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Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages.

The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened. The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested, the drug showed significant bactericidal activity (at least 99% killing or more of the initial inoculum added) at concentrations well within the reported peak concentrations in serum (Cmax) in humans. MICs of sparfloxacin for 7 of 10 Mycobacterium avium complex strains were below the Cmax, with MBC/MIC ratios within the range of 2 to 4. Enhancement of its activity by ethambutol, rifampin, amikacin, and clarithromycin (which were used at sublethal concentrations) assessed by using BACTEC radiometry revealed that its activity was further enhanced in 2 of 10 strains by rifampin and in 7 of 10 strains by ethambutol. The bactericidal effects of various drugs used alone as well as two-drug combinations used at Cmax levels were also screened against four strains of M. avium complex growing intracellularly in two different macrophage systems, namely, mouse bone marrow-derived macrophages and peripheral blood monocyte-derived human macrophages. Our results showed a satisfactory correlation between the extracellular and intracellular drug activity data.

Animals↗

Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex.

Mycobacterium avium complex bacteria are opportunistic human pathogens, and their chemotherapy remains a challenge since these organisms are resistant to a majority of routine antituberculous drugs. Recently, a wide range of new macrolide antibiotics has been developed, among which the drug clarithromycin appears to have a selective action against M. avium bacteria. In the present study, we have investigated the action of clarithromycin alone (MIC and MBC determinations) and in association with the routine antimycobacterial drugs ethambutol and rifampin at sublethal concentrations (1 micrograms/ml; below concentrations obtainable in human serum) against M. avium. Our viable count data showed that clarithromycin was bactericidal against all 10 strains of M. avium studied and that its activity was enhanced by ethambutol (in 8 of 9 strains) and rifampin (in 3 of 9 strains). The use of all three drugs in association resulted in higher bactericidal effects than found with any of the drugs used alone or in two-drug combinations in seven of nine strains. The bactericidal effects of various drugs used alone and in combination at concentrations obtainable in human serum were investigated against the type strain ATCC 15769 by using 7H9 broth and BACTEC radiometry (extracellular action) and a J-774 macrophage cell line (intracellular action). A good agreement between the extracellular and intracellular activities was found. Electron microscopy using a ruthenium red cytochemical staining of the bacteria showed that clarithromycin disorganized the outer wall layer and the cytoplasmic membrane in the mycobacterial cell envelope and resulted in formation of large vacuoles inside the cytoplasm, with solubilization of ribosomal structures and consequent plasmolysis. Its association with ethambutol and rifampin resulted in more drastic alterations in the bacterial morphology than were seen with any of the drugs used alone, leading to the removal of the bacterial outer layer, homogenization of cytoplasm, complete cell lysis, and formation of ghosts.

Cell Division↗

Treatment of vasospastic disease with prostaglandin E1.

Prostaglandin E1, a vasodilator and potent inhibitor of platelet aggregation, was administered to 26 patients with severe vasospastic disease of the hands. Patients tolerated infusions well and reported appreciable symptomatic improvement. Five of eight ischaemic ulcers healed in six weeks. Non-invasive studies of blood flow were used to observe haemodynamic changes during and after infusions. The Doppler-derived radial artery pulsatility index fell from 8.8 +/- 0.6 to 4.6 +/0 0.5 (mean +/- SEM), indicating hand vasodilatation. This fall was maintained 24 hours after infusion (5.9 +/- 0.9), but the index had returned to normal values at two weeks. The amplitude of finger pulse volume recordings increased (5.6 +/- 0.7 mm to 23.8 +/- 3.4 mm) and was raised two and six weeks after infusion (13.5 +/- 2.1 mm). Hand temperature measured by infrared radiometry also increased (27.4 +/- 0.7 degrees C to 31.2 +/- 1.2 degrees C). Intensity of digital vasospasm induced by cold water challenge was not objectively affected by prostaglandin E1 despite an increased finger temperature after infusion. Nevertheless, patients reported less frequent and severe attacks. Prostaglandin E1 given by central venous infusion is a safe new vasoactive agent that can produce appreciable symptomatic improvement by increasing digital perfusion, which may last for several weeks after treatment. Further study will define its mode of action and its place in the management of peripheral vascular disease.

