Severe Obesity Hypoventilation Syndrome Treated with Auto-CPAP

Summary Obesity hypoventilation syndrome (OHS) is a serious medical condition that remains undiagnosed in seriously ill hospitalized patients. Significant improvement of daytime hypercapnia can be achieved with positive airway pressure (PAP) therapy. Bi-level PAP is generally employed with the goal of improving ventilation. A 50-year-old woman with OHS and severe hypercapnia was successfully treated with an auto titrating continuous PAP (Auto-CPAP) device. The major role in the pathogenesis of daytime hypercapnia in patients with OHS, is the progressive accumulation of carbon dioxide (CO2) caused by repetitive obstructive events at night, which can be eliminated with the low cost approach of treating with Auto CPAP. Background OHS, an interaction between sleep disordered breathing and obesity-related respiratory impairment leading to chronic daytime hypercapnia, remains under recognized and definitive treatment is often delayed.[1] Treatment of sleep disordered breathing with PAP therapy results in significant improvement of daytime hypercapnia.[2] Auto-CPAP is generally not recommended to treat obesity hypoventilation syndrome.[3,4] We present a patient with OHS and severe daytime hypercapnia who was successfully treated with Auto CPAP. Case Presentation: A fifty-year-old morbidly obese (BMI 52) non-smoking female with a history of hypertension and untreated obstructive sleep apnea (OSA) was admitted to the hospital with severe dyspnoea on exertion in July 2012. She was hypoxemic at admission. Arterial blood gas (ABG) on 2 liters of supplemental oxygen revealed a pH of 7.34, pCO2 of 88 mm Hg and a pO2 of 79 mm Hg. Serum bicarbonate level was elevated at 44mEq/L. Cardiac enzymes were normal. Brain natriuretic peptide (BNP) was elevated at 2161 pg/ml. D-dimer was normal. Chest x-ray was notable for prominence of main pulmonary artery, suggestive of pulmonary artery hypertension. EKG had non-specific changes. Echocardiogram revealed normal left ventricular systolic and diastolic function with mild pulmonary hypertension. Nuclear medicine stress test was normal. Computed tomography angiogram was normal. Pulmonary/Sleep medicine was consulted, and a presumptive diagnosis of OHS was made given the patient\u27s morbid obesity, previous history of OSA and hypoventilation on ABG. She was placed on CPAP at 10 cm water pressure in the hospital and demonstrated significant clinical improvement with relief of shortness of breath. Supplemental oxygen requirements improved from as high as 4 liters per minute via nasal cannula to 2 liters per minutes

Block of impulse propagation at an abrupt tissue expansion: evaluation of the critical strand diameter in 2- and 3-dimensional computer models

Objective: Unidirectional conduction block in the heart can occur at a site where the impulse is transmitted from a small to a large tissue volume. The aim of this study was to evaluate the occurrence of conduction block in a 2-dimensional and 3-dimensional computer model of cardiac tissue consisting of a narrow strand abruptly emerging into a large area. In this structure, the strand diameter critical for the occurrence of block, hc, was evaluated as a function of changes in the active and passive electrical properties of both the strand and the large medium. Methods: The effects of changes in the following parameters on hc were analysed: (1) maximum sodium conductance (gNamax), (2) longitudinal (Rx) and transverse (Ry) intracellular resistivities, and (3) inhomogeneities in gNamax and Rx and Ry between the strand and the large area. Three ionic models for cardiac excitation described by Beeler-Reuter, Ebihara-Johnson, and Luo-Rudy ionic current kinetics were compared. Results: In the 2-dimensional simulations, hc was 175 μm in Ebihara-Johnson and Beeler-Reuter models and 200 μm in the Luo-Rudy model. At the critical strand diameter, the site of conduction block was located beyond the transition, i.e. a small circular area was activated in the large medium, whereas with narrower strands conduction block occurred within the strands. The decrease of gNamax resulted in a large increase of hc. This increase was mainly due to the change of gNamax in the large area, while hc was almost independent of gNamax in the strand. Changing Rx had no effect on hc, whereas the increase of Ry decreased hc and reversed conduction block. Inhomogeneous changes of Rx and Ry in the strand versus the large medium had opposite effects on hc. When the resistivities of the strand alone were increased, hc also increased. In contrast, the increase of the resistivities in the large area reduced hc. In the 3-dimensional model, hc was 2.7 times larger than the corresponding 2-dimensional values at the various levels of gNamax and resistivity. Conclusions: (1) At physiological values for active and passive electrical properties, hc in the 2D simulations is close to 200 μm in all three ionic models. In the 3-dimensional simulations, hc is 2.7 larger than in the 2-dimensional models. (2) The excitable properties of the large area but not of the strand modify hc. The decrease of intercellular coupling in the large medium facilitates impulse conduction and reduces hc, while the same change in the strand increases hc. (3) Occurrence of conduction block at an abrupt geometrical transition can be explained by both the impedance mismatch at the transition site and the critical curvature beyond the transitio

