effect of curcumin on some of traditional and non-traditional cardiovascular risk factors: a pilot randomized, double-blind, placebo-controlled trial

Numerous interventional studies in clinical and preclinical setting stated that intake of curcumin may provide protection against cardiovascular disease. The aim of this trial was investigation of curcumin efficiency on some cardiovascular risk factors in patients with coronary artery disease [CAD]. A total of 33 patients with CAD who fulfilled inclusion and exclusion criteria were entered the study. Patients were randomly assigned to receive curcumin or placebo, 500 mg capsules, four times daily for 8 weeks. Lipid profile, blood glucose and high sensitive C-reactive protein [hs-CRP] levels were analyzed at baseline and two months after treatment. Serum levels of triglycerides [P=0.01], LDL-cholesterol [P=0.03] and VLDL-cholesterol [P=0.04] significantly decreased in the curcumin group compared to baseline, without significant changes in total cholesterol, HDL-cholesterol, blood glucose and hs-CRP levels. In all mentioned laboratory parameters, significant difference was not detected between curcumin and placebo. Although curcumin improved some of lipid profile components, it did not show appreciable effect on inflammatory markers in patients with CAD. Therefore, more detailed assessment of metabolic effects or anti-inflammatory activities of curcumin need to perform by extensive human study

Comparison of the effects of enoxaparin and heparin on inflammatory biomarkers in patients with ST-segment elevated myocardial infarction: a prospective open label pilot clinical trial

Heparin and enoxaparin possess anti-inflammatory properties. We compared the effects of these drugs on inflammatory biomarkers in patients with ST-segment Elevated Myocardial Infarction [STEMI]. Thirty four patients with STEMI randomly separated in two groups and received standard doses of heparin and enoxaparin. The serum concentration of Serum Amyloid A [SAA], C-Reactive Protein [CRP], Interleukin [IL]-6. ferritin and Myeloperoxidase [MPO] were measured at baseline ,12 .24 and 48 hours after drug administration. Serum concentrations of SAA [P: 0.02], CRP [P: 0.02] and ferritin [P: 0.01] significantly reduced in heparin group during measurements compared to baseline, circulating levels of IL-6 [P: 0.002], SAA [P: 0.009], CRP [P: 0.01] were significantly decreased in enoxaparin group. The overall difference in inflammatory biomarkers between heparin and enoxaparin group was not significant. Both heparin and enoxaparine reduced serum levels of inflammatory biomarkers in patients with STEMI. This effect may provide additional clinical benefit of these drugs in the treatment of STEMI patients

Intensive care unit staff and resource utilization: is it an effective factor?

The aim of present study was to determine the impact of two different ICU management model, open and semi closed, on resources utilization in intensive care unit. Retrospective cohort analysis using data from hospital database was applied to compare the effect of ICU management model on ICU length of stay and bed disposition of 1064 patients admitted to the general ICU of Imam Khomeini Hospital of Tehran, Iran during the two consecutive 12-month periods from Mar, 2009 to Feb, 2010. In open and semi closed interval 380 and 684 patients were admitted to ICU respectively. There was no significant difference in age, gender and severity of illness [based on APACHE-II score] and nurse to bed ratio between two groups. Average ICU length of stay, net mortality rate and bed turnover rate were lower in semi closed model than open model management significantly [P<0.05]. Semi closed model improves patient care and lead to lower mortality rate and resources utilization too

Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units [ICUs]. In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic [PK] and pharmacodynamic [PD] properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution [Vd] and clearance [CL] of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs [increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis], therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations

Pharmacokinetics alterations of midazolam infusion versus bolus administration in mechanically ventilated critically ill patients