Adult↗

Graded doses of recombinant interleukin-1beta induce generalized osteopenia in rats without altering skeletal growth and joint integrity.

BACKGROUND: Whereas a primary role of interleukin-1beta (IL-1beta) in local bone remodelling and articular inflammation has been well established, the effect of prolonged systemic administration of this cytokine on total skeletal Ca, somatic growth and joint tissue has not yet been investigated. METHODS: Five groups of 14 rats each, aged 7-8 weeks, had miniosmotic pumps (Alzet 200 microl) implanted and primed to release 100, 200, 500, 1,000 and 2,000 ng/kg/24 h of human recombinant IL-1beta (rIL-1beta) daily for 14 days. On days 0 and 14 total skeletal mineral content (BMC) was assessed by means of X-ray absorptiometry and vertebral and tibial growth was measured by computer-assisted radiometry. On the same days, blood was drawn and analyzed for rat growth hormone (rGH), insulin-like growth factor (IGF-1), and osteocalcin. Also 24-hour urine was collected for d-pyridinoline (dpd) determinations. Hind- and forepaw diameter as a parameter of joint inflammation was assessed using a micrometric calliper. Subsequently the animals were sacrificed and one tibia dissected for measurement of trabecular volume by computerized histomorphometry. RESULTS: BMC decreased in a dose-dependent manner reaching significance at 1,000 and 2,000 ng/kg (p < 0.03 and 0.04) in close correlation with tibial trabecular volumes (r = 0.84; p < 0.02). Normal vertebral and tibial growth was recorded at all dosages. There was no evidence of joint involvement. Blood rGH and IGF-1 remained normal as did osteocalcin, the latter reflecting lack of osteoblast activation. In contrast dpd increased in a dose-dependent manner indicating enhanced bone matrix turnover. CONCLUSION: It is concluded that graded infusions of supraphysiological doses of rIL-1beta capable of inducing osteopenia did not affect skeletal growth in the absence of articular reaction. This is in contrast with the experience recorded in experimental arthritis in which growth retardation, in addition to osteopenia, may be caused by factors other than circulating IL-1beta.

Animals↗

Objective and subjective assessments of temperature differences between the hands in reflex sympathetic dystrophy.

OBJECTIVE: A difference in temperature between the affected and normal extremity is one of the signs or symptoms of reflex sympathetic dystrophy (RSD). These temperature differences are scored anamnestically, by palpation, or by measurements. We investigated the relationship between objective and subjective differences in skin temperature between the hands. SUBJECTS AND DESIGN: Fifty-one patients with RSD of one upper extremity participated (mean age 55 years, range 18-80). In the first 16 we investigated the reliability of the visual analogue scale (VAS) for recording perceived differences in skin temperature. In the remaining 35 patients the relationship between the VAS and objective infrared radiometry of the hands was investigated. SETTING: Outpatients clinics of two university hospitals. RESULTS: The VAS was found to be reliable in terms of response stability. There was no significant correlation between the objective and subjective outcomes. CONCLUSIONS: There is lack of correspondence between objective and subjective temperature measurements, which may be due to a normal discrepancy between objective and perceived temperature, and/or to alterations in perception due to RSD.

Adolescent↗

Adhesion of Phytophthora palmivora zoospores: detection and ultrastructural visualization of concanavalin A-receptor sites appearing during encystment.

The binding of concanavalin A (Con A) to the cell surface of zoospores and cysts of Phytophthora palmivora was studied by radiometry (125I-Con A), ultraviolet microscopy (fluorescein-Con A) and electron microscopy peroxidase-diaminobenzidine technique). Zoospores were found to secrete during the early stages of encystment a Con A-binding material susceptible to trypsin digestion. This glycoprotein is contained in the so-called peripheral vesicles and is probably responsible for the adhesion of the encysting zoospores to solid surfaces.

