Intravenous paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: a double blind randomized controlled trial.

BACKGROUND: Nonsteroidal anti-inflammatory drugs and opioids are routinely used after cardiac surgery in order to mitigate postoperative pain; however, these drugs are burdened by side effects. Tramadol and paracetamol are believed to be lacking in such side effects. The aim of this study was to examine the efficacy of intravenous paracetamol as an adjunctive analgesic to a tramadol-based background analgesia after cardiac surgery. METHODS: A total of 113 patients participated in this single center, placebo-controlled, double-blind, randomized trial. Fifty-six patients were randomized to receive paracetamol and 57 to placebo. Intravenous study drug (1 g) was administered 15 min before the end of surgery and every 6h for 72 h. Standard analgesia (tramadol) and anti-emetic prophylactic regimen (ondansetron) were available to both patient groups. Postoperative pain was evaluated by visual analog scale, and it was measured at rest and during a deep breath. A rescue dose of 2-5 mg of intravenous morphine was administered whenever the VAS score was greater than 3. RESULTS: Baseline characteristics were equivalent between the two groups. At 12, 18, 24 h after the end of operation, patients who received paracetamol had significantly less pain at rest (p=0.0041, 0.0039, 0.0044, respectively); after this time the two groups did not differ. During a deep breath the difference was significant only at 12 h (p=0.0040). Paracetamol group required less cumulative morphine than placebo group (48 mg vs 97 mg) even if the difference did not reach statistical significance (p=0.274). CONCLUSIONS: In patients undergoing cardiac surgery, intravenous paracetamol in combination with tramadol provides effective pain control.     

Alteration of A(3) adenosine receptors in human neutrophils and low frequency electromagnetic fields

The present study was designed to evaluate the binding and functional characterization of A(3) adenosine receptors in human neutrophils exposed to low frequency, low energy, pulsing electromagnetic fields (PEMFs). Great interest has grown concerning the use of PEMF in the clinical practice for therapeutic purposes strictly correlated with inflammatory conditions. Saturation experiments performed using the high affinity and selective A(3) adenosine antagonist 5N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine ([3H]-MRE 3008F20) revealed a single class of binding sites with similar affinity in control and in PEMF treated human neutrophils (K(D)=2.36+/-0.16 and 2.45+/-0.15 nM, respectively). PEMFs treatment revealed that the receptor density was statistically increased (P<0.01) (B(max)=451+/-18 and 736+/-25fmolmg(-1) protein, respectively). Thermodynamic data indicated that [3H]-MRE 3008F20 binding in control and in PEMF-treated human neutrophils was entropy and enthalpy driven. Competition of radioligand binding by the high affinity A(3) receptor agonists, N(6)-(3-iodo-benzyl)-2-chloro-adenosine-5'-N-methyluronamide (Cl-IB-MECA) and N(6)-(3-iodo-benzyl)adenosine-5'-N-methyl-uronamide (IB-MECA), in the absence of PEMFs revealed high and low affinity values similar to those found in the presence of PEMFs. In both experimental conditions, the addition of GTP 100 microM shifted the competition binding curves of the agonists from a biphasic to a monophasic shape. In functional assays Cl-IB-MECA and IB-MECA were able to inhibit cyclic AMP accumulation and their potencies were statistically increased after exposure to PEMFs. These results indicate in human neutrophils treated with PEMFs the presence of significant alterations in the A(3) adenosine receptor density and functionality.     

Retrospective evaluation of the influence of the interleukin-1 genotype on radiographic bone levels in treated periodontal patients over 10 years.

