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PubMed2002

Economic evaluation of MARS--preliminary results on survival and quality of life.

OBJECTIVES: The short-term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here. STUDY DESIGN: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 micro mol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis. PRELIMINARY RESULTS: MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P <0.05). There was no significant difference in health related quality of life (SF12 and EQ-D). Calculations of quality adjusted life years (QALYs) result in 0.116 QALYs gained by treatment of one patient with MARS in one year. DISCUSSION: First preliminary results suggest that 1 year after therapy MARS seems to have a positive effect concerning survival rate, survival time and QALYs gained. Final results of cost-effectiveness and cost-utility analysis will soon be presented.

Adult↗
PubMed2002

Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.

Adolescent↗
PubMed2000

Expression of the multiple antibiotic resistance operon (mar) during growth of Escherichia coli as a biofilm.

The multiple antibiotic resistance (mar) operon is a global regulator controlling the expression of various genes in Escherichia coli which constitutes the mar regulon. Upregulation of mar leads to a multi-drug resistant phenotype, which includes resistance towards structurally unrelated antibiotics, organic solvents and the disinfectant pine oil. Biofilms also display similar decreases in susceptibility to antimicrobial agents. A marOII-lacZ fusion strain (SPC105) of E. coli was used to monitor mar expression under various growth conditions including batch, continuous and biofilm culture. In chemically-defined media (CDM), mar expression was maximal in mid-log and declined in the stationary phase. Conversely, in rich media (Luria-Bertani broth), minimal expression in mid-log was followed by an increase in the stationary phase. In continuous culture, expression was inversely related to specific growth rate (mu = 0.05-0.4 h-1). LacZ expression by the marOII-lacZ fusion was generally low within the total biofilm population and equivalent to that of stationary phase cultures grown in batch culture. When the expression of mar in CDM batch culture was compared with that in biofilm populations, beta-galactosidase activity was generally higher throughout batch culture than in the attached population. Overall, these results suggest that while mar expression will be greatest within the depths of a biofilm where growth rates are suppressed, its probable induction within biofilms cannot explain the elevated levels of antibiotic resistance observed.

Bacterial Proteins↗
PubMed2000

An evaluation of the potential of the multiple antibiotic resistance operon (mar) and the multidrug efflux pump acrAB to moderate resistance towards ciprofloxacin in Escherichia coli biofilms.

The chromosomal multiple antibiotic resistance operon, mar, is widely represented amongst Gram-negative bacteria and has been implicated in resistance towards oxidative stress agents, organic solvents and a large number of structurally unrelated antimicrobial agents. The major mechanism associated with such increased resistance is an upregulation of the efflux pump acrAB. Growth as a biofilm is often associated with similar generalized reductions in susceptibility to inimical agents. Escherichia coli K12 (AG100), an isogenic mutant of AG100 constitutive for mar expression (AG102) and an isolate deleted of the mar locus (MCH164) were grown as biofilms in cellulose-fibre depth filters and perfused with a simple salts, minimal medium (CDM) over 120 h. Biofilms were exposed to various concentrations of ciprofloxacin (0.004, 0.015 and 0.1 mg/L) for 42 h. The numbers of viable cells within the perfusate and within the biofilm were estimated throughout. Whereas no differences were seen between the wild-type and mar-deleted isolates, that constitutive for mar displayed reduced susceptibility to ciprofloxacin at concentrations of 0.004 mg/L (MIC for AG100 was 0.0052 mg/L). Similar antibiotic perfusion experiments were conducted using isolates in which the efflux pump acrAB was either deleted (AG100-A) or constitutively expressed (AG100-B). Exposure of AG100-A biofilms to ciprofloxacin at 0.004 and 0.1 mg/L showed similar susceptibilities to those seen in the wild-type (AG100) and mar-deleted (MCH164) isolates and suggested that acrAB was not induced within the attached population. On the other hand, constitutive expression of acrAB (AG100-B) protected biofilms against the lower concentration of ciprofloxacin used (0.004 mg/L). This protection was again lost at concentrations of 0.1 mg/L. Overall, these results show that ciprofloxacin resistance in biofilms is not mediated by the upregulation of the mar or acrAB operons.

