Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography

Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies.

Gender differences in CF phenotype associated with low bone mineral density

Adolescents and adults with CF have lower bone mineral density (BMD) than normal, but its relationship with phenotype is not well understood. Point FEV1% predicted (FEV) and rate of change of FEV are biased estimates of disease severity, because progressively older subjects represent a selected survivor population, with females at greater risk of death than males. To investigate the relationship between BMD and phenotype we used an index (predicted age at death) derived from Bayesian estimates of slope and intercept of FEV, age at last measurement and survival status. Predictive equations for the index were derived from 97 subjects (78 survivors) from the RCH CF clinic, and applied to a group of 102 comparable subjects who had BMD measured, classified as having‘mild’ ()75th), ‘moderate’ (25– 75th), or ‘severe’ (-25th centile) phenotype. Total body (TB) and lumbar spine (LS) BMD z-scores (Z) were compared, adjustingfor gender effects, using 2-way ANOVA. Annual mean change in FEV segregated, as expected, according to phenotype, ‘severe’ (ns25), ‘moderate’ (ns51) and ‘mild’ (ns25) y3.01(y3.73 to y2.30)%, y0.85(y1.36 to y0.35)%, 2.70(1.92 to 3.46)%, respectively, with no gender difference. LS and TB BMDZ were different in each phenotype (P-s 0.002), LS BMDZ for ‘severe’, ‘moderate’ and ‘mild’ y1.63(CI: y2.07 to y 1.19), y0.86(CI: y1.17 to y0.55), y0.06(CI: y0.54 to 0.41). Males had lower LS BMDZ than females overall (y1.22 (CI: y1.54 to y0.91) vs. y0.48(CI: y 0.84 to y0.12) Ps0.002). In the ‘severe’ group, males had lower TB BMDZ and LS BMDZ (PF0.002). Low BMD is associated with ‘moderate’ and ‘severe’ phenotypes, with relative preservation in females in the ‘severe’ group. Female biology (reproductive fitness) might promote resistance to bone resorption at a critical level of BMD loss.

Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months

CONTEXT: Despite more than 2 decades of outcomes research after very preterm birth, clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight (ELBW) infants. OBJECTIVE: To determine the individual and combined prognostic effects of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 18-month outcomes of ELBW infants. DESIGN: Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms (TIPP). SETTING AND PARTICIPANTS: A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks. MAIN OUTCOME MEASURES: Combined end point of death or survival to 18 months with 1 or more of cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. RESULTS: Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome. Odds ratios were 2.4 (95% confidence interval [CI], 1.8-3.2) for BPD, 3.7 (95% CI, 2.6-5.3) for brain injury, and 3.1 (95% CI, 1.9-5.0) for severe ROP. In children who were free of BPD, brain injury, and severe ROP the rate of poor long-term outcomes was 18% (95% CI, 14%-22%). Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 42% (95% CI, 37%-47%), 62% (95% CI, 53%-70%), and 88% (64%-99%), respectively. CONCLUSION: In ELBW infants who survive to a postmenstrual age of 36 weeks, a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment.

Production of proteinases by psychrotrophic bacteria in raw milk stored at low temperature

Raw milk samples from two different sources were stored at 2degreesC, 4degreesC and 7degreesC for 10 days and the growth of psychrotrophic bacteria, production of proteinase and proteolysis in the milks were measured during storage. Peptide analyses by the fluorescamine method and RP-HPLC were used in determination of proteolysis and proteinase activity. The average times taken for the psychrotroph counts to reach 10(7) cfu/mL at 2degreesC, 4degreesC and 7degreesC were approximately 9, 7 and 4 days, although there was considerable variation in growth rates in the different milks. There was little correlation between psychrotroph counts and either proteolysis or proteinase activity levels. At 2degreesC, no milk stored showed significant proteolysis by the fluorescamine method after 10 days' storage, but significant proteinase activity could be measured in some of these milks at 8 and 10 days. RP-HPLC analysis was a more sensitive means of detecting peptides than the fluorescamine method.