BACKGROUND: A difference in genetic susceptibility to plaque accumulation has been advocated to explain different responses to periodontal therapy. The purpose of this study is to assess the role of the interleukin-1 (IL-1) polymorphism on the rate of bone and tooth loss in non-smoking periodontally treated patients during maintenance. METHODS: Sixty consecutive non-smoking patients (mean age 46.8 +/- 5.0) with moderate to severe periodontitis, treated and maintained for over 10 years were selected. At baseline (T0), radiographic evaluation (cemento-enamel junction [CEJ]-root apex, CEJ-bottom of defect mesial and distal, CEJ-bone crest mesial and distal, crown-root ratio) was performed. All patients received scaling and root planing; 36 patients then underwent surgical therapy. Subsequently, all patients were enrolled in a periodontal maintenance program with recall visits every 3.4 +/- 1.0 months for at least 10 years. At the latest recall visit (T2) the same radiographic measurements evaluated at baseline were taken and a DNA sample for IL-1 genetic susceptibility testing was collected and sent for analysis. RESULTS: Twenty-three of the 60 patients (38.3%) were IL-1 genotype positive. A total of 52 teeth (3.3%) out of 1,566 were lost due to periodontitis between T0 and T2; 28 of 957 (2.9%) in the IL-1 genotype negative group and 24 of 609 (3.9%) in IL-1 genotype positive group. The mean variation in bone defect level (DeltaBD) averaged -0.04 mm in IL-1 genotype negative patients and 0.01 mm in IL-1 genotype positive patients. The mean variation in bone crest level (DeltaBC) averaged -0.24 mm in IL-1 genotype negative patients and -0.28 mm in IL-1 genotype positive patients. However, a few patients showed significant differences in response to therapy based on initial bone levels and genotype. IL-1 negative patients who showed minimal initial bone loss responded to the therapy better than the IL-1 positive patients. IL-1 positive patients with severe initial bone loss showed a better response to the therapy than IL-1 negative patients. CONCLUSIONS: On average, there were no significant differences related to IL-1 genotype in tooth loss after 10 years in a non-smoking, well-maintained periodontal population. On an individual patient basis, the IL-1 genotype, in combination with the initial bone level, seems useful at the beginning of therapy for predicting bone level variation.     

A controlled multicenter study of adjunctive use of tetracycline periodontal fibers in mandibular class II furcations with persistent bleeding

Abstract. The aim of this randomized single-blind multicenter controlled clinical trial was to clinically evaluate the effectiveness of adjunctive local controlled drug delivery in the control of bleeding on probing in mandibular class II furcations during maintenance care. 127 patients presenting with a class II mandibular furcation with bleeding on probing were included in the study. They had been previously treated for periodontitis and were participating in supportive care programs in periodontal speciality practices. Treatments consisted of scaling and root planing with oral hygiene instructions (control) and scaling and root planing and oral hygiene combined with local controlled drug delivery with tetracycline fibers (test). The following outcomes were evaluated at baseline and 3 and 6 months after therapy at the furcation site: bleeding on controlled force probing (BOP), probing pocket depth (PD) and clinical attachment levels (CAL). Levels of oral hygiene and smoking status were also assessed. Both test and controls resulted in significant improvements of BOP and PD at 3 and 6 months. The test treatment, however, resulted in significantly better improvements: BOP decreased by 52% in the control group and by 70% in the test group at 3 months; at 6 months, however, the difference was no longer significant. The test treatment resulted in a 0.5 mm greater reduction of PD than the control at 3 months, the improvement was highly significant but its duration did not extend until the 6 months evaluation. No differences were observed in terms of changes in CAL. These data indicate that addition of tetracycline fibers to mechanical therapy alone resulted in improved control of periodontal parameters during periodontal maintenance of class II mandibular furcations. Short duration of the effect, however, requires further investigations to optimize conservative treatment of these challenging defects.     

