Effects of orlistat, simvastatin, and orlistat + simvastatin in obese patients with hypercholesterolemia: a randomized, open-label trial

Background: Many obese patients have comorbidities that worsen their prognoses, particularly if hypercholesterolemia is present. In these patients, dietary restrictions are not sufficient to reduce hypercholesterolemia and lose body weight.Objective: This 1-year, single-center, randomized, open-label study assessed the effects of diet and exercise plus treatment with orlistat, simvastatin, and orlistat + simvastatin on lipid profile, body composition, and blood pressure in obese patients with hypercholesterolemia.Methods: Obese, normotensive patients with hypercholesterolemia aged > 45 years were eligible. Patients were prescribed a restricted-calorie diet and were randomized to receive orlistat 120 mg TID (group O), Simvastatin 20 mg/d (group S), or orlistat 120 mg TID plus simvastatin 20 mg/d (group OS) for 1 year. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels; body mass index (BMI); waist-circumference reduction (WCR); body weight loss (BWL); and diastolic blood pressure (DBF) and systolic blood pressure (SBP) were measured at baseline and after 6 months and 1 year of treatment.Results: We enrolled 87 patients (45 women, 42 men; mean age, 55 years). Four patients dropped out due to nontransient adverse events. After 1 year of treatment, significant improvements were found in all measured parameters in all treatment groups versus baseline values, except for HDL-C in group O. Significant between-group differences at 1 year included the following: TC, LDL-C, and TG levels and BMI, WCR, and BWL were significantly decreased in group OS versus groups O and S; DBP was significantly decreased in group OS versus group O; SBP and DBF were significantly decreased in group OS versus group S. HDL-C was significantly increased in group OS but not in groups O and S. Five patients in group O and 1 patient in group OS experienced transient gastrointestinal adverse events.Conclusions: In this study population, all 3 treatments produced significant improvements in most measured parameters from baseline. The combination treatment showed significantly greater reductions in serum TC and LDL-C levels, BMI, WCR, and BWL than with either orlistat or simvastatin alone. Small but significant differences in blood pressure were found with combination treatment.     

Effects of a Stimulant-Free Dietary Supplement on Body Weight and Fat Loss in Obese Adults: A Six-Week Exploratory Study

Background: Obesity is a well-established risk factor for cardiovascular disease, diabetes, hyperlipidemia, hypertension, osteoarthritis, and stroke. Stimulants, such as ephedrine and caffeine and their herbal counterparts, have proved effective in facilitating body weight loss, but their use is controversial due to their undesired effects. Other nutraceuticals have shown moderate success in reducing body weight, whereas several other compounds have demonstrated little or no effect. Therefore, a tolerable and effective nutraceutical that can increase energy expenditure and/or decrease caloric intake is desirable for body weight reduction.Objective: The primary purpose of this study was to assess the tolerability and effectiveness of a novel, stimulant-free, dietary supplement containing glucomannan, chitosan, fenugreek, Gymnema sylvestre, and vitamin C on body weight and fat loss and change in body composition in obese adults.Methods: In this single-center, prospective, randomized, double-blind, placebo-controlled study conducted at the University of Guelph (Guelph, Ontario, Canada), obese adults (aged 20-50 years; body mass index [BMI], ≥30 kg/m²) were randomized to the treatment or placebo group. The treatment group received 6 capsules of a dietary supplement containing a proprietary blend of glucomannan, chitosan, fenugreek, G sylvestre, and vitamin C daily for 6 weeks, and the placebo group received 6 capsules of rice flour daily for 6 weeks. Body weight; percentage of body fat; absolute fat mass; lean body mass; BMI; upper abdominal, waist, and hip circumference; and anthropometric measurements were recorded at baseline and at study end. Patients completed daily dietary intake records on days 1 to 3 and days 40 to 42. They also completed weekly activity logs throughout the study.Results: Twenty-four subjects (mean [SD] age, 37.0 [8.2] years [range, 21-48years]; mean [SD] BMI, 35.7 [6.2] kg/m² [range, 28.9-50.9 kg/m²]) were assigned to the treatment group (8 women, 4 men) or the placebo group (9 women,3 men). Two subjects (8.3%; 1 patient [8.3%] from each group) dropped out for personal reasons unrelated to the study. No significant changes in the consumption of total calories; the percentage of calories ingested as carbohydrates, fat, or protein; or activity levels were found in either group throughout the study. Compared with the placebo group, the treatment group lost significantly more body weight (−2.3 kg vs 0.0 kg; P<0.01), percentage of body fat (−1.1% vs 0.2%; P<0.05), and absolute fat mass (−2.0 kg vs 0.2 kg; P<0.001). The treatment group also experienced a significantly greater reduction in upper abdominal circumference (−4.5 cm vs −0.7 cm), waist circumference (−4.1 cm vs 0.1 cm), and hip circumference (−2.9 cm vs 0.6 cm) compared with the placebo group (P<0.05 for all). No significant changes in heart rate or blood pressure were found in either group. Both the treatment and the placebo were well tolerated.Conclusion: Within the context of this study, the novel combination of glucomannan, chitosan, fenugreek, G sylvestre, and vitamin C results in significant body weight and fat loss in obese adults.Disclosure: Derek E. Woodgate, MSc, is president and owner of NxCare Inc., which produces the dietary supplement containing glucomannan, chitosan, fenugreek, Gymnema sylvestre, and vitamin C (trade name Calorie-Care™).     

