Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors.

BACKGROUND: Antioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species (ROS). The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity, inflammatory and metabolic measures in patients with multiple cardiovascular risk factors. METHODS: Study participants were randomly assigned to two groups. Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard, SupHerb, Israel. In each capsule vitamin C (500 mg) vitamin E (200 iu), co-enzyme Q10 (60 mg) and selenium (100 mcg), Group 2 received matching placebo(SupHerb) for 6 months. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, hs-CRP, endothelin, aldosterone, plasma renin activity and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). RESULTS: Antioxidant-treated patients exhibited significant increases in large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed. In the placebo group, significant changes in LAEI, SAEI or metabolic measures were not observed. CONCLUSIONS: Antioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors. This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure.

Adenosine and TNF-alpha exert similar inotropic effect on heart cultures, suggesting a cardioprotective mechanism against hypoxia.

When cardiomyocytes were subjected to hypoxia, tumor necrosis factor-alpha (TNF-alpha; 3-50 ng/ml) or adenosine (1-100 microM), decreased hypoxic damage as was detected by lactate dehydrogenase (LDH) release, MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) absorbance, ROS (reactive oxygen species) measurement or desmin immunostaining. This cardioprotection was not prevented in TNF-alpha-treated cultures by 5-hydroxydecanoic acid (5-HD). Our aim was to elucidate whether adenosine and TNF-alpha mediate a similar protective mechanism against hypoxia in primary heart cultures and in H9c2 cardiomyocytes. Adenosine and TNF-alpha are known for their negative inotropic effects on the heart. We have suggested that deoxyglucose uptake reflects heart contractility in cell cultures; therefore, we assayed its accumulation under various conditions. Treatment for 20 min with adenosine, R-PIA [(-)-N(6)-phenylisopropyladenosine] (10 microM), or TNF-alpha reduced (3)H-deoxyglucose uptake in primary heart cultures and also in H9c2 cardiomyocytes by 30-50%. Isoproterenol accelerated (3)H-deoxyglucose uptake by 50%. Adenosine, R-PIA, or TNF-alpha attenuated the stimulatory effect of isoproterenol on (3)H-deoxyglucose uptake to control levels. Hypoxia reduced (3)H-deoxyglucose uptake by 50%, as in the treatment of the hypoxic cultures with TNF-alpha or adenosine. Glibenclamide (2 microM), 5-HD (300 microM), or diazoxide (50 microM) increased (3)H-deoxyglucose uptake by 50-80%. Adenosine (100 microM) and TNF-alpha (50 ng/ml) stimulated (86)Rb efflux. Glibenclamide attenuated this effect. We demonstrate that TNF-alpha, like adenosine, accelerated Ca(2+) uptake into the sarcoplasmic reticulum (SR) by 50-100% and therefore prevented cardiomyocyte Ca(2+) overload. Our findings further suggest that TNF-alpha, as well as adenosine, may mediate an adaptive effect in the heart by preventing Ca(2+) overload via activation of SR Ca-ATPase (SERCA(2)a).

Comparison of hemodynamic profiles in transurethral resection of prostate vs transurethral resection of urinary bladder tumors during spinal anesthesia: a bioimpedance study.

STUDY OBJECTIVE: Transurethral resection of prostate (TURP) is more frequently associated with perioperative fluid and electrolyte disturbances than transurethral resection of bladder tumors (TURT) because of irrigating fluid absorption. Because fluid overload may cause hypertension, we compared the patients' intraoperative hemodynamic profiles (including the incidence of hypertension) during TURP vs TURT, both performed during spinal anesthesia, by using the bioimpedance method. DESIGN: Prospective single-blind study. SETTING: University hospital. PATIENTS: 80 (40 in each group) men, ASA physical status I and II. INTERVENTIONS: Patients underwent TURP or TURT surgery with spinal anesthesia. MEASUREMENTS: Mean arterial pressure, heart rate, cardiac index, and systemic vascular resistance were compared between the 2 groups. A mean arterial pressure greater than 30% from the baseline value was considered as hypertension. Plasma sodium was measured preoperatively, intraoperatively, and postoperatively. MAIN RESULTS: Transurethral resection of prostate patients received more irrigating fluid (7900 +/- 2310 vs 5650 +/- 21560, P < 0.05) and had a higher calculated volume of fluid absorbed: 638 +/- 60 vs 303 +/- 40 mL for the TURT patients (P < 0.05). Mean arterial pressures were higher with TURP, 30 minutes after the onset of surgery and at the end of the procedure (111 +/- 15 vs 100 +/- 10 and 109 +/- 14 vs 99 +/- 14 mmHg, respectively; P < 0.05). However, there was no hypertension in either group. There were no differences in hemodynamic measurements of hyponatremic vs normonatremic patients. Plasma sodium decreased postoperatively more in the TURP group (140.4 +/- 2.6 mEq/L baseline to 134.1 +/- 3.5 mEq/L, P < 0.05) and was lower postoperatively in the TURP group compared with TURT (134.1 +/- 3.5 vs 137.2 +/- 2.9 mEq/L, P = 0.04). CONCLUSIONS: Although more irrigating fluid was absorbed in the TURP group, there were no episodes of hypertension in either group.

Morbidly obese patients are hemodynamically stable during laparoscopic surgery: a thoracic bioimpedance study.

