Should all adjunctive corticosteroid therapy be avoided in the management of hemodynamically stabile Staphylococcus aureus bacteremia?

The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone >10 mg/day for ≥1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2-4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose >100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95%CI, 1.27-7.65; p < 0.05) and at 90 days (30 % vs. 10 %) (OR, 4.01; 95%CI, 1.82-8.81; p < 0.001). Considering all prognostic markers, early initiated corticosteroid therapy predicted 28-day (HR, 3.75; 95%CI, 1.60-8.79; p = 0.002) and 90-day (HR, 3.10; 95%CI, 1.50-6.39; p = 0.002) mortality in Cox proportional hazards regression analysis. When including only patients receiving early initiated corticosteroid therapy with prednisone ≥100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p = 0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.

Galega orientalis is more diverse than Galega officinalis in Caucasus--whole-genome AFLP analysis and phylogenetics of symbiosis-related genes.

Legume plants can obtain combined nitrogen for their growth in an efficient way through symbiosis with specific bacteria. The symbiosis between Rhizobium galegae and its host plant Galega is an interesting case where the plant species G. orientalis and G. officinalis form effective, nitrogen-fixing, symbioses only with the appropriate rhizobial counterpart, R. galegae bv. orientalis and R. galegae bv. officinalis, respectively. The symbiotic properties of nitrogen-fixing rhizobia are well studied, but more information is needed on the properties of the host plants. The Caucasus region in Eurasia has been identified as the gene centre (centre of origin) of G. orientalis, although both G. orientalis and G. officinalis can be found in this region. In this study, the diversity of these two Galega species in Caucasus was investigated to test the hypothesis that in this region G. orientalis is more diverse than G. officinalis. The amplified fragment length polymorphism fingerprinting performed here showed that the populations of G. orientalis and R. galegae bv. orientalis are more diverse than those of G. officinalis and R. galegae bv. officinalis, respectively. These results support the centre of origin status of Caucasus for G. orientalis at a genetic level. Analysis of the symbiosis-related plant genes NORK and Nfr5 reveals remarkable diversity within the Nfr5 sequence, although no evidence of adaptive evolution could be found.

Symbiotic and genetic diversity of Rhizobium galegae isolates collected from the Galega orientalis gene center in the Caucasus.

This paper explores the relationship between the genetic diversity of rhizobia and the morphological diversity of their plant hosts. Rhizobium galegae strains were isolated from nodules of wild Galega orientalis and Galega officinalis in the Caucasus, the center of origin for G. orientalis. All 101 isolates were characterized by genomic amplified fragment length polymorphism fingerprinting and by PCR-restriction fragment length polymorphism (RFLP) of the rRNA intergenic spacer and of five parts of the symbiotic region adjacent to nod box sequences. By all criteria, the R. galegae bv. officinalis and R. galegae bv. orientalis strains form distinct clusters. The nod box regions are highly conserved among strains belonging to each of the two biovars but differ structurally to various degrees between the biovars. The findings suggest varying evolutionary pressures in different parts of the symbiotic genome of closely related R. galegae biovars. Sixteen R. galegae bv. orientalis strains harbored copies of the same insertion sequence element; all were isolated from a particular site and belonged to a limited range of chromosomal genotypes. In all analyses, the Caucasian R. galegae bv. orientalis strains were more diverse than R. galegae bv. officinalis strains, in accordance with the gene center theory.

Silver stained polyacrylamide gels and fluorescence-based automated capillary electrophoresis for detection of amplified fragment length polymorphism patterns obtained from white-rot fungi in the genus Trametes.

Silver stained denaturing polyacrylamide gels (PAGEs) and fluorescent denaturing automated capillary electrophoresis (CE) were used to detect amplified fragment length polymorphism (AFLP) patterns obtained from white-rot fungi belonging to the genus Trametes. AFLP fingerprinting detected by the fluorescence-based method as well as by silver staining showed a high discriminatory power in differentiating nine strains of Trametes ochracea, nine strains of Trametes hirsuta and ten isolates of Trametes versicolor. UPGMA dendrograms derived from fluorescently labelled and silver stained AFLP patterns were similar, but a few differences were detected especially in the clustering of T. ochracea and T. hirsuta strains. Compared to silver-stained AFLP, detection of fluorescent AFLP was fast, reliable and easy to perform and it facilitated surveying with a computerized analysis system. Fluorescent CE seems to be well suited for studying similarity between Trametes species.

