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1 | TITLE: Efficacy of albendazole and short-course dexamethasone treatment in children with 1 or 2 ring-enhancing lesions of neurocysticercosis: a randomized controlled trial.ABSTRACT: To determine the efficacy of albendazole plus dexamethasone in children with 1 or 2 ring-enhancing lesions (by computed tomography scan) on resolution of lesions and recurrence of seizure.Randomized controlled open trial.Children of either sex, 1 to 14 years of age, with seizures and 1 or 2 ring-enhancing lesions <20 mm in diameter on computed tomography scan, likely to have neurocysticercosis, were assigned to treatment l groups. Children assigned to the treatment group (n=61) were given 0.15 mg/kg per day dexamethasone for 5 days plus 15 mg/kg per day albendazole for 28 days, starting on the third day of dexamethasone. Control group (n=62) children were given neither dexamethasone or albendazole. Anti-epileptic therapy was given to both the study groups.The lesions resolved completely or partially in more children in the treated group compared with the control group (79% versus 57%; P=.02). The proportion of children who had seizures was significantly lower in the treated group compared with the control group at 3 months (10% versus 32%; P=.006) and 6 months (13% versus 33%; P=.03).Albendazole plus dexamethasone increased complete or partial resolution of lesions and reduced the risk of subsequent recurrence of seizures among children with neurocysticercosis who had with seizures and 1 or 2 ring-enhancing lesions on computed tomography. |
1 | TITLE: Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).ABSTRACT: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD. |
0 | TITLE: Clinical observations on postoperative vomiting treated by auricular acupuncture.ABSTRACT: We studied the effect of auricular acupuncture on postoperative nausea and vomiting (PONV). One hundred female patients undergoing transabdominal hysterectomy were entered into the study. The patients were divided into two groups (auricular acupuncture treatment group and non-treatment group) in order to test the effectiveness of auricular acupuncture. There was no significant difference in age, weight, height or duration of anesthesia among the two groups of patients. There was a significant difference between the control and auricular acupuncture treatment groups in the incidence of vomiting 12 hours after surgery (68% and 30%, respectively, p < 0.01). No noteworthy side effects from treatment were observed. Auricular acupuncture is effective in reducing vomiting following transabdominal hysterectomy in female patients. |
1 | TITLE: Timing of the effect of acetaminophen on body temperature in patients with acute ischemic stroke.ABSTRACT: The authors assessed the time of onset of the hypothermic effect of acetaminophen in 102 patients with acute ischemic stroke. These patients were randomized to treatment with either 1000 mg of acetaminophen (n = 52) or placebo (n = 50), given six times daily. Treatment with high-dose acetaminophen resulted in a 0.26 degrees C (95% CI 0.07 to 0.46 degrees C) lower mean body temperature than placebo treatment within 4 hours. This effect remained present throughout the next 20 hours. A large phase III trial seems warranted. |
1 | TITLE: Acupuncture facilitates neuromuscular and oculomotor responses to skin incision with no influence on auditory evoked potentials under sevoflurane anaesthesia.ABSTRACT: More sevoflurane was recently found to be required to prevent movement in response to surgical incision in anaesthetized patients subjected to electro-acupuncture (EA) than to sham procedures. The present study was designed to compare differences in movement, dilatation of the pupils, divergence of the eye axes and activity of auditory evoked potentials (AEPs) between patients given and those not given EA under standardized sevoflurane anaesthesia.Neuromuscular, oculomotor and AEP responses to skin incision were assessed with and without a bilateral 2-Hz burst EA in patients under steady-state anaesthesia maintained with 1.8% of sevoflurane. Forty-five healthy patients, scheduled for laparoscopic sterilization, were randomized for EA (n = 22) or sham (n = 23) procedures between induction of anaesthesia and start of surgery. Middle latency AEP activity was recorded and interpreted by the A-line ARX (autoregression with exogenous input) index (AAI).More acupuncture than sham patients were found to respond to skin incision with movement of the neck or limbs (77% vs. 43%; P = 0.021), dilatation of the pupils (77% vs. 39%; P = 0.001) and divergence of the eye axes (72% vs. 39%; P = 0.023), whereas there was no difference in AAI response.Electro-acupuncture facilitates physiological responses to nociceptive stimulation under sevoflurane anaesthesia. Differences in neuromuscular and oculomotor responses between acupuncture and sham patients under general anaesthesia are probably not associated with interaction between EA and the depth of anaesthesia, as AEP activity was similar in the two groups. |
1 | TITLE: Oral appliance therapy reduces blood pressure in obstructive sleep apnea: a randomized, controlled trial.ABSTRACT: To investigate the short-term effect (4 weeks) of oral appliance therapy for obstructive sleep apnea on blood pressure.Randomized, controlled, crossover trial.Multidisciplinary sleep disorders clinic in a university teaching hospital.Sixty-one patients diagnosed with obstructive sleep apnea on polysomnography (apnea hypopnea index > or = 10 per hour and at least 2 of the following symptoms--daytime sleepiness, snoring, witnessed apneas, fragmented sleep; age > 20 years; and minimum mandibular protrusion of 3 mm).A mandibular advancement splint (MAS) and control oral appliance for 4 weeks each.Polysomnography and 24-hour ambulatory blood pressure monitoring were carried out at baseline and following each 4-week intervention period. Patients showed a 50% reduction in mean apnea hypopnea index with MAS compared with the control and a significant improvement in both minimum oxygen saturation and arousal index. There was a significant reduction with the MAS in mean (+/- SEM) 24-hour diastolic blood pressure (1.8 +/- 0.5 mmHg) compared with the control (P = .001) but not in 24-hour systolic blood pressure. Awake blood-pressure variables were reduced with the MAS by an estimated mean (+/- SEM) of 3.3 +/- 1.1 mmHg for systolic blood pressure (P = .003) and 3.4 +/- 0.9 mmHg for diastolic blood pressure (P < .0001). There was no significant difference in blood pressure measured asleep.Oral appliance therapy for obstructive sleep apnea over 4 weeks results in a reduction in blood pressure, similar to that reported with continuous positive airway pressure therapy. |
1 | TITLE: Effect of short-term hyperglycaemia on haemodynamics in type 1 diabetic patients.ABSTRACT: Mechanisms underlying glucose-mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short-term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients.We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single-blinded cross-over trial using insulin-glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L(-1) (euglycaemia) and 15 mmol L(-1) (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period.Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P=0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P=0.02], angiotensin II [17 (8, 25)%, P<0.01] and adrenaline [20 (10, 29)%, P<0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL(-1) (P<0.01) from 43 (2) pg mL(-1). We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7-5.3)% and 5.0 (-4.7 to 8.6)%, respectively.In type 1 diabetic patients without signs of autonomic neuropathy short-term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin-angiotensin system, possibly caused by PV expansion because of fluid shift from intra- to extracellular compartment. |
1 | TITLE: Abciximab reduces monocyte tissue factor in carotid angioplasty and stenting.ABSTRACT: Abciximab, a nonselective glycoprotein IIb/IIIa inhibitor, was shown to reduce peri-interventional stroke rate in carotid stenting. We evaluated the effect of adjunct abciximab therapy on monocyte-platelet cross talk and neurological deficit in unprotected carotid stenting and compared its efficacy with distal filter protection.Fifty patients were randomized to either standard antithrombotic therapy (n=30) consisting of aspirin, clopidogrel, and heparin or adjunct bolus (0.25 mg/kg) and 12-hour infusion (0.125 microg x kg(-1) x min(-1)) of abciximab (n=20). A third cohort of patients was stented with filter protection (n=30). Monocyte-platelet aggregate formation and monocyte tissue factor expression were determined by whole blood flow cytometry, and F1.2 generation and soluble CD40 ligand (sCD40L) were determined by immunoassay.The incidence of peri-interventional ischemic episodes (23% versus 10%; P=0.2) and the number of de novo ischemic lesions detected by diffusion-weighted MRI (47% versus 30%; P=0.17) were not significantly different between standard antithrombotic therapy and adjunct abciximab but were reduced with filter protection (P=0.023). However, the number of transient ischemic attacks was lower (P=0.05) and the National Institutes of Health Stroke Score rapidly decreased in patients with adjunct abciximab. This clinical improvement was paralleled by a reduction in the postinterventional percentage of activated monocyte-platelet aggregates (CD62P+/CD14+; P=0.018) and the number of tissue factor-positive monocytes (TF+/CD14+; P=0.005). Both abciximab and filter protection suppressed F1.2 generation and significantly reduced sCD40L.Abciximab limits thrombus propagation and thrombus stabilization after carotid stenting by reducing monocyte-platelet cross talk and sCD40L. Although abciximab seems inferior to filter devices in peri-interventional cerebral protection, it may be considered in patients who do not allow placement of protection devices. |
1 | TITLE: Evidence of a lack of effect of a phytoestrogen regimen on the levels of C-reactive protein, E-selectin, and nitrate in postmenopausal women.ABSTRACT: Phytoestrogens are thought to be beneficial to vascular health. Possible mechanisms of action could involve C-reactive protein (CRP), endothelial E-selectin, and nitric oxide. We therefore designed a randomized, placebo-controlled, double-blind trial in which we studied the effects of isoflavonoids on CRP, E-selectin, and nitrate-nitrite (NO(x); reflecting the release of nitric oxide) in postmenopausal women. Fifty-six postmenopausal women (FSH > 30 U/liter) with a history of breast cancer used (in a randomized order) phytoestrogen (114 mg isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were crossed over after a 2-month washout period. The serum levels of CRP and E-selectin, and plasma levels of NO(x) were measured before and on the last day of each treatment. The phytoestrogen regimen did not affect the levels of either CRP (P = 0.584) or NO(x) (P = 0.270), but the levels of E-selectin were reduced by 4.0% (2.9 ng/ml; P = 0.031) during phytoestrogen use and by 2.2% (1.3 ng/ml; P = 0.023) during placebo use. No difference was found at any marker at 3 months between the groups. In conclusion, our data, suggesting neutral effects of phytoestrogens on CRP, E-selectin, and nitric oxide, fail to support a vasoprotective role of phytoestrogens. |
1 | TITLE: Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.ABSTRACT: Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation. |
1 | TITLE: The effect of body mass index and wound irrigation on outcome after bilateral breast reduction.ABSTRACT: Thirty patients undergoing bilateral breast reduction by inferior pedicle technique were entered into a prospective, randomized study to determine the effect of unilateral saline wound irrigation and body mass index (BMI) on outcome. Each patient was assessed at 1, 4, and 8 weeks after surgery for wound dehiscence, infection, fat necrosis, and breast comfort by means of a visual analog pain score. The mean patient age was 33 years; mean weight, 67.7 kg; mean BMI, 26.3; and mean weight of breast tissue excised per patient, 1270 g. In 60 breasts there were 13 cases of minor wound breakdown, all of which had healed by 8 weeks postoperatively. Wound irrigation had no significant effect on the rate of T-junction breakdown or on postoperative pain. BMI was associated significantly with wound breakdown (BMI > 26.3, 33% wound breakdown rate; BMI < 26.3, 10% wound breakdown rate; P < 0.05, chi2 test). Patients with a high BMI are more likely to have delayed healing after breast reduction. |
1 | TITLE: Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine.ABSTRACT: Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia.The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg).The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups.We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine. |
1 | TITLE: A comparison of duration of analgesia of intrathecal 2.5 mg of bupivacaine, ropivacaine, and levobupivacaine in combined spinal epidural analgesia for patients in labor.ABSTRACT: We assessed the duration of labor analgesia rendered by intrathecal (IT) local anesthetics as the sole drugs. In this randomized, controlled, and double-blinded study, labor analgesia was induced using combined spinal-epidural technique in 60 ASA physical status I nulliparous parturients with IT bupivacaine 2.5 mg (group B), ropivacaine 2.5 mg (group R), or levobupivacaine 2.5 mg (group L). Pain scores (0-100 visual analog scale) and blood pressure were recorded pre-block and for the first 30 min post-block. The degree of motor block and the highest sensory block were also monitored. The duration of analgesia (our primary outcome) was the longest in group B but was similar between groups R and L (mean +/- SE, 76.3 +/- 5.9 min versus 52.6 +/- 4.0 min and 51.5 +/- 3.4 min, respectively, P < 0.05). Group B had the most frequent incidence of lower limb motor block but there was no difference between groups R and L (5 of 20 parturients versus 2 of 20 and 0 of 20, respectively, P < 0.05). The profile of the other side effects was indistinguishable between the groups. With the current regimen, IT bupivacaine produced the longest duration of labor analgesia.Intrathecal 2.5 mg bupivacaine significantly prolongs the duration of analgesia in laboring patients compared with ropivacaine or levobupivacaine. This suggests that, at clinically relevant doses, bupivacaine may have greater potency. |
1 | TITLE: Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.ABSTRACT: To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3).HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide.For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent. |
1 | TITLE: A comparison of albumin and saline for fluid resuscitation in the intensive care unit.ABSTRACT: It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU.We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization.Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (+/-SD) numbers of days spent in the ICU (6.5+/-6.6 in the albumin group and 6.2+/-6.2 in the saline group, P=0.44), days spent in the hospital (15.3+/-9.6 and 15.6+/-9.6, respectively; P=0.30), days of mechanical ventilation (4.5+/-6.1 and 4.3+/-5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5+/-2.3 and 0.4+/-2.0, respectively; P=0.41).In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days. |
