Fair Extent Research Articles

Implementation barriers for general practice guidelines on low back pain a qualitative study.

Qualitative study design, using semi-structured interviews. To explore factors that determine non-adherence to the guidelines for low back pain. Guidelines for low back pain have been published in the past decade in various countries. In the Netherlands, general practitioners adhere to them to a fair extent, and it is unclear whether room for improvement remains. Forty semistructured, in-depth interviews were conducted with twenty patients who consulted for low back pain, and with their general practitioners. The interviews were fully transcribed and analyzed qualitatively. Patients often had limited expectations of the consultation. They wanted to hear a diagnosis or expected to receive simple advice. The general practitioners said they were well informed about the guideline and mostly agreed with its content. Reasons for non-adherence were mainly related to patients' experiences in the past and general practitioners' interpretations of their preferences. General practitioners stated that they were inclined to give in to patients' demands, for example the request for radiographic films or a referral to a physical therapist. In general, patients and their general practitioners were satisfied with the chosen management. Improvement of the quality of back pain care may still be possible. Implementation strategies should aim at training physicians in communication skills, especially about subjects for debate, where patients' beliefs and experiences color their expectations.

Pharmacokinetics of prolonged-release CPT-11-loaded microspheres in rats

CPT-11-containing microspheres composed of poly- d,l-lactic acid or poly ( d,l-lactic acid-co-glycolic acid) copolymers were prepared by an oil-in-water evaporation method. The size and shape of the microspheres were examined, and the drug release rates were analyzed from the in vitro release profiles. CPT-11 aqueous solution was intravenously or intraperitoneally injected at 10 mg/kg, and microspheres were intraperitoneally administered at 50 mg eq CPT-11/kg in rats. The microspheres had an average diameter of around 10 μm and their shape was spherical. All the microspheres contained CPT-11 in a lactone form, and their drug contents and release profiles were basically similar to those of previous microspheres. After i.v. injection of CPT-11 solution, the CPT-11 plasma concentration decreased quickly, SN-38 decreased slowly at a much lower level, and SN-38 glucuronide (SN-38G) declined very slowly at a higher level than SN-38. The plasma concentration of CPT-11 reached a maximum at 30 min after i.p. administration of CPT-11 solution. The area under the plasma concentration–time curve (AUC) of CPT-11 after i.p. administration was somewhat lower compared with that after i.v. administration, but the plasma concentration–time profiles of SN-38 and SN-38G were nearly identical between i.v. and i.p. administration. An i.p. administration of the microspheres resulted in gradually increasing or almost constant CPT-11 levels. The levels of SN-38 were also stable during the observation period (4 days) except for the slowest releasing microsphere in which SN-38 was not detected after 24 h following administration. Intraperitoneal administration of any of the microspheres resulted in stable and similar levels of SN-38G after 24 h following administration. When judging from apparent simple pharmacokinetic analysis, an inconsistency was found between the in vitro drug release and the plasma level to a fair extent, but overall the in vivo drug release rate from microspheres was considered parallel to the in vitro one. The microspheres showing a faster release of CPT-11 exhibited higher plasma levels of CPT-11 and SN-38, explaining the previous results that efficacy was better when the in vitro release rate was higher. That the SN-38 level could be attained to a certain extent even at the range of modest or low plasma concentration of CPT-11 in each administration may be related to the non-linear metabolic conversion from CPT-11 to SN-38.

Martensitic transformation in nanometer-sized particles of Fe–Ni alloys

Abstract We studied the martensitic transformation in nanometer(nm)-sized particles of Fe–Ni alloys with the composition range from 15 to 30 at.% Ni by means of transmission electron microscopy and electron diffraction. Here are reported results obtained mainly for nm-sized particles of an Fe-25.0 at.% Ni alloy. The forward transformation temperatures were depressed to a fair extent, compared to those in bulk, while the reverse transformation temperatures were less affected by size. It appeared that both the austenite and martensite particles were faceted by certain crystallographic planes. The temperature parameter in the Debye–Waller factor measured for the austenite particles was found to be about one order larger than those for Fe and Ni in bulk. These results suggested that the observed size-dependence of transformation temperatures is accounted for in terms of the surface free energy difference between the fcc and bcc nm-sized particles.

Topological analysis of the MraY protein catalysing the first membrane step of peptidoglycan synthesis.

