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Biomedical subjects

David A Lipson

Publications and source records attributed to David A Lipson.

17 recordsLinked to original sources

Effects of abiotic factors on the phylogenetic diversity of bacterial communities in acidic thermal springs.

Acidic thermal springs offer ideal environments for studying processes underlying extremophile microbial diversity. We used a carefully designed comparative analysis of acidic thermal springs in Yellowstone National Park to determine how abiotic factors (chemistry and temperature) shape acidophile microbial communities. Small-subunit rRNA gene sequences were PCR amplified, cloned, and sequenced, by using evolutionarily conserved bacterium-specific primers, directly from environmental DNA extracted from Amphitheater Springs and Roaring Mountain sediment samples. Energy-dispersive X-ray spectroscopy, X-ray diffraction, and colorimetric assays were used to analyze sediment chemistry, while an optical emission spectrometer was used to evaluate water chemistry and electronic probes were used to measure the pH, temperature, and E(h) of the spring waters. Phylogenetic-statistical analyses found exceptionally strong correlations between bacterial community composition and sediment mineral chemistry, followed by weaker but significant correlations with temperature gradients. For example, sulfur-rich sediment samples contained a high diversity of uncultured organisms related to Hydrogenobaculum spp., while iron-rich sediments were dominated by uncultured organisms related to a diverse array of gram-positive iron oxidizers. A detailed analysis of redox chemistry indicated that the available energy sources and electron acceptors were sufficient to support the metabolic potential of Hydrogenobaculum spp. and iron oxidizers, respectively. Principal-component analysis found that two factors explained 95% of the genetic diversity, with most of the variance attributable to mineral chemistry and a smaller fraction attributable to temperature.

Bacteria↗

Relationships between microbial community structure and soil processes under elevated atmospheric carbon dioxide.

There is little current understanding of the relationship between soil microbial community composition and soil processes rates, nor of the effect climate change and elevated CO(2) will have on microbial communities and their functioning. Using the eastern cottonwood (Populus deltoides) plantation at the Biosphere 2 Laboratory, we studied the relationships between microbial community structure and process rates, and the effects of elevated atmospheric CO(2) on microbial biomass, activity, and community structure. Soils were sampled from three treatments (400, 800, and 1200 ppm CO(2)), a variety of microbial biomass and activity parameters were measured, and the bacterial community was described by 16S rRNA libraries. Glucose substrate-induced respiration (SIR) was significantly higher in the 1200 ppm CO(2) treatment. There were also a variety of complex, nonlinear responses to elevated CO(2). There was no consistent effect of elevated CO(2) on bacterial diversity; however, there was extensive variation in microbial community structure within the plantation. The southern ends of the 800 and 1200 ppm CO(2) bays were dominated by beta-Proteobacteria, and had higher fungal biomass, whereas the other areas contained more alpha-Proteobacteria and Acidobacteria. A number of soil process rates, including salicylate, glutamate, and glycine substrate-induced respiration and proteolysis, were significantly related to the relative abundance of the three most frequent bacterial taxa, and to fungal biomass. Overall, variation in microbial activity was better explained by microbial community composition than by CO(2) treatment. However, the altered diversity and activity in the southern bays of the two high CO(2) treatments could indicate an interaction between CO(2) and light.

Biodiversity↗

Risk factors for death of patients with cystic fibrosis awaiting lung transplantation.

RATIONALE: The optimal timing for listing of cystic fibrosis patients for lung transplantation is controversial. OBJECTIVES: We conducted a retrospective cohort study of 343 patients listed for lung transplantation at four academic medical centers to identify risk factors for death while awaiting transplantation. METHODS: Data on possible risk factors were abstracted from medical records. MEASUREMENTS: Time to death, patient demographic characteristics, and risk factors for death while awaiting transplantation were assessed. Univariate and multivariate survival analyses were performed using Cox regression. RESULTS: By univariate analyses, FEV1 < or = 30% predicted (HR, 3.8; 95% CI, 2.0-7.5), Pa(CO2) > or = 50 mm Hg (HR, 1.85; 95% CI, 1.1-3.0), and shorter height (HR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of death. Referral from an accredited cystic fibrosis center was associated with a lower risk (HR, 0.53; 95% CI, 0.30-0.92). The final multivariate model included referral from an accredited cystic fibrosis center (HR, 0.5; 95% CI, 0.3-1.0) and listing year after 1996 (HR, 0.4; 95% CI, 0.2-0.7); both were associated with a lower risk of death. FEV1 < or = 30% predicted (HR, 6.8; 95% CI, 2.4-19.3), Pa(CO2) > or = 50 mm Hg (HR, 6.9; 95% CI, 1.5-32.1), and use of a nutritional intervention (HR, 2.3; 95% CI, 1.3-4.1) were associated with increased risk. Patients with FEV1 > 30% predicted had a higher risk of death only when their Pa(CO2) was > or = 50 mm Hg (HR, 7.0; 95% CI, 1.5-32), while the increased risk of death with FEV1 < or = 30% was not further influenced by the presence of hypercapnia. CONCLUSIONS: We identified risk factors for waiting list mortality that could impact on transplant listing and allocation guidelines.