The effects of four weeks of ribose supplementation on body composition and exercise performance in healthy, young, male recreational bodybuilders: a double-blind, placebo-controlled trial

Background: Ribose is a pentose sugar that is present in ribonucleic acids, riboflavin, nucleotides, and adenosine triphosphate. Whether exogenous ribose administration affects skeletal muscle concentrations of total adenine nucleotides is unknown. Whether supplementation with ribose positively affects body composition or exercise performance in recreational bodybuilders also is unknown.Objective: The purpose of this double-blind, placebo-controlled trial was to determine the effects of 4 weeks of ribose supplementation on body composition and exercise performance in healthy, young, male recreational bodybuilders.Methods: Healthy, male recreational bodybuilders aged 18 to 35 years were recruited and randomized to a ribose-supplemented group (10 g/d in powder formulation) or a placebo group (dextrose). Each subject participated in a heavy-resistance training program designed to increase skeletal muscle mass. Body composition (ie, body weight, body fat, lean body mass, fat mass, and bone mineral content) was assessed using dual-energy x-ray absorptiometry analysis. Muscular strength (as measured by a 1-repetition maximum-strength [1-RM] bench press) and total work performed (as measured by total repetitions for 10 sets of bench presses before muscular failure; 1-minute resting interval between sets) to muscular failure at a submaximal load (100% of pretest body weight) were ascertained. In addition, 24-hour dietary recalls were obtained before and after the study.Results: Twenty men (mean age ± SE, 23.9 ± 1.4 years) were enrolled; 19 subjects completed 24-hour dietary recalls and exercise performance testing; 12 subjects completed the study (24-hour dietary recalls, exercise performance, and body composition). No baseline differences were found between the 2 groups for any of the measured parameters. The ribose-supplemented group experienced a significant pretreatment-to-posttreatment increase in the total work performed, whereas the placebo group did not change significantly (24.5 ± 7.6 to 29.3 ± 7.5 repetitions; 19.6% ribose [P = 0.028] vs 34.1 ± 8.6 to 38.2 ± 8.0 repetitions, 12.0% placebo). In addition, the ribose-supplemented group experienced a significant increase in 1-RM bench press strength, whereas the placebo group did not change significantly (114.1 ± 13.6 to 117.7 ± 14.0 kg, 3.2% ribose [P = 0.008] vs 129.6 ± 14.2 to 131.8 ± 14.5 kg, 1.7% placebo). No pretreatment-to-posttreatment within-group or between-group differences were found for any of the measures of body composition or the 24-hour dietary data.Conclusion: The results of this study indicate that supplementation with ribose 10 g/d for 4 weeks resulted in significant increases in muscular strength and total work performed in recreational bodybuilders in this study, although no significant changes in body composition or 24-hour dietary data were found.     