The two-dimensional membrane topology of the Escherichia coli and Staphylococcus aureus MraY transferases, which catalyse the formation of the first lipid intermediate of peptidoglycan synthesis, was established using the beta-lactamase fusion system. All 28 constructed mraY-blaM fusions produced hybrid proteins. Analysis of the ampicillin resistance of the strains with hybrids led to a common topological model possessing 10 transmembrane segments, five cytoplasmic domains and six periplasmic domains including the N- and C-terminal ends. The agreement between the topologies of E. coli and S. aureus, their agreement to a fair extent with predicted models and a number of features arising from the comparative analysis of 25 orthologue sequences strongly suggested the validity of the model for all eubacterial MraYs. The primary structure of the 10 transmembrane segments diverged among orthologues, but they retained their hydrophobicity, number and size. The similarity of the sequences and distribution of the five cytoplasmic domains in both models, as well as their conservation among the MraY orthologues, clearly suggested their possible involvement in substrate recognition and in the catalytic process. Complementation tests showed that only fusions with untruncated mraY restored growth. It was noteworthy that S. aureus MraY was functional in E. coli. An increased MraY transferase activity was observed only with the untruncated hybrids from both organisms.

In vivo properties of the conjugates of mitomycin C with estradiol benzoate and estradiol: pharmacokinetics and antitumor characteristics against P388 leukemia and sarcoma 180.

Conjugates of mitomycin C (MMC) with estradiol benzoate and estradiol via glutaric acid, abbreviated to EB-glu-MMC and E-glu-MMC, respectively, as previously reported, were examined concerning their pharmacokinetic behaviors and antitumor effects against two kinds of general and popular tumors, P388 leukemia and Sarcoma 180. EB-glu-MMC and E-glu-MMC were dissolved in propylene glycol. Their solution was administered intraperitoneally to rats and mice in order to examine their plasma concentration-time profiles and antitumor characteristics, respectively. After the administration of EB-glu-MMC, EB-glu-MMC was detected slightly in blood only in the initial stage, while E-glu-MMC and MMC were observed there for a prolonged period. In the administration of E-glu-MMC, a similar phenomenon was observed but the drug retention effect seemed lower than that in EB-glu-MMC. In the antitumor test against P388 leukemia, E-glu-MMC exhibited a better effect than EB-glu-MMC; however, neither conjugate surpassed the effect of MMC. The toxic side effect was improved in each conjugate. As to the growth inhibition against Sarcoma 180, EB-glu-MMC and E-glu-MMC produced good effect and improved the toxic side effect. Especially, in the administration of EB-glu-MMC at the dose of 30 mg eq MMC/kg, a decrease in tumor volume was observed in the latter stage. EB-glu-MMC and E-glu-MMC were demonstrated to produce prolonged retention, to enter the systemic circulation to a fair extent, and to exhibit a good effect against the general solid tumor, Sarcoma 180, in vivo.

Effect of recombinant human gamma interferon on intracellular activities of antibiotics against Listeria monocytogenes in the human macrophage cell line THP-1.

Listeria monocytogenes is a facultative intracellular pathogen which enters cells by endocytosis and reaches phagolysosomes from where it escapes and multiplies in the cytosol of untreated cells. Exposure of macrophages to gamma interferon (IFN-gamma) restricts L. monocytogenes to phagosomes and prevents its intracellular multiplication. We have tested whether IFN-gamma also modulates the susceptibility of L. monocytogenes to antibiotics. We selected drugs from three different classes displaying marked properties concerning their cellular accumulation and subcellular distribution, namely, ampicillin (not accumulated by cells but present in cytosol), azithromycin (largely accumulated by cells but mostly restricted to lysosomes), and sparfloxacin (accumulated to a fair extent but detected only in cytosol). We used a continuous line of myelomonocytic cells (THP-1 macrophages), which display specific surface receptors for IFN-gamma, and examined the activity of these antibiotics against L. monocytogenes Hly+ (virulent variant) and L. monocytogenes Hly- (a nonvirulent variant defective in hemolysin production). Untreated THP-1 and phorbol myristate acetate-differentiated THP-1 were permissive for infection and multiplication of intracellular L. monocytogenes Hly+ (virulent variant). All three antibiotics tested were bactericidal against this Listeria strain when added to an extracellular concentration of 10x their MIC. After preexposure of THP-1 to IFN-gamma, L. monocytogenes Hly+ was still phagocytosed but no longer grew intracellularly. The activity of ampicillin became almost undetectable (antagonistic effect), and that of azithromycin was unchanged (additive effect with that of IFN-gamma), whereas that of sparfloxacin was markedly enhanced (synergy). A similar behavior (lack of bacterial growth, associated with a loss of activity of ampicillin, an enhanced activity of sparfloxacin, and unchanged activity of azithromycin) was observed in cells infected with L. monocytogenes Hly-. This modulation of antibiotic activity, which we ascribe to the change of subcellular localization of L. monocytogenes caused by IFN-gamma or by the lack of virulence factor, could result from a change in bacterial responsiveness to antibiotics, a modification of the drug activity, or differences in drug bioavailabilities between cytosol and phagosomes.

