Search

Reported complication rates after vascular closure device deployment or femoral manual compression (MC) are similar. However, the features and severity of such complications have never been thoroughly evaluated.A consecutive series of 1241 patients treated from 2008 to 2010 with Angio-Seal (AS) was prospectively evaluated for vascular complications (VC). As control group, we used a consecutive series of 672 patients treated with MC in the 7 months preceding AS adoption at our institution. VC were observed in 88 patients, 55 with AS and 33 with MC (relative risk, 0.90; 95% confidence interval, 0.59-1.38; P=.63). The clinical profile of complications observed in the 2 groups was different. Groin hematomas were more frequent with MC (100% vs 65.5%; P=.0005) and retroperitoneal bleedings were more common with AS (41.8% vs 6.1%; P=.0005). AS complications required more frequently transfusions (49.1% vs 18.2%; P=.006), while MC complications significantly delayed hospital discharge, in comparison to AS (4.3 ± 4.0 days vs 2.7 ± 1.9 days; P=.01). Differences in groin hematoma and retroperitoneal bleeding rates were confirmed after propensity score matching. Finally, a different allocation of diagnostic/therapeutic resources was observed in the 2 groups.AS and MC were associated with similar incidences of VC, with a higher prevalence of severe complications (retroperitoneal hemorrhages and transfusions) after using AS. However, complications after MC were associated with significantly prolonged hospital stay. Comparison between different hemostatic strategies should consider the logistic burden imposed by different vascular complications.

Biocompatibility of root canal filling materials is of great interest because they can come into permanent contact with the living periapical tissue, and induce mild or severe inflammatory responses. Usually biocompatibility tests only determine non-cytotoxic effects of dental materials, even if their functional interactions with cells also play a role in the host responses. The purpose of this study is to evaluate peripheral blood monocyte (PBM) vitality and functionality after contact with 5 different root canal filling materials: Thermafil (gutta-percha), Real Seal and Real Seal 1 (methacrylic resins), AureoSeal (MTA) and SuperSeal (EBA). Cellular vitality was determined by MTT test and cellular functionality by Chemiluminescence (CL) technique. Dishes of the materials were covered with cell culture medium (0.5 cm2/mL) and incubated for 24 h. The extracts were added to PBMs and the latter, after 2 h of incubation, were analysed by MTT and by Chemiluminescence (CL). All results are expressed as mean ± SEM. The group means were compared by analysis of variance. Results showed that SuperSeal and AuroSeal exhibited a moderate cytotoxic effect, while the toxicity induced by RealSeal, RealSeal 1 and Thermafil was lower. SuperSeal and AuroSeal induced a significant decrease of both oxidative burst and basal reactive oxygen species (ROS) production. RealSeal 1 caused a doubling of basal ROS production in respect to control. The results demonstrate that a low cytotoxic effect does not guarantee a total integrity of cellular functionality and more differences among biocompatibility of root canal materials can be detected when a functionality test is used.

The association of variant angina (VA) and myocardial bridges is a rare finding. We describe a case of VA with recurrent coronary spasm triggered by different stimuli at the site of a myocardial bridge. The interplay of endothelial dysfunction, coronary vasoconstriction and myocardial bridging was detected by intracoronary acetylcholine test and IVUS. We speculate that mechanical stimulation at the bridge site caused endothelial dysfunction and enhanced local susceptibility to vasoconstrictor stimuli. Variant angina should always be suspected in cases of ST-elevation acute coronary syndrome without any significant angiographic coronary stenosis.

