Viral emergence in marine mammals in the North Pacific may be linked to Arctic sea ice reduction.

Climate change-driven alterations in Arctic environments can influence habitat availability, species distributions and interactions, and the breeding, foraging, and health of marine mammals. Phocine distemper virus (PDV), which has caused extensive mortality in Atlantic seals, was confirmed in sea otters in the North Pacific Ocean in 2004, raising the question of whether reductions in sea ice could increase contact between Arctic and sub-Arctic marine mammals and lead to viral transmission across the Arctic Ocean. Using data on PDV exposure and infection and animal movement in sympatric seal, sea lion, and sea otter species sampled in the North Pacific Ocean from 2001-2016, we investigated the timing of PDV introduction, risk factors associated with PDV emergence, and patterns of transmission following introduction. We identified widespread exposure to and infection with PDV across the North Pacific Ocean beginning in 2003 with a second peak of PDV exposure and infection in 2009; viral transmission across sympatric marine mammal species; and association of PDV exposure and infection with reductions in Arctic sea ice extent. Peaks of PDV exposure and infection following 2003 may reflect additional viral introductions among the diverse marine mammals in the North Pacific Ocean linked to change in Arctic sea ice extent.

Stable Isotope Models Predict Foraging Habitat of Northern Fur Seals (Callorhinus ursinus) in Alaska.

We developed models to predict foraging habitat of adult female northern fur seals (Callorhinus ursinus) using stable carbon (δ13C) and nitrogen (δ15N) isotope values from plasma and red blood cells. Binomial generalized linear mixed models were developed using blood isotope samples collected from 35 adult female fur seals on three breeding colonies in Alaska during July-October 2006. Satellite location and dive data were used to define habitat use in terms of the proportion of time spent or dives made in different oceanographic/bathymetric domains. For both plasma and red blood cells, the models accurately predicted habitat use for animals that foraged exclusively off or on the continental shelf. The models did not perform as well in predicting habitat use for animals that foraged in both on- and off-shelf habitat; however, sample sizes for these animals were small. Concurrently collected scat, fatty acid, and dive data confirmed that the foraging differences predicted by isotopes were associated with diet differences. Stable isotope samples, dive data, and GPS location data collected from an additional 15 females during August-October 2008 validated the effective use of the models across years. Little within year variation in habitat use was indicated from the comparison between stable isotope values from plasma (representing 1-2 weeks) and red blood cells (representing the prior few months). Constructing predictive models using stable isotopes provides an effective means to assess habitat use at the population level, is inexpensive, and can be applied to other marine predators.

Dispersal provided resilience to range collapse in a marine mammal: insights from the past to inform conservation biology.

Population loss is often a harbinger of species extinction, but few opportunities exist to follow a species' demography and genetics through both time and space while this occurs. Previous research has shown that the northern fur seal (Callorhinus ursinus) was extirpated from most of its range over the past 200-800 years and that some of the extirpated populations had unique life history strategies. In this study, widespread availability of subfossils in the eastern Pacific allowed us to examine temporal changes in spatial genetic structure during massive population range contraction and partial recovery. We sequenced the mitochondrial control region from 40 ancient and 365 modern samples and analyzed them through extensive simulations within a serial Approximate Bayesian Computation framework. These analyses suggest that the species maintained a high abundance, probably in subarctic refugia, that dispersal rates are likely 85% per generation into new breeding colonies, and that population structure was not higher in the past. Despite substantial loss of breeding range, this species' high dispersal rates and refugia appear to have prevented a loss of genetic diversity. High dispersal rates also suggest that previous evidence for divergent life history strategies in ancient populations likely resulted from behavioral plasticity. Our results support the proposal that panmictic, or nearly panmictic, species with large ranges will be more resilient to future disturbance and environmental change. When appropriately verified, evidence of low population structure can be powerful information for conservation decision-making.

Successful thrombolytic therapy of pulmonary embolism associated with urosepsis in an infant.

Childhood pulmonary embolism (PE) is a rare but serious condition marked by hypoxemia, shock, right-sided heart failure, and significant risk for fatality. Recommended treatment options include surgical embolectomy, anticoagulation, and thrombolysis. This report describes the successful use of recombinant tissue plasminogen activator to treat PE associated with urosepsis in a 34-day-old infant and reverse severe hemodynamic compromise. Diagnosis of proximal PE and monitoring its treatment were successfully achieved by echocardiography.

Efficacy of IV theophylline in children with severe status asthmaticus.

STUDY OBJECTIVE: To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists, inhaled ipratropium, and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU (PICU). DESIGN: A prospective, randomized, controlled trial. Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment. SETTING: The PICU of an urban, university-affiliated, tertiary-care children's hospital. PATIENTS: Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress, as indicated by a modified Wood-Downes clinical asthma score (CAS) of > or = 5. INTERVENTIONS: All subjects initially received continuous albuterol nebulizations; intermittent, inhaled ipratropium; and IV methylprednisolone. The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily. MEASUREMENTS AND RESULTS: Forty-seven children (median age, 8.3 years; range, 13 months to 17 years) completed the study. Twenty-three children received theophylline. The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group. All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion. Among the 41 subjects who were not receiving mechanical ventilation, those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects (18.6 +/- 2.7 h vs 31.1 +/- 4.5 h; p < 0.05). Theophylline had no effect on the length of PICU stay or the total incidence of side effects. Subjects receiving theophylline had more emesis (p < 0.05), and control patients had more tremor (p < 0.05). CONCLUSIONS: Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol, ipratropium, and methylprednisolone. The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined.