PURPOSE: Morbid obesity caries an increased risk of cardiovascular morbidity and might be associated with intraoperative hemodynamic instability. Based on clinical observation, we hypothesized that during laparoscopic surgery, morbidly obese patients behave hemodynamically similar to the nonobese patients and remain hemodynamically stable. METHODS: In a prospective trial, thirty nonobese and tthirty morbidly obese (BMI > or = 35 kg/m(2)) patients scheduled for elective laparoscopic surgery were assigned to receive standard balanced anesthesia. We aimed at equianesthetic levels by keeping the BIS (bispectral index) value between 40-50 throughout surgery. End-tidal isoflurane was measured every 5 min. Noninvasive hemodynamic measurements included cardiac index (CI), mean arterial pressure (MAP) and heart rate (HR), recorded every 5 min and at specific predetermined times. Systemic vascular resistance (SVR) was calculated. Episodes of MAP < or = 60 and MAP > or = 130 mmHg or HR < or = 50 and HR > or = 110 bpm occurring throughout surgery and requiring pharmacological intervention were considered main end-points. Additionally, hemodynamic variables were compared at specific time points and overall throughout surgery. Secondary end-points were CI and SVRI. RESULTS: Heart rate was higher in obese patients in head-up position (79 +/- 15 mmHg vs. 65 +/- 12 mmHg - P=0.011). SVR was higher in the nonobese group with head-up position (1978 +/- 665 dynes s cm(-5) vs. 1394 +/- 496 dynes s cm(-5) P=0.01). Mean overall intraoperative MAP, HR, CI and SVR were similar. There were no episodes of MAP < or = 60 and > or =130 mmHg or HR < or = 50 and > or =110 bpm in either of the groups. CONCLUSION: Our study confirmed our hypothesis that for the most periods of laparoscopic surgery, obese patients are hemodynamically as stable as their nonobese counterparts.

Similar incidence of hypotension with combined spinal-epidural or epidural alone for knee arthroplasty.

BACKGROUND: We hypothesized that the incidence of hypotension during total knee replacement (TKR) surgery is lower in patients given combined spinal-epidural (CSE) anesthesia vs those receiving epidural anesthesia alone. METHODS: In a prospective study, 80 American Society of Anesthesiologists I-II patients (aged 40-80 yr), undergoing elective TKR surgery were randomly assigned to either CSE anesthesia (CSE, n = 40) or epidural anesthesia alone (Epidural, n = 40). Hemodynamic measurements included oscillometric mean arterial blood pressure (MAP), heart rate (HR), and cardiac index (CI) as determined by thoracic bioimpedance; systemic vascular resistance (SVR) was calculated. Our primary endpoint (outcome) was the number of hypotension episodes (defined as MAP < 70 mmHg). RESULTS: Using univariate analysis, we found no differences between the groups in regards to MAP, HR, CI, or SVR during the perioperative period. The incidence of hypotension was similar in both groups (two patients in each group), as was the incidence of bradycardia (12 patients in CSE, 7 in Epidural; P = 0.2). There were no differences between groups in other hemodynamic measurements including CI and calculated SVR. Analgesia supplementation with fentanyl was more frequently required in the Epidural group (20 vs 6 patients - P = 0.03). CONCLUSION: Combined spinal-epidural anesthesia and epidural anesthesia alone during TKR surgery are associated with the same incidence of hypotension with statistically and clinically similar hemodynamic responses.

Does acetylcholinesterase inhibition affect catecholamine secretion by adrenomedullary cells?

BACKGROUND: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells. OBJECTIVES: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release. METHODS: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48-72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10(-7) to 10(-3) M), for 1-20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether coincubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times. RESULTS: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+. CONCLUSION: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

Efficacy and safety of a prothrombin complex concentrate (Octaplex) for rapid reversal of oral anticoagulation.

Bleeding is the most serious adverse event of oral anticoagulants and is a major cause of morbidity and mortality in such patients. Rapid reversal of anticoagulation in bleeding patients or prior to urgent surgery is mandatory. The therapeutic options in these situations include administration of fresh frozen plasma (FFP), and recently of prothrombin complex concentrates (PCCs). However, viral safety and thrombogenicity of PCCs remain issues of concern. In the present study, we administered Octaplex, a new solvent/detergent (S/D) treated and nanofiltered PCC, to excessively anticoagulated bleeding patients or to anticoagulated patients facing urgent surgery. Ten excessively anticoagulated patients with major bleeding and 10 anticoagulated patients awaiting surgery (median age 72.5 (43-83) years, 9 females) received a median dose of 26.1 IU/kg body weight (BW) of Octaplex for reversal of anticoagulation. Response to Octaplex was rapid with decline of INR within 10 min after Octaplex administration (from 6.1+/-2. to 1.5+/-0.3). Clinical response was graded as good in most patients (85%) and as moderate in the rest. Octaplex administration was uneventful in all patients. Following Octaplex administration, a small increase in F1+2 levels was observed in bleeding patients, whereas D-dimer level did not change significantly. We conclude that Octaplex is effective and safe in situations where rapid reversal of anticoagulation is needed.

Opisthorchiasis from imported raw fish.

Liver fluke infection caused by Opisthorchiidae is a major public health problem in many parts of the Far East, Southeast Asia, and eastern Europe. However, with the growing volume of international travel and population migration, the infection is increasingly diagnosed in countries where the disease is not endemic, particularly in North America. We report an outbreak of acute opisthorchiasis in a family that was infected in a non-disease-endemic area after eating raw carp illegally imported from a highly disease-endemic area in Siberia. With the growing numbers of former Soviet Union citizens immigrating to other countries, western physicians need to be alert regarding Opisthorchis-associated pathology in this population. The epidemiology and biology of Opisthorchiidae in the former Soviet Union are reviewed.

Follow-up in a lipid clinic improves the management of risk factors in cardiovascular disease patients.

BACKGROUND: The implementation of treatment guidelines is lacking worldwide. OBJECTIVES: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. METHODS: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP target level was assessed. RESULTS: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of < 100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA1C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up. CONCLUSION: Follow-up of patients in a specialized clinic enhances the achievement of LDL-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.