The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: A randomized double-blind controlled trial

Background: Dyspnea represents a very frequent and distressing symptom in patients with advanced cancer. This study was undertaken to assess the efficacy of morphine on dyspnea and its safety for ventilatory function in elderly advanced cancer patients. Patients and methods: Nine elderly patients with dyspnea due to lung involvement were randomized to receive either morphine subcutaneously (5 mg in seven opioid-naïve patients and 3.75 mg in two patients on top of their regular oral dose of 7.5 mg q4h) or placebo on day 1. On day 2, they were crossed over to receive the alternate treatment. Dyspnea was assessed every fifteen minutes using a visual analogue scale (VAS: 0-100 mm) and the ordinal scale developed by Borg (0-10 points). Pain, somnolence and anxiety were assessed using VAS. Respiratory effort, respiratory rate and oxygen saturation were also measured repeatly. Results: Mean changes in dyspnea 45 minutes after injection were −25 ± 10 mm and −1.2 ± 1.2 points for morphine, versus 0.6 ± 7.7 mm (P < 0.01) and −0.1 ± 0.3 points (P = 0.03) for placebo on VAS and Borg scale, respectively. No relevant changes were observed in somnolence, pain, anxiety, respiratory effort and rate, and oxygen saturation. Conclusions: Morphine appears effective for cancer dyspnea, and it does not compromise respiratory function at the dose level use

Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

We report here a combination of site-directed mutations that eliminate the high-affinity Ca2+ response of the large-conductance Ca2+-activated K+ channel (BKCa), leaving only a low-affinity response blocked by high concentrations of Mg2+. Mutations at two sites are required, the “Ca2+ bowl,” which has been implicated previously in Ca2+ binding, and M513, at the end of the channel's seventh hydrophobic segment. Energetic analyses of mutations at these positions, alone and in combination, argue that the BKCa channel contains three types of Ca2+ binding sites, one of low affinity that is Mg2+ sensitive (as has been suggested previously) and two of higher affinity that have similar binding characteristics and contribute approximately equally to the power of Ca2+ to influence channel opening. Estimates of the binding characteristics of the BKCa channel's high-affinity Ca2+-binding sites are provided

Same but different — pseudo-pectin in the charophytic alga Chlorokybus atmophyticus

All land‐plant cell walls possess hemicelluloses, cellulose and anionic pectin. The walls of their cousins, the charophytic algae, exhibit some similarities to land plants’ but also major differences. Charophyte ‘pectins’ are extractable by conventional land‐plant methods, although they differ significantly in composition. Here, we explore ‘pectins’ of an early‐diverging charophyte, Chlorokybus atmophyticus, characterising the anionic polysaccharides that may be comparable to ‘pectins’ in other streptophytes. Chlorokybus ‘pectin’ was anionic and upon acid hydrolysis gave GlcA, GalA and sulphate, plus neutral sugars (Ara≈Glc>Gal>Xyl); Rha was undetectable. Most Gal was the l‐enantiomer. A relatively acid‐resistant disaccharide was characterised as β‐d‐GlcA‐(1→4)‐l‐Gal. Two Chlorokybus ‘pectin’ fractions, separable by anion‐exchange chromatography, had similar sugar compositions but different sulphate‐ester contents. No sugars were released from Chlorokybus ‘pectin’ by several endo‐hydrolases [(1,5)‐α‐l‐arabinanase, (1,4)‐β‐d‐galactanase, (1,4)‐β‐d‐xylanase, endo‐polygalacturonase] and exo‐hydrolases [α‐ and β‐d‐galactosidases, α‐(1,6)‐d‐xylosidase]. ‘Driselase’, which hydrolyses most land‐plant cell wall polysaccharides to mono‐ and disaccharides, released no sugars except traces of starch‐derived Glc. Thus, the Ara, Gal, Xyl and GalA of Chlorokybus ‘pectin’ were not non‐reducing termini with configurations familiar from land‐plant polysaccharides (α‐l‐Araf, α‐ and β‐d‐Galp, α‐ and β‐d‐Xylp and α‐d‐GalpA), nor mid‐chain residues of α‐(1→5)‐l‐arabinan, β‐(1→4)‐d‐galactan, β‐(1→4)‐d‐xylan or α‐(1→4)‐d‐galacturonan. In conclusion, Chlorokybus possesses anionic ‘pectic’ polysaccharides, possibly fulfilling pectic roles but differing fundamentally from land‐plant pectin. Thus, the evolution of land‐plant pectin since the last common ancestor of Chlorokybus and land plants is a long and meandering path involving loss of sulphate, most l‐Gal and most d‐GlcA; re‐configuration of Ara, Xyl and GalA; and gain of Rha

