Methodological approach for measuring the effects of organisational-level interventions on employee withdrawal behaviour.

BACKGROUND: Theoretical frameworks have recommended organisational-level interventions to decrease employee withdrawal behaviours such as sickness absence and employee turnover. However, evaluation of such interventions has produced inconclusive results. The aim of this study was to investigate if mixed-effects models in combination with time series analysis, process evaluation, and reference group comparisons could be used for evaluating the effects of an organisational-level intervention on employee withdrawal behaviour. METHODS: Monthly data on employee withdrawal behaviours (sickness absence, employee turnover, employment rate, and unpaid leave) were collected for 58 consecutive months (before and after the intervention) for intervention and reference groups. In total, eight intervention groups with a total of 1600 employees participated in the intervention. Process evaluation data were collected by process facilitators from the intervention team. Overall intervention effects were assessed using mixed-effects models with an AR (1) covariance structure for the repeated measurements and time as fixed effect. Intervention effects for each intervention group were assessed using time series analysis. Finally, results were compared descriptively with data from process evaluation and reference groups to disentangle the organisational-level intervention effects from other simultaneous effects. RESULTS: All measures of employee withdrawal behaviour indicated statistically significant time trends and seasonal variability. Applying these methods to an organisational-level intervention resulted in an overall decrease in employee withdrawal behaviour. Meanwhile, the intervention effects varied greatly between intervention groups, highlighting the need to perform analyses at multiple levels to obtain a full understanding. Results also indicated that possible delayed intervention effects must be considered and that data from process evaluation and reference group comparisons were vital for disentangling the intervention effects from other simultaneous effects. CONCLUSIONS: When analysing the effects of an intervention, time trends, seasonal variability, and other changes in the work environment must be considered. The use of mixed-effects models in combination with time series analysis, process evaluation, and reference groups is a promising way to improve the evaluation of organisational-level interventions that can easily be adopted by others.

Nitro-oxidative stress biomarkers in active and inactive men.

Oxidative stress markers are novel factors shown to be related to cardiovascular (CVD) risk. We examined the effects of long-term exercise, age, and their interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO) levels, all biomarkers of oxidative stress, and determined their association with plasma nitric oxide (NOx) levels as an index of NO bioavailability. Older (62±2 yr) active men (n=12) who had exercised for >30 years and young (25±4 yr) active men (n=7) who had exercised for >3 years were age- and BMI-matched to older (n=11) and young (n=8) inactive men. Young subjects had lower plasma nitrotyrosine levels than older subjects (P=0.047). Young inactive subjects had higher ox-LDL levels than either the young active (P=0.042) or the older active (P=0.041) subjects. In addition, plasma oxidative stress levels, particularly ox-LDL, were correlated with various conventional plasma lipoprotein-lipid levels, and in older subjects were associated with Framingham risk score (r=0.49, P=0.015). We found no relationships between plasma oxidative stress markers and NOx levels. The findings suggest that a sedentary lifestyle may be associated with higher ox-LDL levels and that the levels of oxidative stress markers are related to levels of other conventional CVD risk factors and overall CVD risk.

Computerized assessment of production of multiple human cytokines at the single-cell level using image analysis.

A technique using a computerized image analysis system was developed for evaluating and quantifying human cytokine production. This system registered single cells as positive or negative cytokine producers based on a specific juxtanuclear staining pattern generated by accumulation of the proteins in the Golgi-endoplasmatic reticulum compartment. The characteristic morphology of the immunocytochemical staining offered the opportunity to register individual producer cells within multicomponent cell populations. A color camera was then adapted to transfer on-line images directly into the computer-controlled operating system. In this study cultured human peripheral blood mononuclear cells were polyclonally stimulated and then analyzed for interleukin-1alpha (IL-1alpha), IL-1beta, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor production. The image-analyzing system detected cytokine-producing cells in a sensitive and reproducible manner, which was in total congruence with enumeration by conventional microscopy. Furthermore, accurate assessments of cell distributions by signal intensity and cell area were applied at the single-cell level. The image-analyzing system allowed the detection of at least 1 in 1,000 events by using unique cytokine-associated morphometric criteria. The results of kinetic studies measuring cytokine production following activation and cell transformation provided data supporting increases in intensity of intracellular localized specific immunostaining and in cell size within the cytokine-producing cells.

Quantification of superantigen induced IFN-gamma production by computerised image analysis--inhibition of cytokine production and blast transformation by pooled human IgG.