Ampicillin↗
PubMed2005

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

PURPOSE: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. RESULTS: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. CONCLUSIONS: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.

Adult↗
PubMed1989

Identification of mar mutations in herpes simplex virus type 1 glycoprotein B which alter antigenic structure and function in virus penetration.

Analysis of six monoclonal antibody-resistant (mar) mutants in herpes simplex virus type 1 glycoprotein B identified two type-common (II and III) and two type-specific (I and IV) antigenic sites on this molecule. To derive additional information on the location of these sites, mar mutations were mapped and nucleotide alterations were identified by DNA sequencing. Each mutant carried a single amino acid substitution resulting from a G-to-A base transition. Alterations affecting antibody neutralization were identified at residues 473, 594, 305, and 85 for mutants in sites I through IV, respectively. Two clonally distinct site II antibodies each selected mar mutants (Gly to Arg at residue 594) that exhibited a reduction in the rate of entry (roe) into host cells. A site II mar revertant that regained sensitivity to neutralization by site II antibodies also showed normal entry kinetics. DNA sequencing of this virus identified a single base reversion of the site II mar mutation, resulting in restoration of the wild-type sequence (Arg to Gly). This finding demonstrated that the mar and roe phenotypes were the result of a single mutation. To further define structures that contributed to antibody recognition, monoclonal antibodies specific for all four sites were tested for their ability to immune precipitate a panel of linker-insertion mutant glycoprotein B molecules. Individual polypeptides that contained single insertions of 2 to 28 amino acids throughout the external domain were not recognized or were recognized poorly by antibodies specific for sites II and III, whereas no insertion affected antibody recognition of sites I and IV. mar mutations affecting either site II or III were previously shown to cause temperature-sensitive defects in glycoprotein B glycosylation, and variants altered in both these sites were temperature sensitive for virus production. Taken together, the data indicate that antigenic sites II and III are composed of higher-order structures whose integrity is linked with the ability of glycoprotein B to function in virus infectivity.

Amino Acid Sequence↗
PubMed2006

MARS in the treatment of liver failure: controversies and evidence.

Molecular Adsorbent Recirculation System (MARS) is a form of extracorporeal detoxification system used as an artificial liver support system. Numerous studies have been published on the topic, with the majority of them describing the capability of MARS in removing albumin-bound toxins and improving systemic hemodynamics. Whether such improvement could be translated into survival benefit is still uncertain, given the paucity of randomized controlled trials available. The outcome of patients receiving MARS treatment is difficult to analyze because liver failure patients constitute a heterogeneous population and different subgroups carry different prognoses. An evidence-based recommendation on the timing of MARS initiation is not available and currently MARS is usually commenced for hyperbilirubinemia or presence of complications of liver failure. MARS is in general a safe procedure, but there are still potential complications that need to be cautioned, along with various operative issues that are worth attention. The future prospects of MARS would rely on the completion of adequately powered randomized controlled trials.

Bilirubin↗
PubMed1999

Evidence that the Igkappa gene MAR regulates the probability of premature V-J joining and somatic hypermutation.

The Igkappa gene contains an evolutionarily conserved nuclear matrix association region (MAR) adjacent to the intronic enhancer. To test for the function of this MAR, we created mouse lines with a targeted MAR deletion. In MAR knockout animals, the immune system was normal in nearly all respects, including the distributions of various B cell populations and Ab levels. However, in pro-B cells, enhanced rearrangement was noted on the MAR- allele in heterozygotes. In addition, the efficiencies for targeting and generating somatic mutations were reduced on MAR-deleted alleles. These results provide evidence for the MAR negatively regulating the probability of premature rearrangement and positively regulating the probability of somatic hypermutation.