Adult↗

Measurements of regional alveolar oxygen pressure using hyperpolarized 3He MRI.

RATIONALE AND OBJECTIVES: The aim of this work is to review hyperpolarized (HP) helium-3 (3He) magnetic resonance imaging (MRI) methods to measure regional alveolar oxygen partial pressure (P(A)O2) and oxygen depletion rate (R) in the lung. We point out limitations of the methods and suggest improvements to increase their accuracy. MATERIALS AND METHODS: P(A)O2 and R can be extracted from series of HP gas images acquired during breath hold by making use of the depolarizing effect of oxygen on HP gas. To separate oxygen-induced depolarization from other depolarizing effects, several techniques can be used. We review currently used techniques and point out their advantages and limitations. RESULTS: We show that the precision of oxygen measurements depends on a variety of parameters and can vary within the measurement volume. Accuracy of the measurement also can be influenced by diffusion of oxygen and polarized 3He and generally is different for single-slice and multislice measurements. We present numerical simulations, phantom data, and in vivo data for illustration. CONCLUSION: HP 3He MRI is a noninvasive, nonionizing, and repeatable imaging method that allows for quantitative analysis of lung function. The current techniques for measuring P(A)O2 have the potential to deliver clinically relevant functional images.

Animals↗

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.

Administration, Inhalation↗

Effects of elevated atmospheric CO2 on soil microbial biomass, activity, and diversity in a chaparral ecosystem.

This study reports the effects of long-term elevated atmospheric CO2 on root production and microbial activity, biomass, and diversity in a chaparral ecosystem in southern California. The free air CO2 enrichment (FACE) ring was located in a stand dominated by the woody shrub Adenostoma fasciculatum. Between 1995 and 2003, the FACE ring maintained an average daytime atmospheric CO2 concentration of 550 ppm. During the last two years of operation, observations were made on soil cores collected from the FACE ring and adjacent areas of chaparral with ambient CO2 levels. Root biomass roughly doubled in the FACE plot. Microbial biomass and activity were related to soil organic matter (OM) content, and so analysis of covariance was used to detect CO2 effects while controlling for variation across the landscape. Extracellular enzymatic activity (cellulase and amylase) and microbial biomass C (chloroform fumigation-extraction) increased more rapidly with OM in the FACE plot than in controls, but glucose substrate-induced respiration (SIR) rates did not. The metabolic quotient (field respiration over potential respiration) was significantly higher in FACE samples, possibly indicating that microbial respiration was less C limited under high CO2. The treatments also differed in the ratio of SIR to microbial biomass C, indicating a metabolic difference between the microbial communities. Bacterial diversity, described by 16S rRNA clone libraries, was unaffected by the CO2 treatment, but fungal biomass was stimulated. Furthermore, fungal biomass was correlated with cellulase and amylase activities, indicating that fungi were responsible for the stimulation of enzymatic activity in the FACE treatment.

Air↗

Detection of simulated pulmonary embolism in a porcine model using hyperpolarized 3He MRI.

Several radiological imaging modalities are available to assist with the clinical diagnosis of pulmonary embolism (PE). The most frequently used techniques-nuclear medicine ventilation-perfusion (VP) scan, computed tomography (CT), magnetic resonance angiography (MRA), and pulmonary angiography (PA)-all have literature-supported, substantial limitations with respect to timeliness and patient safety. Hyperpolarized 3He magnetic resonance gas distribution imaging (HP 3He MRI) recently has shown potential as a safer and faster alternative. In this study, we performed HP 3He MRI on a porcine model (N = 6) of simulated PE using selective occlusion balloon catheterization (N = 4) and nonselective aged autologous clot injection (N = 1). The technique was also performed on a normal pig and again after the animal was killed. Temporal depletion of regional HP 3He MRI signal intensity provided for a qualitative assessment of simulated PE (N = 4), and regional PAO2 (alveolar partial pressure of oxygen) was calculated in affected airspaces for a quantitative assessment of simulated PE (N = 1). The preliminary results suggest that HP (3)He MRI shows promise as a means of assessing regional pulmonary perfusion abnormalities in the porcine models of simulated PE that were used in this study.

Animals↗

Determination of regional VA/Q by hyperpolarized 3He MRI.