1 | TITLE: Biventricular pacing reduces the induction of monomorphic ventricular tachycardia: a potential mechanism for arrhythmia suppression.ABSTRACT: The aim of the present study was to evaluate in a prospective randomized fashion the electrophysiologic effects of acute biventricular (BV) pacing. We hypothesized that (1) the local coupling interval in the left ventricle in response to right-sided ventricular premature beats is prolonged when BV pacing is applied during the drive train compared with right ventricular (RV) pacing, and (2) BV programmed electrical stimulation (PES) decreases the induction of ventricular arrhythmias compared with standard RV-PES, regardless of the presence of intraventricular conduction delay.Previous studies have suggested that BV pacing might decrease the frequency of ventricular arrhythmias; however, the mechanism of arrhythmia suppression remains unclear.Eighteen patients with coronary artery disease were randomized to RV-PES or BV-PES with a repeat study using the other pacing mode. The RV effective refractory periods were measured during RV-PES and BV-PES. In addition, the local LV S(1)-S(2) coupling interval was measured at 600/450 ms and 400/350 ms during RV-PES and BV-PES.BV-PES had no effect on RV effective refractory periods. On the other hand, the local LV S(1)-S(2) coupling intervals increased significantly during BV-PES compared with RV-PES (P < .0001). Ventricular tachycardia was induced in six patients using RV-PES but in only one patient with BV-PES (RR = 83%, P = .01). No difference was observed in the induction of ventricular fibrillation.BV-PES significantly reduced the induction of ventricular tachycardia compared to RV-PES, with no significant effect on ventricular fibrillation induction. Our findings may help explain the reduced incidence of ventricular arrhythmias noted with chronic BV pacing. |
1 | TITLE: Laryngeal mask airway can be inserted with inhaled desflurane induction.ABSTRACT: In this prospective, randomized, controlled trial, we investigated the reliability of laryngeal mask airway (LMA) insertion with inhaled desflurane.Eighty patients undergoing elective surgery were randomized into two groups to receive either 2.5 mg x kg(-1) propofol (n = 40) or tidal breath desflurane (n = 40) induction followed by LMA insertion. All patients received fentanyl 1 microg x kg(-1) 2 min before induction. Inhalation of desflurane was started at 3% and increased by 3% every 3-5 breaths up to settings of 12%.Insertion of the LMA was faster in the propofol group (131.8 s versus 228.6 s, P < 0.01). The number of patients in whom the jaw opening was described as good (95% versus 72.5%, P = 0.27, for the desflurane and propofol groups, respectively) and the ease of LMA insertion described as good (87.5% versus 72.5%, P = 0.6) were comparable. The LMA was inserted in a single attempt in the majority of patients in both groups (80% versus 77.5%, P = 0.90). There were more complications at insertion in the propofol group than in the desflurane group (2.5% versus 19.5%, P < 0.01), especially for apnea (7.5% versus 70%, P < 0.01) and excitatory movements (2.5% versus 25%, P < 0.01). There were significant decreases in the mean arterial pressure in the propofol group compared to baseline data over the first 5 min of induction. Mean arterial pressure, heart rate, and S(p)(O2) remained stable during the same period in the desflurane group.We demonstrated that inhaled desflurane when used with caution in a controlled manner provided acceptable conditions for LMA insertion. |
1 | TITLE: Safety and efficacy of phacoemulsification compared with manual small-incision cataract surgery by a randomized controlled clinical trial: six-week results.ABSTRACT: To compare the efficacy, safety, and refractive errors of astigmatism after cataract surgery by phacoemulsification and manual small-incision cataract surgery techniques.Masked randomized control clinical trial.Four hundred eyes of 400 patients, 1:1 randomization with half in each arm of the trial.A total of 400 eyes was assigned randomly to either phacoemulsification or small-incision groups after informed consent and were operated on by 4 surgeons. They were masked to the technique of surgery before, during, and after cataract surgery and followed up to 1 year after surgery. The intraoperative and postoperative complications, uncorrected and best-corrected visual acuity, and astigmatism were recorded at 1 and 6 weeks postoperatively.The proportion of patients achieving visual acuity better than or equal to 6/18 with and without spectacles after cataract surgery in the operated eye up to 6 weeks, postoperative astigmatism, and complications during and after surgery.This article reports clinical outcomes up to 6 weeks. Three hundred eighty-three of 400 (95.75%) patients completed the 1-week follow-up, and 372 of 400 (93%) patients completed the 6-week follow-up. One hundred thirty-one of 192 (68.2%) patients in the phacoemulsification group and 117 of 191 (61.25%) patients in the small-incision group had uncorrected visual acuity better than or equal to 6/18 at 1 week (P = 0.153). One hundred fifty of 185 (81.08%) patients of the phacoemulsification group and 133 of 187 (71.1%) patients of the small-incision group (P = 0.038) were better than or equal to 6/18 at the 6-week follow-up for presenting visual activity. Visual acuity improved to > or = 6/18 with best correction in 182 of 185 patients (98.4%) and 184 of 187 (98.4%) patients (P = 0.549), respectively. Poor outcome (postoperative visual acuity < 6/60) was noted in 1 of 185 (0.5%) in the phacoemulsification group and none in the small-incision group. The mode of astigmatism was 0.5 diopters (D) for the phacoemulsification group and 1.5 D for the small-incision group, and the average astigmatism was 1.1 D and 1.2 D, respectively. There was an intra-surgeon variation in astigmatism. The phacoemulsification group had 7 posterior capsular rents compared with 12 in the small-incision group, but the phacoemulsification group had more corneal edema on the first postoperative day.Both the phacoemulsification and the small-incision techniques are safe and effective for visual rehabilitation of cataract patients, although phacoemulsification gives better uncorrected visual acuity in a larger proportion of patients at 6 weeks. |
1 | TITLE: Percutaneous translaryngeal versus surgical tracheostomy: A randomized trial with 1-yr double-blind follow-up.ABSTRACT: To compare the outcomes and the short- and long-term complications of percutaneous translaryngeal tracheostomy (TLT) and surgical tracheostomy (ST).Prospective, randomized clinical trial with 1-yr double-blind follow-up.A general intensive care unit of a university hospital.A total of 139 consecutive critically ill patients who required a tracheostomy between February 2001 and June 2002 were randomly assigned to receive either ST or TLT.TLTs were performed more rapidly than STs (17 +/- 10 mins vs. 22 +/- 6 mins, p = .003). Early complications were rare in both groups. Major postoperative bleeding was less frequent with TLT (0 [0%] vs. 6 [8%], p = .03). Only one case of bleeding (in the ST group) required blood transfusion. Immediately after tracheostomy, six TLT patients (9%) and six patients (8%) in the ST group (p = .56) developed culture-confirmed bacteremia with microbes previously isolated from the pharynx or trachea. Group rates for stomal infections and pneumonia after tracheostomy were similar. At 1-yr follow-up, the overall survival rate was 27%, and 14 patients (45% of survivors) still had open tracheostomies. Both groups rated their quality of life as moderately to severely compromised, and the deterioration was strictly related to the presence of tracheostomy. One TLT and two ST survivors (p = .53) had clinical signs of tracheal stenosis, and bronchoscopy revealed narrowing of >50%.Compared with ST, the main advantages of TLT are that it is more rapid and associated with less postoperative bleeding. Infectious complications, particularly postoperative bacteremia, and long-term effects (physical and emotional) are similar with the two procedures. |
1 | TITLE: Urinary sucrose and fructose as biomarkers for sugar consumption.ABSTRACT: The use of 24-hour urinary sucrose and fructose as potential biomarkers for sugars consumption was investigated in two studies of 21 healthy participants living in a volunteer suite where dietary intake was known and all specimens collected. The dose-response was assessed in 12 males using a randomized crossover design of three diets containing constant levels of 63, 143, and 264 g of sugars for 10 days each. Both sugars and sucrose intake were significantly correlated with the sum of sucrose and fructose concentration in urine (0.888; P < 0.001). To assess effects with volunteers consuming their habitual varying diets, seven males and six females were fed their usual diet (assessed beforehand from four consecutive self-completed 7-day food diaries) for 30 days under controlled conditions in the volunteer suite. The mean (+/-SD) calculated total sugars intake was 202 +/- 69 g/d, 41% from sucrose. Mean (+/-SD) urinary sucrose and fructose were 36.6 +/- 16.6 and 61.8 +/- 61.3 mg/d, respectively. The sum of sucrose and fructose in urine was significantly correlated with sugars (0.841; P < 0.001) and sucrose intake (0.773; P = 0.002). In the regression, 200 g of sugars intake predicted approximately 100 mg of sucrose and fructose in urine. The correlation between individual means of randomized 16 days of sugars intake and 8 days of sugars excretion data (as used in validation studies) remained as high as that obtained with the means of 30-day measurements and the regression estimates were very similar. Twenty-four-hour urinary sucrose and fructose could be grouped into a new category of biomarkers, predictive biomarkers, that can be used in studies determining the structure of dietary measurement error in free living individuals and to relate sugars intake to disease risk. |
1 | TITLE: Increasing smoking cessation care in a preoperative clinic: a randomized controlled trial.ABSTRACT: Evidence suggests that preoperative clinics, like other hospital outpatient clinics and inpatient wards, fail to systematically provide smoking cessation care to patients having planned surgery.The aim of the study was to assess the efficacy, acceptability, and cost of a multifaceted intervention to facilitate the provision of comprehensive smoking cessation care to patients attending a preoperative clinic. Two hundred ten smoking patients attending a preoperative clinic at a major teaching hospital in Australia took part in the study. One hundred twenty-four patients were randomly assigned to an experimental group and 86 patients to a usual cessation care group. A multifaceted intervention was developed that included the use of opinion leaders, consensus processes, computer-delivered cessation care, computer-generated prompts for care provision by clinic staff, staff training, and performance feedback.Ninety-six percent of experimental group patients received behavioral counseling and tailored self-help material. Experimental group patients were significantly more likely than usual care patients to report receiving brief advice by nursing (79% vs. 47%; P < 0.01) and anaesthetic (60% vs. 39%; P < 0.01) staff. Experimental group patients who were nicotine dependent were also more likely to be offered preoperative nicotine replacement therapy (NRT) (82% vs. 8%; P < 0.01) and be prescribed postoperative NRT (86% vs. 0%; P < 0.01). The multifaceted intervention was found to be acceptable by staff.A multifaceted clinical practice change intervention may be effective in improving the delivery of smoking cessation care to preoperative surgical patients. |
1 | TITLE: Cardiovascular risk estimates and risk factors in renal transplant recipients.ABSTRACT: Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease. |
1 | TITLE: Oral famciclovir for the suppression of recurrent genital herpes: the combined data from two randomized controlled trials.ABSTRACT: Genital herpes is a very common sexually transmitted disease. Safe and effective therapies are needed for patients with frequent recurrences.The aim of our study was to determine the efficacy and safety of famciclovir for suppression of herpes simplex virus (HSV) infection in patients with history of clinically diagnosed recurrent genital HSV infection.An analysis was conducted of the combined data from two randomized, double-blind, placebo-controlled studies of 52 weeks' duration involving a total of 469 patients (201 men, 268 women) from 47 university, hospital, or private referral centers in Europe and North America. The patients were 18 years or older with a history of six or more episodes of genital herpes during 12 of the 14-months prior to study entry and were not receiving suppressive therapy. They were randomized to receive oral famciclovir 250 mg twice daily or placebo for 52 weeks. The primary outcome measures were (1) the proportion of patients who remained free from clinical HSV recurrences, confirmed by viral culture, for at least 6 months after the start of study medication; (2) the time to first clinically confirmed lesional episode; and (3) the frequency of adverse events.A significantly greater proportion of famciclovir-treated patients (151/191, 79%) were free from HSV recurrences at 6 months compared with placebo recipients (48/184, 26%) (p<0.001); efficacy was maintained at 12 months. The median time for the first clinically confirmed lesional episode was significantly prolonged for famciclovir recipients (more than one year) compared with placebo recipients (59 days; p<0.0001). Famciclovir was well tolerated, with an adverse-experience profile comparable with placebo.Oral famciclovir 250 mg twice daily is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences. |
1 | TITLE: Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.ABSTRACT: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment.The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure.Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%.Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients. |
1 | TITLE: Hydroxocobalamin reduces hyperhomocysteinemia in end-stage renal disease.ABSTRACT: Renal failure causes hyperhomocysteinemia, an important risk factor for cardiovascular disease and venous access thrombosis in end-stage renal disease (ESRD). Folic acid is necessary for homocysteine (Hcy) metabolism, and therapy with 1 mg/d or more of folic acid reduces plasma total Hcy (tHcy) concentrations in ESRD, although seldom to normal. In contrast to folic acid, the Hcy-lowering effect of vitamin B(12) has not been well studied in ESRD. We performed a prospective randomized controlled clinical trial involving 24 maintenance hemodialysis patients with normal or supranormal serum folate and vitamin B(12) concentrations who received either standard therapy, which included 5 to 6 mg folic acid, 5 to 10 mg pyridoxine, and 6 to 10 microg oral vitamin B(12) per day, or standard therapy plus 1 mg hydroxocobalamin administered subcutaneously once per week after dialysis. Plasma tHcy and serum methylmalonic acid (MMA) concentrations were measured before and after 8 and 16 weeks of continuous treatment. Hydroxocobalamin reduced plasma tHcy by an average of 32% (P <.005) and serum MMA by an average of 19% (P <.001). The Hcy-lowering effect of hydroxocobalamin was independent of baseline serum vitamin B(12), folic acid, and MMA concentrations. Patients with higher baseline plasma tHcy concentrations had the greatest response (r = 0.80; P <.002). These results show that parenteral hydroxocobalamin reduces plasma tHcy dramatically in vitamin B(12)-replete hemodialysis patients. Persons with considerable persisting hyperhomocysteinemia despite high-dose folic acid therapy are likely to respond to the addition of hydroxocobalamin, irrespective of their serum vitamin B(12) concentrations. |
1 | TITLE: Acute haemodynamic effects of a hypertonic saline/dextran solution in stable patients with severe sepsis.ABSTRACT: To study the haemodynamic effects of a hypertonic saline/dextran solution compared with a normal saline solution in patients with severe sepsis.Prospective double blind and control-randomised study.Adult intensive care unit in a university hospital.Twenty-nine patients with sepsis with a pulmonary artery occlusion pressure (PAOP) lower than 12 mmHg.Patients were randomised to receive 250 ml of blinded solutions of either normal saline (SS group, n=16) or hypertonic saline (NaCl 7.5%)/dextran 70 8% (HSS group, n=13) solutions.Haemodynamic, blood gas, and sodium data were collected at the following time points: baseline, 30 min, 60 min, 120 min, and 180 min. PAOP was higher in the HSS group at 30 min (10.7+/-3.2 mmHg vs 6.8+/-3.2 mmHg) and 60 min (10.3+/-3 mmHg vs 7.4+/-2.9 mmHg); P<0.05. The cardiac index increased in the HSS group and it was greater than the SS group at 30 min (6.5+/-4.7 l min(-1) m(-2) vs 3.8+/-3.4 l min(-1) m(-2)), 60 min (4.9+/-4.5 l min(-1) m(-2) vs 3.7+/-3.3 l min(-1) m(-2)), and 120 min (5.0+/-4.3 l min(-1) m(-2) vs 4.1+/-3.4 l min(-1) m(-2)); P<0.05. The stroke volume index followed a comparable course and it was higher at 30 min [53.6(39.2-62.8) ml m(-2) vs 35.6(31.2-49.2) ml m(-2)] and 60 min [46.8(39.7-56.6) ml m(-2) vs 33.9(32.2-47.7) ml m(-2)]; P<0.05. Systemic vascular resistance decreased in the HSS group and became significantly lower at 30 min (824+/-277 dyne s(-1) cm(-5) m(-2) vs 1139+/-245 dyne s(-1) cm(-5) m(-2)), 60 min (921+/-256 dyne s(-1) cm(-5) m(-2) vs 1246+/-308 dyne s(-1) cm(-5) m(-2)), and 120 min (925+/-226 dyne s(-1) cm(-5) m(-2) vs 1269+/-494 dyne s(-1) cm(-5) m(-2)). Sodium levels increased in the HSS group (P=0.056) and were higher than in the SS group at 30 min (145+/-3 mEq l(-1)vs 137+/-7 mEq l(-1)), 60 min (143+/-4 mEq l(-1) vs 136+/-7 mEq l(-1)), 120 (142+/-5 mEq l(-1)vs 136+/-7 mEq l(-1)), and 180 min (142+/-5 mEq l(-1) vs 136+/-8 mEq l(-1)).Hypertonic saline/dextran solution may improve cardiovascular performance in severe sepsis without significant side effects. The haemodynamic effect appears related mainly to a volume effect. |