Alleles↗
PubMed1994

First measurement of helium on Mars: implications for the problem of radiogenic gases on the terrestrial planets.

108 +/- 11 photons of the martian He 584-angstroms airglow detected by the Extreme Ultraviolet Explorer satellite during a 2-day exposure (January 22-23, 1993) correspond to the effective disk average intensity of 43 +/- 10 Rayleigh. Radiative transfer calculations, using a model atmosphere appropriate to the conditions of the observation and having an exospheric temperature of 210 +/- 20 K, result in a He mixing ratio of 1.1 +/- 0.4 ppm in the lower atmosphere. Nonthermal escape of helium is due to electron impact ionization and pickup of He+ by the solar wind, to collisions with hot oxygen atoms, and to charge exchange with molecular species with corresponding column loss rates of 1.4 x 10(5), 3 x 10(4), and 7 x 10(3) cm-2 sec-1, respectively. The lifetime of helium on Mars is 5 x 10(4) years. The He outgassing rate, coupled with the 40Ar atmospheric abundance and with the K:U:Th ratio measured in the surface rocks, is used as input to a single two-reservoir degassing model which is applied to Mars and then to Venus. A similar model with known abundances of K, U, and Th is applied to Earth. The models for Earth and Mars presume loss of all argon accumulated in the atmospheres during the first billion years by large-scale meteorite and planetesimal impacts. The models show that the degassing coefficients for all three planets may be approximated by function delta = delta (0)(t(0)/t)1/2 with delta (0) = 0/1, 0.04, and 0.0125 Byr-1 for Earth, Venus, and Mars, respectively. After a R2 correction this means that outgassing processes on Venus and Mars are weaker than on Earth by factors of 3 and 30, respectively. Mass ratios of U and Th are almost the same for all three planets, while potassium is depleted by a factor of 2 in Venus and Mars. Mass ratios of helium and argon are close to 5 x 10(-9) and 2 x 10(-8) g/g in the interiors of all three planets. The implications of these results are discussed.

Argon↗
PubMed1995

Paleolakes on Mars.

Observational evidence such as outflow channels and valley networks suggest that in the past there was flowing water on Mars. The images of fluvial features on Mars logically suggest that there must exist downstream locations in which the water pooled and the sediment load deposited (i.e. lakes). Sediments and morphological features associated with the martian paleolakes are believed to occur in Valles Marineris, and several large basins including Amazonis, Chryse and Elysium planitia. As Mars became progressively colder over geological time, any lakes on its surface would have become seasonally, and eventually perennially ice-covered. We know from polar lakes on Earth that ice-covered lakes can persist even when the mean annual temperature falls below freezing. Thus, the most recent lacustrine sediments on Mars were probably deposited in ice-covered lakes. While life outside of the Earth's atmosphere has yet to be observed, there is a general consensus among exobiologists that the search for extraterrestrial life should be based upon liquid water. The inference that there was liquid water on Mars during an earlier epoch is the primary motivation for considering the possibility of life during this time. It would be of enormous interest from both an exobiological and paleolimnological perspective to discover lakes or the evidence of former lakes on another planet such as Mars. Limnology would then become an interplanetary science.

Atmosphere↗
PubMed1992

Testing a Mars science outpost in the Antarctic dry valleys.

Field research conducted in the Antarctic has been providing insights about the nature of Mars in the science disciplines of exobiology and geology. Located in the McMurdo Dry Valleys of southern Victoria Land (160 degrees and 164 degrees E longitude and 76 degrees 30' and 78 degrees 30' S latitude), research outposts are inhabited by teams of 4-6 scientists. We propose that the design of these outposts be expanded to enable meaningful tests of many of the systems that will be needed for the successful conduct of exploration activities on Mars. Although there are some important differences between the environment in the Antarctic dry valleys and on Mars, the many similarities and particularly the field science activities, make the dry valleys a useful terrestrial analog to conditions on Mars. Three areas have been identified for testing at a small science outpost in the dry valleys; 1) studying human factors and physiology in an isolated environment; 2) testing emerging technologies (e.g., innovative power management systems, advanced life support facilities including partial bioregenerative life support systems for water recycling and food growth, telerobotics, etc.); and 3) conducting basic scientific research that will enhance our understanding of Mars while contributing to the planning for human exploration. We suggest that an important early result of a Mars habitat program will be the experience gained by interfacing humans and their supporting technology in a remote and stressful environment.