A quantitative image analysis technique was developed to assess the cytokine content of immunocytochemically stained cytokine producing cells. Peripheral blood mononuclear cells were stimulated to induce cytokine production with the superantigen streptococcal pyrogenic exotoxin-A. We have developed a method based on indirect immunocytochemistry which identifies IFN-gamma producing cells by a characteristic morphology generated by the accumulation of IFN-gamma in the Golgi organelle. An image analysis technique permitted discrimination between these producer cells and IFN-gamma binding target cells, which showed a different appearance, with staining restricted to the cell surface membrane. A semi-automated routine programme allowed the signal from a video camera to be processed by computerised image analysis methodology. This enabled us to measure the number of cytokine producing cells, the cytokine staining intensity in individual cells and the cell size expressed in actual cell area. The incidence of IFN-gamma producing cells determined by image analysis measurement was compared to results obtained using manual microscopy. Cell size was assessed by the image analysis system as well as by flow cytometry. Administration of pooled human IgG for intravenous use (IVIg) to the superantigen stimulated cells significantly down-regulated IFN-gamma production, both in terms of the numbers of producer cells and in terms of cytokine staining intensity in individual cells. In addition blast transformation of cells was substantially reduced. These effects, mediated by IVIg, were also evident following delayed IVIg administration 24 h after the initial cell stimulation.

Resolved N,N-dialkylated 2-amino-8-hydroxytetralins: stereoselective interactions with 5-HT1A receptors in the brain.

The enantiomers of the N,N-dimethylamino (1), N,N-diethylamino (2), and N,N-dibutylamino (4) derivatives of 8-hydroxy-2-(dipropylamino)tetralin (8-OH DPAT; 3) have been synthesized. The compounds have been tested for activity at central 5-hydroxytryptamine and dopamine receptors by use of biochemical and behavioral tests in rats. In addition, the ability of the enantiomers of 1-4 to displace [3H]-8-OH DPAT from 5-HT1A binding sites was evaluated. Rank order of potencies in the in vivo tests corresponded to that observed in the 5-HT1A binding assay. In all three tests, the enantiomeric potency ratio was about 10 for 1 and 2 and only around 2-4 for 3 and 4. The more potent enantiomer of 1-3 had the R configuration. In contrast, (S)-4 seemed to be slightly more potent than (R)-4.

Central dopaminergic and 5-hydroxytryptaminergic effects of C3-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin.

A number of stereochemically well defined C3-methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been synthesized, and their stereochemical characteristics have been studies by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations. The compounds were tested for activity at central 5-HT and dopamine (DA) receptors, by use of biochemical and behavioral tests in rats. In addition, the ability of the cis- and trans-8-hydroxy-3-methyl-2-(di-n-propylamino)tetralins (15 and 11) to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The stereoselectivity of the interaction of 11 and 15 with 5-HT receptors was much greater than that of 8-OH-DPAT. Observed rank order of potencies in the 5-HT1A binding assay corresponds to that in the in vivo biochemical assay.

(R)- and (S)-5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten- 8-ylamine. Stereoselective interactions with 5-HT1A receptors in the brain.

The enantiomers of 5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-++ +ylamine (3) have been synthesized and evaluated for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor activity by use of behavioral and biochemical tests in rats. In addition, the ability of the compounds to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The absolute configuration of the enantiomers of 3 was determined indirectly by X-ray diffraction of (+)-(8R,alpha R)-5,6,7,8-tetrahydro-1-methoxy-N-(alpha-phenethyl)-9H- benzocyclohepten-8-ylamine hydrochloride (9.HCl), a resolved synthetic precursor. The stereoselectivity of the interaction of 3 with 5-HT1A receptors was more pronounced than that of 8-hydroxy-2-(dipropylamino)tetralin (1; 8-OH-DPAT); only (R)-3 displayed 5-HT activity. However, (R)-3 was of lower potency than any of the enantiomers of 1. The enantiomer (S)-3, which was found to be inactive as a 5-HT-receptor agonist, appeared to be a weakly potent DA-receptor agonist whereas (R)-3 seemed to be devoid of dopaminergic activity. The conformational preferences of 3 were studied by use of NMR spectroscopy and molecular mechanics calculations. Preferred conformations of (R)-3 are similar in shape to those of the stereoselective 5-HT1A-receptor agonist (2R,3S)-8-hydroxy-3-methyl-2-(dipropylamino)tetralin.

A 3-D model for 5-HT1A-receptor agonists based on stereoselective methyl-substituted and conformationally restricted analogues of 8-hydroxy-2-(dipropylamino)tetralin.