Estimating the geographic diffusion of the videocassette recorder market

The majority of studies concerning diffusion or product growth of consumer durables have treated the U.S. market as a whole and have applied the diffusion model on the assumption that the market exhibits a homogeneous response in its diffusion process. If the market is heterogeneous, however, an aggregate model entails a misspecification problem which could adversely affect the applicability and efficiency of the model. A modeling framework is developed for analyzing the diffusion process in a possibly heterogeneous market. Empirical analysis using data on the videocassette recorder (VCR) market reveals that the modeling framework captures to a fair extent heterogeneous diffusion processes across different regions in the U.S. market. Managerial implications are derived and discussed.

Monoclonal antibody uptake in B-cell lymphomas: experimental studies in nude mouse xenografts.

Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values.

Preequilibrium versus thermalized light-charged particle emissions in the40Ar (1100MeV)+24Mg reaction. Dynamical calculations

In an attempt to separate preequilibrium and thermalised emissions of light particles in low impact parameter heavy-ion collisions, the40Ar+24Mg reaction has been studied at 27.5 MeV/nucleon. Exclusive measurements have permitted us to examine, in some detail, heavy fragments and charged particles (p, d, t,α-particle). The fragments recognized as evaporation residues have been selected and, due to inverse kinematic conditions, the related preequilibrium and statistical emissions of light particles resulting from incomplete fusion reaction appear to be distinguishable to a fair extent. This separation is fully supported by Monte Carlo calculations. Some experimental characteristics of the light particles have been examined and compared to the predictions of dynamical calculations. These calculations, associating a preequilibrium (interpreted as prompt emitted particles) model with a statistical-decay model, follow the evolution of the collision from the point of contact between the projectile and the target to the final evaporation-residue formation on an event by event basis. The predictions of these calculations have been compared to experimental data and satisfactory agreement is achieved for fragment-mass distribution, proton-energy spectra, and proton-angular distribution.

Large‐scale three‐dimensional even‐degree structure of the Earth from splitting of long‐period normal modes

Spectra of the Earth's free oscillations, which depart significantly from those predicted for spherically symmetric Earth models, contain important information on the large‐scale aspherical structure of the Earth. In this paper we present theory, techniques, and numerical results for retrieval of Earth models (including mantle heterogeneity, topography of the core‐mantle boundary (CMB), and inner core anisotropy), using such data. The inversions for Earth models in this study are based upon spectral splitting of 33 isolated multiplets, observed in long‐period accelerograms of 10 large events recorded by the International Deployment of Accelerometers network. Approximately 1000 spectra are involved. Although the data set is insufficient to yield independent results for perturbations in P velocity, S velocity, and density, it is demonstrated that it is possible to obtain large‐scale (spherical harmonic degrees s = 0, 2, 4) models of mantle heterogeneity from such a data set under the constraint that aspherical perturbations in seismic velocities and density are proportional to one another. The mantle models developed from modal data are remarkably similar to preexisting models based upon other kinds of seismic data, demonstrating that heterogeneity in seismic velocities is, at most, weakly dependent on frequency. The pattern of the inferred CMB topography is consistent with geodynamic predictions and agrees to a fair extent with results based on travel time anomalies of PcP and PKP, indicating that modal data can add independent constraints on CMB topography. The anomalous splitting of core modes is attributed to inner core anisotropy which is assumed to possess cylindrical symmetry about the Earth's rotation axis. We consider a relatively simple model which varies smoothly with radius (only with radially constant terms and terms varying with r2). Theoretically, 14 parameters are required to describe such an anisotropic tensor field if it is restricted to spherical harmonic degrees 2 and 4 and if analyticity of the field is required. The inversion for such an anisotropic inner core yields a model which can explain the splitting of anomalously split modes, without violating the constraints imposed by PKIKP travel time information. We solve the inverse problem by following two approaches: (1) using splitting function coefficients as data, we derive Earth models by solving linear inverse problems for each spherical harmonic degree and order; and (2) we directly solve the nonlinear inverse problem in which the data are observed modal spectra and the unknowns are the structural parameters. The second procedure has advantages in the case that there are insufficient data to obtain stable results for the splitting functions of some modes. The mantle models generated in these two ways are essentially identical, verifying that splitting functions can serve as a very convenient intermediate stage in modeling Earth structure using the split spectra of free oscillations.