Antarctic Regions↗
PubMedDate not supplied

Phoenix--the first Mars Scout mission.

NASA has initiated the first of a new series of missions to augment the current Mars Program. In addition to the systematic series of planned, directed missions currently comprising the Mars Program plan, NASA has started a series of Mars Scout missions that are low cost, price fixed, Principal [correction of Principle] Investigator-led projects. These missions are intended to provide an avenue for rapid response to discoveries made as a result of the primary Mars missions, as well as allow more risky technologies and approaches to be applied in the investigation of Mars. The first in this new series is the Phoenix mission which was selected as part of a highly competitive process. Phoenix will use the Mars 2001 Lander that was discontinued in 2000 and apply a new set of science objectives and mission objectives and will validate this soft lander architecture for future applications. This paper will provide an overview of both the Program and the Project.

Climate↗
PubMed1999

Radiation: microbial evolution, ecology, and relevance to mars missions.

Ultraviolet (UV) radiation has been an important environmental parameter during the evolution of life on Earth, both in its role as a mutagen and as a selective agent. This was probably especially true during the time from 3.8 to 2.5 billion years ago, when atmospheric ozone levels were less than 1% of present levels. Early Mars may not have had an "ozone shield" either, and it never developed a significant one. Even though Mars is farther away from the Sun than the Earth, a substantial surficial UV flux is present on Mars today. But organisms respond to dose rate, and on Mars, like on Earth, organisms would be exposed to diurnal variations in UV flux. Here we present data on the effect of diurnal patterns of UV flux on microbial ecosystems in nature, with an emphasis on photosynthesis and DNA synthesis effects. These results indicate that diurnal patterns of metabolism occur in nature with a dip in photosynthesis and DNA synthesis in the afternoon, in part regulated by UV flux. Thus, diurnal patterns must be studied in order to understand the effect of UV radiation in nature. The results of this work are significant to the success of human missions to Mars for several reasons. For example, human missions must include photosynthetic organisms for food production and likely oxygen production. An evolutionary approach suggests which organisms might be best suited for high UV fluxes. The diurnal aspect of these studies is critical. Terraforming is a potential goal of Mars exploration, and it will require studies of the effect of Martian UV fluxes, including their diurnal changes, on terrestrial organisms. Such studies may suggest that diurnal changes in UV only require mitigation at some times of day or year.

Atmosphere↗
PubMed1996

Why exobiology on Mars?

Processing of organic molecules by liquid water was probably an essential requirement towards the emergence of terrestrial primitive life. According to Oparin's hypothesis, organic building blocks required for early life were produced from simple organic molecules formed in a primitive reducing atmosphere. Geochemists favour now a less reducing atmosphere dominated by carbon dioxide. In such an atmosphere, very few building blocks are formed. Import of extraterrestrial organic molecules may represent an alternative supply. Experimental support for such an alternative scenario is examined in comets, meteorites and micrometeorites. The early histories of Mars and Earth clearly show similarities. Liquid water was once stable on the surface of Mars attesting the presence of an atmosphere capable of decelerating C-rich micro-meteorites. Therefore, primitive life may have developed on Mars, as well. Liquid water disappeared from the surface of Mars very early, about 3.8 Ga ago. The Viking missions did not find, at the surface of the Martian soil, any organic molecules or clear-cut evidence for microbial activities such as photosynthesis, respiration or nutrition. The results can be explained referring to an active photochemistry of Martian soil driven by the high influx of solar UV. These experiments do not exclude the existence of organic molecules and fossils of micro-organisms which developed on early Mars until liquid water disappeared. Mars may store below its surface some well preserved clues of a still hypothetical primitive life.

