Hyperammonemic encephalopathy in multiple myeloma

HISTORY AND CLINICAL FINDINGS A 54-year old man had suffered from advanced multiple myeloma for two years. After initially good response the myeloma was refractrory to treatment with dexamethasone, cyclophosphamide, bortezomibe, zoledronate and additionally doxorubicine. The patient then complained of dyspnea without clinical signs of cardiopulmonary disease. INVESTIGATIONS Arterial blood gas analysis showed hyperventilation with respiratory alkalosis and normal alveolo-arterial gradient as the reason for the dyspnea. With a normal MRI of the brain and lumbal puncture, a neurological disease could be excluded. Serum calcium, creatinine and serum viscosity were normal. Eventually, serum ammonia levels were found to be substantially elevated (144 µmol/l) and hyperammonemic encephalopathy was diagnosed. TREATMENT AND COURSE Therapy with bortezomib and high dose dexamethason was repeated, and the patient also received bendamustin. Despite this treatment, he lost consciousness and died after two weeks because of aspiration pneumonia. CONCLUSION The existence of respiratory alkalosis and multiple myeloma should prompt a search for hyperammonemia.

Two-dimensional and three-dimensional oxygen mapping by 3He-MRI validation in a lung phantom

The aim of this study was to validate oxygen-sensitive 3He-MRI in noninvasive determination of the regional, two- and three-dimensional distribution of oxygen partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung phantom, oxygen sensitive two- and three-dimensional 3He-MRI measurements were performed at different oxygen concentrations which had been equilibrated in a range of normal and pathologic values. The oxygen partial pressure distribution was determined from 3He-MRI using newly developed software allowing for mapping of oxygen partial pressure. The reference bulk oxygen partial pressure inside the phantom was measured by conventional respiratory gas analysis. In two-dimensional measurements, image-based and gas-analysis results correlated with r=0.98; in three-dimensional measurements the between-methods correlation coefficient was r=0.89. The signal-to-noise ratio of three-dimensional measurements was about half of that of two-dimensional measurements and became critical (below 3) in some data sets. Oxygen-sensitive 3He-MRI allows for noninvasive determination of the two- and three-dimensional distribution of oxygen partial pressure in gas-filled airspaces.

Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS)

This paper describes informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography (GCxGC) and high-resolution mass spectrometry (HRMS). GCxGC-HRMS analysis produces large data sets that are rich with information, but highly complex. The size of the data and volume of information requires automated processing for comprehensive cross-sample analysis, but the complexity poses a challenge for developing robust methods. The approach developed here analyzes GCxGC-HRMS data from multiple samples to extract a feature template that comprehensively captures the pattern of peaks detected in the retention-times plane. Then, for each sample chromatogram, the template is geometrically transformed to align with the detected peak pattern and generate a set of feature measurements for cross-sample analyses such as sample classification and biomarker discovery. The approach avoids the intractable problem of comprehensive peak matching by using a few reliable peaks for alignment and peak-based retention-plane windows to define comprehensive features that can be reliably matched for cross-sample analysis. The informatics are demonstrated with a set of 18 samples from breast-cancer tumors, each from different individuals, six each for Grades 1-3. The features allow classification that matches grading by a cancer pathologist with 78% success in leave-one-out cross-validation experiments. The HRMS signatures of the features of interest can be examined for determining elemental compositions and identifying compounds.

Long-term gas exchange characteristics as marker of deterioration in patients with cystic fibrosis

Background and Aim In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process. Methods Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination. Results PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes. Conclusion In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation.

A versatile gas interface for routine radiocarbon analysis with a gas ion source

In 2010 more than 600 radiocarbon samples were measured with the gas ion source at the MIni CArbon DAting System (MICADAS) at ETH Zurich and the number of measurements is rising quickly. While most samples contain less than 50 mu g C at present, the gas ion source is attractive as well for larger samples because the time-consuming graphitization is omitted. Additionally, modern samples are now measured down to 5 per-mill counting statistics in less than 30 min with the recently improved gas ion source. In the versatile gas handling system, a stepping-motor-driven syringe presses a mixture of helium and sample CO2 into the gas ion source, allowing continuous and stable measurements of different kinds of samples. CO2 can be provided in four different ways to the versatile gas interface. As a primary method. CO2 is delivered in glass or quartz ampoules. In this case, the CO2 is released in an automated ampoule cracker with 8 positions for individual samples. Secondly, OX-1 and blank gas in helium can be provided to the syringe by directly connecting gas bottles to the gas interface at the stage of the cracker. Thirdly, solid samples can be combusted in an elemental analyzer or in a thermo-optical OC/EC aerosol analyzer where the produced CO2 is transferred to the syringe via a zeolite trap for gas concentration. As a fourth method, CO2 is released from carbonates with phosphoric acid in septum-sealed vials and loaded onto the same trap used for the elemental analyzer. All four methods allow complete automation of the measurement, even though minor user input is presently still required. Details on the setup, versatility and applications of the gas handling system are given. (C) 2012 Elsevier B.V. All rights reserved.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.