1 | TITLE: Basal-bolus insulin therapy in Type 1 diabetes: comparative study of pre-meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin.ABSTRACT: To ascertain whether pre-meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog Mix50, human soluble (regular) insulin as a basal-bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin.This was a multinational, multicentre, randomized, open-label, two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight-point BG profiles, frequency of hypoglycaemia, HbA1c, insulin dose, time of injection, and frequency of snacking were assessed during each treatment.Total daily insulin dose was similar for both treatments, but the total pre-meal doses were higher (P < 0.001) and the bedtime dose of isophane was lower (P < 0.001) with Mix50. The pre-meal dose before breakfast and lunch, although statistically different (P = 0.006 and P < 0.001, respectively), was of similar magnitude, but the pre-evening meal dose was higher with Mix50 (P < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre-meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 +/- 2.95 mmol/l vs. 9.60 +/- 3.47 mmol/l) (P = 0.049). BG after breakfast and lunch, mean HbA1c, frequency of hypoglycaemia, frequency of snacks, and body weight were not different.The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals. |
1 | TITLE: A new calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris.ABSTRACT: Topical corticosteroids and calcipotriol have been used separately for many years to treat psoriasis. A new combination ointment has been formulated, which contains both calcipotriol and the corticosteroid betamethasone dipropionate.To compare the combination ointment with betamethasone dipropionate ointment, calcipotriol ointment and ointment vehicle in patients with psoriasis vulgaris.1,603 patients were randomised to one of the 4 double-blind treatments used once daily for 4 weeks.The mean percentage change in the PASI at the end of treatment was -71.3 (combination), -57.2 (betamethasone), -46.1 (calcipotriol) and -22.7 (vehicle). The mean difference of combination minus betamethasone was -14.2 (95% CI: -17.6 to -10.8, p < 0.001), of combination minus calcipotriol -25.3 (95% CI: -28.7 to -21.9, p < 0.001) and of combination minus vehicle -48.3 (95% CI: -53.2 to -43.4, p < 0.001). 6.0% of patients (combination) reported local adverse reactions compared to 4.9% (betamethasone), 11.4% (calcipotriol) and 13.6% (vehicle).Calcipotriol/betamethasone dipropionate combination ointment used once daily is well tolerated and more effective than either active constituent used alone. |
1 | TITLE: Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children.ABSTRACT: Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community-acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996-January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.Forty-seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X-ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X-rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children. In conclusion, azithromycin is an effective therapeutic option for the treatment of community-acquired classic and atypical pneumonia in children. |
1 | TITLE: G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils.ABSTRACT: In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects. |
1 | TITLE: The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial.ABSTRACT: Because alpha-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy. |
1 | TITLE: Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders.ABSTRACT: Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 +/- 0.39 vs 1.50 +/- 0.32 mg/ml, P < 0.001) and basal (3.31 +/- 0.38 vs 2.28 +/- 0.36 mg/ml, P < 0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 +/- 0.08 vs 0.36 +/- 0.06 mg/ml, P < 0.0001) and 41% (0.82 +/- 0.09 vs 0.58 +/- 0.09 mg/ml, P < 0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P < 0.01) and basal (P < 0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge. |
1 | TITLE: Pneumoperitoneum after concomitant resection of the right middle and lower lobes (bilobectomy).ABSTRACT: Removal of the right middle and lower lobes often leaves a pleural space problem that can cause prolonged air leaks.A single surgeon prospectively randomized 16 patients who underwent bilobectomy. Eight patients had 1200 mL of air injected under the right hemidiaphragm after bilobectomy and 8 did not. The air was injected through a small transdiaphragmatic opening made in the right hemidiaphragm at the time of pulmonary resection.The age of the patients, preoperative pulmonary function, preoperative comorbidities, indications for surgery, and final pathology were not significantly different between the two groups. On postoperative day #1, a pneumothorax was present in 1 patient (13%) in the pneumoperitoneum group (P group) and in 4 patients (50%) in the nonpneumoperitoneum group (N-P group). On postoperative day 1, an air leak was present in 1 patient (13%) in the P group and 5 patients (63%) in the N-P group (p < 0.001). By the third postoperative day, no patient in the P group had an air leak; however, a leak was present in 4 patients (50%) in the N-P group (p < 0.001). Median hospital stay in the P group was 4 days (range, 3 to 6 days), compared with 6 days (range, 4 to 8 days) in the N-P group (p < 0.001). Three patients in the N-P group were sent home with a Heimlich valve. There was no operative mortality and no complications from the pneumoperitoneum.We conclude that pneumoperitoneum after bilobectomy is safe and easy to do. It decreases the incidence of air leaks and of pneumothoraces and shortens hospital stay without increasing morbidity. We recommend pneumoperitoneum after bilobectomy at the time of thoracotomy, especially if there are residual small air leaks that cannot be sealed before chest closure. |
1 | TITLE: A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome.ABSTRACT: Chronic fatigue syndrome is characterized by prolonged and disabling fatigue and a range of neuropsychiatric symptoms including depressed and/or irritable mood. To date, no medical or psychotropic therapies have provided clear symptomatic benefit.Ninety patients with chronic fatigue syndrome, diagnosed with our system that approximates CDC criteria, participated in a randomized, placebo-controlled, double-blind trial of 450 to 600 mg/day of moclobemide, a novel reversible inhibitor of monoamine oxidase-A.Fifty-one percent (24/47) of patients receiving moclobemide improved compared with 33% (14/43) of patients receiving placebo (odds ratio = 2.16, 95% confidence interval [CI] = 0.9 to 5.1). Drug response was best characterized symptomatically by an increase in the subjective sense of vigor and energy rather than a reduction in depressed mood. The effect of moclobemide on subjective energy was detectable within the first 2 weeks of treatment and increased across the course of the study. The greatest reduction in clinician-rated disability was in patients with concurrent immunologic dysfunction (mean difference in standardized units of improvement = 0.8, 95% CI = 0.03 to 1.6).Moclobemide produces some improvement in key symptoms experienced by patients with chronic fatigue syndrome. This effect is not dependent on the presence of concurrent psychological distress and is likely to be shared with other monoamine oxidase inhibitors. |
1 | TITLE: Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomised placebo controlled trial.ABSTRACT: To study the effect of epoprostenol (prostacyclin, PGI2) given before, during, and for 36 h after coronary angioplasty on restenosis at six months and to evaluate the transcardiac gradient of platelet aggregation before and after percutaneous transluminal coronary angioplasty (PTCA) in treated and placebo groups.Double blind placebo controlled randomised study.135 patients with successful coronary angioplasty.Intravenous infusion of PGI2 (4 ng/kg/ml) or buffer was started before balloon angioplasty and continued for 36 hours. Platelet aggregation was measured in blood from the aorta and coronary sinus before and after PTCA in each group. Routine follow up was at six months with repeat angiography and there was quantitative assessment of all angiograms (those undertaken within the follow up period and at routine follow up). PRESENTATION OF RESULTS: Restenosis rates in treated and placebo groups determined according to the National Heart, Lung and Blood Institute definition IV. Comparison at follow up between the effect of treatment on mean absolute luminal diameter and mean absolute follow up diameter in the placebo group. Comparison of acute gain and late loss between groups.Of 125 patients available for assessment 23 were re-admitted because of angina within the follow up period. Quantitative angiography showed restenosis in 15 (10 in the PGI2 group and five in the placebo group). Of 105 patients evaluated at six month angiography there was restenosis in nine more in the PGI2 group and 18 more in the placebo group. Total restenosis rates (for patients) were 29.2% for PGI2 and 38.3% for placebo (NS). The mean absolute gain in luminal diameter was 1.84 (0.76) mm in the PGI2 group and 1.58 (0.56) mm in the placebo group (p = 0.04); the late loss in the PGI2 group was also greater (0.65 (0.94) mm vs 0.62 (0.89) mm (NS) and there was no significant difference in final luminal diameter at follow up between the two groups (1.83 (0.88) mm v 1.59 (0.60) mm). The transcardiac gradient of quantitative platelet aggregation increased after PTCA in both groups, indicating that PGI2 in this dose did not affect angioplasty-induced platelet activation. Mean (SD) platelet activation indices in the PGI2 group were pre PTCA aorta 8.4 (4.1) v coronary sinus 8.8 (4.0) (p = 0.001) and post PTCA aorta 8.9(3.0) v coronary sinus 12.9 (5.7) (p = 0.001). In the placebo group the values were pre PTCA aorta 7.6 (3.3) v coronary sinus 7.4 (3.6) (p = 0.001) and post PTCA aorta 7.6(2.8) v coronary sinus 11.2(4.3) (p = 0.001).The dose of PGI2 given was designed to limit side effects and as a short-term infusion did not significantly decrease the six month restenosis rate after PTCA. The sample size, which was determined by the original protocol and chosen because of the potency of the agent being tested, would have detected only a 50% reduction in restenosis rate. There was, however, no effect in the treated patients on the increased platelet aggregation seen in placebo group as a result of angioplasty. Angioplasty is a powerful stimulus to blood factor activation. Powerful agents that prevent local platelet adhesion and aggregation are likely to be required to reduce restenosis. |
0 | TITLE: Cigarette smoking and stroke in a cohort of U.S. male physicians.ABSTRACT: To examine the association between cigarette smoking and the risk for stroke in men.Prospective cohort study.Participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians.22,071 men, 40 to 84 years of age at entry, free from self-reported myocardial infarction, stroke, and transient ischemic attack; followed for an average of 9.7 years; and classified as never-smokers, current smokers, and former smokers based on self-report.Incidence rates of total, ischemic, and hemorrhagic stroke.With never-smokers as the reference group (relative risk, 1.00), relative risks (adjusted for age and treatment assignment) for total nonfatal stroke (n = 312) were as follows: former smoking, 1.20 (95% CI, 0.94 to 1.53); currently smoking fewer than 20 cigarettes daily, 2.02 (CI, 1.23 to 3.31); and currently smoking 20 or more cigarettes daily, 2.52 (CI, 1.75 to 3.61) (P for trend, < 0.0001). For participants who had total fatal stroke (n = 28), the risk for stroke was not increased with smoking (P > 0.2). In proportional-hazards models that controlled simultaneously for other risk factors, these associations were not materially altered.Current but not former cigarette smoking was significantly associated with an increased risk for stroke in men. Smoking may account for a substantial amount of stroke-associated morbidity and mortality. |
0 | TITLE: Risk stratification by early exercise testing after an episode of unstable coronary artery disease. The RISC Study Group.ABSTRACT: After stabilization of symptoms by medication a predischarge exercise test was performed in 855 men admitted with suspected unstable angina (54%) or non-Q-wave myocardial infarction (46%). Multiple logistic regression analysis demonstrated that the number of leads with ST-depression at exercise, low maximal work load, increasing age and ST-elevation in electrocardiogram at rest had independent prognostic value concerning the risk of myocardial infarction or death during the following year. Therefore a combination of extension of ST-depression and peak work load was used to define 'high and low risk response' at the exercise test. After 1 year the mortality in patients with 'high risk' compared to 'low risk' exercise response was 3.6% and 0% (P < 0.001) and the risk of either myocardial infarction or death was 15.4% and 3.9% (P < 0.0001), respectively. ST-depression, occurrence of angina and low peak load at exercise were independent predictors of future severe angina. After 1 year 29.5% of patients with any of these indicators at exercise had incapacitating symptoms that necessitated referral for coronary angiography compared to 4.8% in the group without these findings (P < 0.0001). The predictive value of the exercise test remained high in subgroups based on inclusion diagnosis, age or findings in electrocardiogram at rest and independently of treatment with beta-blockade, other antianginal medication or aspirin at the time of the exercise test. |
1 | TITLE: Differential effects of fluticasone and montelukast on allergen-induced asthma.ABSTRACT: Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients. |
1 | TITLE: A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients: 15-year results.ABSTRACT: In renal transplantation, the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity. Although cyclosporine improves short-term graft survival, its long-term effects are unclear.Recipients of first cadaver renal transplants were randomized into three groups between 1983 and 1986: azathioprine and prednisolone alone (AP, n = 158), long term cyclosporine alone (Cy, n = 166), and short-term cyclosporine followed by azathioprine and prednisolone (CyAP, n = 165). All groups received methylprednisolone induction.There were no significant differences in patient survival at 15 years (48 vs. 56 vs. 51%, P = 0.14), and 15-year graft survival (censored for death) in those patients in the CyAP group (47 vs. 44 vs. 59%, P = 0.06) was not significantly different statistically. When deaths or graft losses before 12 months were censored, the differences in 15-year graft survival between the groups were significant (58%, 51%, 70%, P = 0.01). The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years (143 vs. 169 vs. 131 micromoles/L, P = 0.04). Per protocol analysis, after censoring patients at change in therapy, increased the observed differences in 15-year graft survival between the groups (54 vs. 38 vs. 65%, P = 0.01).Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone. Long-term cyclosporine use reduces long-term graft survival. |