Serum trypsinlike immunoreactivity measurement for the diagnosis of subclinical exocrine pancreatic insufficiency.

Dogs (n = 158) with serum trypsinlike immunoreactivity (TLI) concentrations < or = 5.0 microg/L were studied. The diagnosis of clinical exocrine pancreatic insufficiency (EPI) was made in 114 of 158 dogs based on TLI concentration < 2.5 microg/L and clinical signs typical of EPI (eg, polyphagia, voluminous feces, weight loss). In 44 of 158 dogs, a single TLI measurement and clinical signs were not diagnostic. In 9 of 44 dogs, TLI was < 2.5 microg/L, indicating EPI, but the gastrointestinal signs were atypical or the dogs were asymptomatic. In 35 of 44 dogs, TLI was 2.5-5.0 microg/L. All 44 dogs were retested for TLI within 1-27 months (mean, 11.9 months). In 20 of 44 dogs, the retested TLI was normal (> 5.0 microg/L). In 4 of 44 dogs with clinically diagnosed EPI, the retested TLI was < 2.5 microg/L. In the remaining 20 of 44 dogs, TLI was persistently < 5.0 microg/L (range, 1.0-4.9 microg/L; mean, 3.1 microg/L). Of these dogs, 15 had no clinical signs of gastrointestinal disease, and 5 had occasional clinical signs atypical for EPI. Gross examination of the pancreas (12 dogs) showed that the amount of normal pancreatic tissue was remarkably diminished. These dogs were diagnosed with subclinical EPI. The TLI-stimulation test, in which TLI is measured before and after stimulation with secretin and cholecystokinin, showed a significant response (P < .05) both in dogs with subclinical EPI and in control dogs, but showed no response in dogs with clinical EPI. In this study, EPI was diagnosed in its subclinical phase by TLI concentrations persistently < 5.0 microg/L, and a single TLI concentration < 5.0 microg/L was not diagnostic. Retesting after TLI concentrations < 5.0 microg/L is recommended even in clinically normal dogs, because of the possibility of subclinical EPI.

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats.

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.

The development of a multicenter database for reference values in clinical neurophysiology--principles and examples.

This paper describes the work undertaken to establish principles for the development of multicenter databases for reference values in clinical neurophysiology. The study was initiated because of interest of the involved laboratories in knowledge-based systems in electromyographic diagnosis, for which it was necessary to formalize the key concepts in the diagnostic process: diseases, pathophysiology and test results. The paper deals specifically with the structuring of results of motor and sensory nerve conduction studies.

Distribution of Chlorophyll-Protein Complexes during Chilling in the Light Compared with Heat-Induced Modifications.

The effects of chilling in the light (4 days at 5 degrees C and 100-200 micromoles of photons per square meter per second) on the distribution of chlorophyll (Chl) protein complexes between appressed and nonappressed thylakoid regions of pumpkin (Cucurbita pepo L.) chloroplasts were studied and compared with the changes occurring during in vitro heat treatment (5 minutes at 40 degrees C) of isolated thylakoids. Both treatments induced an increase (18 and 65%, respectively) in the relative amount of the antenna Chl a protein complexes (CP47 + CP43) of photosystem II (PSII) in stroma lamellae vesicles. Freeze-fracture replicas of light-chilled material revealed an increase in the particle density on the exoplasmic fracture face of unstacked membrane regions. These two treatments differed markedly, however, in respect to comigration of the light-harvesting Chl a/b protein complex (LHCII) of PSII. The LHCII/PSII ratio in stroma lamellae vesicles remained fairly constant during chilling in the light, whereas it dropped during the heat treatment. Moreover, it was a minor light-harvesting Chl a/b protein complex of PSII, CP29, that increased most in stroma lamellae vesicles during light-chilling. Changes in the organization of LHCII during chilling were suggested by a shift to particles of smaller sizes on the protoplasmic fracture face of stacked membrane regions and a decrease in the amount of trans-Delta(3)-hexadecenoic acid in the phosphatidyldiacylglycerol fraction.

Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers.

The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective beta-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced beta-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity.

Effects of calcium and deoxycorticosterone on blood pressure, plasma renin activity and vascular reactivity in spontaneously hypertensive rats.

The effects of calcium and deoxycorticosterone (DOC) on blood pressure, plasma renin activity (PRA), urinary sodium excretion and aortic responses were studied in spontaneously hypertensive rats (SHR). The animals (age 9 weeks) were divided into four treatment groups: control, calcium, DOC and DOC+calcium (n = 12 and the mean systolic blood pressure 174-177 mmHg in each). Calcium was given as 1.5% CaCl2 in drinking fluid, and DOC trimethylacetate by weekly injections (25 mg/kg s.c.). During the 4-week study systolic blood pressure rose in all groups, but the increase was attenuated by calcium (final levels: control 201 +/- 3, calcium 186 +/- 3, DOC 206 +/- 2, DOC + calcium 203 +/- 2 mmHg, mean +/- SE). PRA was reduced in both groups receiving DOC, but it was not affected by calcium. Calcium supplementation increased urinary excretion of sodium in DOC-treated animals. DOC enhanced the in vitro contractility of helically cut aortic strips to noradrenaline, and decreased the relaxation of the strips to nitroprusside and nifedipine. The results indicate that calcium supplementation attenuates the development of hypertension in SHR, and that this attenuation is not mediated by the renin-angiotensin system. DOC abolished this lowering effect of calcium on blood pressure possibly by its action on vascular smooth muscle, resulting in increased vascular contractility and impaired relaxation.

Deoxycorticosterone prevents the blood pressure-lowering effect of calcium in spontaneously hypertensive rats.

To study the effects of prolonged oral calcium loading on the development of hypertension in spontaneously hypertensive rats (SHR), 48 male animals (age 9 weeks) were divided into four groups according to the treatment: control, calcium, deoxycorticosterone (DOC) and calcium/DOC. Both calcium groups received 1.5% calcium chloride solution ad libitum as their drinking fluid. The animals in the DOC groups were treated with a mineralocorticoid, deoxycorticosterone trimethylacetate 25 mg kg-1 s.c. once a week. Systolic blood pressure (BP) was measured twice a week during the 4-week study period. Calcium loading alone lowered BP (p less than 0.01) after four weeks. Combined with DOC treatment, calcium administration had no significant effect on BP. Calcium loading increased the total plasma calcium concentration in the calcium group (p less than 0.05). Urinary excretions of sodium and potassium were augmented in both groups receiving calcium compared to DOC group. DOC treatment alone increased the excretion of calcium (P less than 0.05). Calcium supplementation decreased the plasma phosphate concentration in both groups (calcium p less than 0.05; calcium/DOC p less than 0.01) as well as the excretion phosphate (p less than 0.005) compared to control. The urinary excretion of cAMP remained unaffected by the calcium treatment. The present results indicate that mineralocorticoid treatment can prevent the BP-lowering effect of calcium in SHR. The mechanism of this action remains unclear, but it does not seem to depend on electrolyte or phosphate balance. The investigation of this action of DOC may provide a means for further exploration of the mechanisms by which increased calcium intake lowers BP in SHR.

Temperature-dependent changes in Photosystem II heterogeneity of attached leaves under high light.

Attached leaves of pumpkin (Cucurbita pepo L. cv. Jattiläismeloni) were exposed to high light intensity at room temperature (ca 23°C) and at 1°C. Fluorescence parameters and electron transport activities measured from isolated thylakoids indicated faster photoinhibition of PSII at low temperature. Separation of the α and ß components of the complementary area above the fluorescence induction curve of dichlorophenyl-dimethylurea-poisoned thylakoids revealed that at low temperature only the α-centers declined during exposure to high light intensity while the content of functional ß-centers remained constant. Freeze-fracture electron microscopy showed no decrease in the density of particles on the appressed exoplasmic fracture face, indicating that the photoinhibited α-centers remained in the appressed membranes at 1°C. Because of the function of the repair and protective mechanisms of PSII, strong light induced less photoinhibition at room temperature, but more complicated changes occurred in the α/ß-heterogeneity of PSII. During the first 30 min at high light intensity the decrease in α-centers was almost as large as at 1°C, but in contrast to the situation at low temperature the decrease in α-centers was compensated for by a significant increase in PSIIß-centers. Changes in the density and size of freeze-fracture particles suggest that this increase in ß-centers was due to migration of phosphorylated light-harvesting complex from appressed to non-appressed thylakoid membranes while the PSII core remained in the appressed membranes. This situation, however, was only transient and was followed by a rapid decrease in the functionalß-centers.

