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Biomedical subjects

M Leuenberger

Publications and source records attributed to M Leuenberger.

15 recordsLinked to original sources

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Journal Article↗

Fast high-precision on-line determination of hydrogen isotope ratios of water or ice by continuous-flow isotope ratio mass spectrometry.

A new fast high-precision on-line technique is described for the determination of hydrogen isotope ratios of water by continuous-flow mass spectrometry. For the first time H(2)/H(2)O-equilibration using a platinum catalyst has been used in a fully continuous process. A significant reduction in the H(2)/H(2)O-equilibration time is achieved by a complete vaporization of the water and by increasing the exchange temperature to 100 degrees C. The analysis time is only approximately 5 min/sample which includes equilibration and processing. Measurement precision and accuracy are better than 1 per thousand and sample consumption is only approximately 5 microL. This new technique allows the measurement of a wide range of aqueous samples either in a semi-continuous way (discrete samples are injected one after another) or in a fully continuous way. This allows us, for the first time, to make continuous measurements of ice cores.

Calibration↗

On-line determination of oxygen isotope ratios of water or ice by mass spectrometry.

Oxygen isotope ratio determination on any of the water phases (water vapor, water, ice) is of great relevance in different research fields such as climate and paleoclimate studies, geological surveys, and hydrological studies. The conventional technique for oxygen isotope measurement involves equilibration with carbon dioxide gas for a given time with a subsequent isotope determination. The equilibration technique is available in different layouts, but all of them are rather time-consuming. Here we report a new on-line technique that processes water samples as well as ice samples. The same principal, CO2 hydration, is used but speeded up by (i) a direct injection and full dissolution of CO2 in the water, (ii) an increased isotope exchange temperature at 50 degrees C, and (iii) a rapid gas extraction by means of an air-permeable membrane into a continuous helium flux supplying the isotope ratio mass spectrometer with the sample gas. The precision is better than 0.1/1000 which is only slightly larger than with the conventional equilibration technique. This on-line technique allows analysis of 1 m of ice with a resolution of 1-3 cm, depending on the meltwater flux, within 1 h. Similarly, continuous and fast analysis can be performed for aqueous samples for hydrological, geological, and perhaps medical applications.

Journal Article↗

A new gas inlet system for an isotope ratio mass spectrometer improves reproducibility

We have developed a new inlet system for a gas sample isotope ratio mass spectrometer (IRMS). It is based on the well-known open split design from the gas chromatography/mass spectrometry (GC/MS) system due to its simplicity. The advantages over the conventional double inlet system with the metal bellows design include an improved reproducibility mainly due to a highly controllable pressure and temperature adjustment, a markedly lowered memory effect due to an uninterrupted gas flow through the ion source which limits adsorption/desorption processes on surfaces, and a single inlet capillary circumventing problems of asymmetrical behavior of sample and reference inlet paths. Furthermore, sample consumption is of the same order as for conventional measurements (i.e. about 0.4 mmol per hour), of which however only 2 &mgr;mol/h is used for the actual isotope ratio determination since the major gas amount acts as a gas flow seal against the atmosphere, corresponding to a 100-200 fold overkill. This may be improved in future systems. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

CO(2) concentration measurements on air samples by mass spectrometry

A new technique for measuring CO(2) concentration in air samples, based on mass spectrometry, is described as an alternative to the common gas chromatographic method. Using a dual inlet isotope ratio mass spectrometer (IRMS), the ratio of the abundances of the m/z peaks 44 and 28 is determined. The precision of measurements (standard deviation <3 ppmv) is generally as good as the analysis with gas chromatography for small air samples (<1 ml STP of air). A major advantage of this new method is the possibility of parallel elemental and isotopic measurements of many air components. The technique is further improved by new wide mass range mass spectrometers allowing simultaneous intensity measurements of several m/z values between 28 and 44, resulting in an uncertainty of <0.5 ppm. The precision is somewhat limited by the production of N(2)O and NO(2) from N(2) and O(2) in the ion source, which accounts for about half of the signal strength at m/z 44. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