1 | TITLE: Using cost of infection as a tool to demonstrate a difference in prophylactic antibiotic efficacy: a prospective randomized comparison of the pharmacoeconomic effectiveness of ceftriaxone and cefotaxime prophylaxis in abdominal surgery.ABSTRACT: The purpose of this study was to test the hypothesis that cost, as well as frequency of infection, could be used to demonstrate a difference in the performance of prophylactic antibiotics. In a prospective, randomized, double-blind study, 1013 patients undergoing abdominal surgery were given 1 g of intravenous ceftriaxone (R) or cefotaxime (C) at induction of anesthesia, and an additional 500 mg of metronidazole for colorectal surgery. Infection was checked for during the hospital stay and at 30 days postoperatively. The inpatient, outpatient, and community costs of infection were prospectively collected. The frequency of wound infection for appendectomies when additional metronidazole was not administered was greater with cefotaxime (R 6%, C 18%, p < 0.05), but the cost of infection was the same (average cost R $994 +/- SD $1101, C $878 +/- $1318). For all other procedures, the frequency of wound infection was similar (R 8%, C 10%), but the cost was less with ceftriaxone (R $887 +/- $1743, C $2995 +/- $6592, p < 0.05). Ceftriaxone decreased the frequency but not the cost of chest and urinary infection (frequency R 6%, C 11%, p < 0.02, cost R $1273 +/- 2338, C $1615 +/- 4083). Differences in both the frequency and cost of all infection are also presented. Ceftriaxone decreased either the frequency or the cost of different postoperative infections. The cost of infection can increase the discriminatory power of trials comparing antibiotic effectiveness. |
1 | TITLE: Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis.ABSTRACT: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo.Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71).This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved. |
1 | TITLE: Reaching recommended lipid and blood pressure targets with amlodipine/atorvastatin combination in patients with coronary heart disease.ABSTRACT: The effects of combined atorvastatin and amlodipine on blood pressure (BP) and low-density lipoprotein (LDL) cholesterol levels were investigated in 134 patients with documented coronary heart disease treated for 1 year. BP at baseline was 128 +/- 15/79 +/- 9 mm Hg and was controlled by the treating physician; no calcium channel blockers were allowed. Baseline means for plasma cholesterol were 6.4 +/- 1.1 mmol/L (147 +/- 39 mg/dl), triglycerides 2.0 +/- 0.9 mmol/L (177 +/- 88 mg/dl), LDL cholesterol 4.4 +/- 1.0 mmol/L (170 +/- 39 mg/dl), and high-density lipoprotein cholesterol 1.2 +/- 0.3 mmol/L (46 +/- 12 mg/dl). Patients were all given atorvastatin 10 mg, then increased to 80 mg if the LDL cholesterol was <2.5 mmol/L (100 mg/dl). At 3 months, patients were randomized to amlodipine 10 mg or placebo. Plasma LDL cholesterol was decreased by 50%, and the LDL cholesterol target of <2.5 mmol/L was achieved in 81% of the patients. BP targets were achieved in 69% of the atorvastatin + placebo group, versus 96% in the atorvastatin + amlodipine group (p = 0.0002). With use of combination atorvastatin + amlodipine at doses ranging from 10 to 80 mg and 5 to 10 mg, respectively, recommended therapeutic goals were reached in most select subjects with coronary artery disease who were concomitantly receiving aspirin and antihypertensive therapy. |
1 | TITLE: Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans.ABSTRACT: The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state. |
1 | TITLE: Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes.ABSTRACT: Increased (intra)renal activity of the renin-angiotensin system may cause a persistent increase in renovascular resistance and intraglomerular pressure in patients with diabetes, thus contributing to the development of diabetic renal damage. The effect of chronic angiotensin II subtype 1 receptor blockade on (intra)renal hemodynamics in patients with type 2 diabetes was examined in a double-blind parallel group study. Patients were treated with 40 mg of olmesartan (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and after 12 wk of treatment using inulin and para-aminohippurate clearance techniques. Olmesartan significantly reduced 24-h ambulatory systolic and diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas filtration fraction and renovascular resistance decreased significantly (all P < 0.05). With placebo treatment, effective renal plasma flow decreased and filtration fraction increased significantly (both P < 0.05). GFR was not affected by both treatments. Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment. Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric dimethylarginine blood levels were not affected by olmesartan and placebo therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor blockade decreases (intra)renal vascular resistance and increases renal perfusion despite significant BP reduction. In addition, it significantly reduces oxidative stress. These effects of angiotensin II receptor antagonists may contribute to their beneficial long-term renal effects in patients with type 2 diabetes. |
1 | TITLE: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial.ABSTRACT: We assessed the relationship between antibodies to infliximab (ATI) and the loss of response postinfliximab, infusion reactions and, in a randomized trial, investigated whether intravenous hydrocortisone premedication can reduce ATI.Initially, we prospectively evaluated clinical response, adverse events, and ATI levels in 53 consecutive patients with Crohn's disease who received 199 infliximab (5 mg/kg) infusions. Subsequently, 80 patients with Crohn's disease were randomized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions. The primary endpoint was reduction in median ATI levels at week 16. Analysis was by intention to treat.Nineteen of our initial 53 patients (36%) developed ATI, including all 7 patients with serious infusion reactions (median ATI level, 19.6 microg/mL). Eleven of 15 patients (73%) who lost their initial response were ATI positive compared with none of 21 continuous responders, (8.9 vs. 0.7 microg/mL, P < 0.0001). Administering a second infusion within 8 weeks of the first (OR, 0.13; 95% CI, 0.03-0.5; P = 0.0007) or concurrent immunosuppressants (OR, 0.19; 95% CI, 0.04-1.03; P = 0.007) significantly reduced ATI formation. In the placebo-controlled trial, ATI levels were lower at week 16 among hydrocortisone-treated patients (1.6 vs. 3.4 microg/mL, P = 0.02), and 26% of hydrocortisone-treated patients developed ATI compared with 42% of placebo-treated patients, P = 0.06.Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level. Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation. Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions. |
1 | TITLE: A prospective randomized multicenter study to evaluate the best day for embryo transfer: does the outcome justify prolonged embryo culture?ABSTRACT: This study aimed to evaluate the best day for embryo transfer in a prospective unrestricted randomized multicenter trial.Data were collected on a preformed Excel-sheet which contained random numbers from 1 to 5 for each subsequent patient as a preprogrammed day for embryo transfer. Information was requested on patient's age, indication for sterility treatment, stimulation protocol used, numbers of oocytes retrieved, fertilized oocytes, cryopreserved embryos, and cell stage of embryos transferred.A total of 329 embryo transfers were performed, resulting in 106 clinical pregnancies (32.2%). Pregnancy rates achieved were 20.0% on day 1, 30.4% on days 2 and 3, and 50.0% on days 4 and 5 (p = 0.03).Within the scope of the present randomized multicenter trial, embryo transfers performed on days 4 and 5 enhanced the pregnancy rate significantly, compared to those of days 1, 2, and 3. |
1 | TITLE: Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.ABSTRACT: In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA. |
1 | TITLE: Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen.ABSTRACT: To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen.Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu.For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P =.008), clinical benefit (CB; 57% v 45%; P =.016), time to progression (TTP; median, 12.2 v 8.5 months; P =.0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P =.0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P =.45) or CB (33% v 26%; P =.31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P =.0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P =.0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP.Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole. |
1 | TITLE: Patient education strategies to improve pneumococcal vaccination rates: randomized trial.ABSTRACT: The pneumococcal vaccine is widely underused. Patient education is one mechanism not widely explored for increasing vaccination rates.To evaluate the effects of a culturally appropriate patient education videotape on pneumococcal vaccination rates among the clinic population of an inner-city public hospital.Randomized, controlled trial comparing (1) a videotape-brochure group who both viewed the videotape and received a low-literacy brochure, (2) a videotape only group, and (3) a control group.Of 2,962 charts reviewed, 558 patients were randomized. The study population was 94% black, 73% female, and elderly (mean age 63.0 years) and 64% had less than a high school education. Patients in the videotape-brochure group were 2.5 (1.8, 3.5 95% CI) times more likely to discuss the vaccine with their physician (p < .001) and 3.5 (1.9, 6.5 95% CI) times more likely to receive the vaccine (p < .001) than the control group. The videotape-brochure group was 1.6 (1.2, 2.1 95% CI) times more likely to discuss the vaccine (p < .001) and 2.3 (1.4, 3.8 95% CI) times more likely to receive the vaccine (p = .002) than the video only group. Patients in the video only group were 1.6 (1.1, 2.3 95% CI) times more likely to discuss the vaccine with their physician than the control group (p = .041) but were not more likely to receive the vaccine.A culturally appropriate videotape along with a low-literacy brochure significantly increased pneumococcal vaccination rates and physician-patient discussion about the vaccine. These significant outcomes were not observed with use of videotape alone and were likely attributable to the effect of the brochure. We recommend that patient education initiatives to increase vaccination rates not focus solely on audiovisual media. |
0 | TITLE: The effect of rosiglitazone on serum lipoprotein(a) levels in Korean patients with type 2 diabetes mellitus.ABSTRACT: The aim of the study was to determine if rosiglitazone increases serum levels of lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total of 118 patients were divided into 2 groups: those with rosiglitazone (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n = 69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group continued previous treatment with some dose modification for glycemic control. The patients had their blood glucose, lipid levels, as well as Lp(a) levels assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased significantly in both groups as compared with the baseline. The fasting glucose and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to 212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did not change in either group. Significant increases in high-density lipoprotein (HDL) cholesterol levels were observed in the rosiglitazone group as compared with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low-density lipoprotein (LDL) cholesterol levels increased significantly in the rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P =.015), approximately a 15% increase in average values. In contrast, there was no change in Lp(a) levels in the control group. There was no correlation between the changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus. Considering that patients with type 2 diabetes mellitus have increased risks for cardiovascular disease, caution should be taken when prescribing rosiglitazone to patients who already have other risk factors, such as hypertension and smoking. |
1 | TITLE: Uric acid reduces exercise-induced oxidative stress in healthy adults.ABSTRACT: Uric acid (UA) possesses free-radical-scavenging properties, and systemic administration is known to increase serum antioxidant capacity. However, it is not known whether this protects against oxidative stress. The effects of raising UA concentration were studied during acute aerobic physical exercise in healthy subjects, as a model of oxidative stress characterized by increased circulating 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) concentrations. Twenty healthy subjects were recruited to a randomized double-blind placebo-controlled crossover study, and underwent systemic administration of 0.5 g of UA in 250 ml of 0.1% lithium carbonate/4% dextrose vehicle or vehicle alone as control. Subjects performed high-intensity aerobic exercise for 20 min to induce oxidative stress. Plasma 8-iso-PGF2alpha concentrations were determined at baseline, after exercise and after recovery for 20 min. A single bout of high-intensity exercise caused a significant increase in plasma 8-iso-PGF2alpha concentrations from 35.0 +/- 4.7 pg/ml to 45.6 +/- 6.7 pg/ml (P<0.01). UA administration raised serum urate concentration from 293 +/- 16 to 487 +/- 16 micromol/l (P<0.001), accompanied by increased serum antioxidant capacity from 1786+/-39 to 1899 +/- 45 micromol/l (P<0.01). UA administration abolished the exercise-induced elevation of plasma 8-iso-PGF2alpha concentrations. High UA concentrations are associated with increased serum antioxidant capacity and reduced oxidative stress during acute physical exercise in healthy subjects. These findings indicate that the antioxidant properties of UA are of biological importance in vivo. |
1 | TITLE: Study comparing the stroke unit outcome and conventional ward treatment: a randomized study in Joinville, Brazil.ABSTRACT: To assess the impact of a stroke unit (SU) on acute phase treatment when compared to a conventional general ward treatment (GW).Seventy-four patients with acute stroke were randomized between a SU and conventional general ward (GW). We compared both groups regarding the length of hospital stay, lethality and functional and clinical status within 6 months, using the Scandinavian scale and Barthel index.Thirty-five and thirty-nine patients were allocated at SU and GW, respectively. Lethality on the 10th day at SU and GW achieved 8.5% and 12.8% respectively (p= 0.41), whereas 30-days mortality rates achieved 14.2% and 28.2% (p= 0.24), 17.4% and 28.7% on the 3rd month (p= 0.39), and 25.7% and 30.7% on the 6th month (p= 0.41). Thirty-day survival curve achieved 1.8 log rank (p= 0.17), with a trend for lower lethality in the SU. In order to save one death in 6 months in SU, NNT (the number need to treat) was 20; to get one more home independent patient NNT was 15. No significant difference was found between the length of hospital stay and morbidity.No significant benefit was found in SU patients compared to GW group. However,an evident benefit in absolute numbers was observed in lethality, survival curve and NNT in thirty days period after stroke. Further collaborative studies or incresead number of patients are required to define the role of SU. |
1 | TITLE: Efficacy and tolerability of acarbose in Asian patients with type 2 diabetes inadequately controlled with diet and sulfonylureas.ABSTRACT: The objective of this study was to investigate the efficacy, tolerability, and safety of acarbose in the improvement of glycemic control in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas. A 24-week, double-blind, placebo-controlled multicenter group comparison study was conducted. Patients were randomized to receive acarbose titrated up to 100-mg tid (n=36) or matching placebo (n=33). Concomitant sulfonylurea treatment remained unchanged throughout the study. The primary efficacy parameter was the change in HbA(1c) from baseline to double-blind endpoint. Secondary efficacy variables consisted of the change from baseline to endpoint in blood glucose (fasting and 1-h postprandial), serum insulin (fasting and 1-h postprandial), and urinary glucose. In the intention-to-treat (ITT) analysis, acarbose treatment was associated with significantly greater reductions in glycated hemoglobin (HbA(1c)) (-0.91% vs. placebo 0.13%, P=.0018) and 1-h postprandial blood glucose levels (-2.84 mmol/l vs. placebo -0.28 mmol/l, P=.002) compared to placebo. There were no significant differences between the treatment groups regarding changes in fasting blood glucose, fasting or 1-h postprandial serum insulin, urinary glucose, or body weight. Adverse events occurred with similar frequency in both treatment arms except for drug-related gastrointestinal side-effects associated with acarbose (acarbose 48.5% and placebo 12.5%). This study has shown that the use of acarbose in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas is efficacious in improving metabolic control and that acarbose is safe and well tolerated. |