Binding Sites↗

Metrology of pulsed radiation for 157-nm lithography.

In the framework of current development in 157-nm lithography we have investigated the performance of photodetectors with emphasis to their stability and linearity. The measurements were performed in the radiometry laboratories of the Physikalisch-Technische Bundesanstalt at the Berlin electron-storage rings BESSY I and BESSY II with spectrally dispersed synchrotron radiation as well as with highly pulsed F2 laser radiation at 157 nm in combination with a cryogenic radiometer as the primary detector standard. Relative standard uncertainties of as little as 1% were achieved for the calibration of photodetectors in the spectral range of ultraviolet and vacuum-ultraviolet radiation.

Journal Article↗

Dynamic spectroscopic measurements of the temperature and pressure cycles in a MOPITT pressure modulator cell.

The temperature and pressure cycles inside a pressure modulator cell (PMC) of the type used for gas-correlation radiometry aboard the Measurements of Pollution in the Troposphere (MOPITT) satellite instrument have been determined from dynamic measurements of the spectral line shapes of the R(0) and R(18) transitions in the fundamental vibrational-rotational band of carbon monoxide. The line strengths and linewidths were used to calculate the temperature and pressure, respectively, with a temporal resolution of approximately 200 micros, or 1/100 of a PMC cycle. The results are compared with a thermodynamic box model.

Journal Article↗

Silver halide photonic crystal fibers for the middle infrared.

Photonic crystal fibers are normally holey silica fibers, which are opaque in the mid- and far-infrared. We have fabricated novel fibers by multiple extrusions of silver halide crystalline materials, which are highly transparent in the mid-infrared. These fibers are composed of two solid materials; The core consists of pure AgBr, and the cladding includes AgCl fiberoptic elements arranged in two concentric hexagonal rings around the core. Flexible fibers of outer diameter 1 mm and length of approximately 1 m were fabricated, and their optical properties were measured. These fibers exhibited core-clad behavior and would be extremely useful for IR laser power transmission, IR radiometry, and IR spectroscopy.

Journal Article↗

Carbon monoxide total column retrievals by use of the measurements of pollution in the troposphere airborne test radiometer.

The Measurements of Pollution in the Troposphere (MOPITT) Airborne Test Radiometer (MATR) uses gas correlation filter radiometry from high-altitude aircraft to measure tropospheric carbon monoxide. This radiometer is used in support of the ongoing validation campaign for the MOPITT instrument aboard the Earth Observation System Terra satellite. A recent study of MATR CO retrievals that used data from the autumn of 2001 in the western United States is presented. Retrievals of the CO total column were performed and compared to in situ sampling with less than 10% retrieval error. Effects that influence retrieval, such as instrument sensitivity, retrieval sensitivity, and the bias between observations and the radiative transfer model, are discussed. Comparisons of MATR and MOPITT retrievals show promising consistency. A preliminary interpretation of MATR results is also presented.

Journal Article↗

Passive standoff detection of chemical warfare agents on surfaces.

Results are presented on the passive standoff detection and identification of chemical warfare (CW) liquid agents on surfaces by the Fourier-transform IR radiometry. This study was performed during surface contamination trials at Defence Research and Development Canada-Suffield in September 2002. The goal was to verify that passive long-wave IR spectrometric sensors can potentially remotely detect surfaces contaminated with CW agents. The passive sensor, the Compact Atmospheric Sounding Interferometer, was used in the trial to obtain laboratory and field measurements of CW liquid agents, HD and VX. The agents were applied to high-reflectivity surfaces of aluminum, low-reflectivity surfaces of Mylar, and several other materials including an armored personnel carrier. The field measurements were obtained at a standoff distance of 60 m from the target surfaces. Results indicate that liquid contaminant agents deposited on high-reflectivity surfaces can be detected, identified, and possibly quantified with passive sensors. For low-reflectivity surfaces the presence of the contaminants can usually be detected; however, their identification based on simple correlations with the absorption spectrum of the pure contaminant is not possible.

Algorithms↗

Stability of photodiodes under irradiation with a 157-nm pulsed excimer laser.