The Angio-Seal Evolution (ASE) is a novel vascular closure device (VCD) engineered to reduce the individual skills needed for deployment. A clinical comparison of ASE with manual femoral compression (MC) has never been reported.A total of 451 consecutive patients treated by ASE following cardiac catheterization were compared with 451 propensity-score matched controls treated by MC. Early failure of ASE and in-hospital major vascular complications (any retroperitoneal hemorrhage, limb-threatening ischemia or surgical repair) and minor vascular complications (any groin hematoma ≥ 5 cm or pseudoaneurysm) following ASE deployment were prospectively assessed. Early failure of ASE was rare (1.8%). In the two groups, the major vascular complication rate was similar [odds ratio (OR), 2.5; 95% confidence interval (CI), 0.5-13.0; p = NS]. However, patients treated by ASE showed a significantly higher risk for minor vascular complications (OR, 2.2; 95% CI, 1.1-4.3; p = 0.029). In comparison to successful deployment, early ASE failure was associated with a very high risk for both major (OR, 15.7; 95% CI, 1.56-158.7; p = 0.002) and minor (OR, 6.1; 95% CI, 1.2-31.8; p = 0.015) vascular complications.In a large, single-center experience, early ASE failure was rare and the rate of major vascular complications following ASE deployment was similar to controls. However, an excess of minor vascular complications (generally large groin hematomas) was observed in patients treated by ASE. Our study confirms that early ASE failure is an important risk factor for severe vascular complications.

In a variant proportion of patients presenting with chest pain and electrocardiographic changes characteristic for ST – elevation myocardial infarction, percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not the myocardial reperfusion (ranging from 5p to 50p). Furthermore, prolonged myocardial ischemia often breaks down the coronary microvasculature and the flow to the infarct myocardium may seem to be markedly reduced. This condition is known as no reflow – phenomenon. The no reflow - phenomenon is associated with an increased incidence of malignant ventricular arrhythmias, heart failure and 30-days mortality. In the recent years in literature, several articles (subsequently discussed in the present review) have been published and made relevant to the study of the pathophysiology regarding no reflow – phenomenon. This knowledge has assisted in the development of new treatment strategies, such as prophylactic use of vasodilators, mechanical devices and drugs inhibiting platelet. The review has focused on the current literature about intra – coronary injection of drugs to treat no – reflow and microvascular dysfunction.

Objectives Methacrylic monomers are released, from dental composite resins, either into the oral cavity or in pulpal tissues, where they can cause local or systemic adverse effects. The mechanisms of these effects are not well understood, probably because such molecules can act at different levels also inducing a depletion of intracellular glutathione (GSH). GSH can detoxify methacrylates by conjugating their α,β-unsaturated carbon–carbon moiety to the thiol group, with the catalysis of glutathione S-transferases (GST). This reaction determines a GSH cellular depletion and belongs to the metabolism of α,β-unsaturated esters, protecting the body against the toxic effects of electrophiles. On the basis of the above considerations, this work aim is to set up a method for the detection of the adducts formed by methacrylic monomers with GSH in cells using HPLC coupled to mass spectrometry (HPLC–MS) and micellar electrokinetic capillary chromatography (MECK) techniques. Methods and results Adducts of glutathione with triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA) were incontrovertibly identified by HPLC–MS and MECK in human gingival fibroblasts and erythrocytes, both outside and inside cells. Molecular docking simulations of HEMA and TEGDMA in the experimental structure of glutathione S-transferase, are also reported to rationalize the effectiveness of such enzyme in the catalysis of the above described reaction. Significance The setup of a method for the identification of GSH-methacrylate adducts allows to determine when the metabolic pathway involving such compounds is employed by cells for the detoxification of monomers leached from composite resins.

Evidence supporting the use of drug-eluting stents (DES) in saphenous vein graft (SVG) disease is uncertain. Previous studies have suggested that DES might reduce the re-intervention rate in SVG disease, with conflicting data on mortality. Thus, a meta-analysis was performed to compare outcomes of DES vs. bare metal stent (BMS) in SVG disease.Medline and Web databases were searched for studies comparing DES and BMS for SVG disease, reporting rates of overall mortality, target vessel revascularization (TVR) and myocardial infarction (MI) with a follow-up of ≥6 months. The meta-analysis included 23 studies (7,090 patients). Compared with BMS, DES-treated patients had lower rates of TVR (odds ratio (OR), 0.53; confidence interval (CI), 0.39-0.72; P0.0001) and overall mortality (OR, 0.63; CI, 0.40-0.99; P=0.05), but similar rates of MI (OR, 0.92; CI, 0.64-1.33; P=0.7). Subgroup analysis highlighted differences between non-randomized studies, in which DES improved mortality rates, and randomized trials, in which benefit from DES was not evident. Meta-regression analysis showed that DES were more effective in the presence of older grafts and type 2 diabetes.The present meta-analysis showed that, in SVG disease, DES significantly reduced TVR, but did not provide clear benefits on mortality and MI, with an opposite direction of results in mortality observed from randomized and observational data.