Studies on factors influencing stability and recovery of paclitaxel from suspension media and cultures of Taxus cuspidata cv Densiformis by high-performance liquid chromatography.

An HPLC method was developed for quick scanning of taxanes from large numbers of plant cell suspension samples. The method was optimized for analysis of a range of taxanes of differing polarity. Identification of a standard mixture of paclitaxel and 12 related taxanes was achieved in less than 15 min using a gradient mode and a Microsorb-MV C8 column. The method was used to investigate the influence of several factors on stability and recovery of paclitaxel from suspension media and cultures of Taxus cuspidata cv Densiformis. Incubation time had the most significant influence on stability of paclitaxel, contributing 88% to the total variation. Shaking contributed 6% to the total variation. Light contributed only 0.25% to the total variation. Analysis of test samples of suspension cultures of T. cuspidata cv Densiformis over a 4 week period show paclitaxel, 10-deacetylbaccatin III, and baccatin III levels ranging from 0 to 149 microg/L, from 0 to 1.9 mg/L, and from 0 to 583 microg/L, respectively.

Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure.

OBJECTIVE: To describe the effects of inhaled nitric oxide on oxygenation and ventilation in patients with acute, hypoxic respiratory failure and to characterize those who respond to low doses with a significant improvement in PaO2. DESIGN: Prospective dose response trial of inhaled nitric oxide. Patients who demonstrated a > or =15% improvement in PaO2 were randomized to receive conventional mechanical ventilation with or without prolonged inhaled nitric oxide. SETTING: Pediatric intensive care unit of a tertiary care children's hospital serving as a regional referral center for respiratory failure. PATIENTS: Pediatric patients with an acute parenchymal lung disease requiring mechanical ventilation, an F(IO2) of > or =0.5, a positive end-expiratory pressure of > or =7 cm H2O, and whose PaO2/FIO2 ratio was < or =160. INTERVENTIONS: PaO2, PaCO2, pH, heart rate, blood pressure, and methemoglobin were recorded at baseline and after inhaling 1, 5, 10, and 20 ppm of nitric oxide. Peak expiratory flow rate and mean airway resistance were measured while subjects received 0 and 20 ppm of inhaled nitric oxide. Patients were followed up until extubation or death. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (median age, 2.6 yrs [range, 1 mo-18.2 yrs]) were enrolled in the study. PaO2 increased (p< .001) and Pa(CO2) fell (p< .0001) from baseline with the administration of inhaled nitric oxide. There was no statistical difference among 1, 5, 10, and 20 ppm with regard to effects on oxygenation. Sixteen patients (62%) responded to inhaled nitric oxide with a > or =15% improvement in PaO2; 14 of these responses occurred at a dose of 1 or 5 ppm. Response to inhaled nitric oxide was not associated with age, length of intubation, presence of primary lung disease, chest radiograph, or illness severity. Among patients weighing < or =20 kg, responders showed a greater fall in mean airway resistance (p < .05) than nonresponders. Mortality was not influenced by prolonged inhaled nitric oxide when analyzed by intention to treat. Patients receiving prolonged inhaled nitric oxide at doses of < or =20 ppm maintained methemoglobin levels of <3.0% and circuit concentrations of NO2 of <1 ppm. CONCLUSIONS: Inhaled nitric oxide at doses of < or =5 ppm improves the oxygenation and (to a lesser extent) ventilation of most children with acute, hypoxic respiratory failure. The unpredictable response of patients necessitates individualized dosing of inhaled nitric oxide, starting at concentrations of < or =1 ppm. Inhaled nitric oxide at < or =20 ppm may exert a small salutary effect on bronchial tone. The benefits of prolonged inhaled nitric oxide remain unknown.

Volumetric capnography in children. Influence of growth on the alveolar plateau slope.

BACKGROUND: Lung growth in children is associated with dramatic increases in the number and surface area of alveolated airways. Modelling studies have shown the slope of the alveolar plateau (phase III) is sensitive to the total cross-sectional area of these airways. Therefore, the influence of age and body size on the phase III slope of the volumetric capnogram was investigated. METHODS: Phase III slope (alveolar dcCO2/dv) and airway deadspace (VDaw) were derived from repeated single-breath carbon dioxide expirograms collected on 44 healthy mechanically ventilated children (aged 5 months-18 yr) undergoing minor surgery. Ventilatory support was standardized (VT = 8.5 and 12.5 ml/kg, f = 8-15 breaths/min, inspiratory time = 1 s, end-tidal partial pressure of carbon dioxide = 30-45 mmHg), and measurements were recorded by computerized integration of output from a heated pneumotachometer and mainstream infrared carbon dioxide analyzer inserted between the endotracheal tube and anesthesia circuit. Experimental data were compared to simulated breath data generated from a numeric pediatric lung model. RESULTS: An increased VDaw, a smaller VDaw/VT, and flatter phase III slope were found at the larger tidal volume (P < 0.01). Strong relationships were seen at VT = 12.5 ml/kg between airway deadspace and age (R2 = 0.77), weight (R2 = 0.93), height (R2 = 0.78), and body surface area (R2 = 0.89). The normalized phase III slopes of infants were markedly steeper than that of adolescents and were reduced at both tidal volumes with increasing age, weight, height, and body surface area. Phase III slopes and VDaw generated from modelled carbon dioxide washout simulations closely matched the experimental data collected in children. CONCLUSIONS: Morphometric increases in the alveolated airway cross-section with lung growth is associated with a decrease of the phase III slope. During adolescence, normalized phase III slopes approximate those of healthy adults. The change in slope with lung growth may reflect a decrease in diffusional resistance for carbon dioxide transport within the alveolated airway resulting in diminished acinar carbon dioxide gradients.