Defining Multiple Characteristic Raman Bands of α-Amino Acids as Biomarkers for Planetary Missions Using a Statistical Method.

Biomarker molecules, such as amino acids, are key to discovering whether life exists elsewhere in the Solar System. Raman spectroscopy, a technique capable of detecting biomarkers, will be on board future planetary missions including the ExoMars rover. Generally, the position of the strongest band in the spectra of amino acids is reported as the identifying band. However, for an unknown sample, it is desirable to define multiple characteristic bands for molecules to avoid any ambiguous identification. To date, there has been no definition of multiple characteristic bands for amino acids of interest to astrobiology. This study examined L-alanine, L-aspartic acid, L-cysteine, L-glutamine and glycine and defined several Raman bands per molecule for reference as characteristic identifiers. Per amino acid, 240 spectra were recorded and compared using established statistical tests including ANOVA. The number of characteristic bands defined were 10, 12, 12, 14 and 19 for L-alanine (strongest intensity band: 832 cm(-1)), L-aspartic acid (938 cm(-1)), L-cysteine (679 cm(-1)), L-glutamine (1090 cm(-1)) and glycine (875 cm(-1)), respectively. The intensity of bands differed by up to six times when several points on the crystal sample were rotated through 360 °; to reduce this effect when defining characteristic bands for other molecules, we find that spectra should be recorded at a statistically significant number of points per sample to remove the effect of sample rotation. It is crucial that sets of characteristic Raman bands are defined for biomarkers that are targets for future planetary missions to ensure a positive identification can be made.

The microbe-mineral environment and gypsum neogenesis in a weathered polar evaporite.

Evaporitic deposits are a globally widespread habitat for micro-organisms. The microbe-mineral environment in weathered and remobilized gypsum from exposed mid-Ordovician marine evaporite beds in the polar desert of Devon Island, Nunavut, Canadian High Arctic was examined. The gypsum is characterized by internal green zones of cyanobacterial colonization (dominated by Gloeocapsa/Aphanothece and Chroococcidiopsis spp. morphotypes) and abundant black zones, visible from the surface, that contain pigmented cyanobacteria and fungi. Bioessential elements in the gypsum are primarily provided by allochthonous material from the present-day polar desert. The disruption, uplift and rotation of the evaporite beds by the Haughton meteorite impact 39 Ma have facilitated gypsum weathering and its accessibility as a habitat. No cultured cyanobacteria, bacteria and fungi were halophilic consistent with the expectation that halophily is not required to persist in gypsum habitats. Heterotrophic bacteria from the evaporite were slightly or moderately halotolerant, as were heterotrophs isolated from soil near the gypsum outcrop showing that halotolerance is common in arctic bacteria in this location. Psychrotolerant Arthrobacter species were isolated. No psychrophilic organisms were isolated. Two Arthrobacter isolates from the evaporite were used to mediate gypsum neogenesis in the laboratory, demonstrating a potential role for microbial biomineralization processes in polar environments.

Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring.

More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.

Compound-specific isotope analysis of the organic constituents in carbonaceous chondrites.

The carbonaceous chondrite meteorites contain evidence of the formation of the solar system, part of which is present within organic matter. In recent years, compound-specific isotope analysis (CSIA) has been useful in deciphering this complex record. The current published data set provides an insight into the source environments and reaction mechanisms that have contributed to the final state of the organic constituents in carbonaceous chondrites. This review summarises the CSIA data and related key interpretations.

Altered alveolar macrophage function in calorie-restricted rats.