Alveolar ventilation/perfusion ratio (VA/Q) is a key parameter in functional imaging of the lung. Herein, regional VA/Q was calculated from regional values of alveolar partial pressure of oxygen (PAO2) measured by hyperpolarized 3He gas MRI (HP 3He MRI). Yorkshire pigs (n = 7, mean weight = 25 kg) were paralyzed and maintained under isoflurane anesthesia. Animals were placed into a birdcage coil, then transferred to the bore of a 1.5 T MRI unit. Prior to imaging, animals were manually ventilated with room air for 5 min, then a 3He gas mixture was administered during breathhold and imaging performed. PAO2 was measured based on the decay rate of 3He signal. Subjects' blood gas concentrations were measured and these values and PAO2 values entered into a system of four equations with four unknowns. Calculated VA/Q values were analyzed by preparing frequency distributions for the entire lung and compared to VA/Q frequency distributions previously established in the literature as normal using other diagnostic techniques. Distributions were consistent with those in the literature, indicating that HP 3He MRI may be an accurate, quantitative, noninvasive, and nonradioactive method for acquiring VA/Q for small regions of the lung.

Animals↗

Seasonal changes in an alpine soil bacterial community in the colorado rocky mountains.

The period when the snowpack melts in late spring is a dynamic time for alpine ecosystems. The large winter microbial community begins to turn over rapidly, releasing nutrients to plants. Past studies have shown that the soil microbial community in alpine dry meadows of the Colorado Rocky Mountains changes in biomass, function, broad-level structure, and fungal diversity between winter and early summer. However, little specific information exists on the diversity of the alpine bacterial community or how it changes during this ecologically important period. We constructed clone libraries of 16S ribosomal DNA from alpine soil collected in winter, spring, and summer. We also cultivated bacteria from the alpine soil and measured the seasonal abundance of selected cultured isolates in hybridization experiments. The uncultured bacterial communities changed between seasons in diversity and abundance within taxa. The Acidobacterium division was most abundant in the spring. The winter community had the highest proportion of Actinobacteria and members of the Cytophaga/Flexibacter/Bacteroides (CFB) division. The summer community had the highest proportion of the Verrucomicrobium division and of beta-PROTEOBACTERIA: As a whole, alpha-Proteobacteria were equally abundant in all seasons, although seasonal changes may have occurred within this group. A number of sequences from currently uncultivated divisions were found, including two novel candidate divisions. The cultured isolates belonged to the alpha-, beta-, and gamma-Proteobacteria, the Actinobacteria, and the CFB groups. The only uncultured sequences that were closely related to the isolates were from winter and spring libraries. Hybridization experiments showed that actinobacterial and beta-proteobacterial isolates were most abundant during winter, while the alpha- and gamma-proteobacterial isolates tested did not vary significantly. While the cultures and clone libraries produced generally distinct groups of organisms, the two approaches gave consistent accounts of seasonal changes in microbial diversity.

Altitude↗

Redefining treatment in COPD: new directions in bronchodilator therapy.

COPD is a growing international health concern and it is estimated that by the year 2020 it will rank fifth as a cause of disability worldwide. In response to this problem, the World Health Organization and the US National Institutes of Health convened a panel of experts to draft a consensus strategy to treat patients with COPD. Called the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, they are designed to define and stage the severity of COPD, make recommendations for treatment, and to expand global awareness of the disease. The GOLD guidelines describe a multimodality approach to provide optimal care for the COPD patient population. This includes respiratory and rehabilitative therapy, nutrition services, psychosocial counseling, and surgical care. Bronchodilators form the cornerstone of pharmacologic treatment for COPD. These medications can significantly lessen dyspnea, enhance quality of life, increase airflow, and improve exercise performance. While bronchodilators decrease airway resistance and lessen hyperinflation in patients with COPD, they have not been shown to influence the decline in FEV1 over time or improve survival in this patient population. Recently, long-acting beta2-adrenoceptor agonists (beta2-agonists) such as formoterol and salmeterol and anticholinergic medications including tiotropium bromide have been developed which may further improve symptom management in COPD patients. This article discusses bronchodilator pharmacologic therapy for patients with COPD focusing on beta2-agonists, anticholinergics, and methylxanthines in the light of the recent GOLD consensus statements.

Adrenergic beta-2 Receptor Agonists↗

Seasonal dynamics of previously unknown fungal lineages in tundra soils.

The finding that microbial communities are active under snow has changed the estimated global rates of biogeochemical processes beneath seasonal snow packs. We used microbiological and molecular techniques to elucidate the phylogenetic composition of undersnow microbial communities in Colorado, the United States. Here, we show that tundra soil microbial biomass reaches its annual peak under snow, and that fungi account for most of the biomass. Phylogenetic analysis of tundra soil fungi revealed a high diversity of fungi and three novel clades that constitute major new groups of fungi (divergent at the subphylum or class level). An abundance of previously unknown fungi that are active beneath the snow substantially broadens our understanding of both the diversity and biogeochemical functioning of fungi in cold environments.

