFT) analysis of atrial activity was done on signal-averaged ECGs (n = 11) and atrial electrograms (n = 3) of horses with AF at control (C), after quinidine sulfate (22 mg/kg by mouth every 2 hours) at 50% time to conversion (T50), and immediately before conversion (T90) to sinus rhythm. FFT always revealed a single dominant frequency peak. The mean dominant frequency decreased until conversion (C = 6.84 +/- 0.85 Hz, T50 = 4.87 +/- 1.5 Hz, T90 = 3.41 +/- 1.18 Hz; P < 0.001). Mean AA intervals (n = 500) gradually increased after quinidine. Mean RR intervals (n = 500), standard deviation of the mean (SDM), Poincaré plots, and serial autocorrelograms (SACs) of 500 RR intervals were measured at C and T90 to determine the ventricular response to AF and quinidine-induced changes in the variability of the ventricular response. Mean RR interval and SDM were reduced after quinidine (C = 1431 +/- 266 msec and 695 +/- 23 msec; T90 = 974 +/- 116 msec and 273 +/- 158 msec, respectively; P < 0.01). Poincaré plots and SAC at C and at T90 revealed a significant correlation of consecutive RR intervals typical of a system with a deterministic behavior. At T90, the variability of RR intervals was reduced and the overall periodicity of RR intervals was increased after quinidine administration. CONCLUSION: In the horse, AF is a complex arrhythmia characterized by a high degree of underlying periodicity. The inverse AA-to-RR interval relationship and reduced variability of RR intervals after quinidine suggest that the ventricular response during AF results from rate-dependent concealment of AF wavelets bombarding the AV node, which nevertheless results in a significant degree of short-term predictability of beat-to-beat changes in RR intervals.

Early onset heart failure in transgenic mice with dilated cardiomyopathy.

In children, dilated cardiomyopathy is due to a variety of etiologies and usually carries a grave prognosis. The purpose of the present study was to carefully follow the progression of events leading to cardiac dilatation and congestive heart failure in a dilated cardiomyopathy model in neonatal and juvenile mice. These initial steps are often not well characterized. Furthermore, the loss of gap junctions and reduced electrical coupling of cardiomyocytes frequently found in human cardiomyopathies are also observed in these early stages. By 2 wk of age, molecular markers associated with hypertrophy were already altered. Cardiomyocyte hypertrophy, reduced connexin43 expression, and decreased conduction velocity were apparent by 4 wk, before overt cardiac dysfunction (decreased shortening fraction and chamber remodeling) that was not present until 12 wk of age. Our results show that in this model cardiomyopathic changes are present by 2 wk after birth and progress rapidly during the subsequent 2 postnatal weeks. Combined with the observations of other models of heart disease, we suggest that the first 2 wk of postnatal life are absolutely critical for normal cardiac development, and events that perturb homeostasis during this period determine whether the heart will continue to develop normally. These animals exhibit early symptoms of disease including reduced connexin43 and conduction defects before impaired cardiac function and demonstrate for the first time a temporal association between decreased connexin43 levels and the initiation of a contractility deficit that ends in heart failure.

Tuberculous otitis media-are we missing it ?

Tuberculosis of the middle ear it a rare disease. Due to change in the typical clinical pattern and decrease in incidence, there is a delayed or missed diagnosis and can lead to increased morbidity. We pretent 5 cases of Tuberculous Otitis Media treated over a period of 2 years, highlighting the fact that it must be considered as a differential diagnosis of persistent suppurative otitis media.