The enantiomers of cis- and trans-1,2,3,4,4a,5,10,10a-octahydro-9-hydroxy-1- propylbenzo[g]quinolines (10 and 11, respectively) and the enantiomers of trans-1,2,3,4,4a,5,6,10b-octahydro-10- hydroxy-4-propylbenzo[f]quinoline (12) have been synthesized and their stereochemical and conformational characteristics have been studied by use of X-ray crystallography and molecular mechanics (MMP2) calculations. The compounds, which are conformationally restricted analogues of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2- (dipropylamino)tetralin (8-OH-DPAT; 1) have been evaluated for central 5-HT and dopamine receptor stimulating activity by use of biochemical and behavioral tests in rats. In addition, we have evaluated the ability of these compounds and a number of previously reported analogues to displace [3H]-8-OH-DPAT from 5-HT1A-binding sites. The enantiomers of 12 behave as potent 5-HT1A-receptor agonists, whereas the octahydrobenzo[g]quinoline derivatives are much less potent or inactive. In general, the affinities of the compounds correlate well with their agonist potencies. The set of compounds under study is accommodated by a novel computer-graphics-derived model for 5-HT1A-receptor agonism. The model consists of a flexible pharmacophore and a partial receptor-excluded volume.

Measures of clinical efficacy. III. The value of the lung scan in the evaluation of young patients with pleuritic chest pain.

The usefulness of various modalities in evaluating pleuritic pain in young patients and in isolating cases of pulmonary embolism was assessed using likelihood ratios and the receiver operating characteristic (ROC) curve. History and physical, laboratory, and radiographic finding were used disjunctively to establish an ROC curve. The percentage of patients found to have pulmonary embolism increased monotonically with certain critical pieces of diagnostic data. For example, a history and physical examination alone detected 80% of patients with pulmonary embolism; a chest radiograph raised the percentage to 95%; and the addition of a lung scan increased the percentage to 100%. Thus, with proper interpretation of clinical and radiographic data, the lung scan has only a marginal impact upon the sensitivity with which pulmonary embolism is detected. Its major value is an increased specificity in the diagnosis of pulmonary embolism.

Comparison of observer performance with 16 mm cinefluorography and 70 mm camera fluorography in coronary arteriography.

Clinical 16 mm cinefluorography and 70 mm camera fluorography were compared in 30 unselected patients undergoing coronary arteriography. Accuracy in detecting coronary arterial stenosis and collateral vessels and in assessing the degree of stenosis was similar with the two techniques. With both methods, there were significant inter- and intraobserver differences in estimating the degree of stenosis. These differences indicate that coronary arteriography is only a semiquantitative method for making decisions about treatment, prognosis and follow-up of patients. The use of more than one observer increases the likelihood that stenotic lesions will be detected. Interobserver variation in detecting collateral circulation is small.

(S)-UH-301 antagonizes (R)-8-OH-DPAT-induced cardiovascular effects in the rat.

The 5-HT1A-receptor antagonist (S)-UH-301 (S)-5-fluoro-8-hydroxy-2- (dipropylamino)tetralin) completely antagonized the hypotension and bradycardia induced by (R) = 8-OH DPAT [R)-8-hydroxy-2- (dipropylamino)tetralin) in conscious rats. (S)-UH-301 alone induced a weak hypertension, which might be due to its 5-HT1A-receptor antagonistic properties. (R)-UH-301 induced effects similar to those of (R)-8-OH DPAT, i.e., a short initial phase of hypertension followed by a long-lasting hypotension and bradycardia. Thus, (R)-UH-301 behaves as a 5-HT1A-receptor agonist and (S)-UH-301 as a 5-HT1A-receptor antagonist, abolishing the effects induced by (R)-8-OH DPAT.

Effects of the C3-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on central 5-hydroxytryptamine receptors.

The effects of the four possible C3-methylated stereoisomers of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) ((-)-CM-11, (+)-CM-11, (-)-CM-12, (+)-CM-12) on brain 5-hydroxytryptamine (5-HT) receptor functions were studied in rats. (-)-CM-11 and (+)-CM-12 inhibited dose dependently in all brain parts the accumulation of 5-hydroxytryptophan following decarboxylase inhibition. Their antipodes were inactive. The disappearance of 5-HT induced by alpha-propyldopacetamide was retarded by (-)-CM-11 and (+)-CM-12. The biochemically active isomers produced a flat body posture and forepaw treading. The results indicate that (-)-CM-11 and (+)-CM-12 stimulate 5-HT receptors directly although not as potently as 8-OH-DPAT. The concentration of dopamine was lowered and that of homovanillic acid was elevated by (+)-CM-11 and by both enantiomers of CM-12 in the corpus striatum and in the limbic system of rats. The accumulation of DOPA following decarboxylase inhibition was not markedly changed by any of the compounds. Locomotor activity was enhanced by (+)-CM-11 but not by any of the other compounds, and the effect was haloperidol-resistant. (+)-CM-11 induced no asymmetry in rats in which the corpus striatum was inactivated on one side. Thus, none of the isomers of CM-11 or CM-12 appears to have any effect on the dopamine receptors.