1 | TITLE: Prognostic factors in lateral epicondylitis: a randomized trial with one-year follow-up in 266 new cases treated with minimal occupational intervention or the usual approach in general practice.ABSTRACT: To determine whether minimal intervention by occupational specialists involving information about the disorder, encouragement to stay active and instruction in graded self-performed exercises could enhance the prognosis of lateral epicondylitis compared with the treatment usually given in general practice, to quantify workplace factors associated with the prognosis, and to consider treatments given in general practice.A randomized controlled trial was performed in a cohort of 266 consecutive new cases of lateral epicondylitis diagnosed in general practice. Workplace factors were assessed with questionnaires at the time of inclusion, and patients completed follow-ups at 3, 6 and 12 months. Status at 1 yr was assessed as overall improvement and pain reduction compared with the time of diagnosis. General practitioners (GPs) registered the treatments given for both cases and controls during follow-up. Numbers of contacts with GPs and physiotherapists were obtained from the National Health Insurance registry. Prognostic factors were analysed by multiple logistic regression analysis.After 1 yr, 83% of cases showed improvement in the condition, but the intervention was found to have had no advantage. Poor overall improvement was associated with employment in manual jobs [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.0-8.7], a high level of physical strain at work (OR 8.5, CI 1.0-74.7) and a high level of pain at baseline (OR 2.3, CI 1.0-5.3). Pain reduction less than 50% was associated with manual jobs (OR 2.3, CI 1.1-5.1), high physical strain at work (OR 3.6, CI 1.0-12.9), high baseline distress (OR 1.9, CI 1.0-4.0) and tennis elbow on the dominant side (OR 3.1, CI 1.4-6.8). The intervention group received less treatment and fewer treatment modalities, but the intervention was not followed by a reduction in the number of visits to GPs and physiotherapist clinics during 12 months of follow-up.Poor prognosis at 1 yr of follow-up for lateral epicondylitis was related to manual work and high baseline pain, whilst no relation was found between the type of medical treatment given/chosen and prognosis. This may have implications for the future management of lateral epicondylitis in terms of a greater focus on interaction with the workplace regarding job modification to reduce physical demands during recovery. |
1 | TITLE: Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus.ABSTRACT: Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen. |
1 | TITLE: Combined interferon alpha2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial.ABSTRACT: Only 15% to 20% of patients with chronic hepatitis C have a sustained virological response to interferon monotherapy. The aim of the present study was to compare the efficacy and safety of interferon, in combination with oral cyclosporin A, with interferon monotherapy in the treatment of chronic hepatitis C.We assigned 120 patients with chronic hepatitis C to receive the standard Japanese dose of interferon alpha2b alone for 24 weeks or that dose of interferon alpha2b in combination with cyclosporin A, at doses of 200 mg daily for the first 4 weeks and 100 mg daily for the following 20 weeks. All patients were assessed for drug safety, tolerance, and efficacy at the end of weeks 4, 12, 24, and 48. Efficacy was assessed by the disappearance of serum hepatitis C virus (HCV)-RNA by polymerase chain reaction and normalization of serum aminotransferase. The primary endpoint was a sustained virological response; i.e., sustained undetectable serum HCV RNA at 48 weeks.The sustained virological response rate was significantly higher in the combination therapy group (42/76) than in the monotherapy group (14/44; P = 0.01). The sustained biochemical response rate was also higher in the combination therapy group (46/76) than in the monotherapy group (17/44; P = 0.017). In patients with genotype 1 and high viral loads, the sustained virological response rate was markedly higher in the combination therapy group (16/38) than in the monotherapy group (1/21; P = 0.006). Side-effect profiles were similar in the two groups.In patients with chronic hepatitis C; combined interferon and cyclosporin A treatment was more effective than interferon monotherapy. The benefit was mostly achieved in patients with a high viral load and HCV genotype 1. |
0 | TITLE: Effects of enalaprilat on venoconstriction to norepinephrine: role of prostaglandins.ABSTRACT: Most patients with cardiovascular disease continue to receive both aspirin and an angiotensin-converting enzyme (ACE) inhibitor. This is despite the fact that ACE inhibition also inhibits the enzyme kininase II and leads to accumulation of bradykinin which increases prostaglandins. We hypothesized that in normal veins, vasodilator prostaglandins contribute significantly to ACE inhibitor dilation of norepinephrine-induced venoconstriction, and this would be blocked by cyclooxygenase inhibition.The study was performed using the in vivo dorsal hand vein technique for measuring vascular responses directly. Venoconstriction to norepinephrine infusions (0.5-1024 ng/min) was assessed in eight normal subjects (46+/-5 years, mean+/-S.E.M.) during coinfusion of saline in one hand (control) and enalaprilat (1000 microg/min) in the contralateral hand. On a second morning (7+/-1 days apart, mean+/-S.E.M., random order), the same procedure was repeated with indomethacin (3 microg/min) coinfusion in both hands.Enalaprilat shifted the norepinephrine dose-response curve to the right (P=0.024) and increased the norepinephrine log ED(50) (dose required to cause 50% venoconstriction) from 1.70+/-0.08 to 2.31+/-0.11 log ng/min (P=0.001). Indomethacin shifted the norepinephrine dose-response curve to the left (P=0.018) and decreased the norepinephrine log ED(50) from 1.70+/-0.08 to 1.09+/-0.18 log ng/min (P=0.002). In the presence of indomethacin, enalaprilat caused only a small but significant increase in the norepinephrine log ED(50), from 1.09+/-0.18 to 1.29+/-0.18 log ng/min (P=0.041).The results suggest that vasodilator prostaglandins contribute significantly to the attenuation of sympathetic venoconstriction by enalaprilat. This may have clinical relevance in patients receiving aspirin and ACE inhibitors in the setting of increased sympathetic activity. |
1 | TITLE: Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction.ABSTRACT: Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels. |
1 | TITLE: Two-year clinical follow-up of 90Sr/90 Y beta-radiation versus placebo control for the treatment of in-stent restenosis.ABSTRACT: It is an ongoing concern that intracoronary brachytherapy may possibly just delay the problem of in-stent restenosis ("late catch up"). For gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the initially positive effect after 2 years, but similar data do not exist for beta-radiation. STents And Restenosis Trial (START) was the first placebo-controlled randomized trial for in-stent restenosis with beta-radiation; herein, we report the 2-year clinical follow-up.Two hundred and forty-four patients were randomized to active treatment, 232 patients to placebo (nonactive source train) treatment. The primary end point of efficacy was target vessel revascularization (TVR); primary safety end point was any major adverse cardiac event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan-Meier analysis for TVR and MACE showed improvement beginning approximately 90 days after radiation and remained almost constant for the 2 following years. Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/- 3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P = .035).The START trial shows for the first time that the initial beneficial effects of intracoronary brachytherapy with beta-radiation using 90 Sr/ 90 Y are maintained at 2-year clinical follow-up period. |
1 | TITLE: Guided tissue regeneration associated with bovine-derived anorganic bone in mandibular class II furcation defects. 6-month results at re-entry.ABSTRACT: The use of graft materials with guided tissue regeneration (GTR) in Class II furcation defects is aimed at improving the outcome of the regenerative technique. In this regard, however, there are a limited number of studies discussing the results obtained when GTR and graft materials are used in the treatment of Class II furcation defects. Furthermore, most studies employ either allogeneic or autogenous materials. The present trial sought to determine whether the use of a bovine-derived anorganic bone (ABB) in conjunction with GTR influenced the outcome of mandibular Class II furcation treatment.This study included 14 patients who provided 15 pairs of similar periodontal defects. Each defect was randomly assigned to treatment with either a cellulose membrane in combination with bovine-derived anorganic bone (GTR+ABB) or membrane alone (GTR). Following basic therapy, baseline measurements were recorded including probing depth (PD), clinical attachment level (CAL), and gingival margin position (GMP). Hard tissue measurements were performed during surgery to determine alveolar crestal height (CEJ-AC), and vertical (VDD) and horizontal defect depth (HDD). Membranes remained in position for at least 4 weeks. After 6 months, all sites were re-entered and soft and hard tissue measurements were recorded.Both surgical procedures resulted in statistically significant probing depth reduction and gain in clinical attachment levels, with no significant difference between groups. Gingival recession was more pronounced in the GTR+ABB group (0.87 +/- 0.83 mm), but not statistically different from the GTR group (0.46 +/- 1.19 mm). Vertical defect resolution was significant in both groups (GTR: 1.60 +/- 1.50 mm; GTR+ABB: 1.80 +/- 2.11 mm), without differences between groups. Only horizontal furcation resolution (GTR: 2.47 +/- 0.99 mm; GTR+ABB: 3.27 +/- 1.39 mm) was significantly different between groups (P <0.05).The use of ABB with GTR techniques improved horizontal defect resolution in mandibular Class II furcation defects, but did not yield superior results regarding soft tissue changes when compared to sites treated with GTR alone. Evaluation of a larger sample could indicate differences and advantages between the evaluated approaches and confirm the real necessity of associating filling materials with GTR. |
1 | TITLE: Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?ABSTRACT: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention.The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy.Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036).Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C. |
1 | TITLE: Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure.ABSTRACT: This study evaluated whether cyclosporine (CsA) could be eliminated from a sirolimus (Rapamune, rapamycin, SRL)-CsA-steroid (ST) regimen at 3 months.This was an open-label study conducted in Europe, Australia, and Canada. Upon enrollment, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of sirolimus (troughs>5 ng/ml), CsA, and steroids. At 3 months+/-2 weeks, eligible patients were randomized (1:1) to remain on SRL-CsA-ST or to have CsA withdrawn and therapy continued with SRL (troughs 20-30 ng/ml)-ST.At 12 months, overall graft and patient survival were 89.1% and 94.9%, respectively. In the 430 (82%) randomized patients, there was no difference in graft survival (95.8% vs. 97.2%, SRL-CsA-ST vs. SRL-ST) or patient survival (97.2% vs. 98.1%, respectively). The incidence of biopsy-confirmed primary acute rejection was 13.1% during the prerandomization period. After randomization, the acute rejection rates were 4.2% and 9.8% for SRL-CsA-ST and SRL-ST, respectively (P=0.035). Renal function (calculated glomerular filtration rate, 57 vs. 63 ml/min, P<0.001) and blood pressure significantly improved when CsA was withdrawn. Hypertension, CsA nephrotoxicity, hyperuricemia, and Herpes zoster occurred statistically more frequently in patients remaining on CsA, whereas thrombocytopenia, abnormal liver function tests, and hypokalemia were reported more often for SRL-ST therapy.Sirolimus, CsA, and steroids for 3 months posttransplant, followed by elimination of CsA, is a safe and effective alternative to continuous therapy with sirolimus, CsA, and steroids that can result in better renal function and lower blood pressure. |
1 | TITLE: Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension.ABSTRACT: LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality.Double-blind, randomized pharmacological intervention trial.Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/- 3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid profile. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a beta-blocker.Lag phase of copper-induced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL.At baseline in hypertensives versus controls, lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53 +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the randomized groups.In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a significant improvement, but not a full reversal, of this abnormality. |
1 | TITLE: A comparison of propofol and remifentanil for sedation and limitation of movement during periretrobulbar block.ABSTRACT: To compare clinical conditions in patients sedated with propofol or remifentanil during combined peri-bulbar and retrobulbar block (PRBB) for cataract surgery.Prospective, randomized, double-blind study.Private clinic.106 ASA physical status I and II patients scheduled for cataract surgery.Patients were randomized to receive either 0.5 mg/kg propofol (Group P) or 0.3 microg/kg remifentanil (Group R) as an intravenous (IV) bolus 1 minute prior to PRBB. At the same time, patients in both groups also received 0.5 to 1 mg midazolam IV. Movement of the hands, arms, head, and eyes were counted during each stage of the procedure by an observer who was blinded to the sedation used. Heart rate (HR), blood pressure (BP), respiratory rate (RR), expiratory CO(2) (PECO(2)), and hemoglobin oxygen saturation (SaO(2)) were recorded every minute for 10 minutes after the PRBB. Anesthetic complications, recall, and the pain experienced with the block and surgery were compared between the two groups. Means and variance of the results were compared with one-way analysis of variance and Fisher's exact test.Movements of the hands, arms, and head were significantly greater in Group P during all stages of the block. Almost no movements were recorded in the remifentanil group. Immediately after the PRBB (1 to 6 min), HRs were higher in Group P (73 +/- 11 bpm vs. 67 +/- 10 bpm; p = 0.0075), whereas the RRs were slower in Group R for the period 1 to 5 minutes after the PRBB (16 +/- 5 breaths/min vs.14 +/- 4 breaths/min; p = 0.0206). At these times, the mean PECO(2) was higher in Group R (36 +/- 7 mmHgvs. 32 +/- 9 mmHg; p = 0.0125). Nineteen patients in the propofol group sneezed during the medial peribulbar injection compared with none in the remifentanil group. Anesthetic and surgical complications were unremarkable and similar for the two groups.Respiratory depression with remifentanil was mild and not clinically significant. Remifentanil sedation for this application was superior to sedation with propofol. |