Levosimendan is one of the documented pharmacological agents used in the management and treatment of acute and chronic heart failure; it is a novel inodilator agent which enhanced myocardial performance without changes in oxygen consumption. The combination of positive inotropic and vasodilator effects of levosimendan relates to its Ca(2+) - sensitizing and K(+) channels opening effects. Levosimendan has been proposed, in the recent past, to be non-inferior and may have some advantages to standard inotropes; further possible indications for levosimendan have been described, in some observational studies, such as a perioperative use, cardioprotection, cardiogenic shock, sepsis and right ventricular dysfunction. The ability of levosimendan to improve myocardial function without substantially increasing oxygen consumption may appear paradoxical but is possible via improved efficacy not only with regard to the effects on the contractile apparatus of the cardiomyocytes. The aim of this review is to describe the pharmacological characteristics of levosimendan and its clinical applications. The patent review data regarding the use of levosimendan are also discussed in this review article.

Cytotoxicity of the dental resin monomer 2-hydroxyethyl methacrylate (HEMA) and the protective effects of N-acetyl cysteine (NAC) on monomer-induced cell damage are well demonstrated. The aim of our study was to analyze the hypothesis that the protection of NAC from HEMA cytotoxicity might be due to direct NAC adduct formation. To this end, using HPLC we first measured the actual intracellular HEMA concentrations able to cause toxic effects on 3T3-fibroblasts and then determined the decrease in intracellular and extracellular HEMA levels in the presence of NAC. In addition, by capillary electrophoresis coupled with mass spectrometry analysis (CE-MS), we evaluated NAC-HEMA adduct formation. HEMA reduced 3T3 cell vitality in a dose- and time-dependent manner. The concentration of HEMA inside the cells was 15-20 times lower than that added to the culture medium for cell treatment (0-8 mmol/L). In the presence of 10 mmol/L NAC, both intracellular and extracellular HEMA concentrations greatly decreased in conjunction with cytotoxicity. NAC-HEMA adducts were detected both in the presence and absence of cells. Our findings suggest that the in vitro detoxification ability of NAC against HEMA-induced cell damage occurs through NAC adduct formation. Moreover, we provide evidence that the actual intracellular concentration of HEMA able to cause cytotoxic effects is at least one magnitude lower than that applied extracellularly.

The palladium-catalysed hydroxycarbonylation of vinyl and aryl triflates, under a CO balloon, in the presence of potassium acetate affords α,β-unsaturated and aromatic carboxylic acids with one more carbon in good to high yield. The nature of the solvent and of the ligand have been proved to be crucial for the success of the reaction. Vinyl triflates undergo the hydroxycarbonylation at room temperature in DMF in the presence of Pd(OAc)2(PPh3)2. Aryl triflates produce best results at 60 °C in DMSO in the presence of Pd(OAc)2 and 1,1-bis (diphenylphosphino)ferrocene (dppf).

Background The wide variability of NT-proBNP levels in acute coronary syndromes could arise from sympathetic activation and glomerular impairment. The aim of the study was to investigate, in this setting, the dependence of NT-proBNP from Chromogranin A (CgA) and Cystatin C (CC) levels, respectively assessing sympathetic activation and glomerular impairment. Methods In 132 patients, 90 ST elevation acute coronary syndrome (STE-ACS) and 42 non ST elevation acute coronary syndrome (NSTE-ACS), within 24 h from symptoms and with creatinine levels lower than 141.4 µmol/L, we measured NT-proBNP, CgA and CC levels. In 41 STE-ACS patients we evaluated the kinetic profiles of the markers. Results From the multiple regression model , to investigate the dependence of NT-proBNP from CgA, CC levels, time from symptoms, STE-ACS/NSTE-ACS subsets, gender, adjusting for the effect of left ventricular ejection fraction and age we had evidence of: 1) interactions involving the subsets, the first with CgA levels and the second with age; 2) non linear increasing effect of the delay on NT-proBNP secretion. Conclusions Our data showed that, in the population studied, sympathetic activation and age could affect NT-proBNP secretion yielding different secretory patterns in STE- or NSTE-ACS. Only for STE-ACS we observed higher marker secretion in older patients.