Effects of heat treatment on the nutritional value of raw soybean selected for low trypsin inhibitor activity

1. Two broiler experiments and a layer experiments were conducted on Kunitz trypsin inhibitor (Kti) soybeans (SB) of low trypsin inhibitor (TI) activity to determine their nutritive value when included as mash in least-cost poultry diets. 2. Experiment 1 compared chick performance on the Kti or raw SB using a commercial full-fat SB meal (FFSBM) and a solvent extracted SB meal (SBM) as controls during a 20 d experimental period. Broiler experiment 2 compared Kti and raw SB, non-steamed, or steam-pelleted with and without DL-methionine supplementation added to every treatment containing 170 g SB/kg. For each broiler experiment the levels of each SB were 70, 120 and 170 g/kg with the control birds fed only 170 g SB/kg. 3. The layer experiment, compared steam-pelleted Kti and raw SB against a non-steamed Kti and raw SB each fed at two levels (70 and 110 g/kg) x 30 replicates from 29 weeks of age for 19 weeks in a completely randomised design. Production parameters were measured when diets were formulated to contain minimum required specifications and calculated apparent metabolisable energy (AME). At the completion of each trial, 2 broiler birds from each cage and 5 layer birds per treatment were killed, weighed, and their liver and pancreas weighed. 4. Both broiler experiments indicated that production parameters on the Kti SB treatments were significantly lower (P < 0.05) than on the two commercial control SB treatments. However, the Kti treatments were superior to the raw SB treatments. 5. Pancreas weight increased with increasing inclusion of both raw and Kti SB, suggesting that a TI was causing the depression in performance. The AME of the Kti SB was similar to that of commercial FFSB meal. After steam conditioning, the raw SB meal AME value of 9.5 MJ/kg dry matter (DM) was improved to 14.1 MJ/kg DM by reduced TI activity, but this AME improvement with TI activity reduction, plus the supplementation with DL-methionine on birds fed the raw SB had no effect (P > 0.05) on any parameter evaluated in experiment 2. 6. The layer experiment showed that hens on the Kti SB treatments had significantly greater live weight gain (LWG), egg weight and daily egg mass than birds given raw SB. A reduced food intake (FI) was observed in the Kti treatments but egg mass was generally similar to that on the FFSB control diet, indicating that Kti SB supported excellent egg production at an inclusion of 110 g/kg. The depressed performance observed for broiler chicks suggest that younger birds are more susceptible to the effects of SB TI.

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study

Objective To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. Methods Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 mug/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). Results No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotem cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p < 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p < 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. Conclusion Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.

Low-temperature single-crystal Raman and neutron-diffraction study of the hydrogenous ammonium copper(II) tutton salt and the deuterated analogue in the metastable state

Low-temperature (15 K) single-crystal neutron-diffraction structures and Raman spectra of the salts (NX4)(2)[CU(OX2)(6)](SO4)(2), where X = H or D, are reported. This study is concerned with the origin of the structural phase change that is known to occur upon deuteration. Data for the deuterated salt were measured in the metastable state, achieved by application of 500 bar of hydrostatic pressure at similar to303 K followed by cooling to 281 K and the subsequent release of pressure. This allows for the direct comparison between the hydrogenous and deuterated salts, in the same modification, at ambient pressure and low temperature. The Raman spectra provide no intimation of any significant change in the intermolecular bonding. Furthermore, structural differences are few, the largest being for the long Cu-O bond, which is 2.2834(5) and 2.2802(4) Angstrom for the hydrogenous and the deuterated salts, respectively. Calorimetric data for the deuterated salt are also presented, providing an estimate of 0.17(2) kJ/mol for the enthalpy difference between the two structural forms at 295.8(5) K. The structural data suggest that substitution of hydrogen for deuterium gives rise to changes in the hydrogen-bonding interactions that result in a slightly reduced force field about the copper(II) center. The small structural differences suggest different relative stabilities for the hydrogenous and deuterated salts, which may be sufficient to stabilize the hydrogenous salt in the anomalous structural form.

Structural definition of the low-temperature phase transition of tris(ethane-1,2-diamine)zinc(II) dinitrate

The 93 K X-ray crystal structure of tris(ethane-1,2-diamine)zinc(II) dinitrate is reported. As predicted by the spectroscopic studies of other workers, there is a reversible phase transition of the structure at low temperature. We have determined this temperature to be 143 K. The structure at this temperature and below resembles that of the room temperature structure, except the crystallographic D-3 symmetry of the complex cation (296 K) is lowered to C-2 ( below 144 K) by subtle changes in cation-anion hydrogen bonding. No change in the conformation of the cation or its bond lengths and angles was found.