16 degrees C rapid temperature variation in central greenland 70,000 years Ago

Variations in the (29)N(2)/(28)N(2) ratio of air bubbles trapped in polar ice cores and their relation to variations of the (18)O/(16)O of the ice allow past surface temperature variations and ice age-gas age differences to be determined. High-resolution measurements of (29)N(2)/(28)N(2) in Dansgaard-Oeschger event 19 (around 70,000 years before the present) in ice from Central Greenland show that at the beginning of the event, the ice age-gas age difference was 1090 +/- 100 years. With the use of a combined firn densification, temperature, and gas diffusion model, the delta(18)O(ice)-temperature coefficient alpha was determined to be 0. 42 +/- 0.05 per mil per kelvin. This coefficient implies a mean surface temperature change of 16.0 kelvin (between 14.3 and 18.1 kelvin), which differs substantially from values derived from borehole temperatures and modern spatial delta(18)O(ice)-surface temperature correlations.

Journal Article↗

Carboxylate ions are strong allosteric ligands for the HisB10 sites of the R-state insulin hexamer.

The insulin hexamer is an allosteric protein which displays positive and negative cooperativity and half-site reactivity that is modulated by strong homotropic and heterotropic ligand binding interactions at two different loci. These loci consist of phenolic pockets situated on the dimer-dimer interfaces of T-R and R-R subunit pairs and of anion sites comprising the HisB10 metal ion sites of the R3 units of the T3R3 and R6 states. In this study, we show that suitably tailored organic carboxylates are strong allosteric effectors with relatively high affinities for the R-state HisB10 metal sites. Methods of quantifying the relative affinities of ligands for these sites in both Co(II)- and Zn(II)-substituted insulin hexamers are presented. These analyses show that, in addition to the electron density on the ion, the carboxylate affinity is influenced by polar, nonpolar, and hydrophobic interactions between substituents on the carboxylate and the amphipathic protein surface of the narrow tunnel which controls ligand access to the metal ion. Since the binding of anions to the HisB10 site makes a critically important contribution to the stability of the T3R3 and R6 forms of the insulin hexamer, the design of high-affinity ligands with a carboxylate donor for coordination to the metal ion provides an opportunity for constructing insulin formulations with improved pharmaceutical properties.

Allosteric Site↗

Hormonal and metabolic adjustments during exercise in hypoxia or normoxia in highland natives.

In sea-level natives, exposure to hypoxia for a few weeks is characterized by an increased dependence on blood glucose and a decreased reliance on lactate for energy metabolism during exercise. These metabolic adjustments have been attributed to behavioral changes in the sympathoadrenergic and pancreatic systems. The aim of this study was to test the hypothesis of a reduced sympathoadrenergic activation and subsequent metabolic changes when high-altitude natives are acutely exposed to normoxia. Young Andean natives performed incremental exercise to exhaustion during hypoxia (arterial PO2 55.1 +/- 1.1 Torr) or during acute normoxia (arterial PO2 78.7 +/- 1.7 Torr). As a whole, oxygen uptake was increased in normoxia compared with hypoxia during graded exercise. This finding is not related to a decrease in anaerobic metabolism but rather is interpreted as a consequence of a shift in substrate utilization during exercise (increased contribution of fat as assessed by a reduction in the respiratory exchange ratio). These metabolic changes are not accompanied by modifications of glucoregulatory hormones (catecholamines, insulin, and glucagon). In particular, the exercise-induced catecholamine secretion was similar in chronic hypoxia and acute normoxia. As a consequence, blood lactate accumulation during incremental exercise was similar in both conditions. It is concluded that high-altitude natives do not display any sign of a greater sympathoadrenergic activation during chronic hypoxia and that the exercise-induced hormonal changes remained unaffected by acute inhalation of a normoxic gas mixture.

Adult↗

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia.

Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320-327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.314). The workloads were adjusted to approximately 70% of peak O2 consumption (VO2peak) measured either in hypoxia for the HT group or in normoxia for the NT group. VO2peak determination and biopsies of the vastus lateralis muscle were taken before and after the training program. VO2peak in the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover, VO2peak in the NT group was not further increased by additional O2 delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia.

Acclimatization↗

Training in hypoxia vs. training in normoxia in high-altitude natives.