There is no randomized study carried out in order to compare their pharmacokinetic parameters although midazolam, as a sedative, has been widely administered via continuous infusion as well as intermittent bolus doses in mechanically ventilated critically ill patients. We prospectively investigated the effect of these two principal methods on pharmacokinetic parameters in 23 of mentioned patients [16 males, 7 females] with the mean [ +/- SD] age of 41.22 +/- 17.5. All patients received total dose of 72 mg throughout the test days, 9 of whom received 1 mg/h [continuous infusion] and the rest obtained 4 mg / 4 h [intermittent bolus doses]. Blood samples were collected at 8 and 4 h prior to the end time of drug administration [zero time], zero time and 4, 8, 12, 20 and 30 h after it. APACHE [Acute Physiology and Chronic Health Evaluation] II required data was recorded daily and the patients' mean score was 16.26 +/- 4.38. The mean [ +/- SD] value of pharmacokinetic parameters of Midazolam in continuous infusion and intermittent bolus doses methods were as follows: [t[1/2] = 17.88 +/- 14.65 h, Cl = 21.80 +/- 14.95 L/h] vs. [t[1/2] = 19.74 +/- 12.45 h, Cl = 29.43 +/- 19.45 L/h]. Volume of distribution [Vd] was measured in continuous infusion group which was 612.58 +/- 582.93 L. The calculated clearance and half-life were found not to be significantly different [p < 0.05]. The patients might be exposed to similar undesired effects due to the large volumes of distribution following the administration methods studied

incidences of oxidative-stress occurrence following two metabolic support measures in critically ill patients

A high percentage of patients admitted to the Intensive Care Unit [ICU] have Systemic Inflammatory Response Syndrome [SIRS] criteria. Free radicals play an important role in initiation and development of SIRS. The purpose of this study was to assess and compare the molecular changes of cellular antioxidant power in patients with SIRS who received enteral nutrition [EN] or EN combined with parenteral nutrition [PN]. Two groups of 10 patients were enrolled in this randomized, controlled clinical trial. Those in the treatment group received EN+PN and the control group received only EN. Venous blood samples were taken just prior to initiation of nutritional support and then 24, 48 and 72 hours following entry into the study for examination of antioxidant parameters including total thiol, total antioxidant capacity and lipid peroxidation. The two supportive regimens had different affects on total antioxidant capacity [P=0.005]. In the EN group the amount of total antioxidant capacity was not significantly different in different days [P>0.05], but in the EN+PN group it was significantly different on third and forth days as compared to the first day. The two other parameters had no significant differences between the two groups. These results are suggesting that an increase in oxidative stress bio-markers are not necessarily related to the route of pharmaconutrition and may occur independently during metabolic support measures.

Effect of hypertonic saline infusion versus normal saline on serum ngal and cystatin c levels in patients undergoing coronary artery bypass graft

Acute kidney injury [AKI] is a common and life-threatening complication following coronary artery bypass graft [CABG]. Neutrophil gelatinase-associated lipocalin [NGAL] and Cystatin C have shown to be good predictive factors for AKI. Recently, there has been a growing interest in the use ofhypertonic saline in cardiac operations. The purpose of this study was to evaluate the prophylactic anti-inflammatory effect ofhypertonic saline [Group A] infusion versus normal saline [Group B] on serum NGAL and Cystatin C levels as the two biomarkers of AKI in CABG patients. This randomized double-blinded clinical trial recruited 40 patients undergoing CABG in Tehran Heart Center, Tehran, Iran. After applying exclusion criteria, the effects of preoperative hypertonic saline [294 meq Na] versus normal saline [154 meq Na] infusion on serum NGAL and Cystatin C levels were investigated in three intervals: before surgery and 24 and 48 hours postoperatively. The probable intraoperative or postoperative confounders, including pump time, cross-clamp time, heart rate, systolic and diastolic blood pressures, central venous pressure, arterial pH, partial pressure of arterial oxygen, fraction of inspired oxygen, blood sugar, Na, K, Mg, hemoglobins, white blood cells, hematocrits, and platelets, were recorded and compared between the two groups of study. The study population comprised 40 patients, including 25 [62.5%] males, at a, mean age +/- SD of 61.7 5 +/- 8.13 years. There were no statistically significant differences between the patients' basic, intraoperative, and postoperative characteristics, including intraoperative and postoperative hemodynamic variables and supports such as inotropic use. Intra-aortic balloon pump use and mortality were not seen in our cases. Three patients in the normal saline group and one patient in the hypertonic saline group had serum NGAL levels greater than 400 ng/ml. Moreover, 10 patients in Group A and 17 patients in group B showed a rise in serum Cystatin C levels above 1.16mg/dl. Patients with AKI had significantly elevated NGAL and Cystatin C levels [p value < 0.001], but there were no significant differences in the decrease in the NGAL level in the hypertonic saline group versus the normal saline group [230.91 +/- 92.68 vs. 239.74 +/- 116.58 ng/ml, respectively; p value = 0.792], or in the decrease in the Cystatin C level in the hypertonic saline group versus the normal saline group [1.05 +/- 0.26 vs. 1.06 +/- 0.31, respectively; p value = 0.874]. Pre-treatment of CABG patients with hypertonic saline had no significant effect on serum NGAL and Cystatin C levels compared to the normal saline-receiving group. Our present data, albeit promising, have yet to fully document outcome differences

