The inositol-1,4,5-trisphosphate system is involved in rapid effects of aldosterone in human mononuclear leukocytes

There is increasing evidence for rapid steroid action on electrolyte transport in human mononuclear leukocytes (HML). In HML, aldosterone stimulates the Na+/H+ antiporter within a few minutes. Because a variety of hormones and growth factors activate the Na+/H+ antiporter via protein kinase C and inositol phospholipids, a possible involvement of inositol-1,4,5-trisphosphate (IP3) in the rapid effects of aldosterone in HML was investigated. The stimulation of IP3 generation was started by the addition of aldosterone, concanavalin A, or other steroids. A significant increase in IP3 levels by aldosterone (1 nmol/L, P < 0.05) was found after 1 min, similar to that found after concanavalin A (25 micrograms/mL). Aldosterone caused a concentration-dependent elevation of IP3 levels, with an apparent EC50 of approximately 0.1 nmol/L. Fludrocortisone stimulated IP3 generation at similar concentrations, whereas a weaker IP3 stimulation by glucocorticoids (hydrocortisone, dexamethasone) occurred at micromolar concentrations only. Canrenone, a potent inhibitor of classical aldosterone action, was not effective up to a concentration of 100 nmol/L. These findings show kinetic and pharmacological similarities with both the functional data on Na+/H+ antiport stimulation by aldosterone and the studies of 125I-aldosterone binding to plasma membranes of HML. Thus, these data are the first to indicate an involvement of the phosphoinositide pathway in the rapid membrane effects of aldosterone.     

Damage and strain in pseudomorphic vs relaxed GexSi1−x layers on Si(100) generated by Si ion irradiation

We compare both the strain and damage that 100 keV Si irradiation at room temperature introduces in pseudomorphic and relaxed Ge_xSi_1−x films grown on Si(100) substrates. The ion range is such that the Si/Ge_xSi_1−x interface is not significantly damaged. The amount of damage produced in pseudomorphic and relaxed Ge_xSi_1−x layers of similar x for irradiation doses up to 2.5 × 10¹⁴ Si/cm² is the same, which proves that a pre-existing uniform strain does not noticeably affect the irradiation-induced damage. However, the irradiation-induced strain does depend on the pre-existing strain of the samples. Possible interpretations are discussed. On leave from Inst. voor Kern en Stralingsfysika, Catholic University of Leuven, Belgium.     

Comparing measures of model selection for penalized splines in Cox models

This article presents an application and a simulation study of model fit criteria for selecting the optimal degree of smoothness for penalized splines in Cox models. The criteria considered were the Akaike information criterion, the corrected AIC, two formulations of the Bayesian information criterion, and a generalized cross-validation method. The estimated curves selected by the five methods were compared to each other in a study of rectal cancer mortality in autoworkers. In the stimulation study, we estimated the fit of the penalized spline models in six exposure-response scenarios, using the five model fit criteria. The methods were compared on the basis of a mean squared error score and the power and size of hypothesis tests for any effect and for detecting nonlinearity. All comparisons were made across a range in the total sample size and number of cases.     

Hemodialysis Central Venous Catheter-Related Bacteremia: Time to Onset

Bacteremia (B) is a well-known complication of an indwelling central venous catheter (CVC). Although prophylactic measures such as topical and catheter lock antibiotics have been demonstrated to decrease the risk of B in hemodialysis (HD) in patients with a CVC, there are concerns about the development of resistance to these agents when used for long periods of time.
Objective:  We wondered if we could limit the use of these agents by identifying the period when B was most common after CVC placement.
Method: We prospectively noted all patients with a CVC who developed B in any of our 3 units in CT, U.S.A.; 62 episodes of B occurred between 1/1/03 and 9/18/03. 35% of all of the HD patients had a CVC for access during the study period.
Results: Staphylococcus aureus accounted for 22 (35.5%) episodes; Gram-negative organisms for 21 (33.8%) and other staphylococcal species for 14 (22.6%). The other 3 episodes were other Gram-positive organisms and 6 patients developed B with more than 1 organism. 3 (4.8%) patients expired while being treated for the B. The average time to onset of B was 96 ± 98 CVC days with a range of 1–365 days. There was no difference in time to onset based on organism. 43.5% of the episodes of B occurred less than 60 days after the CVC was inserted, but 27.4% occurred greater than 100 days after CVC insertion.
Conclusion:  The time to onset of CVC-related B was variable among the patients developing B in this study. Preventative strategies aimed at reducing the risk of B in patients with a CVC must be used for the life of the CVC.     

Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort

We measured levels of 10 polybrominated diphenyl ether (PBDE) congeners in serum collected during pregnancy and at delivery from 416 pregnant, predominantly immigrant, women living in Monterey County, CA. The most frequently detected congeners were BDE-47, -99, -100, and -153, all components of the penta mixture, detected in >97% of samples. We used multivariable regression models to examine factors associated with exposure to individual PBDE congeners as well as their total summed concentration (ng/g lipid). Prenatal and delivery total PBDE levels were correlated between sampling times (n = 21; Pearson r = 0.99, p < 0.001). In multivariable models, total PBDE levels increased significantly with time residing in the U.S. (p < 0.001) and among women with ≥3 pieces of stuffed furniture in their homes (p < 0.05). Women's total PBDE levels increased 4.0% (95% CI = 2.8, 5.3) for each additional year residing in the U.S., after adjustment for prepregnancy BMI, weight gain during pregnancy, and SES. Having ≥3 pieces of stuffed furniture in the home was associated with a 26.8% (95% CI = 2.0, 57.5) increase in women's serum PBDE levels. Findings suggest PBDE indoor contamination in California homes is contributing to human exposures in a population of recent immigrants.     

Upward-looking ground-penetrating radar for monitoring snowpack stratigraphy

Operational remote monitoring of snowpack stratigraphy, melt water intrusions and their evolution with time for forecasting snowpack stability is not possible to date. Determination of the spatial variability of snowpack conditions on various scales requires a number of point measurements with various methods. These methods are either destructive or do not provide information about the internal structure of the snowpack. The application of a remotely controlled non-destructive sensor system would help to gain a higher spatio-temporal resolution about information of the snowpack. In this study we present results from upward-looking ground-penetrating radar (GPR) surveys from horizontal caves dug in the front wall of snow pits at the bottom of the snowpack. GPR data are compared with vertical profiles of snow hardness and density, obtained in the snow pit. Data were acquired in different areas with varying snow conditions with various GPR impulse systems, frequencies and polarizations. Radar experiments with high frequencies (> 1 GHz) detect internal layers in the snowpack in dry snow, but fail to provide clear reflections at the upper snow-air transition because of attenuation. In wet snow, the radar signals < 1 GHz are capable to penetrate a meter-thick snowpack and detect the snow surface, although the signal is strongly attenuated. Analysis of reflection phases and magnitudes allows interpretation of their physical origin in terms of changes in electrical permittivity. Varying antenna polarization causes a strongly different signal response, likely caused by the snow-pit wall present in our set-up. Forward calculation of density-based reflection coefficients between neighboring layers of varying hardness yields ambiguous results in terms of correspondence with observed radar reflections apart except for interferences of neighboring reflections. Moreover, we identify several pitfalls for future applications. The system set-up used here represents a basis for further developments towards a system, which is capable of improving information on the spatial and temporal snowpack characteristics.     