1 | TITLE: TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study).ABSTRACT: This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk. Individual L-thyroxine replacement (mean dose, 85.5 +/- 4.3 microg/d) was performed based on blinded TSH monitoring, resulting in euthyroid TSH levels (3.1 +/- 0.3 mIU/liter). Lipid concentrations and clinical scores were measured before and after treatment. Sixty-three of 66 patients completed the study. In the L-thyroxine group (n = 31) total cholesterol and low density lipoprotein cholesterol were significantly reduced [-0.24 mmol/liter, 3.8% (P = 0.015) and -0.33 mmol/liter, 8.2% (P = 0.004), respectively]. Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline. A significant decrease in apolipoprotein B-100 concentrations was observed (P = 0.037), whereas high density lipoprotein cholesterol, triglycerides, apolipoprotein AI, and lipoprotein(a) levels remained unchanged. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02). This is the first double blind study to show that physiological L-thyroxine replacement in patients with subclinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction of cardiovascular mortality of 9-31% can be estimated from the observed improvement in low density lipoprotein cholesterol. |
1 | TITLE: Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: a 24-week randomized controlled trial.ABSTRACT: To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent.In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period.Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% at 4.5 g/d. The reduction in LDL cholesterol levels was maximal after 2 weeks and sustained throughout the study. Mean total cholesterol levels decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups.Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events. |
1 | TITLE: Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study.ABSTRACT: This study aims to determine whether the use of a temporary portocaval shunt (PCS) improves hemodynamic and metabolic evolution during orthotopic liver transplantation (OLT). Preservation of the vena cava during OLT has gained wide acceptance. However, benefits of adding a temporary PCS to the piggyback technique during the anhepatic phase in patients with cirrhosis have not been shown. Eighty patients with cirrhosis were studied prospectively. They were randomly distributed into two groups: patients with a temporary PCS (n = 40) and those without a PCS (n = 40). In all cases, the piggyback technique was used. Hemodynamic profiles and biochemical data during OLT and clinical evolution after OLT were evaluated. Preoperative data were similar in both groups. Surgical time also was similar (403 +/- 77 v 387 +/- 56 minutes; P = .3). Red blood cell requirements were lower in the PCS group (2.3 +/- 2.5 v 3.3 +/- 2.9 units), although differences were not significant. In the PCS group, 45% of patients did not need red blood cell transfusion, whereas in the other group, only 22% were not administered a transfusion (P = .03). During the anhepatic phase, the decrease in cardiac output was lower in the PCS group (-9.6% v -19%; P = .05), whereas diuresis during the anhepatic phase was greater in the PCS group (3.6 +/- 2.97 v 2.1 +/- 1.38 mL/kg/h; P = .005). There were no differences in liver biochemical parameters during the first 3 postoperative days. Nevertheless, creatinine levels increased significantly during this period only in the no-PCS group. The use of a temporary PCS during OLT improves hemodynamic status, reduces intraoperative transfusion requirements, and preserves renal function during and after OLT. |
0 | TITLE: Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.ABSTRACT: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction.We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities).There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction. |
1 | TITLE: Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial.ABSTRACT: Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones.To see if an intestinal prokinetic, cisapride, could overcome these adverse effects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones.A randomised, double blind, placebo controlled, crossover design was used to examine the effects of cisapride (10 mg four times daily) on gall bladder emptying, mouth to caecum and large bowel transit times, and the proportions of deoxycholic acid and other bile acids, in fasting serum from: (i) control subjects (n=6), (ii) acromegalic patients not treated with octreotide (n=6), (iii) acromegalics on long term octreotide (n=8), and (iv) patients with constipation (n=8).Cisapride had no prokinetic effect on the gall bladder. In fact, it significantly increased both fasting and postprandial gall bladder volumes. However, it shortened mouth to caecum (from 176 (13) to 113 (11) minutes; p<0.001) and large bowel (from 50 (3.0) to 31 (3.4) h; p<0.001) transit times. It also reduced the proportion of deoxycholic acid in serum from 26 (2.3) to 15 (1.8)% (p<0.001), with a reciprocal increase in the proportion of cholic acid from 40 (3.5) to 51 (3.8)% (p<0.01). There were significant linear relationships between large bowel transit time and the proportions of deoxycholic acid (r=0.81; p<0.001) and cholic acid (r=-0.53; p<0.001) in fasting serum. INTERPRETATION/SUMMARY: Cisapride failed to overcome the adverse effects of octreotide on gall bladder emptying but it countered octreotide induced prolongation of small and large bowel transit. Therefore, if changes in intestinal transit contribute to the development of octreotide induced gall bladder stones, enterokinetics such as cisapride may prevent their formation. |
0 | TITLE: Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women.ABSTRACT: CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway.The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein (CETP) in the serum of Chinese women was investigated. Serum concentrations of estradiol (E(2)), follicle-stimulating hormone (FSH), CETP and lipid profile were determined in 196 Chinese women (52 premenopausal with ages ranging from 18 to 40 years, 57 perimenopausal from 41 to 60 years, and 87 postmenopausal from 61 to 81 years).Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women (1.39+/-1.06, 2.36+/-1.50 and 2.31+/-1.25 mg/l, respectively, P<0.0001). Even in the women around the menopausal, CETP concentration in postmenopause was significantly lower than that in premenopause (1.93+/-1.33 vs. 3.42+/-1.35 mg/l, P<0.01). In addition, CETP concentration had a highly positive correlation with serum concentration of E(2) (r=0.243, P<0.001), while negative correlation of CETP concentration with serum concentration of FSH was found (r=-0.273, P<0.001).Estrogen may affect the concentration of CETP. |
1 | TITLE: Prospective randomized study of post-operative chemotherapy with levamisole and UFT for head and neck carcinoma.ABSTRACT: A prospective randomized study was conducted to evaluate the benefit of adjuvant levamisole/UFT (futraful and uracil) chemotherapy in head and neck squamous cell carcinoma.Sixty-five patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx with no distant metastasis were randomized for the chemotherapy study. Thirty-one patients were randomized for chemotherapy and two of them were subsequently excluded. In this study, a total of 29 patients on levamisole/UFT therapy and 34 patients on the control group were analysed. The main outcome was measured by the 5-year disease-free actuarial survival rate.The rates of distant metastasis were 10% for chemotherapy group and 32% for control group (P=0.06). The 5-year disease-free actuarial survival rates for patients with and without adjuvant chemotherapy were 57% and 39% respectively (P=0.207).A trend of better distant control in head and neck cancer patients with post-operative adjuvant oral chemotherapy was observed. The side effects were minimal. However, there was no statistically significant improvement in the overall long-term survival. It may be of value to conduct a large-scale multi-centre prospective randomized study to verify the efficacy of levamisole and UFT as post-operative adjuvant chemotherapy for the control of distant metastasis in high-risk population. |
1 | TITLE: Economic evaluation of propofol for sedation of patients admitted to intensive care units.ABSTRACT: The goal of the current study was to evaluate the economic impact of propofol as compared with midazolam for sedating patients in the intensive care unit (ICU).A randomized, unblinded, multicenter pharmacoeconomic trial captured health resource utilization and outcome measurements associated with sedation and treatment of patients in four ICUs across Canada. Statistical analysis was performed to investigate the difference in sedation quality, ICU length of stay, and other health resources used. The authors compared the costs (1997 Canadian dollars) associated with the two treatments. Two types of sensitivity analyses were performed.Although overall sedation duration was similar, propofol patients spent more time at adequately sedated status (60.2% vs. 44%; P = 0.01) and were extubated faster (median extubation time, 2.5 vs. 7.1 h; P = 0.001). The ICU length of stay and health resource utilization did not differ. The total cost per patient, including drug cost and ICU stay cost, did not differ between groups (median, $5,718 for propofol vs. $5,950 for midazolam; P = 0.94). The first sensitivity analysis suggested that the incremental cost (per patient) of propofol varies from an extra cost of $114 to a savings of $2,709. Based on a hypothetical model, the second sensitivity analysis showed a potential saving of $479 per patient as a result of improved discharge planning.The analysis demonstrated that using propofol resulted in a reduction of time to extubation and higher sedative regimen costs. There was no difference in intensity of resource use or ICU length of stay and hence in costs. Issues regarding discharge delay among propofol-treated patients remain to be explored. |
1 | TITLE: Monochromatic infrared irradiation (890 nm): effect of a multisource array upon conduction in the human median nerve.ABSTRACT: Antidromic conduction studies in the human median nerve were used to assess the neurophysiological effects of irradiation of the skin overlying the nerve using a novel treatment unit comprising a multisource monochromatic infrared diode array (Equilight, Denver, CO).Healthy human volunteers (n = 40) were recruited and randomly allocated to one of four groups: control, placebo, or one of two treatment groups (1.7 and 4.0 J/cm2). After baseline recordings of negative peak latency (NPL) were completed on the nondominant arm, subjects were treated according to group allocation. Recordings were subsequently repeated at 5-min intervals over a 45-min period.Analysis of negative peak latency difference scores (ANOVA) demonstrated significant differences in NPL between groups and over time (p < 0.05). While in the control and placebo groups NPL values remained relatively stable, in the two treatment groups such values decreased marginally, with the greatest effects observed in the 4.0 J/cm2 group (e.g., at 5 min, differences in NPL [mean +/- SEM]: control group, 0.02+/-0.03 msec; treatment group 2, 4 J/cm2, -0.07+/-0.03 msec). Similar significant differences were observed in skin temperature; correlation analysis indicated a weak (but expected) positive linear relationship between skin temperature and nerve conduction velocity (r = 0.125).These results suggest that irradiation at the parameters and under the conditions used here produce a direct neurophysiological effect. The magnitude of such effects are in keeping with previous findings using single source arrays at higher radiant exposures or thermal effects of the treatment unit. |
1 | TITLE: A randomized comparison of the value of additional stenting after optimal balloon angioplasty for long coronary lesions: final results of the additional value of NIR stents for treatment of long coronary lesions (ADVANCE) study.ABSTRACT: We sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm).Long coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length.A total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). "Bail-out stenting" was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms.Bailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27+/-9 mm, and the vessel diameter was 2.78+/-0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups.A strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months. |
1 | TITLE: Radiotherapy for subfoveal choroidal neovascularization in age-related macular degeneration: a randomized clinical trial.ABSTRACT: To report results of 18-month follow up of external beam radiation therapy with photons for subfoveal classic or occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD).Randomized clinical trial.A total of 161 patients with subfoveal CNV in ARMD were recruited in a prospective double-masked study. The posterior pole of the afflicted eye was given 1 Gy (4 x 0.25 Gy) in the control group and 8 Gy (4 x 2 Gy) or 16 Gy (4 x 4 Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV size were measured.At the completion of the study 150 (93.2%), 139 (86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months, respectively. The mean number of lines lost in the BCVA was -1.69, -2.2, and -3.23 in the 1 Gy group; -0.94, -1.25, and -1.73 in the 8 Gy group; -0.51, -0.67, and -1.93 in the 16 Gy group. The difference was significant after 12 months (P =.016 for 8 Gy vs. 1 Gy; P =.006 for 16 Gy vs. 1 Gy), and 18 months (P =.011 for 8 Gy vs. 1 Gy; P =.05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with an initial distance visual acuity >or=20/100, benefited more from treatment. A significant difference was not found between control group and treatment groups in the reading ability and in the CNV size. No radiation-associated side effects were reported thus far.The number of lines lost in the BCVA was less in the 8 Gy and 16 Gy treatment groups than in the control group during the complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without showing any difference in efficacy, resulted in a near stabilization of the BCVA in patients with subfoveal classic or occult CNV in ARMD. Further studies are necessary to determine the significance of repeated radiotherapy series with a dose of 8 Gy to improve the effect on the CNV size and thereby to prolong stabilization of distance visual acuity. |
1 | TITLE: Use of delayed pushing with epidural anesthesia: findings from a randomized, controlled trial.ABSTRACT: To compare outcomes between women receiving epidural anesthesia assigned to a group following either a 1-hour "delayed" pushing protocol or directed to initiate pushing at full cervical dilation.Using a randomized, controlled design, multivariate analyses were used to evaluate second stage labor duration and Apgar scores. An estimated odds ratio equation evaluated fetal descent progress.A 13.68-minute difference occurred in second stage labor length (p = 0.225). No differences were found in Apgar scores (p > 0.09). An estimated odds ratio, that progress in terms of one fetal station unit would occur for control group subjects as compared with subjects with similar progress in the experimental group, was 1.51 (95% confidence interval: 1.16, 1.95).Second stage labor was not significantly lengthened, and a similar rate of fetal descent occurred in the absence of directed pushing. Findings support further research on the potential advantages of minimizing the duration of pushing in labor. |
1 | TITLE: Perioperative myocardial ischemia in cataract surgery patients: general versus local anesthesia.ABSTRACT: Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). All intraoperative ischemic events were associated with tachycardia (> or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery. |