The polymerization of methacrylic monomers present in dental composite resins never reaches completion and therefore the leakage of residual monomers into the oral cavity and into biological fluids can cause local and systemic adverse effects. This work was carried out to study the in vitro biochemical interactions of urethane dimethacrylate and 1,4-butanediol dimethacrylate monomers with HL-60 cells, a cell line assumed as an experimental model for simulating granulocyte behaviour. Our main finding was that both monomers induce cell differentiation at toxic concentrations and that cytotoxicity seems to be caused by alterations of glucose metabolism arising from mitochondrial dysfunction rather than from oxidative stress, which could not be altogether verified under our experimental conditions. Our study could be considered as a useful approach to investigate the biochemical mechanisms that contribute to the cytotoxicity of methacrylate compounds and it underlines the importance of assessing such parameters for testing biocompatibility in order to promote the development of better and safer dental materials.

In the last years the studies regarding the biocompatibility of dental materials investigate, in addition to the classic cytotoxic tests, the interactions between the materials and the host cells to better explain the causes of the adverse effects observed sometimes in the clinical practice. In the present study the ability of diurethane dimethacrylate (DUDMA) and 1,4-butanediol dimethacrylate (BDDMA) methacrylic monomers present in dental composite resins to alter the functionality of peripheral blood monocytes (PBMs) and polymorphonucleate cells (PMNs) was examined. These cells are involve in the biological response to materials and in the host ability to respond to bacteria. The results obtained suggest that the examined methacrylates induce a relevant decrease of PBMs oxidative burst whereas the basal ROS production is only slightly decreased. In PMNs DUDMA induces a decrease of both basal and stimulated ROS production. BDDMA, on the contrary, it does not alter total oxidative burst in presence of stimulus while induces a statistically significant decrease of basal ROS production. Moreover this monomer alters the reaction kinetics of stimulated ROS production. The reported finding seems to indicate that this molecule could be able to stabilize PMNs in resting state and maximize their stimulated activity. Copyright © 2008 John Wiley & Sons, Ltd.

Objectives Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA – at a non-cytotoxic concentration – depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). Methods The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. Results All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. Conclusions All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo-polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte–macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte–macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials. Copyright © 2006 John Wiley & Sons, Ltd.

The case of a 67-year-old female patient with persistent pain in the right anterior knee appeared after she had an accidental fall, is discussed. Laboratory tests and imaging were negative. Persistent pain required MRI. Based on MRI findings the diagnosis of patellar fracture responsible for knee pain could be established.

We read with interest the letter of Kwong et al. regarding our recent publication in the journal. Our colleagues, despite recognizing the global value of our study, raised a few methodological concerns about our meta-analysis. First, Kwong et al. point out that our study is a meta-analysis of randomized studies, questioning the inclusion of NOBORI Core and TIVOLI studies which, indeed, are non-randomized trials. Our meta-analysis aimed to summarize the most complete information available in a field in which published data is rather limited. When the question of interest cannot be answered only by the inclusion of randomized trials, authors may be justified in including non-randomized

Binding of Zn 2 + to bacitracin A 1 was studied by capillary electrophoresis in water/ 2,2,2-trifluoroethanol (70/30 v/v) at different apparent pH values in order to estimate the association constant of metal, the acidic dissociation constants and the Stokes radii of both free and bounded peptide in apolar environment. The Stokes radii of the free peptide species were compared with those in aqueous solution, as obtained in a recent study performed by our group, indicating that apolar environment stabilizes bacitracin A 1 in a conformational structure with the lateral chain of apolar amino acids exposed on the external surface. This conformation of the macrocyclic dodecapeptide is ready to interact with Zn 2 + ion, as pointed out by the strong increase of the association constant measured in water/2,2,2-trifluoroethanol with respect to the value obtained in aqueous solution. In addition, whereas Zn 2 + ion binding in aqueous solution provides a sensible reduction of peptide Stokes radius, no sensible variations following to ion binding were observed in hydro-organic solution. The present results suggest that the apolar environment, rather than the metal ion binding, could be responsible for the conformational transition that brings bacitracin A 1 towards its biologically active structure.