Dehydration converts DsbG crystal diffraction from low to high resolution

Diffraction quality crystals are essential for crystallographic studies of protein structure, and the production of poorly diffracting crystals is often regarded as a dead end in the process. Here we show a dramatic improvement of poorly diffracting DsbG crystals allowing high-resolution diffraction data measurement. Before dehydration, the crystals are fragile and the diffraction pattern is streaky, extending to 10 Angstrom resolution. After dehydration, there is a spectacular improvement, with the diffraction pattern extending to 2 Angstrom resolution. This and other recent results show that dehydration is a simple, rapid, and inexpensive approach to convert poor quality crystals into diffraction quality crystals.

Wall mediated transport in confined spaces: Exact theory for low density

We present a theory for the transport of molecules adsorbed in slit and cylindrical nanopores at low density, considering the axial momentum gain of molecules oscillating between diffuse wall reflections. Good agreement with molecular dynamics simulations is obtained over a wide range of pore sizes, including the regime of single-file diffusion where fluid-fluid interactions are shown to have a negligible effect on the collective transport coefficient. We show that dispersive fluid-wall interactions considerably attenuate transport compared to classical hard sphere theory.

Low temperature induced spikelet sterility in rice. I. Nitrogen fertilisation and sensitive reproductive period

Low temperature during panicle development in rice increases spikelet sterility. This effect is exacerbated by high rates of nitrogen (N) application in the field. Spikelet sterility induced by low temperature and N fertilisation was examined in glasshouse experiments to clarify the mechanisms involved. In two glasshouse experiments, 12-h periods of low (18/13degreesC) and high (28/23degreesC) day/night temperatures were imposed over periods of 5-7 days during panicle development, to determine the effects of low temperature and N fertilisation on spikelet sterility. In one experiment, 50% sunlight was imposed together with low temperature to investigate the additive effects of reduced solar radiation and low temperature. The effect of increased tillering due to N fertilisation was examined by a tiller removal treatment in the same experiment. Pollen grain number and spikelet sterility were recorded at heading and harvest, respectively. Although there was no significant effect of low temperature on spikelet sterility in the absence of applied N, low temperature greatly increased spikelet sterility as a result of a reduction in the number of engorged pollen grains per anther in the presence of applied N. Spikelet sterility was strongly correlated with the number of engorged pollen grains per anther. Low temperature during very early ( late stage of spikelet differentiation-pollen mother cell stage) and peak ( second meiotic division stage-early stage of extine formation) microspore development caused a severe reduction in engorged pollen production mainly as a result of reduced total pollen production. Unlike low temperature, the effect of shading was rather small. The increased tillering due to application of high rates of N, increased both spikelet number per plant and spikelet sterility under low temperature conditions. The removal of tillers as they appeared reduced the number of total spikelets per plant and maintained a large number of engorged pollen grains per anther which, in turn, reduced spikelet sterility. The number of engorged pollen grains per anther determined the numbers of intercepted and germinated pollen grains on the stigma. It is concluded that N increased tillering and spikelet number per plant and this, in turn, reduced the number of engorged pollen grains per anther, leading into increased spikelet sterility under low temperature condition.

Low temperature induced spikelet sterility in rice. II. Effects of panicle and root temperatures

Low temperatures impose restrictions on rice (Oryza sativa L.) production at high latitudes. This study is related to low temperature damage that can arise mid-season during the panicle development phase. The objective of this study was to determine whether low temperature experienced by the root, panicle, or foliage is responsible for increased spikelet sterility. In temperature-controlled glasshouse experiments, water depth, and water and air temperatures, were changed independently to investigate the effects of low temperature in the root, panicle, and foliage during microspore development on spikelet sterility. The total number of pollen and number of engorged pollen grains per anther, and the number of intercepted and germinated pollen grains per stigma, were measured. Spikelet sterility was then analysed in relation to the total number of pollen grains per spikelet and the efficiency with which these pollen grains became engorged, were intercepted by the stigma, germinated, and were involved in fertilisation. There was a significant combined effect of average minimum panicle and root temperatures on spikelet sterility that accounted for 86% of the variation in spikelet sterility. Total number of pollen grains per anther was reduced by low panicle temperature, but not by low root temperature. Whereas engorgement efficiency ( the percentage of pollen grains that were engorged) was determined by both root and panicle temperature, germination efficiency (the percentage of germinated pollen grains relative to the number of engorged pollen grains intercepted by the stigma) was determined only by root temperature. Interception efficiency (i.e. percentage of engorged pollen grains intercepted by the stigma), however, was not affected by either root or panicle temperature. Engorgement efficiency was the dominant factor explaining the variation in spikelet sterility. It is concluded that both panicle and root temperature affect spikelet sterility in rice when the plant encounters low temperatures during the microspore development stage.