Seasonal variation in the photosynthetic capacity of a willow (Salix cv. Aquatica gigantea) canopy. 2 Comparison of the structure and function of chloroplasts at different levels in the canopy.

Development of leaf chloroplast ultrastructure at five levels in a willow (Salix cv. Aquatica gigantea) canopy was followed during one growing season in the field. Changes in chloroplast ultrastructure were compared with the rate of CO(2) uptake of the same leaves. The highest rates of CO(2) uptake were recorded in young leaves exposed to full available sunlight. In these leaves, the area of the grana stacks was less than 20% of the total chloroplast area and the degree of thylakoid stacking was less than 1.5. The chloroplasts of these leaves contained large amounts of starch and small amounts of plastoglobuli. As the canopy grew and the leaves in the lower parts of the canopy became shaded, the structure of the chloroplast thylakoids gradually changed. In leaves at the two lowest levels of the canopy, the degree of stacking at the end of the growing season was close to 2 and correspondingly the rate of CO(2) uptake was low. The areas of grana stacks and plastoglobuli in these chloroplasts increased and were about 30 and 10% of the chloroplast area, respectively, by the end of the growing season. The increase in the degree of thylakoid stacking was caused by increased biosynthesis of grana lamellae, which in general were thinner than the lamellae of young leaves. The length of the stroma lamellae did not change with leaf age. Morphometric measurements showed that the structure of the chloroplasts in leaves 160 cm above ground was dynamic and responsive to environmental conditions so that photosynthetic capacity remained high for 7 weeks despite an increase in leaf shading.

Pharmacokinetics of clodronate in patients with metastatic breast cancer.

Pharmacokinetics of clodronate was studied in six breast cancer patients with only bone metastases. 14C-clodronate was administered intravenously (10 muCi/200 mg) and orally (20 muCi/400 mg) on separate occasions. Vc of clodronate averaged 6.3 +/- 3.0 (SD) 1 and Vdss 16.3 +/- 3.81 corresponding to the extracellular water volume. Distribution and elimination were fast with t1/2 alpha of 0.22 +/- 0.22 h and t1/2 beta of 2.3 +/- 0.9 h. The elimination occurred mainly by renal excretion of the unchanged drug CLP averaging 107 +/- 27 ml/min and CLR 80 +/- 18 ml/min. The protein unbound, free fraction in plasma was 64%. On the basis of urinary excretion data, there was a slow terminal elimination phase with a half-life of 12.8 +/- 6.9 h. Thus about 20% of the intravenous dose was retained in the body, most likely in the bones, 3 days after drug administration. About 75% of the intravenous dose was recovered in urine and 5% in feces. Based on cumulative excretion data into urine after both routes of administration, the bioavailability of oral clodronate was 1.9 +/- 0.4%. These findings correspond closely to those obtained in healthy volunteers in previous studies.

Blood pressure responses to enalapril in rats with one- and two-kidney DOC-NaCl hypertension.

Blood pressure responses to the angiotensin-converting enzyme (ACE) inhibitor enalapril were investigated in rats with salt-dependent hypertension. In both one- and two-kidney deoxycorticosterone (DOC)-NaCl hypertension, enalapril (50 mg/kg p.o.) caused a similar, slight blood pressure fall, which passed off with continuation of the treatment. Changes in the salt concentration of the drinking fluid (from 1% NaCl to 0.2% NaCl in the one-kidney rats and from 1% NaCl to 2% NaCl in those with intact kidneys) did not alter the depressor effect of enalapril. Plasma renin activity in all DOC-NaCl hypertensive groups was negligible. Our results indicate that in DOC-NaCl hypertensive rats, the presence of intact kidneys vs. one kidney has no influence on the blood pressure response to ACE inhibition. The blood pressure-lowering effect of enalapril may result from local converting enzyme inhibition in tissues.