Measurements by capillary electrophoresis (CE) of bacitracin A 1 effective mobility at different pH values permitted to estimate the five acidic dissociation constants and the Stokes radii at different protonation stages of the macrocyclic dodecapeptide. The pK a values were 3.6 and 4.4 for the two carboxylic groups of the lateral chains of D-Asp-11 and D-Glu-4, respectively, 6.4 for the aza-atom of the imidazole ring of His-10, 7.6 for the amino group of N-terminal Ile-1 and 9.7 for the δ-amino group of D-Orn-7, very close to the values obtained by other researchers by titration experiments. In agreement with a rigid macrocyclic structure the Stokes radii of different protonated forms ranged only between 14.3 and 14.8 A. Best fitting procedures performed on experimental mobility measured at two different pH values (5.50 and 6.72) in the presence of increasing Zn + 2 concentration allowed confirming the model that assumes the binding of Zn + 2 to P° peptide form with a 1.5 ×10 3 M - 1 intrinsic association constant. Following to Zn + 2 binding, the pK a of the amino group of N-terminal lle-1 is shifted from 7.6 to 5.9 and the Stokes radius is reduced of about 3 A. The mean charge of the bacitracin A 1 -Zn + 2 complex resulted +1.67 and +1.12 at pH 5.50 and 6.72, respectively. These results suggest that the amino group of N-terminal lle-1 is not essential for Zn + 2 binding.

In vitro cell cultures have been widely used as a means of evaluating cytotoxicity of root canal filling materials. Following ANSI/ADA spec. no. 41, the aim of the present study was to investigate the biological compatibility of a new sealer (FibreFill) and compare it with some commercially available endodontic sealers (Bioseal and Acroseal). Mouse 3T3 fibroblasts were seeded and cultured and subsequently extracts of the cements were added. After 24 hours incubation, the cellular vitality of fibroblasts was evaluated by the neutral red uptake test (NRU), which measures the membrane permeability. Data were collected and statistically analysed. Results showed that all tested materials exhibited mild cytotoxic effects, which are compatible with normal clinical use, and no statistically significant difference was noted between FibreFill and the other tested materials. Therefore, selection amongst these sealers should be based on other factors.

Human saliva from a healthy donor was subjected to fractionation by gel chromatography and six pools were collected and analysed by MALDI-TOF-MS and HPLC-ESI-MS. Three peptides, corresponding to 888.3, 687.3, and 524.1 amu and SNYLYDN, YLYDN, and LYDN sequences (determined by automated Edman sequencing), were isolated from pool 4. YLYDN was not previously described in human saliva. The peptides show the common C-terminal sequence of histatin 3 and histatin 1. To exclude the possibility that the three peptides were an artifact of the purification procedure, nine samples of human saliva were collected from healthy donors, immediately acidified with 0.2% TFA, and analysed by RP-HPLC-ESI-MS. The three peptides were detected in all the analyzed samples. SNYLYDN was always found at a concentration higher than that of YLYDN and LYDN. A correlation analysis performed on quantitative data indicated that the three peptides derive only from histatin 3. Other already known histatins also were searched for in the chromatogram. Histatins 1, 2, 3, 5, 6, 7, 8, and 10 were observed, although not in all samples analyzed, whereas other minor histatins were not detected.

Human salivary cystatins, five major (S, S1, S2, SA, SN) and two minor (C and D), are multifunctional proteins playing a different role in the oral environment. Salivary cystatin SN is able to effectively inhibit lysosomal cathepsins B, C, H and L and cystatin SA inhibits cathepsins C and L in vitro. These activities suggest, particularly for cystatin SN, an important role in the control of proteolytic events in vivo. Differently, cystatins S are involved, together with statherin, in the mineral balance of the tooth. Due to their distinct role, a reliable method for identification and quantification of the different cystatins, as well as of possible truncated and derived forms, could be helpful for the assessment of the status of the oral cavity. To this purpose high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI MS) was applied to the analysis of human saliva obtained from healthy subjects. All known salivary cystatins, with the exception of cystatin C, were detected. Strong evidence was also obtained for the presence in saliva of post-translational modified isoforms of cystatins, which may be related to donor habits. Cystatin SN and cystatins S, S1 and S2 were well separated by HPLC-ESI MS coupling from other components and thus this approach can be successfully applied to their quantification.