Ascomycota↗

Operating characteristics of hyperpolarized 3He and arterial spin tagging in MR imaging of ventilation and perfusion in healthy subjects.

RATIONALE AND OBJECTIVES: The authors tested the feasibility of a magnetic resonance (MR) imaging method combining the use of hyperpolarized helium 3 (3He) for ventilation imaging and an arterial spin-tagging sequence for perfusion imaging in six healthy human subjects. MATERIALS AND METHODS: High-resolution sagittal images depicting 3He distribution were acquired after the subjects' inhalation of 500 mL of laser-hyperpolarized 3He produced by spin-exchange optical pumping. Perfusion MR imaging was performed with a steady-state arterial spin-tagging sequence that enabled the acquisition of three-dimensional images of pulmonary perfusion without the need for subject breath holding. RESULTS: The 3He ventilation images display, with high signal intensity and detailed anatomic localization, the airspace of the lung parenchyma. The signal intensity on the perfusion images decreased by 23.2% with the use of arterial spin tagging. Ventilation and perfusion were matched, as is expected in healthy subjects. CONCLUSION: This method may have important applications in the assessment of lung function, enabling the calculation of regional ventilation-perfusion ratios. It may also aid in the selection of candidates for lung volume-reduction surgery.

Adult↗

Bronchoscopy for atelectasis in the ICU: a case report and review of the literature.

Fiberoptic bronchoscopy has become a commonplace procedure in ICUs. Despite the fact that one of the most common indications for bronchoscopy is the presence of retained secretions and atelectasis, there is little research dedicated to its safety and utility in this clinical situation. This article presents a case of an intubated trauma victim who had undergone numerous bronchoscopic procedures, with varying degrees of success, for retained secretions and atelectasis. This review then seeks to answer the following three main questions regarding bronchoscopy in critically ill patients: (1) Is bronchoscopy effective in resolving atelectasis? (2) Is bronchoscopy superior to other means of resolving atelectasis? (3) Is bronchoscopy safe in critically ill patients? The patient was a 28-year-old man with no significant medical history who presented to the emergency department after his car was hit by a dump truck. He was found to have multiple leg fractures and a splenic rupture, and he was taken to the operating room for an exploratory laparotomy, splenectomy, and reduction of his fractures. He was then brought to the surgical ICU intubated, sedated, and receiving mechanical ventilation. Over the next 6 h, he developed progressive hypoxemia and diffuse, bilateral alveolar infiltrates on a chest radiograph (CXR). Four days postoperatively, a routine CXR revealed total atelectasis of his right upper lobe (RUL). Emergent bronchoscopy was performed, and a large mucus plug obscuring the RUL bronchus was removed. Follow-up CXR demonstrated resolution of the atelectasis. The next day, RUL atelectasis was again seen on his CXR. A repeat bronchoscopic examination and BAL failed to reveal any plug. A follow-up CXR showed continued atelectasis. Over the next week, the patient underwent daily bronchoscopy for atelectasis with variable degrees of improvement. Over the next 3 weeks, his pulmonary status improved until he was eventually extubated, and 1 month after hospital admission he was discharged to rehabilitation.

Adult↗

Pulmonary ventilation and perfusion scanning using hyperpolarized helium-3 MRI and arterial spin tagging in healthy normal subjects and in pulmonary embolism and orthotopic lung transplant patients.

Conventional nuclear ventilation/perfusion (V/Q) scanning is limited in spatial resolution and requires exposure to radioactivity. The acquisition of pulmonary V/Q images using MRI overcomes these difficulties. When inhaled, hyperpolarized helium-3 ((3)He) permits MRI of gas distribution. Magnetic labeling of blood (arterial spin-tagging (AST)) provides images of pulmonary perfusion. Three normal subjects, two patients who had undergone single lung transplantation for emphysema, and one subject with pulmonary embolism (PE), were imaged. (3)He distribution and blood perfusion appeared uniform in the normal subjects and throughout the lung allografts. Gas distribution and perfusion in the emphysematous lungs were non-uniform and paralleled radiographic abnormalities. AST imaging alone revealed a lower-lobe wedge-shaped perfusion defect in the patient with PE that corresponded to computed tomography (CT) imaging. Hyperpolarized (3)He gas is demonstrated to provide ventilation images of the lung. Blood perfusion information may be obtained during the same examination using the AST technique. The sequential application of these imaging methods provides a novel tool for studying V/Q relationships.

Helium↗