Alveolar macrophage functions associated with clearance of bacteria from the lung were assessed in male Fischer 344 rats maintained on a 25% calorie-restricted diet. Calorie-restricted and ad libitum-fed (control) rats were exposed to concentrations of ozone known to compromise phagocytic function of alveolar macrophages. Ozone suppressed alveolar macrophage phagocytosis of latex beads in vitro in ad libitum-fed rats, but not in calorie-restricted rats. In fact, caloric restriction enhanced phagocytic function in both control and ozone-exposed animals. Ad libitum-fed rats exposed to ozone and challenged with Streptococcus zooepidemicus experienced a prolonged infection and influx of polymorphonuclear leukocytes (PMN), whereas calorie-restricted rats exposed to ozone cleared the bacteria in 24 h without an inflammatory response. Bacterial endotoxin-stimulated in vitro production of nitric oxide and tumor necrosis factor (TNF)-alpha as well as expression of TNF-alpha and interleukin-6 messenger RNAs were all lower in alveolar macrophages isolated from calorie-restricted rats. Together, the data suggest that caloric restriction enhances resistance to gram-positive bacteria, while lowering the production of proinflammatory mediators elicited by endotoxin, a component of gram-negative bacteria. Although increased bacterial resistance is considered beneficial, reduction in the lung's ability to induce inflammatory mediators can have both positive and pathophysiologic consequences.

The use of stable carbon isotope analysis to detect the abuse of testosterone in cattle.

The use of stable carbon isotope analysis to detect the administration of anabolic steroids to cattle was investigated. Samples were extracted by solid-phase extraction on C18 cartridges. Stable isotope ratios (13C:12C) were measured by gas chromatography-isotope ratio mass spectrometry (GC-IRMS) of the underivatised extracts. A programmed temperature vaporiser (PTV) injector was installed in the GC-IRMS system, which conferred a number of advantages. First, it allowed large volumes of sample to be injected whilst the injector liner was cool. The solvent was subsequently vented to the atmosphere prior to transfer of the sample to the GC column. Thus a significantly greater amount of sample could be presented for analysis, thereby increasing the sensitivity. Second, by this means virtually all the solvent could be removed prior to analysis. This eliminates solvent peak tailing, which can be a major problem in GC-IRMS. Finally, the PTV allowed the use of higher initial GC oven temperatures, which in turn facilitated the analysis of underivatised steroids by reducing the GC run time and improving the chromatographic peak shape. The carbon isotope composition of 5 beta-androstane-3 alpha,17 alpha-diol, the major metabolite of testosterone found in bovine bile, was measured in bile samples from untreated cattle and from cattle injected intramuscularly with testosterone or a mixture of testosterone esters. There was considerable inter-animal variation in the values obtained and there was no significant difference between samples from treated and untreated animals. However, when the isotopic composition of the metabolite was normalised with respect to that of an endogenous reference compound (cholesterol) in the same sample, the difference between treated and untreated animals become statistically significant.

Isolation and characterization of an attenuated strain of Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader.

Pseudomonas aeruginosa AC869, a 3,5-dichlorobenzoate degrader, is a mouse pathogen and has a reported 50% lethal dose (LD50) of 1.05 x 10(7) CFU when given intranasally to C3H/HeJ mice (S.E. George, M.J. Kohan, M.I. Gilmour, M.S. Taylor, H.G. Brooks, J.P. Creason, and L.D. Claxton, Appl. Environ, Microbiol. 59:3585-3591, 1993). AC869 was serotyped as O6 when grown in CD-1 mouse cecal and lung mucus but could not be assigned an O serotype when grown in Luria broth (LB). After growth in mouse cecal mucus, a less virulent mutant, AC869-11, was isolated from AC869 by using bacteriophage E79, which adsorbs to the O side chain of lipopolysaccharide (LPS). AC869-11 produced significantly less O antigen on its LPS than AC869 when grown in mouse lung and cecal mucus. The mutant also produced half the amount of exoenzyme S and 16-fold less extracellular protease than AC869 and was more sensitive than its parent to a number of antibiotics when grown either in LB or in mouse lung mucus. AC869-11 had ninefold higher LD50 than AC869 in CD-1 mice when administered intranasally. AC869-11 was found in the lungs, small intestine, cecum, and large intestine in numbers at least 100-fold below AC869, 3 h after intranasal exposure of mice to a sublethal dose of the two strains. Moreover, AC869-11 induced a decreased pulmonary inflammatory response relative to AC869. In contrast to AC869, AC869-11 did not translocate to the mesenteric lymph nodes, liver, and spleen following a sublethal dose. Despite attenuation, AC869-11 grew as well as AC869 with 3,5-dichlorobenzoate as the sole carbon and energy source. However, although AC869-11 survived in 3,5-dichlorobenzoate-contaminated soil as well as AC869 for 1 week, it failed to survive as well thereafter. These results suggest the possibility that mutations that lead to pulmonary attenuation of P. aeruginosa in mice also lead to weakness in the environment, despite such mutants maintaining the ability to degrade toxic substances under laboratory conditions.