Effects of pantoprazole on systemic and gastric pro- and anti-inflammatory cytokines in critically three patients

Stress-related mucosal damage [SRMD] is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of SRMD with proton pump inhibitors or histamine-2 blockers has gained widespread use in intensive care units. Both demonstrated to be effective in reducing clinically significant bleedings, while PPIs has shown to exert some anti inflammatory effects including the inhibition of producing pro-inflammatory cytokines. As cytokines have role in developing SRMD, the aim of this study was to evaluate the effect of PPIs on the inhibition of cytokine release following the critical illness. A total of 27 critically ill patients with risk factors of developing stress ulcer and intragastric pH < 3.0 enrolled to this Randomized clinical trial study. Patients were randomly assigned in three treatment groups; group one received 40 mg of intravenous pantoprazole every 12 h for 48 h [four doses], group two received 80 mg of intravenous pantoprazole every 24 h continuous infusion for 48 h and the third group received 150 mg of ranitidine intravenously as 24 h continuous infusion for 48 h. Plasma and gastric juice samples were obtained at 0th, 12th, 24th and 48th h for the measurement of EGF, IL-1beta, IL-6, IL-10 and TNF-alpha. Pantoprazole infusion have decreased the plasma IL-1beta concentrations [p = 0.041]. No other significant differences in concentrations of EGF, IL-6, IL-10 and TNF-alpha were detected. There were reverse correlations between the intragastric pH with gastric juice IL-1beta and TNF-alpha concentrations and a direct correlation between the intragastric pH and gastric juice EGF in pantoprazole groups. Our data suggest that pantoprazole may have some anti-inflammatory effects on patients. However, the exact impact of this effect on patients should be assessed by further studies

Loss of consciousness secondary to lead poisoning

Diagnosis of lead toxicity could be difficult in IC setting because of overlap of signs and symptoms with other diseases. This is a report of two Iranian patients [father and son] with severe level of whole blood concentration, developing into unconsciousness

Quadriplegia due to lead-contaminated opium - case report

Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed: anemia [Hb 7.7 g/dl]. slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. FMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 micro g/dl. He received dimercaprol [BAL] and calcium disodium edetate [CaEDTA] for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. The delayed treatment of lead poisoning may lead to irreversible motor neuron defect

therapeutic effect of gamma interferon in chronic bronchiolitis due to mustard gas

Bronchiolitis has been known as one of the pathological features of lung injuries in mustard gas exposed patients The purpose of this research was to evaluate the efficacy of interferon gamma-1b on the lung function in mustard gas exposed patients with bronchiolitis. In multicenter research interferon gamma-1b was effective in pulmonary fibrosis with unknown reason, but assessment of effect of interferon gamma-1b in the chemical injured patients has not so far been reported. Thirty six patients with bronchiolitis whose lung lesion had been diagnosed through the chest high resolution computerized tomography [HRCT] and pathological study were divided into two eighteen member case and control groups. The case group was treated for 6 months with a combination of 200 µg of interferon gamma-1b [given three times per week subcutaneously] and 7.5mg of prednisolone [given once a day], while the control group received their previous medications [prednisolone 7.5mg/day + salbutamol and beclomethasone spray PRN]. In the two groups, FEV1 did not have statistical differences at base line [49.3 +/- 2.9 and 48.7 +/- 4.1, respectively, p = 0.6], whereas after treatment the data for FEV1 showed a significant increase in the case group [66.3 +/- 5.4] when compared with those in the control group [57.3 +/- 8.6, p=0.001]. The findings of this study indicate that a 6-month treatment with interferon gamma -1b plus a low-dose of prednisolone is associated with the improvement of the lung function in mustard gas exposed patients with bronchiolitis