Background The main limitation of myocardial single photon emission computed tomography (SPECT) in detecting hibernating myocardium is the poor delivery of radiotracers in hypoperfused areas supplied by severely stenotic coronary arteries. Increasing local availability of radiotracers by intracoronary injection might represent an attractive solution. The hypothesis that the intracoronary administration of sestamibi could improve myocardial SPECT accuracy in detecting hibernating myocardium was addressed in this pilot study. Methods and results Seven patients with prior myocardial infarction and severe stenosis of the infarct-related artery underwent myocardial SPECT after intracoronary injection of technetium 99m sestamibi immediately before percutaneous transluminal coronary angioplasty (PTCA). Wall motion and perfusion were evaluated, before and 1 month after PTCA, by 2-dimensional echocardiography and rest-redistribution thallium 201 SPECT. A “low-flow area” was identified on the pre-PTCA Tl-201 SPECT image as the area with less than 50% of maximum radiotracer uptake. Changes in wall motion and perfusion in the low-flow area were compared with results of intracoronary sestamibi imaging. On a pixel-by-pixel analysis, intracoronary sestamibi predicted perfusion recovery within the low-flow area with a 91% sensitivity, a 78% specificity, and an 82% overall accuracy. Only in the 5 patients with an extent of sestamibi uptake greater than one third of the low-flow area was an improved regional and global left ventricular wall motion observed after PTCA (wall motion score index decreased from 1.95 ± 0.28 to 1.60 ± 0.34, P = .007; left ventricular ejection fraction increased from 42% ± 7% to 49% ± 7%, P = .001; asynergic segments in the low-flow area decreased from 3.6 ± 0.9 to 1.8 ± 1.5, P = .021). Conclusions In patients with prior myocardial infarction and severe stenosis of the infarct-related artery, sestamibi uptake after intracoronary administration identified viable myocardium that was undetected after rest-redistribution thallium SPECT but capable of clinically significant contractile improvement after revascularization.

The circadian rhythms of histatins 1, 3, 5, of statherin and uric acid were investigated in whole human saliva. Histatins showed a rhythm approximately synchronous with salivary flow rate (acrophas...

Most patients with chronic stable angina show an improvement in ischemic threshold when a second exercise test is performed a few minutes after a first positive test. In this study we evaluated whether this “warm-up” phenomenon also occurs in patients with syndrome X. We performed 2 consecutive exercise tests in 14 patients with chronic stable angina and 11 patients with syndrome X. The second exercise test was performed after 10 minutes from the end of the first one, always after complete recovery to baseline of ST segment. In patients with stable angina, heart rate (108 ± 18 vs 99 ± 16 beats/min, p = 0.005), rate-pressure product (17,020 ± 4,541 vs 15,215 ± 3,734 beats/min × mm Hg, p = 0.028), and exercise time (587 ± 297 vs 444 ± 244 seconds, p = 0.002) at 1-mm ST depression were higher in the second test than in the first one and a significant improvement in these parameters during the second test was also observed at peak exercise. Conversely, in patients with syndrome X, there were no significant differences between the 2 tests in heart rate (128 ± 18 vs 131 ± 23 beats/min), rate–pressure product (19,922 ± 5,153 vs 19,390 ± 5,654 beats/min × mm Hg), and exercise time (592 ± 243 vs 566 ± 228 seconds) at 1-mm ST-segment depression. Similarly, in this group of patients, no significant differences in exercise variables between the 2 tests were observed at peak exercise. Thus, unlike patients with chronic stable angina, patients with syndrome X have no evidence of warm-up in response to repeated exercise testing.

A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction40% and a number of ventricular premature beatsor = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).