Safety and efficacy of a ventilator database interface.

This report describes a ventilator dysfunction that arose during the mechanical ventilation of a lung transplant recipient. The problem was discovered because the data on the computer-based information management system (CIMS) was different from that on the ventilator's dials. This incident is important because of the continued extensive use of analog mechanical ventilators, the increasing popularity of CIMS, and the patient safety implications of the incident.

The effects of circuit and humidifier type on contamination potential during mechanical ventilation: a laboratory study.

BACKGROUND: This study was undertaken because of concerns that ventilator humidifiers could be exacerbating the problem of nosocomial pneumonia in patients receiving mechanical ventilation. METHODS: Four different brands of humidifiers were used in conjunction with a siemens Servo 900B mechanical ventilator (Siemens Life Support Services, Solna, Sweden). In the first part, the ventilator was operated with humidifiers filled with contaminated water at room temperature. The viability of airborne particles and the effect of flow rates on the number of particles produced were assessed. In the second part, we measured the effect of time and temperature on bacterial survival in humidifier chambers. Because only bubble-through humidifiers were determined to produce infectious particles, the speed with which a contaminated bubble-through humidifier could infect circuit condensate was also determined. Aliquots of chamber water and circuit condensate, as well as air samples and distal circuit swabs, were cultured. RESULTS: Humidifiers other than bubble-through humidifiers did not produce aerosols. Particle production by bubble-through humidifiers varied directly with flow rate (R2 = 0.91). Chamber temperatures did not affect chamber colony counts except in bubble-through humidifiers. Although chamber colony counts in bubble-through humidifiers decreased with time, organisms remained viable throughout the study. When bubble-through humidifiers were heated, both condensate and effluent gas became heavily contaminated within minutes of flow initiation. CONCLUSIONS: Bubble-through humidifiers produce aerosols that readily contaminate both circuit condensate and effluent gas. Avoiding bubble-through humidifiers should improve patient safety while allowing changes in practice that can result in significant cost savings.

Comparison of antialgal activity of brown-rotted and white-rotted wood andIn situ analysis of lignin.

Brown-rotted wood has been used as a source of lignin to investigate further the antialgal effects of lignocellulosic materials such as decomposing barley straw. The antialgal activity of brown-rotted and white-rotted wood has been determined in a laboratory bioassay. Using pyrolysis gas chromatography-mass spectrometry, the lignin of the rotted wood samples has been compared and the significance of the structure of the lignin in antialgal activity is discussed.

Ondansetron prevents postoperative nausea and vomiting in women outpatients.

Three doses of intravenous (i.v.) ondansetron, 1 mg, 4 mg, and 8 mg, were compared to placebo for their antiemetic effect and safety. The drugs or placebo were administered in a double-blind manner, prophylactically to 589 women undergoing elective outpatient surgical procedures under nitrous oxide opioid-based general endotracheal anesthesia. In the postanesthesia care unit, the number of emetic episodes, periodic assessments of nausea severity using an 11-point scale (0 = no nausea; 10 = worst nausea), vital signs, and adverse events were collected by an independent observer for 2 h. Upon discharge, identical information, with the exception of vital signs, was collected from the patients' diary and via phone call. One pre- and two poststudy blood specimens for hematology and chemistries were evaluated. During the initial 2 h, patients receiving any dose of ondansetron had significantly better complete response rates (no emesis) than those receiving placebo. Over the 24-h study period, patients who received either 4 mg or 8 mg ondansetron continued to have significantly greater complete response rates. Adverse events were minor, and ondansetron-treated patients had profiles similar to those of the placebo. Heart rate, blood pressure, respiratory rate, and laboratory safety variables were not different among the groups. Ondansetron did not prolong awakening time. This study indicates that ondansetron is a safe and effective prophylactic antiemetic for women who have outpatient surgery under nitrous oxide opioid-based general anesthesia.