Pharmacological characterization of novel adenosine ligands in recombinant and native human A2B receptors

The present study was designed to evaluate the effects of novel and recognised compounds at human recombinant A(2B) adenosine receptors expressed in Chinese hamster ovary (hA(2B)CHO), in human embryonic kidney 293 (hA(2B)HEK-293) and at endogenous A(2B) receptors in human mast cells (HMC-1). Saturation binding experiments performed using the new high affinity A(2B) adenosine radioligand [(3)H]-N-benzo[1,3]dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetra hydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]-acetamide ([(3)H]-MRE 2029F20) revealed a single class of binding sites in hA(2B)CHO, hA(2B)HEK-293 and HMC-1 cells with K(D) (nM) of 1.65+/-0.18, 2.83+/-0.34, 2.62+/-0.27 and B(max) (fmol/mg protein) of 36+/-4, 475+/-50 and 128+/-15, respectively. The pharmacological profile of new compounds, determined in inhibition binding experiments in hA(2B)HEK-293 cells using [(3)H]-MRE 2029F20, showed a rank order of potency typical of the A(2B) receptors with K(i) values in the range 3.2-28nM. In functional assays, recognised agonists and antagonists were studied by evaluating their capability to modulate the cAMP production in hA(2B)CHO and in HMC-1 cells. Novel compounds were able to decrease NECA-stimulated cAMP production in hA(2B)CHO and in HMC-1 cells showing a high potency. New compounds were also able to inhibit cAMP levels in the absence of NECA and in the presence of forskolin stimulation in hA(2B)CHO and in HMC-1 cells. In HEK-293 cells MRE 2029F20 reduced cAMP basal levels with an IC(50) value of 2.9+/-0.3nM. These results suggest that novel compounds are antagonists with an inverse agonist activity in recombinant and native human A(2B) receptors.     

Influence of gingival crevicular washing on the expression of polymorphonuclear leukocyte membrane receptors before and after periodontal therapy

Abstract. Extensive data demonstrate that polymorphonuclear leukocytes (PMN) are the predominant cell type involved in periodontal disease and that gingival crevicular fluid constituents are influenced by the inflamed gingiva. The aim of the present study was to evaluate the ability of gingival crevicular washing (GCW) (a dilution of gingival crevicular fluid) from periodontal sites in different clinical conditions of modulating the PMN membrane receptors involved in motility, adhesion and phagocytosis before and after periodontal treatment. 10 patients affected by adult periodontitis (AP) were selected. From each patient. 2 test sites (TS) were chosen on the basis of a probing depth > 5 mm and attachment loss, and 2 control sites (CS) with probing depth < 3 mm without attachment loss. Modifications of membrane receptor density of PMN from healthy donors incubated with GCW harvested from TS and CS was evaluated using fluorescent probes and flow cytometry. Compared to CS-GCW. TS-GCW before therapy increased the expression of the β2 integrin CD 11b and the chemotactic receptor for the oligopeptide N-formyl methionyl leucyl phenylalanine (FMLP-R) while it reduced the expression of L-selection. GCW collected from the same TS after the successful completion of periodontal treatment did not influence PMN receptors, indicating that the clinical improvement paralleled the disappearance of the PMN modulating capability contained in TS-GCW before therapy. In conclusion, the present data illustrate the relevant modifications occurring at PMN membrane in chronic adult periodontitis exerted by GCW obtained by a simple fluid collection technique. Thus, monitoring gingival crevicular fluid PMN activating capability may help disclose the presence of chronic periodontitis and may be useful in assessing successful treatment.     

Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils

The present study describes the effect of low frequency, low energy, pulsing electromagnetic fields (PEMFs) on A2A adenosine receptors in human neutrophils. Saturation experiments performed using a high affinity adenosine antagonist [3H]-ZM 241385 revealed a single class of binding sites in control and in PEMF-treated human neutrophils with similar affinity (KD=1.05+/-0.10 and 1.08+/-0.12 nM, respectively). Furthermore, after 1 h of exposure to PEMFs the receptor density was statistically increased (P<0.01) (Bmax =126+/-10 and 215+/-15 fmol mg-1 protein, respectively). The effect of PEMFs was specific to the A2A adenosine receptors. This effect was also intensity, time and temperature dependent. In the adenylyl cyclase assays the A2A receptor agonists, HE-NECA and NECA, increased cyclic AMP accumulation in untreated human neutrophils with an EC50 value of 43 (40 - 47) and 255 (228 - 284) nM, respectively. The capability of HE-NECA and NECA to stimulate cyclic AMP levels in human neutrophils was increased (P<0.01) after exposure to PEMFs with an EC50 value of 10(8 - 13) and 61(52 - 71) nM, respectively. In the superoxide anion (O2-) production assays HE-NECA and NECA inhibited the generation of O2- in untreated human neutrophils, with an EC50 value of 3.6(3.1 - 4.2) and of 23(20 - 27) nM, respectively. Moreover, in PEMF-treated human neutrophils, the same compounds show an EC50 value of 1.6(1.2 - 2.1) and of 6.0(4.7 - 7.5) nM respectively. These results indicate the presence of significant alterations in the expression and in the functionality of adenosine A2A receptors in human neutrophils treated with PEMFs.     

Clinical experience with polyclonal IgM-enriched immunoglobulins in a group of patients affected by sepsis after cardiac surgery

OBJECTIVE: The purpose of this study was to evaluate the efficiency, in terms of decreasing overall mortality (primary endpoint), of an immunoglobulin M (IgM)-enriched, polyclonal intravenous immunoglobulin preparation (IVIg) (Pentaglobin; Biotest AG, Dreieich, Germany) in the treatment of a group of patients affected by sepsis after cardiac surgery. A secondary endpoint was to evaluate which subgroup, on the basis of the infectious state when the patient enrolled, could benefit the most from the treatment. Another secondary endpoint was the evaluation of an improvement in the severity score or in other variables such as Glasgow Coma Scale; arterial pressure (systolic, average, and diastolic); heart rate; central venous pressure; cardiac index; respiratory rate; PaO(2), F(I)O(2), and the ratio of PaO(2) to F(I)O(2); pH, base excess, and bicarbonate; C reactive protein and leukocytes; platelets, prothrombin time, partial thromboplastin time, fibrinogen, and anti-thrombin III; creatinine; and bilirubin. DESIGN: Retrospective case-controlled study. SETTING: Cardiovascular intensive care unit of a university hospital. PARTICIPANTS: Sixty-six patients who developed sepsis in the postoperative period after cardiac surgery were admitted to the cardiovascular intensive care unit from June 1, 2001, to June 30, 2003: 30 patients (45.5%) had valvular surgery, 18 (27.5%) had myocardial revascularization, 14 (21%) had thoracic aorta surgery, and 4 (6%) had other surgery. INTERVENTIONS: From the 66 patients diagnosed with sepsis, 22 patients (IVIg group) received IgM-enriched immunoglobulins in addition to the conventional therapy, whereas the other 44 patients (control group) were treated only with conventional therapy. The decision as to whether or not to administer the immunoglobulins was made by physicians in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Of the 66 patients, 8 patients (3 from the IVIg group and 5 from the control group) had sepsis, 47 patients (15 from the IVIg group and 32 from the control group) had severe sepsis, and 11 patients had septic shock (4 from the IVIg group and 7 from the control group). The overall mortality rate was 31.8% without significant differences between groups (22.7% IVIg group v 36.4% control group, p = not significant). Among the 47 patients affected by severe sepsis, those from the control group had a mortality rate significantly higher than that of the IVIg group (12/32 [37.5%] v 1/15 [6.6%], p = 0.036 [2-sided Fisher exact test]). The 70-day survival rate was significantly higher in the IVIg group than in the control group (log-rank test, p < 0.04). No significant differences were found between study groups in Acute Physiology and Chronic Health Evaluation II or SOFA scores. CONCLUSIONS: The polyclonal IgM-enriched immunoglobulins did not significantly reduce the mortality rate in the overall study population. However, in the subgroup of patients with severe sepsis, they improved the survival rate significantly.