Earth, Planet↗
PubMedDate not supplied

The Mars Sample Return Project.

The Mars Sample Return (MSR) Project is underway. A 2003 mission to be launched on a Delta III Class vehicle and a 2005 mission launched on an Ariane 5 will culminate in carefully selected Mars samples arriving on Earth in 2008. NASA is the lead agency and will provide the Mars landed elements, namely, landers, rovers, and Mars ascent vehicles (MAVs). The French Space Agency CNES is the largest international partner and will provide for the joint NASA/CNES 2005 Mission the Ariane 5 launch and the Earth Return Mars Orbiter that will capture the sample canisters from the Mars parking orbits the MAVs place them in. The sample canisters will be returned to Earth aboard the CNES Orbiter in the Earth Entry Vehicles provided by NASA. Other national space agencies are also expected to participate in substantial roles. Italy is planning to provide a drill that will operate from the Landers to provide subsurface samples. Other experiments in addition to the MSR payload will also be carried on the Landers. This paper will present the current status of the design of the MSR missions and flight articles.

Equipment Design↗
PubMedDate not supplied

Mars scientific investigations as a precursor for human exploration.

In the past two years, NASA has begun to develop and implement plans for investigations on robotic Mars missions which are focused toward returning data critical for planning human missions to Mars. The Mars Surveyor Program 2001 Orbiter and Lander missions will mark the first time that experiments dedicated to preparation for human exploration will be carried out. Investigations on these missions and future missions range from characterization of the physical and chemical environment of Mars, to predicting the response of biology to the Mars environment. Planning for such missions must take into account existing data from previous Mars missions which were not necessarily focused on human exploration preparation. At the same time, plans for near term missions by the international community must be considered to avoid duplication of effort. This paper reviews data requirements for human exploration and applicability of existing data. It will also describe current plans for investigations and place them within the context of related international activities.

Climate↗
PubMedDate not supplied

Following the water, the new program for Mars exploration.

In the wake of the loss of Mars Climate Orbiter and Mars Polar Lander in late 1999, NASA embarked on a major review of the failures and subsequently restructured all aspects of what was then called the Mars Surveyor Program--now renamed the Mars Exploration Program. This paper presents the process and results of this reexamination and defines a new approach which we have called "Program System Engineering". Emphasis is given to the scientific, technological, and programmatic strategies that were used to shape the new Program. A scientific approach known as "follow the water" is described, as is an exploration strategy we have called "seek--in situ--sample". An overview of the mission queue from continuing Mars Global Surveyor through a possible Mars Sample Return Mission launch in 2011 is provided. In addition, key proposed international collaborations, especially those between NASA, CNES and ASI are outlined, as is an approach for a robust telecommunications infrastructure.

Equipment Design↗
PubMed2004

Mission to Mars using integrated propulsion concepts: considerations, opportunities, and strategies.

The aim of this paper is to evaluate the feasibility of a mission to Mars using the Integrated Propulsion Systems (IPS) which means to couple Nuclear-MPD-ISPU propulsion systems. In particular both mission analysis and propulsion aspects are analyzed together with technological aspects. Identifying possible mission scenarios will lead to the study of possible strategies for Mars Exploration and also of methods for reducing cost. As regard to IPS, the coupling between Nuclear Propulsion (Rubbia's engine) and Superconductive MPD propulsion is considered for the Earth-Mars trajectories: major emphasis is given to the advantages of such a system. The In Situ Resource Utilization (ISRU) concerns on-Mars operations; In Situ Propellant Utilization (ISPU) is foreseen particularly for LOX-CH4 engines for Mars Ascent Vehicles and this possibility is analyzed from a technological point of view. Tether Systems are also considered during interplanetary trajectories and as space elevators on Mars orbit. Finally strategic considerations associated to this mission are considered also.

Atmosphere↗