1 | TITLE: Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units.ABSTRACT: To study the effect of a parenteral nutrition solution enriched with potential precursors of glutamine, i.e., arginine and glutamate, on plasma glutamine concentrations and protein metabolism.Prospective, randomized, single-blind, comparative study.Two intensive care units in two different hospitals.Fifteen surgical patients.Patients were randomized to receive total parenteral nutrition for 5 days with the enriched glutamine precursor solution (GlnP+ group) or a conventional solution (control group), both total parenteral nutrition providing 0.25 gN/kg per day and 35 kcal/kg per day (glucose/lipids, 70%:30%).Plasma amino acid concentrations before (T0) and after 3 hrs (T3) of perfusion, nitrogen balance (daily and cumulated), and urinary excretion of 3-methylhistidine were measured daily from day 1 to day 5. The two groups were identical for age, weight, severity score, and nitrogen and energy intakes. After a 3-hr perfusion, plasma concentrations of arginine, ornithine, and glutamine increased, and the differences (T3 - T0) were significantly higher in the GlnP+ group: arginine, 107.6+/-7.0 vs. 51.9+/-3.3 (mean over 5 days; p < .001); ornithine, 78.9+/-7.1 vs. 43.6+/-3.1 (p < .001); and glutamine, 32.4+/-8.6 vs. 6.7+/-5.0 micromol/L (p < .05), respectively. A positive correlation was found between arginine and glutamine plasma increases only in the GlnP+ group: r = .45; p < .01 (Spearman's rank-correlation test). Daily and cumulated nitrogen balances were not significantly different between the two groups but were positive (difference from 0) only in the GlnP+ group. The urinary 3-methylhistidine/creatinine ratio decreased significantly from day 1 to day 5 only in the GlnP+ group: 24.5+/-2.7 vs. 18.8+/-2.7 micromol/mmol (p < .05).Total parenteral nutrition enriched with arginine and glutamate promotes a better nitrogen balance, limits protein myofibrillar catabolism, and generates glutamine, with arginine (not glutamate) probably being the main contributor to the glutamine-generating effect of the solution through the formation of ornithine. |
1 | TITLE: 5-day vs. 7-day triple therapy with rabeprazole, clarithromycin and amoxicillin for Helicobacter pylori eradication.ABSTRACT: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen.A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test.On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance.Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended. |
1 | TITLE: Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.ABSTRACT: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction.3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model.Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group).Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin. |
1 | TITLE: Immunomodulatory effects of acupuncture in the treatment of allergic asthma: a randomized controlled study.ABSTRACT: According to Traditional Chinese Medicine (TCM) acupuncture is a suitable treatment for complex chronic diseases such as bronchial asthma. In a randomized, controlled study we investigated immunologic effects of Chinese acupuncture on patients with allergic asthma.The effects of acupuncture treatment given according to the principles of TCM (TCM group, n = 20) were compared with those of acupuncture treatment using points not specific for asthma (control group, n = 18). All patients were treated 12 times for 30 minutes over a time period of 4 weeks. Patients' general well-being and several peripheral blood parameters (eosinophils, lymphocyte subpopulations, cytokines, in vitro lymphocyte proliferation) were determined before and after acupuncture treatment.In the TCM group, significantly more patients indicated an improvement in general well-being (79% in the TCM group versus 47% in the control group; p = 0.049) after acupuncture treatment. The following changes were found in the TCM group: within the lymphocyte subpopulations the CD3+ cells (p = 0.005) and CD4+ cells (p = 0.014) increased significantly. There were also significant changes in cytokine concentrations: interleukin (IL)-6 (p = 0.026) and IL-10 (p = 0.001) decreased whereas IL-8 (p = 0.050) rose significantly. Additionally, the in vitro lymphocyte proliferation rate increased significantly (p = 0.035) while the number of eosinophils decreased from 4.4% to 3.3% after acupuncture (p > 0.05). The control group, however, showed no significant changes apart from an increase in the CD4+ cells (p = 0.012).The results imply that asthma patients benefit from acupuncture treatment given in addition to conventional therapy. Furthermore, acupuncture performed in accordance with the principles of TCM showed significant immune-modulating effects. |
0 | TITLE: Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study.ABSTRACT: Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28-0.62) in women and 0.69 (0.46-1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45-3.10) in women and 1.61 (1.07-2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight. |
1 | TITLE: Sustained benefit over four years from an initial combined antiplatelet regimen after coronary stent placement in the ISAR trial. Intracoronary Stenting and Antithrombotic Regimen.ABSTRACT: Combined antiplatelet therapy after coronary stent placement is superior to anticoagulation with respect to early outcome. It is unclear if this benefit is maintained during long-term follow-up. This study reports on the 4-year clinical outcome of patients randomized in the Intracoronary Stenting and Antithrombotic Regimen trial. In the Intracoronary Stenting and Antithrombotic Regimen trial, 517 patients were randomized after successful placement of Palmaz-Schatz stents: 257 to aspirin and ticlopidine, and 260 to aspirin and phenprocoumon. Ticlopidine and phenprocoumon were given for 4 weeks. At 30 days, patients with ticlopidine had significantly fewer adverse cardiac events (1.6% vs 6.2%; p = 0.007), nonfatal myocardial infarction (0.8% vs 3.5%; p = 0.034), and target vessel revascularization procedures (1.2% vs 5.4%; p = 0.007). At 4 years, rates for any adverse cardiac events were 22.6% versus 28.5% (p = 0.078), for nonfatal myocardial infarction 0.9% versus 5.8% (p = 0.003), and for target vessel revascularization 18.3% versus 22.7% (p = 0.21). The absolute difference in event rates (4.6% after 30 days) was maintained after 4 years (5.9%). Event rates beyond day 30 were not significantly different (21.1% vs 22.5%; p = 0.78), nor were the rates beyond the first year, which were very low (5.2% vs 3.6%; p = 0.50). This study shows that the benefit of combined antiplatelet therapy evident after 30 days is maintained after 4 years. Independent of the initial regimen, rates of adverse cardiac events are low beyond the first year. |
1 | TITLE: Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.ABSTRACT: GH increases bone turnover and stimulates osteoblast activity. We hypothesized that administration of MK-677, an orally active GH secretagogue, together with alendronate, a potent inhibitor of bone resorption, would maintain a higher bone formation rate relative to that seen with alendronate alone, thereby generating greater enhancement of bone mineral density (BMD) in women with postmenopausal osteoporosis. We determined the individual and combined effects of MK-677 and alendronate administration on insulin-like growth factor I levels and biochemical markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) and resorption [urinary N-telopeptide cross-links (NTx)] for 12 months and BMD for 18 months. In a multicenter, randomized, double blind, placebo-controlled, 18-month study, 292 women (64-85 yr old) with low femoral neck BMD were randomly assigned in a 3:3:1:1 ratio to 1 of 4 daily treatment groups for 12 months: MK-677 (25 mg) plus alendronate (10 mg); alendronate (10 mg); MK-677 (25 mg); or a double dummy placebo. Patients who received MK-677 alone or placebo through month 12 received MK-677 (25 mg) plus alendronate (10 mg) from months 12-18. All other patients remained on their assigned therapy. All patients received 500 mg/day calcium. The primary results, except for BMD, are provided for month 12. MK-677, with or without alendronate, increased insulin-like growth factor I levels from baseline (39% and 45%; P < 0.05 vs. placebo). MK-677 increased osteocalcin and urinary NTx by 22% and 41%, on the average, respectively (P < 0.05 vs. placebo). MK-677 and alendronate mitigated the reduction in bone formation compared with alendronate alone based on mean relative changes in serum osteocalcin (-40% vs. -54%; P < 0.05, combination vs. alendronate) and reduced the effect of alendronate on resorption (NTx) as well (-52% vs. -61%; P < 0.05, combination vs. alendronate). MK-677 plus alendronate increased BMD at the femoral neck (4.2% vs. 2.5% for alendronate; P < 0.05). However, similar enhancement was not seen with MK-677 plus alendronate in BMD of the lumbar spine, total hip, or total body compared with alendronate alone. GH-mediated side effects were noted in the groups receiving MK-677, although adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the anabolic effect of GH, as produced through the GH secretagogue MK-677, attenuated the indirect suppressive effect of alendronate on bone formation, but did not translate into significant increases in BMD at sites other than the femoral neck. Although the femoral neck is an important site for fracture prevention, the lack of enhancement in bone mass at other sites compared with that seen with alendronate alone is a concern when weighed against the potential side effects of enhanced GH secretion. |
1 | TITLE: Improving outcomes in acute coronary syndromes--the FRISC II trial.ABSTRACT: The FRISC II study addressed two key questions in the management of acute coronary syndromes: is it beneficial to extend low-molecular-weight heparin (LMWH) therapy with dalteparin beyond the initial period of acute treatment; and, is a strategy of early invasive therapy, including angioplasty and surgical revascularization, preferable to a more conservative strategy? The study focused on patients with unstable coronary artery disease (UCAD), that is, angina and non-ST-segment-elevation myocardial infarction (MI). Patients were allocated in a randomized, factorial study design to either an invasive or a conservative management strategy. Within each of these groups, patients were further randomized to receive either 3 months of extended treatment with dalteparin or placebo, following at least 5 days' treatment with open-label dalteparin. After 1 year, patient survival and MI-free survival were significantly higher in the invasive therapy group than in the noninvasive group. Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month (relative risk reduction 47%; p = 0.002), a benefit still evident after 60 days, but after 3 months there was no longer any significant clinical advantage compared with placebo. There was, however, a significant reduction in the combined incidence of death, MI, or revascularization at 3 months in the extended dalteparin treatment group (relative risk reduction 13%; p = 0.031). The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin-T or ST-segment depression. A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment (relative risk reduction 35%; p = 0.02). Extended dalteparin treatment is, however, associated with a small increase in bleeding risk. In conclusion, early invasive therapy (following combined treatment with aspirin and dalteparin) is recommended in a majority of patients with UCAD. Furthermore, extended dalteparin treatment for up to 45 days is efficacious and well tolerated, and therefore provides a useful "bridge" to revascularization when early revascularization is not immediately available. |
1 | TITLE: Is a dissection balloon beneficial in totally extraperitoneal endoscopic hernioplasty (TEP)? A randomized prospective multicenter study.ABSTRACT: Laparoscopic hernioplasty has been criticized because of its technical complexity and increased costs. Disposable dissection balloons can be used to facilitate the creation of the initial working space in totally extraperitoneal endoscopic hernioplasty (TEP), but their use adds to the cost of the operation.A total of 322 men with unilateral, primary, or recurrent inguinal hernias were randomized to undergo TEP with or without a dissection balloon.In the group with the balloon, three of 161 patients (2.5%) required conversion to transabdominal preperitoneal hernioplasty (TAPP), or open herniorraphy, whereas 17 of 161 patients (10.6%) were converted to TAPP or open herniorraphy in the group without the balloon (p = 0.002). The mean operation time was 55 min in the group with the balloon and 63 min in the group without the balloon (p = 0.004). There was no difference between them in postoperative morbidity, and there were no major complications in either group. The recurrence rate was 3.1% in the group with the balloon and 3.7 % in the group without the balloon (p = 0.8).The use of a dissection balloon in TEP reduces the conversion rate and may be especially beneficial early in the learning curve. |
1 | TITLE: Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication.ABSTRACT: In vitro omega-3-fatty acids (Eicosapen) are bacteriostatic to Helicobacter pylori and have a variety of immuno-modulating effects.To investigate the efficacy and tolerability of eicosapen (E) as an antibiotic-sparing component of a triple H. pylori eradication regimen in non-ulcer dyspepsia patients in a randomized, double-blind trial.Non-ulcer dyspepsia patients (n=199), with a normal upper endoscopy and a positive (13)C-urea breath test (UBT) were randomly assigned to either pantoprazole, clarithromycin and metronidazole (PCM) or pantoprazole, clarithromycin and eicosapen (PCE) for 7 days. Four weeks after treatment, H. pylori eradication was determined by UBT. Symptoms were followed up to 16 months.In the intention-to-treat population, PCM eradicated infection in 78% but PCE was successful in only 34% (P < 0.001). Symptomatic improvement occurred in both groups, and was not related to H. pylori eradication.Eicosapen is unlikely to be useful in H. pylori eradication regimens. |
1 | TITLE: Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial.ABSTRACT: Glycoprotein IIb/IIIa blockers reduce procedure-related thrombotic complications of percutaneous coronary intervention, and the risk of death and myocardial infarction in patients with acute coronary syndromes. The effect on risk of death and myocardial infarction is particularly apparent in patients undergoing early percutaneous coronary interventions. We did a randomised, multicentre trial to study the effect of the glycoprotein IIb/IIIa blocker abciximab on patients with acute coronary syndromes who were not undergoing early revascularisation.We enrolled 7800 patients who were admitted to hospital with chest pain and either ST-segment depression or raised troponin T or I concentrations. 2598 were randomly assigned placebo, 2590 an abciximab bolus and 24 h infusion, and 2612 an abciximab bolus and 48 h infusion; all patients received aspirin and either unfractionated or low-molecular-weight heparin. The primary endpoint was death or myocardial infarction at 30 days after randomisation. Analysis was by intention to treat.There were no drop-outs. 209 (8.0%) patients on placebo, 212 (8.2%) on 24 h abciximab, and 238 (9.1%) on 48 h abciximab died or had a myocardial infarction before day 30 (odds ratio 1.0 [95% CI 0.83-1.24], for difference between placebo and 24 h abciximab, and 1.1 [0.94-1.39] for difference between placebo and 48 h abciximab). The lack of benefit from treatment with abciximab was consistent in most subgroups investigated; in particular, no benefit was seen in patients with raised cardiac troponin T or I concentrations at enrolment, although these patients did have a strongly increased risk of subsequent events. Bleeding rates were low, but increased with abciximab, particularly when continued for 48 h. Additionally, thrombocytopenia was more frequent with abciximab than with placebo.Although the explanations for our findings are unclear, this study indicates that abciximab is not beneficial as first-line medical treatment in patients admitted with acute coronary syndromes. |