To determine the interactions between endurance training and hypoxia on maximal exercise performance, we performed a study on sedentary high-altitude natives who were trained in normoxia at the same relative (n = 10) or at the same absolute (n = 10) intensity of work as hypoxia-trained subjects (n = 10). The training-induced improvement of maximal oxygen uptake (VO2max) in hypoxia-trained subjects was similar to that obtained in normoxia-trained sea-level natives submitted to the same training protocol (H. Hoppeler, H. Howald, K. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. W. Weibel. J. Appl. Physiol. 59: 320-327, 1985). Training at the same absolute work intensity in the presence of increased oxygen delivery failed to provide a further increase in VO2max. VO2max was not improved to a greater extent by simultaneously increasing absolute work intensity and O2 delivery during the training sessions. In addition, training in normoxia is accompanied by an increased blood lactate accumulation during maximal exercise, leading to greater drops in arterial pH, bicarbonate concentration, and base excess. We conclude that, in high-altitude natives, 1) training at altitude does not provide any advantage over training at sea level for maximal aerobic capacity, whether assessed in chronic hypoxia or in acute normoxia; 2) VO2max improvement with training cannot be further enhanced by increasing O2 availability alone or in combination with an increased work intensity during the exercising sessions; and 3) training in normoxia in these subjects results in a reduced buffer capacity.

Adult↗

Gas leakage in eight anaesthesia circle systems.

Eight currently used factory-new anaesthesia circle systems (Dräger Cicero, Dräger Sulla, Dräger AV1, Gambro Engström Elsa, Megamed 700A, Ohmeda Modulus II Plus, Siemens Ventilator 710 and Siemens Servo Ventilator 900 D with circle system) and a Megamed 077 which had been clinically used for 11 years were tested for gas leaks according to the Draft European Standard Anaesthetic Workstations and Their Modules. All measurements were performed using the Cicero ventilator developed by Dräger with its integrated test program for the detection of system leakage. All the factory-new systems showed leakage rates of less than 50 ml min-1 at a test pressure of 3 kPa (30 cmH2O). In the 'manual' position and with the soda-lime canister and the volumeter (or flow-sensor) included, the following leak rates were determined: Dräger Cicero, 5.0 ml min-1; Dräger Sulla, 22.8 ml min-1; Dräger AV1, 7.7 ml min-1; Gambro Engström Elsa, 33.4 ml min-1; Megamed 700A, 11.5 ml min-1; Ohmeda Modulus II Plus, less than 0.1 ml min-1; Siemens Ventilator 710, 0.3 ml min-1; Siemens Servo Ventilator 900D with circle system 985, 9.6 ml min-1; Megamed 077, 47.5 ml min-1. All anaesthesia breathing circle systems tested performed below the leakage limit of 100 ml min-1 proposed by the draft standard.

Anesthesia, Closed-Circuit↗

[Diagnostic results of pediatric-child psychiatric cooperation exemplified by the Pediatric Clinic of the Winterthur Canton Hospital 1971-1980].

This article reports on the diagnostic results of 232 patients who were examined in close collaboration by the paediatrician and the child psychiatrist at a Swiss children's hospital between 1971 and 1980. The main diagnosis was psychogenic disorders with mainly psychic symptoms in 53.9% of the cases, psychogenic disorders with mainly somatic symptoms in 37.1%, minimal brain damage in 11.2%, and disturbances of development in 8.6%. Psychosomatic symptoms as accessory findings were found in another 30%. Thus, functional somatic disorders were components of the polysymptomatic syndromes in more than 60% of the patients.

Child↗

[Cooperation between pediatrics and child psychiatry in a pediatric hospital; possibilities and limits].

Cooperation between pediatrics and child psychiatry in a children's hospital is becoming more and more important and necessary in dealing with many common problems such as psychological reactions to physical illness, psychosomatic disturbances, physical examination of psychiatric patients, and disorders and retardation of growth and development. The authors describe a cooperative model which has been developed and proved its usefulness during a period of 10 years. This method is an alternative to the traditional referral or consulting system, which involves little real cooperation between the two specialties, and also to excessive penetration of nonmedical psychology into pediatrics.

Child Psychiatry↗

[Psychosomatic aspects of pseudocroup].

Based on 14 paediatric case histories we present a hypothesis--to our knowledge for the first time--concerning the role of psychogenetic factors for the occurrence of pseudocroup attacks. Anxieties, insecurity and impaired ability to communicate with each other characterize the relationship of the patient and his mother. The developing independence of the child is hindered. The frightening pseudocroup attack tightens mother and child close together, allows a regression to an early childhood state of mother-child relationship, and demonstrates in a pathological way their interdependence and the dangers of autonomy.

Child↗