The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: a randomized double-blind controlled trial

BACKGROUND: Dyspnea represents a very frequent and distressing symptom in patients with advanced cancer. This study was undertaken to assess the efficacy of morphine on dyspnea and its safety for ventilatory function in elderly advanced cancer patients. PATIENTS AND METHODS: Nine elderly patients with dyspnea due to lung involvement were randomized to receive either morphine subcutaneously (5 mg in seven opioid-naive patients and 3.75 mg in two patients on top of their regular oral dose of 7.5 mg q4 h) or placebo on day 1. On day 2, they were crossed over to receive the alternate treatment. Dyspnea was assessed every fifteen minutes using a visual analogue scale (VAS: 0-100 mm) and the ordinal scale developed by Borg (0-10 points). Pain, somnolence and anxiety were assessed using VAS. Respiratory effort, respiratory rate and oxygen saturation were also measured repeatedly. RESULTS: Mean changes in dyspnea 45 minutes after injection were -25 +/- 10 mm and -1.2 +/- 1.2 points for morphine, versus 0.6 +/- 7.7 mm (P &lt; 0.01) and -0.1 +/- 0.3 points (P = 0.03) for placebo on VAS and Borg scale, respectively. No relevant changes were observed in somnolence, pain, anxiety, respiratory effort and rate, and oxygen saturation. CONCLUSIONS: Morphine appears effective for cancer dyspnea, and it does not compromise respiratory function at the dose level used

Socioeconomic and living conditions are determinants of hip fracture incidence and age occurrence among community-dwelling elderly

Summary: In this prospective, 10-year study in community-dwelling elderly aged 50years and over, hip fracture incidence and accordingly age at hip fracture were inversely associated with the area-level income, independently of the geographical area. Age at hip fracture also depended of marital status but in a gender-specific way. Purpose: The purpose of this study is to investigate the impact of socioeconomic and living conditions on hip fracture incidence and age occurrence among community-dwelling elderly. Method: Between January 1991 and December 2000, 2,454 hip fractures were recorded in community-dwelling adults aged 50years and over in the Geneva University Hospital, State of Geneva, Switzerland. Median annual household income by postal code of residence (referred to as area-level income) based on the 1990 Census was used as a measure of socioeconomic condition and was stratified into tertiles (<53,170; 53,170-58,678; and ≥58,678 CHF). Hip fracture incidence and age occurrence were calculated according to area-level income categories and adjusted for confounding factors among community-dwelling elderly. Results: Independently of the geographical area (urban versus rural), community-dwelling persons residing in areas with the medium income category presented a lower hip fracture incidence [OR 0.91 (0.82-0.99), p = 0.049] compared to those from the lowest income category. Those in the highest income category had a hip fracture at a significant older age [+1.58 (0.55-2.61) year, p = 0.003] as compared to those in the lowest income category. Age at hip fracture also depended on marital status but in a gender-specific way, with married women fracturing earlier. Conclusions: These results indicate that incidence and age occurrence of hip fracture are influenced by area-level income and living conditions among community-dwelling elderly. Prevention programs may be encouraged in priority in communities with low incom

Reversal of the hip fracture secular trend is related to a decrease in the incidence in institution-dwelling elderly women