Effects of (R)-8-OH-DPAT and the enantiomers of UH-301 on motor activities in the rat: antagonism of (R)-8-OH-DPAT-induced effects.

The effects of the enantiomers of 5-fluoro-8-hydroxy-2-(dipropylamino)tetralin, UH-301 and the potent 5-HT1A-receptor agonist (R)-8-hydroxy-2-(dipropylamino)tetralin, (R)-8-OH-DPAT, on locomotion, rearing and total activity were studied in rats. The experiments were performed as tests either of exploratory activity in non-habituated rats or of motor activity of rats habituated to the environment for 2 h before drug injection. (R)-8-OH-DPAT increased locomotion and total activity and decreased rearing in both conditions. (R)-UH-301 increased locomotion and slightly also total activity in habituated rats and decreased rearing in both conditions. (S)-UH-301 decreased locomotion and rearing in both conditions but only in doses of 10 mumol/kg and above. Lower doses of (S)-UH-301 (10 mumol/kg) antagonized (R)-8-OH-DPAT-induced increases of locomotion and total activity. As (S)-UH-301 decreased rearing, per se, it was not able to antagonize the (R)-8-OH-DPAT induced decrease. These results further support previous data that (S)-UH-301 is a 5-HT1A antagonist while (R)-UH-301 is a 5-HT1A agonist.

Interleukin-1 stimulates the expression of type I and type II interleukin-1 receptors in the rat insulinoma cell line Rinm5F; sequencing a rat type II interleukin-1 receptor cDNA.

The insulin secreting rat Rinm5F cells are often used to study the cytotoxic actions of interleukin-1 (IL-1) on pancreatic beta-cells. We demonstrate here that Rinm5F insulinoma cells express both type I and type II interleukin-1 receptor (IL-1R) mRNAs and gene products. IL-1R agonists, recombinant murine IL-1 alpha (rmIL-1 alpha, 10 ng/ml) and recombinant rat IL-1 beta (rrIL-1 beta, 100 pg/ml or 10 ng/ml) induce the upregulation of mRNA expression for both types of IL-1 receptors (IL-1Rs). This effect of rrIL-1 beta is antagonised by preincubation with recombinant human interleukin 1 receptor antagonist protein (rhIL-1ra, 5 micrograms/ml). Furthermore, this rrIL-1 beta induced upregulation of IL-1R mRNAs is blocked by actinomycin D (7.5 micrograms/ml), whereas cycloheximide (20 micrograms/ml) has no effect. The phorbol ester PMA (20 nM) upregulates the expression of mRNAs both IL-1 receptors, whereas glucose (50 mM) upregulates the expression of the type I IL-1R mRNA only. Pretreatment of cells with pertussis toxin (100 ng/ml) partially blocks the rrIL-1 beta induced expression of mRNA for the type I and, to a lesser extent, the type II IL-1R. Incubation of the cells with rrIL-1 beta also induces a time-dependent expression of c-fos, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) mRNAs. Binding studies with 125I-recombinant human IL-1 beta (125I-rhIL-1 beta) indicate that IL-1R gene products, with the ligand binding characteristics of the type I IL-1R, are constitutively present on Rinm5F cells. Treatment with rrIL-1 beta (6h) increases the number of 125I-rhIL-1 beta binding sites on Rinm5F cells. We have also demonstrated that the number of type II IL-1R binding sites increases after induction with rrIL-1 beta (6h), by indirect immunofluorescence using a monoclonal antibody (ALVA 42) raised against the human type II IL-1R. Furthermore, we have sequenced the type II IL-1R cDNA in the rat insulinoma Rinm5F cells. The comparison of the amino acid sequence of the rat type II IL-1R with that of the mouse and human type II IL-1Rs shows 90% and 62% amino acid identity, respectively. The most important difference between the human and murine type II IL-1Rs, and this rat type II IL-1R cDNA, is an open reading frame coding for a six amino acid longer, strongly charged (QIKEMK), cytosolic domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracavitary metastasis to the left ventricle: an angiocardiographic diagnosis.