0 | TITLE: Vascular adhesion molecule-1 and markers of platelet function before and after a treatment with iloprost or a supervised physical exercise program in patients with peripheral arterial disease.ABSTRACT: Platelet function and levels of vascular adhesion molecule-1 (VCAM-1) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost (0.5-2 ng/kg/h i.v. infused, 6 h/day) or a 2 weeks supervised physical training, randomly assigned. Patients were studied before (T0) and after (T14) treatments and 10 days later (T24). The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost (1.9+/-0.4 vs 6.8+/-0.7%; T24 vs T0; M+/-SEM; p<0.05) and physical exercise (3.0+/-1.0 vs 6.7+/-0.7; p<0.05) while adhesion to human plasma coated microwells was reduced only after treatment with iloprost (1.9+/-0.8 vs 5.8+/-0.9; p<0.05). The expression of fibrinogen receptor (glycoprotein IIb/IIIa) on platelets, measured by flow-cytometry was also reduced after iloprost treatment (17.1+/-1.5 vs 31.8+/-4.8 AU; p<0.05) and physical exercise (14.6+/-1.5 vs 34.0+/-3.3; p<0.05). Theurinaryexcretion of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost (154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1); p<0.05). Similarly plasma VCAM-1 was lower in patients who were treated with iloprost (827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1); p<0.05). In conclusion, both iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion, whereas only iloprost reduces thromboxane A2 biosynthesis in vivo. This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function. |
1 | TITLE: Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial.ABSTRACT: Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris.A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment.A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of > or =1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different.T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease. |
1 | TITLE: A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition.ABSTRACT: Infectious complications are the main cause of late death in patients with acute pancreatitis. Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial. On the other hand, nutritional support has recently yielded promising clinical results. The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis.We screened 466 consecutive patients with acute pancreatitis. A total of 70 patients with objectively graded severe acute pancreatitis were randomly allocated to receive either total enteral nutrition (TEN) or total parenteral nutrition (TPN), within 72 h of onset of symptoms. Baseline characteristics were well matched in the two groups.The incidence of pancreatic infectious complications (infected pancreatic necrosis, pancreatic abscess) was significantly lower in the enterally fed group (7 vs. 16, p = 0.02). In the TEN group, 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure (p = 0.02). Overall mortality was 20% with two deaths in the TEN group and twelve in the TPN group (p < 0.01).Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality. |
0 | TITLE: Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes.ABSTRACT: Laparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial.Characteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy.During the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older--and had more complications from gallstone disease, higher co-morbidity, and higher ASA--score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy.Non-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials. |
1 | TITLE: Comparison of remifentanil with fentanyl for deep sedation in oral surgery.ABSTRACT: The aim of this study was to compare recovery for oral surgery patients given a deep sedation regimen of midazolam, propofol, and remifentanil with a standard control of fentanyl in place of remifentanil.This investigation was designed as a randomized, prospective, single-blinded controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1 microg/kg, and propofol initially at 140 microg/kg/min. Group 2 received midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given at an initial propofol infusion rate of 40 microg/kg/min. Outcome measures included time to response to verbal command, Aldrete score = 9, Postanesthesia Discharge Scoring System = 7, and assessment by the Digit Symbol Substitution Test.Forty-seven subjects were entered in the study. Baseline findings were homogenous between the 2 groups. Subjects in group 2 recovered earlier (P < .005) and required less propofol for both the induction (0.8 +/- 0.4 versus 1.2 +/- 0.6 mg/kg; mean +/- SD, P < .01) and maintenance of deep sedation (46 +/- 9 versus 131 +/- 17 microg/kg/min; P < .005). There were minor differences in vital signs.This study demonstrated that this remifentanil regimen provided significantly more rapid recovery and used significantly less propofol compared with the fentanyl regimen. |
1 | TITLE: Allograft versus no graft with a posterior multisegmented hook system for the treatment of idiopathic scoliosis.ABSTRACT: A prospective, randomized study.To compare the clinical results of posterior spinal fusion (PSF) with allograft augmentation versus no graft for patients with adolescent idiopathic scoliosis (AIS).The use of allograft has become a standard means of augmenting a PSF. Many studies have shown equal rates of fusion when comparing allograft with autogenous iliac crest. There have been no studies to directly compare the results obtained with allograft with those achieved without the use of any bone graft at all.Ninety-one patients with AIS were randomized into two treatment groups. Seventy-six patients had greater than 2-year follow-up and are included in this review. The Allograft Group consisted of 37 patients who underwent a standard PSF using a multisegmented hook-screw and rod system with the use of corticocancellous allograft for augmentation. The No Graft Group included 39 patients with AIS who underwent the same procedure without any bone graft. All autogenous bone resulting from a thoracoplasty and any local bone (for example, that removed from spinous processes) was discarded in both groups. Patients with at least 2 years of radiographic and clinical follow-up were evaluated using established criteria for possible or definite pseudarthrosis. Treatment groups were similar with respect to age, preoperative deformity, and correction obtained.The overall definitive pseudarthrosis rate for this study was 1.3% (1 of 76 patients). The 1 patient with pseudarthrosis was in the Allograft Group (1 of 37, or 2.7%, P = 0.98 as defined by our criteria), versus none of 39 in the No Graft Group. Two patients in each group (5.4% in the Allograft Group and 5.1% in the No Graft Group) met the radiographic criteria for possible pseudarthrosis. This establishes a P value of 0.65 comparing risk of possible pseudarthrosis in the two groups.Our results suggest that a PSF using newer-generation multisegmented hook-screw and rod systems can be successful with allograft and/or local bonegraft without the use of supplemental autogenous bone graft (from the iliac crest or ribs) in patients with AIS. |
1 | TITLE: Regular vs ad-lib albuterol for patients hospitalized with acute asthma.ABSTRACT: Inhaled, short-acting beta-agonists and systemic corticosteroids form the mainstay of therapy in acute asthma exacerbation. Asthma, however, is an inflammatory disease of the airways, and its underlying pathology is not impacted by short-acting beta-agonists. While the efficacy of ad-lib beta-agonist administration in outpatient management of asthma symptoms is well established, little data exist to support this strategy in patients with acute, severe asthma. We postulate that as long as patients hospitalized with severe asthma exacerbation receive systemic corticosteroids, regular, scheduled administration of short-acting beta-agonists is unnecessary. Similar therapeutic outcomes can be achieved with the ad-lib administration of the short-acting beta-agonists.Prospective, randomized, double-blind, placebo-controlled trial.Pulmonary floor of a 600-bed municipal hospital.Sixty-two patients hospitalized for acute asthma.Patients were randomized to receive either albuterol nebulizations (regular albuterol group) or saline solution nebulizations (ad-lib group) every 4 h with management of breakthrough symptoms with albuterol metered-dose inhaler or nebulizations for both groups. All patients received systemic corticosteroids. Peak expiratory flows, asthma symptoms, and need for rescue bronchodilator were followed up on each patient until discharge.There was no significant difference in the length of hospitalization (median length, 48 h for ad-lib group vs 57.5 h for regular albuterol group, p = 0.82), rate of improvement in peak flow, or symptoms between the two groups. Ad-lib beta-agonist use compared to regular albuterol scheduled use resulted in a significant reduction in the total number of albuterol treatments administered (median, 7 treatments vs 19 treatments, p = 0.001) during hospitalization.In the management of asthma exacerbation, ad-lib administration of albuterol is therapeutically as effective as regular, scheduled administration. This method of drug administration also reduces the total dose of beta-agonists received by the hospitalized patient. |
1 | TITLE: Low-fat, high fruit and vegetable diets and weight loss do not affect biomarkers of cellular proliferation in Barrett esophagus.ABSTRACT: Risk factors for esophageal adenocarcinoma include obesity, high fat intake, and low consumption of fruits and vegetables. This trial tested whether an intervention to reduce these risk factors in patients with Barrett esophagus, a preneoplastic condition for esophageal adenocarcinoma, could reduce biomarkers of cellular proliferation and, by inference, the risk of neoplastic progression. Eighty-seven men and women with Barrett esophagus were randomized to an intensive dietary intervention or control group. At baseline, 18 and 36 months after intervention, biopsies were obtained at 2-cm intervals throughout the length of the Barrett segment. Ki67/DNA content flow cytometry was used to assess (a) % Ki67-positive proliferating diploid G(1) cells, (b) % total Ki67-positive proliferating cells, (c) presence of aneuploidy, and (d) presence of >6% of cells in the 4N (G(2)/tetraploid) fraction of the cell cycle. We also assessed re-epithelialization and length of the Barrett segment, reflux symptoms, and medication use. The intervention effects for energy, fat, fruits and vegetables, and weight were, respectively, -314 kcal, -12.2% energy, 1.8 servings/d, and -4.0 kg at 18 months (all P < 0.005) and were smaller but remained significant at 36 months. There were no significant effects of the intervention on any biomarker of cellular proliferation. The intervention effects +/- SE for mean %G(1) Ki67+ cells were 0.98 +/- 1.58 at 18 months and 1.79 +/- 1.31 at 36 months; the relative risks (95% confidence interval) for developing >6% of cells in 4N were 0.5 (0.1-2.6) at 18 months and 0.75 (0.2-3.1) at 36 months. A single control participant developed aneuploidy. There were no significant effects on re-epithelialization, segment length, or reflux medication use. We conclude that substantial dietary change has no short-term effects on biomarkers of cellular proliferation in Barrett esophagus or on clinical observations of the Barrrett segment. |
1 | TITLE: Respiratory symptom relief related to reduction in cigarette use.ABSTRACT: Many smokers reduce their cigarette consumption during failed attempts to quit. We report the impact of changes in consumption on smoking-related respiratory symptom severity (SRRSS).Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a randomized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation. Cigarette use in the 28 days prior to the interview, and severity of SRRSS using a 7-item respiratory index, were assessed at baseline and at 3-month follow-up.Baseline minus 3-month assessment difference in SRRSS score.Follow-up of 319 participants (83.3%), mean age 40.4 years, 51.4% male, who smoked 26.4 cigarettes per day, demonstrated a mean reduction of 16.7 cigarettes per day. A reduction in cigarette use was positively and significantly (b=0.29, t=5.16, P<.001) associated with a reduction in smoking-related symptom severity after adjusting for age, gender, race, years of regular smoking, baseline nicotine dependence, and history of treatment for asthma or emphysema. A 1 standard deviation reduction in average daily smoking (about 14.1 cigarettes) was associated with a 0.28 standard deviation decrease in smoking-related symptom severity.Reduction in symptom severity increases as absolute reduction in daily smoking increases. This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking. |
1 | TITLE: Recurrence of esophageal varices following endoscopic treatment and its impact on rebleeding: comparison of sclerotherapy and ligation.ABSTRACT: Endoscopic variceal ligation is superior to sclerotherapy because of its lower rebleeding and complication rates. However, ligation is not without drawbacks due to a higher tendency to variceal recurrence. We conducted a randomized cohort study to delineate the long-term history of variceal recurrence following ligation and sclerotherapy, and to clarify the impact of recurrence on rebleeding and on the consumption of endoscopic treatment resources.Two hundred cirrhotic patients with esophageal variceal bleeding were randomized to undergo maintenance endoscopic variceal sclerotherapy or ligation.One hundred and forty-one patients achieved variceal eradication and were regularly followed up for 2.2 to 6.7 (mean: 5.1 +/- 1.2) years. The demographic data, hepatic reserve, bleeding severity, and endoscopic features of both sclerotherapy (n=70) and ligation (n=71) showed no difference. Forty (57.1%) patients who underwent sclerotherapy experienced 58 recurrences of esophageal varices, in contrast to the 46 (64.8%) patients who underwent ligation and experienced 81 episodes of recurrence. Kaplan-Meier analysis showed that within 2 years variceal recurrence was more frequent for ligation than sclerotherapy, and the difference decreased thereafter. Multiple recurrence appeared more common with ligation (1/2/3/4/5 episodes of recurrence: 46/23/8/3/1 vs. 40/14/3/1/0, p=0.08). On multifactorial analysis, the endoscopic treatment method and red wale markings were the two factors determining variceal recurrence. Rebleeding from recurrent esophageal varices was unusual and showed no difference between the two groups (7/58 vs. 6/81, p>0.05). Rebleeding from gastric varices was more common after eradication by sclerotherapy (7/19 vs. 1/16, p=0.085) than by ligation. The number of sessions required for eradication of recurrent varices was no different between the two groups.Early recurrence and multiple recurrence of esophageal varices are more likely in patients undergoing endoscopic ligation, compared to sclerotherapy; however, the recurrence did not lead to a higher risk of rebleeding or require more endoscopic treatment. |
1 | TITLE: The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer.ABSTRACT: Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer.The subset of patients within the early prostate cancer (EPC) program who received radiotherapy with curative intent (n = 1,370) were included in the analysis. These patients were randomized to receive oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671).The median follow-up for patients included in this analysis was 7.2 years. In patients with locally advanced disease (n = 305), bicalutamide adjuvant to radiotherapy significantly improved: progression-free survival (PFS), reducing the risk of objective progression by 44% compared with radiotherapy alone [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate-specific antigen (PSA)-PFS, reducing the risk of PSA progression by 59% compared with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall survival, reducing the risk of death by 35% compared with radiotherapy alone (HR 0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1 vs 24.3%, respectively). There was no significant difference in PFS or overall survival in patients with localized disease (n = 1,065).In patients with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival, PFS and PSA-PFS compared with radiotherapy alone. The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy (Bolla et al. in Lancet 360:103-108, 2002; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285-1290, 2005). In addition, the clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in those with localized disease, is consistent with the overall results from the EPC program (McLeod et al. BJU Int 97:247-254, 2006). Given the quality-of-life advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer. |
1 | TITLE: Effect of ramipril on the incidence of diabetes.ABSTRACT: Previous studies have suggested that blockade of the renin-angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov].). |
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