A scheme for real-time channel establishment in wide-area networks

Multimedia communication involving digital audio and/or digital video has rather strict delay requirements. A real-time channel is defined as a simplex connection between a source and a destination characterized by parameters representing the performance requirements of the client. A study is made of the feasibility of providing real-time services on a packet-switched store-and-forward wide-area network with general topology. A description is given of a scheme for the establishment of channels with deterministic or statistical delay bounds, and the results of the simulation experiments run to evaluate it are presented. The results are judged encouraging: the approach satisfies the guarantees even in worst case situations, uses the network's resources to a fair extent, and efficiently handles channels with a variety of offered load and burstiness characteristics. Also, the packet transmission overhead is quite low, and the channel establishment overhead is small enough to be acceptable in most practical cases. >

The performance of double or mixed pollinations with compatible and self-incompatible or incongruous pollen of pear and apple

Six pear and five apple trials were carried out to ascertain the outcome of combinations of compatible pollen (C) with self (S) or incongruous pollen (I) as to the pollination index (PI=seeds/pollinated flower). The PI of the mixture C+I (1:5) was consistently depressed as compared to that of the control C. The results of the double pollinations S/C and I/C were affected by the temperature at pollination; their PI's at 15°C, being well above and below the PI of C in the former and latter case respectively. The opposite was true for the C/S combination, the PI of which increased with the pollination temperature; the PI of C/I did not differ much from the PI of C, irrespective of temperature. The conclusion was reached that the interaction previously and presently found between compatible and self-incompatible pollen also exists to a fair extent between compatible and incongruous pollen. However, in pear neither the mentor nor the pioneer pollen technique proved to aid its hybridization with apple, the formation of self seed was not observed either. In apple the production of apple × pear hybrids was likewise doubtful, but the double pollinations S/C and C/S formed 4–10% self seed.

The effect of pH and lysosomal extract on rat liver metallothionein (Cd-thionein)

Was studied in vitro. The(109)Cd-labeled protein was isolated by gel filtration and incubated with a lysosomal extract from the same source. No degradation was seen when the pH of the incubation medium was 5 or higher, whereas the degradation of Cd-thionein was completed in 2 h at a pH of 4.5. Dissociation of Cd(2+) from thionein, which takes place to a fair extent at a pH below 5, appears necessary before the enzymatic breakdown of the thionein moiety can take place.

The Magnetic Circular Dichroism of the Conjugated O- and S-Heterocycles

Abstract The MCD spectra of the monobenzo and dibenzo derivatives of thiophene and furan are reported; especially in dibenzofuran, two electronic origins are revealed in its lowest energy absorption band. The quantum-mechanical calculations of the transition energies and the Faraday parameters elucidate the experimental data to a fair extent, suggesting similarities in the electronic structures of the lower-lying excited states of furan and thiophen derivatives.

Tremor in the monkey with a cerebellar lesion

Signs of cerebellar disorder, especially tremor, were observed in monkeys after partial cerebellectomy, and the cerebellar lesion was histologically examined after autopsy. The tremor during motion and/or posture appeared in the monkeys whose lateral and interpositus cerebellar nuclei were concomitantly damaged to a fair extent. Lesion of only the lateral nucleus barely resulted in tremor. Systemic application of ketamine, megimide, or harmaline increased muscular tonus in normal monkeys, and induced spontaneous tremor in monkeys with concomitant lesions of the lateral and interpositus cerebellar nuclei. We suggest that tremor is elicitable in the cerebellectomized monkey during muscular contraction due to voluntary movements as well as during the muscular hypertonus produced by the drugs.