The clinical characteristics of intraoral herpes simplex virus infection in 52 immunocompetent patients

OBJECTIVES: To determine if nonsteroidal anti-inflammatory drugs provide adequate pain control for patients having laparoscopic hernia repair and to compare the effectiveness of ketorolac tromethamine with ibuprofen in reducing postoperative laparoscopic hernia pain. DESIGN AND SETTING: Prospective double-blind randomized study at a 100-bed community hospital. PATIENTS: Seventy patients ranging in age from 16 to 83 years scheduled for elective laparoscopic inguinal hernia repair. INTERVENTIONS: Patients undergoing laparoscopic hernia repair were enrolled in a double-blind randomized study to compare the 2 treatments. Group 1 received a placebo capsule 1 hour before surgery and ketorolac tromethamine, 60 mg intravenously, at the time of trocar insertion. Group 2 received ibuprofen, 800 mg an hour before surgery, and isotonic sodium chloride solution, 2 mL intravenously, at the time of trocar insertion. In addition, all patients received local infiltration of 30 mL of bupivacaine hydrochloride into their trocar sites. All patients were discharged within 5 hours of the operation and were instructed to take 400 mg of ibuprofen orally every 4 hours for 24 hours whether or not they were experiencing pain. A 24-hour supply of ibuprofen was provided to all study patients. Pain was assessed using the Visual Analog Pain Scale with a maximum pain rating of 100. Assessments were done at the time of and 18 hours after discharge. MAIN OUTCOME MEASURE: Postoperative pain 18 and 24 hours after discharge was assessed using a standardized questionnaire in a telephone interview by a registered nurse from the Outpatient Surgical Unit. RESULTS: There was no significant difference in the level of pain experienced by 35 patients who received ketorolac intravenously and 35 who received ibuprofen orally. There was no significant difference between the 2 treatment groups in the amount of pain experienced at discharge and 18 hours after discharge. CONCLUSIONS: Pain relief from ibuprofen, 800 mg, administered orally an hour before laparoscopic hernia repair was not statistically different from that obtained with intravenous ketorolac, 60 mg, administered intraoperatively when comparing the hospital discharge pain score and the mean and highest pain scores 18 hours after discharge. Ibuprofen offers equivalent pain control at a lower cost and reduced potential for adverse drug events compared with intravenous ketorolac in patients having laparoscopic hernia repair. No patient required narcotic supplementation, and pain control was judged satisfactory by all the patients.     

Amyotrophic lateral sclerosis

The final cascade of amyotrophic lateral sclerosis (ALS) coincides with the onset of clinical neurological deficits and involves multifactorial interactive mechanisms. These terminal events include excitotoxicity, free radical accumulation and possibly immunological disturbances. They are probably predated by months or years by thus far unidentified triggers. Selective vulnerability of the corticomotneuronal system in ALS is likely due to degradation of several gene products essential to transmitter, receptor and nerve growth factor maintenance specific to this functional system. Therapeutic strategies involve neuroprotection, symptomatic and combination neuronal therapy targeted to the final cascade of ALS.     

Computer simulation of consumable melted slabs

A mathematical model has been developed to simulate two-dimensional heat flow for a slab ingot produced as a remelted product. Various heat flow parameters have been studied to determine the influence of changes in them on local solidification time. The parameters which show the greatest influence are the heat transfer coefficient and the thickness of the slab. The rate of addition of material changes the depth of the molten pool, but does not affect local solidification time.     

Oxidation behavior of a fine-grained rapidly solidified 18-8 stainless steel

The cyclic oxidation behavior of a fine-grained, rapidly solidified 303 stainless steel was determined at 900 °C in pure oxygen. The rapidly solidified alloy exhibited superior resistance to oxidation compared with that of a wrought 304 stainless steel; its oxidation resistance was as good as that of a wrought 310 stainless steel, even though the latter alloy contained more Cr and Ni. The matrix of the rapidly solidified steel contained a uniform dispersion of fine MnS precipitates (0.2 to 0.5 μm), which were effective in inhibiting grain growth at elevated temperatures. The enhanced resistance to oxidation of the rapidly solidified alloy is attributed to two factors: (1) the formation and growth of protective Cr₂O₃ and SiO₂ scales were promoted by the fine alloy grain size (5 to 8 =gmm) and by the presence of the MnS dispersion, and (2) the adherence of the scale was increased by the formation of intrusions of SiO₂ from the external scale into the alloy, which formed around MnS precipitates and along closely-spaced alloy grain boundaries, and which acted to key the scale mechanically to the alloy.