A patient with an intracavitary metastasis to the outflow tract of the left ventricle diagnosed prior to the primary tumours is presented. It is unique in location, type and diagnosis. Metastatic disease of the heart is far more common than primary cardiac tumours and usually is diagnosed late in the course of the disease or at autopsy. Angiocardiography is the best method of diagnosing tumours of the heart and should be performed whenever such a diagnosis is considered.

Changes in antioxidant effects and their relationship to phytonutrients in fruits of sea buckthorn (Hippophae rhamnoides L.) during maturation.

Different fractions of sea buckthorn fruits were investigated for antioxidant activity and its relationship to different phytonutrients. Capacity to scavenge radicals of the crude extract, like the phenolic and ascorbate extracts, decreased significantly with increased maturation. The changes were strongly correlated with the content of total phenolics and ascorbic acid. Antioxidant capacity of the lipophilic extract increased significantly and corresponded to the increase in total carotenoids. The phenolic fractions made a major contribution to the total antioxidant capacity due to the high content of total phenolics. The lipophilic fractions were most effective if the comparison was based on the ratio between antioxidant capacity and content of antioxidants. The crude extract of fruits showed the highest inhibitory effect in both 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) and ascorbate-iron induced lipid peroxidations. The aqueous and ascorbate-free extracts showed higher inhibition in the AMVN assay, but lower inhibition in ascorbate-iron induced peroxidation, than the lipophilic extract.

Two new contrast media in peripheral arteriography: a double blind study in patients with arterial insufficiency in the legs.

Two new contrast media, Amipaque (metrizamide, Nyegaard & Co A/S, Oslo) and Hexabrix (ioxaglic acid, Laboratoire Guerbet, Paris) were compared in a double blind study in patients with arterial insufficiency in the legs. The incidence of subjective adverse effects (pain and sensation of heat) was low and similar with both contrast agents. Also the effects on heart rate and blood pressure were small and transient and similar with both contrast agents.

Reversibility of stemflow-induced soil acidification in Swedish beech forest.

Stemwater running down the trunks of beech (Fagus sylvatica L.) has an acidifying effect on soil near the stem. The deposition of acidifying substances may be two to four times higher close to the stem compared to in the stand in general. To study reversibility of soil acidification, 72 stumps of beech trees were chosen from five different year classes of felling (3, 6, 9, 14-15, 25-30), representing the years when stemflow ceased to affect the soil. The H(+) concentration (pH KCl) in the topsoil (0-5 cm) differed between the distances 10-30 cm and 230-250 cm from the stumps, the soil close to the stem being more acid. The longer the time since felling the smaller the differences in H(+) concentration became. This reduction in soil acidity amounted to ca. 50% after 15 years, and only small further changes occurred over the next ten years. This indicates that soil may not recover fully from acidification, or does so at a rather slow rate after the initial 15 years of recovery.

Upper airway obstruction--an unusual complication following a minor scalding injury.

A 14-month-old girl suffered a 10 per cent scalding injury from hot water of the type sometimes recognized as 'the teapot syndrome'. The hot water also reached the hypopharynx where it caused marked swelling of the mucosa and hence obstruction of the airway. Increasing respiratory distress made endotracheal intubation necessary 4.5 h after the accident. The girl was extubated 26 h later, and breathing was normal. The external burns were initially treated with baths and dressing changes. They healed mostly spontaneously, but four areas had to be grafted. This case report shows that thermal burns of the mouth and pharynx, followed by oedema and upper airway obstruction, can occur also in a minor scalding injury involving the face. Respiratory distress makes intubation necessary.

Valerenic acid derivatives and valepotriates among individuals, varieties and species of Valeriana.

To investigate the variations of active compounds between species, varieties and individuals of Valeriana cultivated under the same environmental condition, the contents of valerenic acid derivatives and valepotriates in rhizomes and roots of different plant material were analysed by a HPLC method. Different species or varieties of Valeriana yielded 11.65-0.15 mg/g of valerenic acid derivatives, and 1.81-0.03 mg/g of valepotriates. The variation between individuals of one commercial cultivar of V. officinalis ranged from 12.34 to 3.01 mg/g of valerenic acid derivatives, and 3.67-0.92 mg/g of valepotriates. Individuals from self-pollinated mother plants, normal or regenerated, showed a similar variation. The variation of micropropagated plants was much less than the seed propagated plants. The ratio of mean values between valerenic acid derivatives and valepotriates was similar in all groups (3 < ratio < 8) except one group of micropropagated plants (ratio > 20).