Contributions to ecological chemistry CXL: Isolation and identification of a metabolite of pentachlorophenol- 14C in rice plants

Pentachlorophenol (PCP) is a fungicide used in wood protection and a herbicide used against weeds in various crops 2–4, especially in rice. Up to 1971, it contributed more than 50% to the herbicides used in Japan. However, because it has a high fish- and shellfish-toxicity, its application to paddy fields has been restricted since 1971. Today, PCP is still in use to a fair extent in paddy fields and upland crops either as a single herbicide or in combination with others 4. Numerous publications are concerned with its abiotic decomposition 5–8 including photomineralization 9 and microbial degradation 4,10–16 leading to the formation of carbon dioxide 17–18. Furthermore, studies with bacteria using PCP as a sole carbon source have been done 13,19. At least ten metabolites have been isolated from soil and identified 4,10–11,14, 20–21, the main metabolic steps being methylation of the hydroxyl group, dechlorination resulting in tetrachloro- and trichlorophenols, and hydroxylation to chlorinated hydroquinones or catechols. According to our knowledge, no reports are available on identification of metabolites in the protected organisms, the higher plants. In one study it has been suggested that cotton plants accumulate and metabolize PCP, but no metabolites were reported 22. This first paper on our respective experiments deals with the isolation and identification of a metabolite found in rice plants.

ChemInform Abstract: ANOMERIC EFFECT IN SULFUR HETEROCYCLES CARRYING SULFUR SUBSTITUENTS

AbstractEs werden mit 1H‐NMR‐spektroskopischen Methoden die Konformation von 1,3,5‐ Trithianen wie z.B. 2‐Phenylthio‐ und 2,4‐Bis(phenylthio)‐l ,3,5‐trithian sowie im letzteren Falle auch das cis‐trans‐Gleichgewicht untersucht.

Incubation study of effect of pH on nitrogen mineralisation and nitrification in soils treated with 1000 ppm lead and zinc, as oxides

The effects were studied of adding 1000 ppm Pb and Zn, as oxides, to a sandy soil before adjustment to three pH levels on nitrogen mineralisation and nitrification during subsequent aerobic incubation for 6 weeks at 30°C. At pH 6·0 neither element had any significant effect on either process. At pH 7·0 nitrification was decreased slightly by Pb and Zn, whilst nitrogen mineralisation was decreased slightly only by Zn. At pH 7·7 (soil containing 2% CaCO 3) both processes were decreased slightly by Pb and to a fair extent by Zn. Results are discussed in relation to Morgan- and EDTA-extractable levels of Pb and Zn.

Anomeric Effect in Sulfur Heterocycles Carrying Sulfur Substituents

Abstract Conformational analysis of 1,3,5-trithiane derivatives with sulfur-substituents was carried out with the aid of PMR spectra at various temperatures. 2-Phenylthio-1,3,5-trithiane exhibited the strong anomeric effect whereas 2-phenylthiothiane the moderate. This enhanced anomeric effect in trithiane derivatives was attributed to both the stabilization of the axial form and the destabilization of the equatorial form. cis-2,4-Bis(phenylthio)-1,3,5-trithiane was found to possess a diaxial conformation to a fair extent in support of the presence of the strong anomeric effect. Equilibration between cis and trans forms of 2,4-bis(phenylthio)-1,3,5-trithiane was carried out to show that the trans form was more stable than the cis. The barrier to inversion of trans-2,4-bis(phenylthio)-1,3,5-trithiane was obtained as ca. 11 kcal/mol.

Effects of 8-azaguanine on riboflavin production and on the nucleotide pools in non-growing cells of Eremothecium ashbyii.

The effects of a guanine analogue, 8-azaguanine, on the riboflavin biosynthesis and the nucleotide pools were examined using non-growing cell systems of flavinogenic and non-flavinogenic strains of E. ashbyii. 1) 8-Azaguanine, as such, strongly inhibited riboflavin formation at low concentrations. The halfway inhibition point was detected at 5×10-5 M. 2) The inhibition of riboflavin biosynthesis by 8-azaguanine was completely overcome by the supplementation of purines. Xanthine gave the most efficient recovery from this inhibition. 3) Fluctuation of the nucleotide pools in non-growing cells of flavinogenic and non-flavinogenic strains were examined using Dowex 1×2 (formate) in the presence of 8-azaguanine 18 hr after start of incubation. As a result, five new peaks appeared on the chromatogram in the flavinogenic strain whilst only one new peak was observed in non-flavinogenic strain. Furthermore, with the addition of xanthine with 8-azaguanine, peaks I, II and IV disappeared from the column, peak III was unchanged and peak V decreased to a fair extent. 4) Five peaks in flavinogenic strain were identified to be (I) uridine, (II) 8-azaguanine, (III) guanosine, (IV) 8-azaguanosine and (V) 8-azaguanosine triphosphate in the order of elution from the column and one peak in non-flavinogenic strain was found to be 8-azaguanine.