We have measured the stability of a variety of photodiodes exposed to 157-nm light from a pulsed excimer laser by using a radiometry beamline at the Synchrotron Ultraviolet Radiation Facility at the National Institute of Standards and Technology. The intense, pulsed laser light exposed the photodiodes, whereas the low-intensity, continuously tunable light from the synchrotron source measured changes in the characteristics of the photodiodes, such as in the responsivity and the reflectance from the surface of a photodiode. Photodiodes studied include both silicon pn-junction and Schottky-barrier types. Among these photodiodes, we found that the damage mechanism for photodiodes with SiO2-based passivating layers is mainly the buildup of SiO2-Si interface trap states. The interface trap state buildup is well known for other semiconductor devices and is generally recognized as a product induced by radiation with an energy more than the 9-eV SiO2 bandgap energy rather than the 7.9-eV energy of the 157-nm radiation. Based on the generation of interface trap states, a model is proposed to describe the dependence of detector responsivity on exposure to 157-nm radiation. We also observed slow recovery in some of the damaged photodiodes, confirming that some of the interface trap states are only semipermanent. Radiation damage induced by low-power continuous 157-nm synchrotron light was also studied. As for the other photodiodes with no SiO2 layers, measurement results support the assumption that the changes in responsivity are due mainly to the deposition of thin layers on the tops of the detectors during laser irradiation.

Journal Article↗

Simple spectral stray light correction method for array spectroradiometers.

A simple, practical method has been developed to correct a spectroradiometer's response for measurement errors arising from the instrument's spectral stray light. By characterizing the instrument's response to a set of monochromatic laser sources that cover the instrument's spectral range, one obtains a spectral stray light signal distribution matrix that quantifies the magnitude of the spectral stray light signal within the instrument. By use of these data, a spectral stray light correction matrix is derived and the instrument's response can be corrected with a simple matrix multiplication. The method has been implemented and validated with a commercial CCD-array spectrograph. Spectral stray light errors after the correction was applied were reduced by 1-2 orders of magnitude to a level of approximately 10(-5) for a broadband source measurement, equivalent to less than one count of the 15-bit-resolution instrument. This method is fast enough to be integrated into an instrument's software to perform real-time corrections with minimal effect on acquisition speed. Using instruments that have been corrected for spectral stray light, we expect significant reductions in overall measurement uncertainties in many applications in which spectrometers are commonly used, including radiometry, colorimetry, photometry, and biotechnology.

Journal Article↗

Absolute measurement of F2-laser power at 157 nm.

We report a comparison of laser power measurements at the F2-laser wavelength of 157 nm made at two facilities of the Physikalisch-Technische Bundesanstalt (PTB), the German national metrology institute. At the PTB laboratory at the electron storage ring BESSY II in Berlin, the scale for laser power was directly traced to a cryogenic radiometer operating at 157 nm, whereas at the PTB laser radiometry facility in Braunschweig the calibration of transfer detectors was performed with a newly developed standard for laser power at 157 nm, which is traceable in several steps to a cryogenic radiometer operating at 633 nm. The comparison was performed under vacuum conditions with laser pulse energies of approximately 10 microJ, however with different average powers because different primary standard radiometers were used. The relative deviation for the responsivity of the transfer detector was 4.8% and thus within the combined standard uncertainty.

Journal Article↗

Reconstruction of the net emission distribution from the total radiance distribution on a reflecting surface.

The problem is considered of reconstructing, from a measurement of the total radiance distribution on an emitting surface, the radiance distribution that would be observed in the absence of reflected radiation. An explicit solution of the implied inverse problem is derived for the case in which the reflective properties of the surface are given in terms of a bidirectional reflection distribution function. Also considered are the limiting cases of diffuse and specular reflection. Practical considerations are discussed for application of the theory to the nonintrusive and remote measurement of temperatures and pressures on concave surfaces, either by traditional radiometry or by the use of thermographic phosphors and temperature- and pressure-sensitive paints.

Journal Article↗

Spectral depth profiling of arbitrary surfaces by thermal emission decay-Fourier transform infrared spectroscopy.