Summary: In this prospective 10-year study in elderly aged 60years and over, there was a 1.3% per year reduction in the standardized incidence of hip fracture in women but not in men. This decrease was mainly due to changes in the standardized incidence of hip fracture in institution-dwelling women. Introduction: A decrease in age-adjusted hip fracture incidence has been recently demonstrated in some countries. Since a large proportion of hip fractures occur in nursing homes, we analyzed whether this decreasing trend would be more detectable in institution-dwelling elderly compared with community-dwelling elderly. Methods: All hip fracture patients aged 60years and over were identified in a well-defined area. Incidence of hip fracture, age- and sex-adjusted to the 2000 Geneva population, was computed in community- and institution-dwelling elderly. Results: From 1991 to 2000, 1,624 (41%) hip fractures were recorded in institutionalized-dwelling elderly and 2,327 (59%) in community-dwelling elderly. The standardized fracture incidence decreased by 1.3% per year in women (p = 0.039), but remained unchanged in men (+0.5%; p = 0.686). Among institution-dwelling women, hip fracture incidence fell by 1.9% per year (p = 0.044), whereas it remained stable among community-dwelling women (+0.0%, p = 0.978). In men, no significant change in hip fracture incidence occurred among institution- or community-dwelling elderly. Conclusions: The decrease in the standardized hip fracture incidence in institution-dwelling women is responsible for the reversal in secular trend. Future research should include stratification according to the residential status to better identify the causes responsible for the trend in hip fracture incidenc

Hydrogen Variability in the Murray Formation, Gale Crater, Mars

The Mars Science Laboratory (MSL) Curiosity rover is exploring the Murray formation, a sequence of heterolithic mudstones and sandstones recording fluvial deltaic and lake deposits that comprise over 350 m of sedimentary strata within Gale crater. We examine >4,500 Murray formation bedrock points, employing recent laboratory calibrations for ChemCam laser‐induced breakdown spectroscopy H measurements at millimeter scale. Bedrock in the Murray formation has an interquartile range of 2.3–3.1 wt.% H₂O, similar to measurements using the Dynamic Albedo of Neutrons and Sample Analysis at Mars instruments. However, specific stratigraphic intervals include high H targets (6–18 wt.% H₂O) correlated with Si, Mg, Ca, Mn, or Fe, indicating units with opal, hydrated Mg sulfates, hydrated Ca sulfates, Mn‐enriched units, and akageneite or other iron oxyhydroxides, respectively. One stratigraphic interval with higher hydrogen is the Sutton Island unit and Blunts Point unit contact, where higher hydrogen is associated with Fe‐rich, Ca‐rich, and Mg‐rich points. A second interval with higher hydrogen occurs in the Vera Rubin ridge portion of the Murray formation, where higher hydrogen is associated with Fe‐rich, Ca‐rich, and Si‐rich points. We also observe trends in the H signal with grain size, separate from chemical variation, whereby coarser‐grained rocks have higher hydrogen. Variability in the hydrogen content of rocks points to a history of water‐rock interaction at Gale crater that included changes in lake water chemistry during Murray formation deposition and multiple subsequent groundwater episodes