Enhanced activation of the renin-angiotensin-aldosterone system in chronic cigarette smokers: a study of monozygotic twin pairs discordant for smoking.

Plasma renin activity (PRA) and aldosterone concentration were measured before and during submaximal exercise in 10 male monozygotic twin pairs who were discordant for smoking. In nine twin pairs PRA was higher in the smoker both at rest and during exercise. The mean PRA was 99% higher at rest and 84% higher during exercise than in nonsmokers. Plasma aldosterone levels were higher at rest in seven smokers and during exercise in eight smokers compared with the respective nonsmokers. The mean aldosterone level at rest was 23% and during exercise 40% higher in the smokers than in the nonsmokers. Chronic smoking induces increased PRA, which results in increased aldosterone formation, presumably via enhanced generation of angiotensin II. This may partly explain the greater vasoconstrictive reactivity typical of the arteries of chronic smokers.

Effects of the converting enzyme inhibitor quinapril (CI-906) on blood pressure, renin-angiotensin system, and prostanoids in essential hypertension.

Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks. At the end of the baseline period and of each month of the double-blind phase, 12 h overnight urine collections were made and morning blood samples were taken about 12 h after the last dose of medication. During the double-blind phase, blood pressure in the quinapril group (n = 7) decreased from 159 +/- 3/105 +/- 1 to 141 +/- 6/94 +/- 2 mm Hg (mean +/- SEM). Serum ACE activity and plasma angiotensin II concentration were reduced to 4 +/- 1% and 14 +/- 1% of the pretreatment values, respectively. Neither the plasma concentrations nor the urinary excretions of prostaglandin E2, 6-keto-prostaglandin F1 alpha (a prostacyclin metabolite), or thromboxane B2 (a metabolite of thromboxane A2) were affected by quinapril. In the placebo group, blood pressure tended to decline but the biochemical variables remained essentially unchanged. These results indicate that prostanoids are not involved in the antihypertensive action of quinapril, the principal effect of which seems to be inhibition of the renin-angiotensin system.

Effects of indomethacin on hormonal and blood pressure responses to captopril in spontaneously hypertensive rats.

The possible role of vasodilatory prostanoids in the antihypertensive action of captopril was investigated in spontaneously hypertensive rats (SHR). Captopril (100 mg/kg/day for 5 days) decreased systolic blood pressure and increased water consumption, urine excretion and plasma renin activity (PRA). It also enhanced the urinary excretion of the prostacyclin metabolite 6-keto-PGF1 alpha, but did not change the excretion of PGE2. Indomethacin (3 mg/kg/day), given both alone and in combination with captopril, reduced markedly the urinary excretions of 6-keto-PGF1 alpha and PGE2 but did not alter PRA, compared with corresponding groups without indomethacin. The suppression of prostanoid synthesis caused by indomethacin did not affect the antihypertensive effect of captopril or the basal blood pressure in SHR. Neither did indomethacin influence drinking or urine excretion in SHR not receiving captopril, but it reduced the dipsogenic and diuretic effects of captopril. The results suggest that captopril augments the production of vasodilatory prostacyclin. Yet prostanoids have no significant role in the antihypertensive mechanism of captopril in SHR.

Effects of two structurally different angiotensin-converting enzyme inhibitors, captopril and quinapril (CI-906), in rats with one-kidney deoxycorticosterone-salt hypertension.

Possible non-renin antihypertensive actions of two angiotensin-converting enzyme inhibitors, the sulfhydryl compound captopril and the new nonsulfhydryl inhibitor quinapril (CI-906), were compared in rats with one-kidney deoxycorticosterone-salt hypertension. Plasma renin activity remained low during the 12-day treatments and showed very strong suppression of the renin-angiotensin system. Quinapril did not influence the rapidly increasing blood pressure. Although captopril tended to reduce the development of hypertension (p = 0.08), it did not have any significant effect, either. The results indicate that these ACE inhibitors with different chemical structures lack any significant blood pressure lowering mechanism in severe deoxycorticosterone-salt hypertension, a model in which they cannot act through their established antihypertensive mechanism, the inhibition of the renin-angiotensin system.