We report a new spectroscopic technique that combines step-scanning Fourier transform infrared spectroscopy with opto-thermal transient emission radiometry (OTTER) in order to provide near-surface depth-resolved spectra in the range 700-1800 cm(-1). It works nondestructively, without contact, with samples of arbitrary shape and size, without requiring prior preparation. The depth of surface probed depends on the thermal diffusivity of the sample; for organic materials it is approximately 10 microm. With homogeneous samples, absolute absorption coefficients can be measured. With two-layered samples, the technique proved able to distinguish between the spectral properties of the top layer and the substrate and to estimate the thickness of the top layer. We present a theoretical analysis with the main design features of the instrumentation and software, together with studies of homogeneous and layered samples, to validate the methods and illustrate the potential of the technique for practical applications.

Adhesives↗

Quantum yield of the iodide-iodate chemical actinometer: dependence on wavelength and concentrations.

The quantum yield (QY) of the iodide-iodate chemical actinometer (0.6 M KI-0.1 M KIO3) was determined for irradiation between 214 and 330 nm. The photoproduct, triiodide, was determined from the increase in absorbance at 352 nm, which together with a concomitant measurement of the UV fluence enabled the QY to be calculated. The QY at 254 nm was determined to be 0.73 +/- 0.02 when calibration was carried out against a National Institute of Standards and Technology traceable radiometer or photometric device. At wavelengths below 254 nm the QY increased slightly, leveling off at -0.80 +/- 0.05, whereas above 254 nm the QY decreases linearly with wavelength, reaching a value of 0.30 at 284 nm. In addition, the QY was measured at different iodide concentrations. There is a slight decrease in QY going from 0.6 to 0.15 M KI, whereas below 0.15 M KI the QY drops off sharply, decreasing to 0.23 by 0.006 M KI. Calibration of the QY was also done using potassium ferrioxalate actinometry to measure the irradiance. These results showed a 20% reduction in QY between 240 and 280 nm as compared with radiometry. This discrepancy suggests that the QY of the ferrioxalate actinometer in this region of the spectrum needs reexamination.

Iodates↗

Nuclear scintigraphic assessment of radiation-induced intestinal dysfunction.

Radiation-induced damage to the intestine can be measured by abnormalities in the absorption of various nutrients. Changes in intestinal absorption occur after irradiation because of loss of the intestinal absorptive surface and a consequent decrease in active transport. In our study, the jejunal absorption of (99m)Tc-pertechnetate, an actively transported gamma-ray emitter, was assessed in C3H/Kam mice given total-body irradiation with doses of 4, 6, 8 and 12.5 Gy and correlated with morphological changes in the intestinal epithelium. The absorption of (99m)Tc-pertechnetate from the intestinal lumen into the circulation was studied with a dynamic gamma-ray-scintigraphy assay combined with a multichannel analyzer to record the radiometry data automatically in a time-dependent regimen. The resulting radioactivity-time curves obtained for irradiated animals were compared to those for control animals. A dose-dependent decrease in absorptive function was observed 3.5 days after irradiation. The mean absorption rate was reduced to 78.8 +/- 9.3% of control levels in response to 4 Gy total-body irradiation (mean +/- SEM tracer absorption lifetime was 237 +/- 23 s compared to 187 +/- 12 s in nonirradiated controls) and to 28.3 +/- 3.7% in response to 12.5 Gy (660 +/- 76 s). The decrease in absorption of (99m)Tc-pertechnetate at 3.5 days after irradiation correlated strongly (P < 0.001) with TBI dose, with the number of cells per villus, and with the percentage of cells in the crypt compartment that were apoptotic or mitotic. A jejunal microcolony assay showed no loss of crypts and hence no measured dose-response effects after 4, 6 or 8 Gy TBI. These results show that dynamic enteroscintigraphy with sodium (99m)Tc-pertechnetate is a sensitive functional assay for rapid evaluation of radiation-induced intestinal damage in the clinically relevant dose range and has a cellular basis.

Animals↗