Role of wavefront curvature in propagation of cardiac impulse

It is traditionally assumed that impulse propagation in cardiac muscle is determined by the combination of two factors: (1) the active properties of cardiac cell membranes and (2) the passive electrical characteristics of the network formed by cardiac cells. However, advances made recently in the theory of generic excitable media suggest that an additional factor—the geometry of excitation wavefronts—may play an important role. In particular, impulse propagation strongly depends on the wavefront curvature on a small spatial scale. In the heart, excitation wavefronts have pronounced curvatures in several situations including waves initiated by small electrodes, waves emerging from narrow tissue structures, and waves propagating around the sharp edges of anatomical obstacles or around a zone of functional conduction block during spiral wave rotation. In this short review we consider the theoretical background relating impulse propagation to wavefront curvature and we estimate the role of wavefront curvature in electrical stimulation, formation of conduction block, and the dynamic behavior of spiral wave

Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model

Objective: Unidirectional conduction block (UCB) and reentry may occur as a consequence of an abrupt tissue expansion and a related change in the electrical load. The aim of this study was to evaluate critical dimensions of the tissue necessary for establishing UCB in heart cell culture. Methods: Neonatal rat heart cell cultures with cell strands of variable width emerging into a large cell area were grown using a technique of patterned cell growth. Action potential upstrokes were measured using a voltage sensitive dye (RH-237) and a linear array of 10 photodiodes with a 15 μm resolution. A mathematical model was used to relate action potential wave shapes to underlying ionic currents. Results: UCB (block of a single impulse in anterograde direction — from a strand to a large area — and conduction in the retrograde direction) occurred in narrow cell strands with a width of 15(SD 4) μm (1-2 cells in width, n = 7) and there was no conduction block in strands with a width of 31(8) μm (n = 9, P < 0.001) or larger. The analysis of action potential waveshapes indicated that conduction block was either due to geometrical expansion alone (n = 5) or to additional local depression of conduction (n = 2). In wide strands, action potential upstrokes during anterograde conduction were characterised by multiple rising phases. Mathematical modelling showed that two rising phases were caused by electronic current flow, whereas local ionic current did not coincide with the rising portions of the upstrokes. Conclusions: (1) High resolution optical mapping shows multiphasic action potential upstrokes at the region of abrupt expansion. At the site of the maximum decrement in conduction, these peaks were largely determined by the electrotonus and not by the local ionic current. (2) Unidirectional conduction block occurred in strands with a width of 15(4) μm (1-2 cells

Impact of external industrial sources on the regional and local SO2 and O3 levels of the Mexico megacity

The air quality of megacities can be influenced by external emission sources on both global and regional scales. At the same time their outflow emissions can exert an impact to the surrounding environment. The present study evaluates an SO2 peak observed on 24 March 2006 at the suburban supersite T1 and at ambient air quality monitoring stations located in the northern region of the Mexico City Metropolitan Area (MCMA) during the Megacity Initiative: Local and Global Research Observations (MILAGRO) field campaign. We found that this peak could be related to an important episodic emission event coming from Tizayuca region, northeast of the MCMA. Back-trajectory analyses suggest that the emission event started in the early morning at 04:00 LST and lasted for about 9 h. The estimated emission rate is about 2 kg s[superscript −1]. To the best of our knowledge, sulfur dioxide emissions from the Tizayuca region have not been considered in previous studies. This finding suggests the possibility of "overlooked" emission sources in this region that could influence the air quality of the MCMA. This further motivated us to study the cement plants, including those in the state of Hidalgo and in the State of Mexico. It was found that they can contribute to the SO2 levels in the northeast (NE) region of the basin (about 42%), at the suburban supersite T1 (41%) and that at some monitoring stations their contribution can be even higher than the contribution from the Tula Industrial Complex (TIC). The contribution of the Tula Industrial Complex to regional ozone levels is estimated. The model suggests low contribution to the MCMA (1 to 4 ppb) and slightly higher contribution at the suburban T1 (6 ppb) and rural T2 (5 ppb) supersites. However, the contribution could be as high as 10 ppb in the upper northwest region of the basin and in the southwest and south-southeast regions of the state of Hidalgo. In addition, the results indicated that the ozone plume could also be transported to northwest Tlaxcala, eastern Hidalgo, and farther northeast of the State of Mexico, but with rather low values. A first estimate of the potential contribution from flaring activities to regional ozone levels is presented. Results suggest that up to 30% of the total regional ozone from TIC could be related to flaring activities. Finally, the influence on SO2 levels from technological changes in the existing refinery is briefly discussed. These changes are due to the upcoming construction of a new refinery in Tula. The combination of emission reductions in the power plant, the refinery and in local sources in the MCMA could result in higher reductions on the average SO[subscript 2] concentration. Reductions in external sources tend to affect more the northern part of the basin (−16 to −46%), while reductions of urban sources in the megacity tend to diminish SO[subscript 2] levels substantially in the central, southwest, and southeast regions (−31 to −50%).United States. Dept. of Energy (Atmospheric System Research Program, Contract DE-AC06-76RLO 1830)National Science Foundation (U.S.) (NSF award AGS-1135141)Consejo Nacional de Ciencia y Tecnología (Mexico