In order to ascertain whether human adenosine-induced dilatation of epicardial arteries is direct or flow-mediated, we compared the effects of intracoronary adenosine infusion on epicardial coronary arteries with those produced by dipiridamole, a selective arteriolar vasodilator.In 24 patients with angiographically normal coronary arteries, coronary blood flow velocity was measured by a Doppler wire during intracoronary infusion of adenosine or dipyridamole, which is known to increase intramyocardial adenosine concentration. Coronary angiograms were obtained at baseline and immediately after the end of each infusion period; coronary diameters 5 mm distal to the wire tip were measured by computer-assisted quantitative coronary angiography. Peak coronary blood flow velocities during adenosine or dipyridamole infusions were similar (52.0 +/- 15.5 and 47.9 +/- 24.2 cm.s-1, P = ns). Coronary diameters immediately after adenosine and dipyridamole infusions were similar and both higher than that at baseline (2.80 +/- 0.63 and 2.86 +/- 0.64 vs 2.44 +/- 0.69 mm, P0.05). The absolute and percentage increases of coronary artery diameters in response to adenosine were highly correlated to coronary blood flow velocity (R = 0.622, intercept -0.10 +/- 0.14, P = 0.002 and R = 0.617, intercept -15.2 +/- 9.9, P = 0.001, respectively); similar correlations were found in response to dipyridamole (R = 0.708, intercept -0.44 +/- 0.19, P0.001 and R = 0.649, intercept -13.5 +/- 8.7, P0.001, respectively). Finally the absolute and percentage changes of coronary artery diameters caused by adenosine were highly correlated to those caused by dipyridamole (R = 0.840 P0.001 and R = 0.836, P0.001 respectively).A significant correlation exists between epicardial coronary vasodilation and coronary blood flow velocity during intracoronary adenosine infusion, thus suggesting that epicardial coronary vasodilation induced by adenosine is predominantly flow-mediated rather than direct. This conclusion is supported by the observation that similar findings were obtained using dipyridamole, which can only dilate epicardial coronary arteries indirectly, through the increase in coronary blood flow velocity caused by the inhibition of intramyocardial adenosine re-uptake.

There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration.Prospective laboratory study.Normal human subjects.Radioactive [3H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined.Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor.[3H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p.001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 +/- 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [3H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 +/- 12.2%) than with washed blood (1.1 +/- 0.3%) or plasma (11.9 +/- 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C.These studies provide experimental evidence for the prompt, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis.

The general properties of dendrimers and in particular their electrolytic characteristics that are relevant in electrokinetic separations, are described. In order to confirm theoretical considerations on commercial dendrimer charge and hydrodynamic radius, several capillary zone electrophoresis (CZE) experiments were performed. Electrophoretic mobilities measured at different pH values indicated a sensible increase of dendrimer hydrodynamic radius at pH values lower than 2.5. This was probably due to the Coulombic repulsion of charged amine groups of the inner dendrimer shells. The principal reasons that should address the use of dendrimers as pseudostationary phases in micellar electrokinetic chromatography (MEKC) are discussed. Moreover, a survey of different separations performed utilizing dendrimers in MEKC as well as of several future plausible uses of various classes of dendrimers is presented.

A very simple regio- and stereospecific synthesis of 17-noraphidicolan-16-one and 17-norstemodan-16-one by solvolytic rearrangement of suitable bicyclo[2.2.2]--octenyl methanesulfonate is described.

A simple and stereoselective total synthesis of (±)-maritimol (2d) and its conversion into the other title compounds (±)-(2a), ((±)-2b), and ((±)-2c) is described. The unique bicyclo[3.2.1]octane moiety, constituting their C/D-ring system, is stereospecifically obtained by solvolytic rearrangement of the methanesulfonate 23.

A regio- and steroselective conversion of the totally synthetic 3α, 18-di-O-benzyl-17-nor-14-aphidicolen-16-one (5), into (±)-aphidicolin 1, by hydroxylation of the 2-methylidenebicyclo[3.2.1] oct-3-ene derivative 6 is described. Compound 5 was a key intermediate in our previously described total synthesis of 2, which represented a formal synthesis of 1.

A biogenetic-type total synthesis of(±)-2-deoxystemodinone (1), by solvolytic rearrangement of the 1-methyl[2.2.2]oct-2-yl methanesulphonate 4, is described.

A simple, efficient, and stereospecific total synthesis of (±)-3α, 18-dihydroxy-17-noraphidicolan-16-one (2), by solvolytic rearrangement of the endo-bicyclo-[2.2.2]oct-5-en-2-yl methanesulfonate 16, is described. Since aphidicolin (1) has already been obtained from 2, the preparation of the latter formally constitutes a new total synthesis of 1.