The effect of heated wire circuits on humidification of inspired gases.

We performed this study to determine the effect of heated wire circuits on humidity delivered by several humidifiers commonly used during anesthesia. Humidifier bases from three manufacturers with several humidifying chambers for each base were tested using both heated and unheated circuits. Delivered humidity and circuit temperature were measured at the distal end of the circuit. Each chamber was tested under both continuous flow (CF) and intermittent flow (IF) conditions. IF was provided by a Servo 900 B ventilator. Adjustments of flow and volume were made for pediatric chambers. At 90 L/m CF, humidifier performance was unsatisfactory with both heated and unheated circuits. At 15 and 45 L/m CF, both distal circuit temperature (DCT) and humidity were within acceptable limits; unheated circuits delivered more humidity than heated circuits (P < 0.05). Relative humidity was lower at 45 L/m CF than at 15 L/m (P < 0.05). During IF while all chambers provided satisfactory humidity, humidity was greater when unheated circuits were used. We conclude that when heated circuits are used, humidifying systems may fail to deliver 100% humidity to patients.

Clinical performance of a blood gas monitor: a prospective, multicenter trial.

OBJECTIVE: To prospectively assess the clinical performance of a fluorescent optode-based blood gas monitoring system that is designed to perform arterial pH, PCO2, and PO2 measurements as frequently as clinically required without violating the integrity of the arterial catheter tubing system or permanently removing blood from the patient. DESIGN: A prospective, multicenter study to compare modern blood gas analyzer measurements with the coinciding measurements of the blood gas monitoring system. SETTING: Four intensive care units (ICUs) in academic centers with varying patient populations, blood gas measurement routines, and blood gas laboratory facilities. PATIENTS: Adult ICU patients (n = 117), with appropriately functioning radial arterial catheters in place, who were assessed as likely to require multiple arterial blood gas measurements for > or = 2 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 117 patients had 1,341 concurrent blood gas analyzer and monitor measurements of arterial pH, PCO2, and PO2 over a 1- to 4-day period. The range of values were 7.14 to 7.64 for arterial pH, 19 to 98 torr (2.5 to 13.0 kPa) for PaCO2, and 38 to 413 torr (5.1 to 54.9 kPa) for PaO2. Linear regression analysis of the optode-based monitor compared with the electrode-based blood gas analyzer demonstrated r2 values of .85 for pH, .92 for PCO2, and .94 for PO2. Comparative statistical analyses for bias (mean difference between analyzer and monitor) and precision (standard deviation of the mean difference [+/- SD] between analyzer and monitor) were respectively:-0.004 and +/- 0.027 for pH; -0.8 torr (-0.11 kPa) and +/- 2.4 torr (0.32 kPa) for PCO2; -2.2 torr (-0.31 kPa) and +/- 8.7 torr (1.2 kPa) for PO2. CONCLUSIONS: Clinical performance of this fluorescent, optode-based blood gas monitoring system demonstrates stability, consistency, and accuracy comparable to modern blood gas analyzers. This system withstood the normal abuse and rigors of clinical conditions common to the ICU while reliably performing in critically ill patients for up to 80 hrs. Use of the device did not significantly alter the function or longevity normally expected from a 20-gauge radial artery catheter. We submit that this blood gas monitoring system can replace the use of blood gas analyzers for ICU patients with indwelling arterial catheters.

Terrestrial carbon and nitrogen isotopic ratios from cretaceous-tertiary boundary nanodiamonds.