Different Outcomes of Experimental Hepatitis E Virus Infection in Diverse Mouse Strains, Wistar Rats, and Rabbits

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized countries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been demonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable small animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally inoculated C57BL/6 mice (wild-type, IFNAR−/−, CD4−/−, CD8−/−) and BALB/c nude (nu/nu) mice, Wistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication and shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected in one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse strains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their susceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid proteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection may serve as a suitable alternative to the non-human primate and swine models, and as an appropriate basis for vaccine evaluation studies

Quantifying black carbon deposition over the Greenland ice sheet from forest fires in Canada

Black carbon (BC) concentrations observed in 22 snowpits sampled in the northwest sector of the Greenland ice sheet in April 2014 have allowed us to identify a strong and widespread BC aerosol deposition event, which was dated to have accumulated in the pits from two snow storms between 27 July and 2 August 2013. This event comprises a significant portion (57% on average across all pits) of total BC deposition over 10 months (July 2013 to April 2014). Here we link this deposition event to forest fires burning in Canada during summer 2013 using modeling and remote sensing tools. Aerosols were detected by both the Cloud‐Aerosol Lidar with Orthogonal Polarization (on board CALIPSO) and Moderate Resolution Imaging Spectroradiometer (Aqua) instruments during transport between Canada and Greenland. We use high‐resolution regional chemical transport modeling (WRF‐Chem) combined with high‐resolution fire emissions (FINNv1.5) to study aerosol emissions, transport, and deposition during this event. The model captures the timing of the BC deposition event and shows that fires in Canada were the main source of deposited BC. However, the model underpredicts BC deposition compared to measurements at all sites by a factor of 2–100. Underprediction of modeled BC deposition originates from uncertainties in fire emissions and model treatment of wet removal of aerosols. Improvements in model descriptions of precipitation scavenging and emissions from wildfires are needed to correctly predict deposition, which is critical for determining the climate impacts of aerosols that originate from fires

Experimental constraints on a dark matter origin for the DAMA annual modulation effect

A claim for evidence of dark matter interactions in the DAMA experiment has been recently reinforced. We employ a new type of germanium detector to conclusively rule out a standard isothermal galactic halo of Weakly Interacting Massive Particles (WIMPs) as the explanation for the annual modulation effect leading to the claim. Bounds are similarly imposed on a suggestion that dark pseudoscalars mightlead to the effect. We describe the sensitivity to light dark matter particles achievable with our device, in particular to Next-to-Minimal Supersymmetric Model candidates.Comment: v4: introduces recent results from arXiv:0807.3279 and arXiv:0807.2926. Sensitivity to pseudoscalars is revised in light of the first. Discussion on the subject adde

CoGeNT: A Search for Low-Mass Dark Matter using p-type Point Contact Germanium Detectors

CoGeNT employs p-type point-contact (PPC) germanium detectors to search for Weakly Interacting Massive Particles (WIMPs). By virtue of its low energy threshold and ability to reject surface backgrounds, this type of device allows an emphasis on low-mass dark matter candidates (wimp mass of about 10 GeV/c2). We report on the characteristics of the PPC detector presently taking data at the Soudan Underground Laboratory, elaborating on aspects of shielding, data acquisition, instrumental stability, data analysis, and background estimation. A detailed background model is used to investigate the low energy excess of events previously reported, and to assess the possibility of temporal modulations in the low-energy event rate. Extensive simulations of all presently known backgrounds do not provide a viable background explanation for the excess of low-energy events in the CoGeNT data, or the previously observed temporal variation in the event rate. Also reported on for the first time is a determination of the surface (slow pulse rise time) event contamination in the data as a function of energy. We conclude that the CoGeNT detector technology is well suited to search for the annual modulation signature expected from dark matter particle interactions in the region of WIMP mass and coupling favored by the DAMA/LIBRA resultsComment: 20 pages, 31 figures. Several figures have been added, including an updated allowed region (both 90% and 99% confidence level contours) based on this analysis. There is also the addition of a Pb-210 background estimat