evaluation of the possible effect of positive end expiratory pressure [PEEP] on pharmacokinetics of phenytoin in patients with acute brain injury under mechanical ventilation

Positive ventilation has shown to have an influence on pharmacokinetic and disposition of some drugs.Beacause phenytoin with a narrow therapautic range, is the most commonly used drug for prophylaxis and treatment of early seizures after acute brain injuries, in the present study the effect of short term PEEP [5-10 cm H2O for at least 8 hours] on phenytoin serum concentration and pharmacokinetic parameters such as Vmax and clearance in brain injured patients under mechanical ventilation was examined. Ten patients with moderate to severe acute brain injury who were placed on mechanical ventilation with an initial PEEP level of 0-5 cm H2O were included in the study. Patients received phenytoin loading dose of 15 mg/kg followed by a maintenance daily dose of 3-7 mg/kg initiated within 12 hours of loading dose. Sampels were taken on two different occasions before and after PEEP elevation. Total phenytoin serum concentrations were determined by HPLC method. A time invarient Michaelis-Menten pharmacokinetic model was used to calculate Vmax and clearance for each patient.Derrived variables were calculated as follows: Vmax, 3.5-6.8 and 3.7-8.2 mg/kg/day; Clearance, 0.1-0.7 and 0.1-1.2 l/kg/day [before and after PEEP elevation, respectively]. Our data have shown a wide range of variability [2.6-32.5 mg/l] in phenytoin serum concentrations. There were no statistically significant differences in the measured total concentrations [p=0.721] and calculated Vmax and clearance [p=0.285]before and after PEEP elevation. Administration of fluid and inotropic agents, limitation in application of higher levels of PEEP and drug interactions, shall be considered as possible explanations for these findings

Pharmacokinetic behavior of theophylline following PEEP in critically ill patients with acute lung injury

The effect of Positive End Expiratory Pressure [PEEP] on the hepatic elimination of low to moderate extraction ratio drugs has not been clearly defined. We prospectively investigated the effect of PEEP on the clearance of theophylline in 30 [20 males and 10 females] intubated critically ill adult patients with acute lung injury/acute respiratory distress syndrome [ALI/ARDS]. The Mean [ +/- SD] age was 57 +/- 17 years, creatinine clearance 86 +/- 36 ml/min, serum albumin 3.2 +/- 0.57 mg/dl and the median APACHE [acute physiology and chronic health evaluation] two score was 25 [with a range of 16 to 34]. Critically ill patients who had met the diagnostic criteria for ALI/ARDS were enrolled on PEEP in low [5-9 cmH2O] and high [10-15 cmH2O] levels. All patients received the ordered dose of aminophylline infusion [3 mg/kg over 30 min and then 15 mg/h] after 2 h of initiating PEEP. Blood samples were collected after the loading dose, 2 and 6 h the aminophylline continuous infusion. Vital signs were recorded before and after 2 h of PEEP and each blood sampling interval. Cirrhotic patients and those who had received any drug which could interact with the metabolism and clearance of theophylline, were not included. The Mean [ +/- SD] value of the pharmacokinetic key parameters of theophylline in high [n=17] and low [n=13] PEEP groups were as follows: Vd=0.42[ +/- 0.15] L/kg and 0.54[ +/- 0.13] L/kg, clearance = 0.035[ +/- 0.024] L/h/kg and 0.056 [ +/- 0.025] L/h/kg. Mean measured theophylline concentrations following loading dose were 7.08 mg/L and 5.09 mg/L. The calculated volume of distribution [P<0.03], clearance [P<0.05] and theophylline serum concentration [P<0.05], in high versus low peep group, were found to be significantly different. Positive ventilation tends to reduce Vd and clearance of theophylline in critically ill patients