One hypothesis for the origin of the nanometer-size diamonds found at the Cretaceous-Tertiary (K-T) boundary is that they are relict interstellar diamond grains carried by a postulated asteroid. The (13)C/(12)C and (15)N/(14)N ratios of the diamonds from two sites in North America, however, show that the diamonds are two component mixtures differing in carbon and nitrogen isotopic composition and nitrogen abundance. Samples from a site from Italy show no evidence for either diamond component. All the isotopic signatures obtained from the K-T boundary are material well distinguished from known meteoritic diamonds, particularly the fine-grain interstellar diamonds that are abundant in primitive chondrites. The K-T diamonds were most likely produced during the impact of the asteroid with Earth or in a plasma resulting from the associated fireball.

Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial.

The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb-salvage arterial surgery was tested. Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3). The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints. Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 0.05), less postoperative cardiac morbidity (p less than 0.05), and less early graft thrombosis (p less than 0.05) than the control group. The overall study mortality rate was 3.4%, with a mortality rate of 9.5% in the control group and 1.5% in the PA catheter groups. There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 0.05). In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome.

Modular indirect calorimeter suitable for long-term measurements in multipatient intensive care units.

OBJECTIVE: The construction of an indirect calorimeter capable of long-term automated sequential monitoring of multiple patients in adult and pediatric ICUs. DESIGN: A prototype system utilizing modular engineering principles, including central respiratory mass spectrometer; validation by organic solvent combustion and nitrogen dilution methods, and Tissot spirometer. SETTING: Surgical and pediatric ICUs in a tertiary care university hospital. RESULTS: When expired minute volume was measured over a range of 4 to 28 L in six intubated patients, expired minute volume measured by the prototype system demonstrated a correlation coefficient of .998 compared with simultaneous expired minute volume measured by a Tissot spirometer. Organic solvent combustion demonstrated a maximum error of 3.8% for oxygen consumption (VO2) and an average error of 1.73 +/- 1.25% (SEM). The maximum error for the respiratory quotient was 3.0%, with an average error of 1.75 +/- 1.07%. VO2 (predicted) vs. VO2 (measured) demonstrated a correlation coefficient of .997. Validation with the nitrogen dilution method over a range of FIO2 from 0.21 to 0.60 demonstrated a maximum error of 7.9%, with an average error of -1.72 +/- 1.1% (n = 51). CONCLUSIONS: Indirect calorimetry by means of a shared system for measurements in multiple patients in ICUs is feasible and cost effective utilizing modular principles and a centralized respiratory gas analyzer.

Effect of kidney dysfunction on lung volume in patients with diabetes.

OBJECTIVE: Over several years, one of the authors observed what appeared to be a relationship between a decrease in total lung capacity (TLC) and insulin-dependent diabetes mellitus (IDDM) in patients who were candidates for kidney transplantation. RESEARCH DESIGN AND METHODS: In an effort to define this potential relationship, pulmonary function tests (PFTs) were reviewed on all available kidney transplant candidates between 1983 and 1986. The patients were divided into two groups--those with kidney failure caused by IDDM (group 1) and those with kidney failure from other causes (group 2). A third group (control subjects) of volunteers with IDDM but without evidence of kidney failure was evaluated by PFTs in an attempt to determine whether IDDM without kidney failure was also associated with a decrease in TLC. RESULTS: Demographics of the two groups with kidney failure were similar. However, the duration of IDDM in the volunteers with IDDM was significantly shorter than in group 1 patients (19.6 vs. 25.9 yr). The TLC of group 1 patients was significantly smaller than the TLC of both the group 2 patients and the volunteers with IDDM. CONCLUSIONS: We believe that these data suggest that the association between IDDM and decreased TLC is the result of IDDM and not kidney failure. Because our volunteers with IDDM were significantly younger than the patients with IDDM and kidney failure, we can draw no conclusions about any separate contribution of kidney failure to changes in TLC in people with IDDM.