Hydrogen Variability in the Murray Formation, Gale Crater, Mars

The Mars Science Laboratory (MSL) Curiosity rover is exploring the Murray formation, a sequence of heterolithic mudstones and sandstones recording fluvial deltaic and lake deposits that comprise over 350 m of sedimentary strata within Gale crater. We examine >4,500 Murray formation bedrock points, employing recent laboratory calibrations for ChemCam laser‐induced breakdown spectroscopy H measurements at millimeter scale. Bedrock in the Murray formation has an interquartile range of 2.3–3.1 wt.% H₂O, similar to measurements using the Dynamic Albedo of Neutrons and Sample Analysis at Mars instruments. However, specific stratigraphic intervals include high H targets (6–18 wt.% H₂O) correlated with Si, Mg, Ca, Mn, or Fe, indicating units with opal, hydrated Mg sulfates, hydrated Ca sulfates, Mn‐enriched units, and akageneite or other iron oxyhydroxides, respectively. One stratigraphic interval with higher hydrogen is the Sutton Island unit and Blunts Point unit contact, where higher hydrogen is associated with Fe‐rich, Ca‐rich, and Mg‐rich points. A second interval with higher hydrogen occurs in the Vera Rubin ridge portion of the Murray formation, where higher hydrogen is associated with Fe‐rich, Ca‐rich, and Si‐rich points. We also observe trends in the H signal with grain size, separate from chemical variation, whereby coarser‐grained rocks have higher hydrogen. Variability in the hydrogen content of rocks points to a history of water‐rock interaction at Gale crater that included changes in lake water chemistry during Murray formation deposition and multiple subsequent groundwater episodes

The potassic sedimentary rocks in Gale Crater, Mars, as seen by ChemCam on board Curiosity

The Mars Science Laboratory rover Curiosity encountered potassium-rich clastic sedimentary rocks at two sites in Gale Crater, the waypoints Cooperstown and Kimberley. These rocks include several distinct meters thick sedimentary outcrops ranging from fine sandstone to conglomerate, interpreted to record an ancient fluvial or fluvio-deltaic depositional system. From ChemCam Laser-Induced Breakdown Spectroscopy (LIBS) chemical analyses, this suite of sedimentary rocks has an overall mean K2O abundance that is more than 5 times higher than that of the average Martian crust. The combined analysis of ChemCam data with stratigraphic and geographic locations reveals that the mean K2O abundance increases upward through the stratigraphic section. Chemical analyses across each unit can be represented as mixtures of several distinct chemical components, i.e., mineral phases, including K-bearing minerals, mafic silicates, Fe-oxides, and Fe-hydroxide/oxyhydroxides. Possible K-bearing minerals include alkali feldspar (including anorthoclase and sanidine) and K-bearing phyllosilicate such as illite. Mixtures of different source rocks, including a potassium-rich rock located on the rim and walls of Gale Crater, are the likely origin of observed chemical variations within each unit. Physical sorting may have also played a role in the enrichment in K in the Kimberley formation. The occurrence of these potassic sedimentary rocks provides additional evidence for the chemical diversity of the crust exposed at Gale Crater

Identification and Description of a Silicic Volcaniclastic Layer in Gale Crater, Mars, Using Active Neutron Interrogation

The Dynamic Albedo of Neutrons instrument aboard the Mars Science Laboratory rover, Curiosity, has been used to map a stratigraphically conformable layer of high‐SiO² material in Gale crater. Previous work has shown that this material contains tridymite, a high‐temperature/low‐pressure felsic mineral, interpreted to have a volcanic source rock. We describe several characteristics including orientation, extent, hydration, and geochemistry, consistent with a volcaniclastic material conformably deposited within a lacustrine mudstone succession. Relationships with widely dispersed alteration features and orbital detections of hydrated SiO² suggest that this high‐SiO² layer extends at least 17 km laterally. Mineralogical abundances previously reported for this high‐SiO² material indicated that hydrous species were restricted to the amorphous (non‐crystalline) fraction, which is dominated by SiO². The low mean bulk hydration of this high‐SiO² layer (1.85 ± 0.13 wt.% water‐equivalent hydrogen) is consistent with silicic glass in addition to opal‐A and opal‐CT. Persistent volcanic glass and tridymite in addition to opal in an ancient sedimentary unit indicates that the conversion to more ordered forms of crystalline SiO² has not proceeded to completion and that this material has had only limited exposure to water since it originally erupted, despite having been transported in a fluviolacustrine system. Our results, including the conformable nature, large areal extent, and presence of volcanic glass, indicate that this high‐SiO² material is derived from the product of evolved magma on Mars. This is the first identification of a silicic volcaniclastic layer on another planet and has important implications for magma evolution mechanisms on single‐plate planets