Comparison of the analgesic profile and side effectts of tramadol vs pethidine followingurological surgery

The optimization of pain management following surgery with minimal side effects, is one the major goals of surgical and medical teams. In this randomized double blind study, sixty ASA [American Society of Anesthesiologist] class I or II patients, undergoing urological surgery, were assessed to receive either pethidine or tramadol using a standard method for general anesthesia. Pain intensity was assessed by verbal rating, through a 4-step scaling system. Results of this investigation have revealed that the mean total drug administered in tramadol group were 244.53 + 56.95 mg and in pethidine group 176.78+42.99 mg respectively. There were no significant differences in analgesic effect, observed in either group during early hours following surgery, but after 8,12 and 16 hours significant differences were observed. Analgesic properties of tramadol were almost comparable with pethidine nevertheless; pethidine was superior in some extent. No significant differences in patient's PaO2 were found, but PaCO2 at 1 and 4 hours after surgery had a greater retention in pethidine group. [P<0.001]. There was a significant reduction in respiratory rate in pethidine group at 4,8,12 and 16 hours following surgery, compared with tramadol group [P<0.001]. Incidence of dizziness was greater in patients who received pethidine [P<0.001], and sweating was higher in tramadol group [P<0.01]. Also there was a greater need for metoclopramide to overcome nausea in tramadol group [P<0.05]. Results of this study may suggest that tramadol could be considered as a safe and effective analgesic, following urological surgery as compared with pethidine

prospective, randomized, controlled trial of high and low doses of magnesium sulfate for acute tocolysis

At the present, many drugs are used for inhibition of uterine contractions, but the proportions of preterm labors are increasing. Although magnesium sulfate is the most commonly prescribed parenteral tocolytic agent, but its optimal use has yet to be delineated. In this study a high-dose protocol for magnesium sulfate tocolytic therapy was compared with a low-dose regimen. One-hundred patients admitted to the labor unit of Imam Reza's hospital with preterm labor were enrolled in the trial. The median times to successful tocolysis were 8 hours in the low-dose group and 4 hours in the high-dose group [p<0.001]. Patients treated with higher doses were also more likely to spend significantly less time in the labor and delivery unit [p<0.001]. The median gestational age at delivery was 33 weeks in the low-dose group and 36 weeks in the high-dose group [p=0.001]. There were not any statistically significant differences between the two groups with respect to pre- and post magnesium infusion side effects. These results suggest that in the high-dose group, tocolysis was achieved more rapidly and patients required shorter admissions to the labor and delivery unit without increased maternal or neonatal morbidity

comparative study of bolus administration and continuous infusion of ranitidine on gastric PH with intragastric PH-probe

The high mortality rate associated with significant bleeding from stress ulceration has promoted efforts to prevent this complication in critically ill patients. Gastric pH is a key factor in the pathogenesis of stress ulceration and maintaining a pH of 4 or greater reduces the risk for development of the gastric ulceration. Our aim was to compare effects of intravenous bolus administration and continuous intravenous infusion of ranitidine on gastric pH in critically ill patients at the intensive care unit [ICU]. Twenty patients who met the inclusion criteria were entered this prospective, randomized, cross over study. A total of 1500 gastric pH measurement was obtained for each phase of the study. Continuous infusion of ranitidine maintained a gastric pH greater than 4 over a longer period than that of bolus administration [22.1 hrs vs. 14.2 hrs, respectively; P<0.001]. The pH-monitoring device which was made locally, was comparable to a standard international device. This study showed that continuous infusion of ranitidine was more effective than administration of an equivalent dose of the drug by bolus in maintaining the appropriate gastric pH required for the prevention of stress ulceration