Effect of cartilage oligomeric matrix protein angiopoietin-1 on peripheral nerves in db/db diabetic mice

Background: Vascular and inflammatory processes have been reported to be factors in the pathogenesis of diabetic neuropathy. Angiopoietin-1 (Ang1) plays essential roles in regulating vascular growth, development, maturation, permeability, and inflammation.Objective: The aim of this study was to investigate the effect of cartilage oligomeric matrix protein (COMP)-Ang1, which is a soluble, stable, potent Ang1 variant, on peripheral nerves in db/db diabetic mice.Methods: The db/db diabetic mice were randomized into 2 groups based on their weight and glucose level and treated with recombinant adenovirus (Ade), expressing either COMP-Ang1 or the β-galactosidase gene (LacZ) (control), for 8 weeks. Immunohistochemistry was performed using a polyclonal antibody of antiprotein gene product and a secondary antibody. Intraepidermal nerve fiber density (IENFD) was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm). In addition, the total capillary length (TCL) per unit length of epidermis was summed (mm/mm²). All slides were coded and the capillary length and the number of nerve fibers were calculated by a blinded observer.Results: Ten diabetic db/db mice (mean [SD] weight, 38.7 [1.95] g) were randomized to receive Ade-COMP-Ang1 or Ade-LacZ. IENFD was significantly greater in the Ade-COMP-Ang1 group compared with the Ade-LacZ group (mean [SD] 8.95 [3.30] vs 3.57 [0.73]/mm; P < 0.05). TCL was also significantly greater in the Ade-COMP-Ang1 group (2.79 [0.99] vs 2.04 [0.58] mm/mm²; P < 0.05). Compared with baseline, fasting blood glucose concentration after 8 weeks of treatment decreased significantly more in the Ade-COMP-Ang1 group than in the Ade-LacZ group (489 [45] to 361 [81] vs 495 [48] to 521 [70] mg/dL; P < 0.05).Conclusions: These results suggest that Ade-COMP-Ang1 might have had proliferative effects on peripheral nerve and cutaneous capillaries in this small animal study. Further investigation of the metabolic effect, target site, and related mediator of COMP-Ang1 is needed.     

Impaired natural killer cell cytotoxic activity in chronic hepatitis C viral infection: A single-center, controlled study

Background: The role of the innate immune response in hepatitis C virus (HCV)-related chronic liver disease is controversial and poorly understood.Objective: We studied peripheral natural killer (NK) cell cytotoxic activity in relation to liver function and structure, HCV genotype, and viremia and investigated whether NK cell cytotoxic activity detected before 1-year interferon (IFN)-alfa therapy could predict treatment outcome.Methods: Patients with biopsy-proven HCV-related chronic liver disease and age- and sex-matched healthy volunteers were enrolled. Patients were investigated using conventional liver function tests, histology, quantitative HCV-RNA, and genotype. NK cell cytotoxic activity was assessed with a newly developed enzyme-linked immunosorbent assay based on the assessment of NK cell-induced apoptosis of target cells (K562).Results: A total of 38 people (26 men, 12 women; mean [SD] age, 45.5 [1.9] years) were enrolled (15 patients, 23 healthy volunteers). NK cell cytotoxic activity was ∼50% in HCV-positive patients compared with controls (P = 0.003) and was inversely related to age in patients (r² = −0.33; P = 0.017) and controls (r² = −0.58; P = 0.004). However, it did not correlate with fibrosis, sex, alanine aminotransferase levels, necroinflammatory lesions, viremia levels, HCV genotype, or response to treatment.Conclusions: NK cell cytotoxic activity is markedly reduced in chronic HCV infection. Such impairment is independent of viral and host characteristics, except age, and does not seem to help predict the outcome of IFN therapy.     

Effects of valsartan treatment on indicators of cardiovascular damage in newly diagnosed hypertensive patients: A prospective, twelve-month, open-label, pilot study

Background: Myocardial fibrosis and dysfunction can be detected in the early phases of organ damage associated with hypertension. Valsartan, an angiotensin-II receptor blocker, is efficacious in lowering blood pressure (BP) and reducing left ventricular mass in patients with hypertension. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and procollagen type I carboxy-terminal propeptide (PICP) are correlated with organ damage in patients with overt congestive heart failure; however, few data are available in patients with hypertension.Objective: The aim of this study was to assess the effects of 12 months of valsartan treatment on echocardiographic measures and indices of organ damage (NT-proBNP and PICP) in newly diagnosed patients with hypertension.Methods: This was a prospective, open-label, single-center, exploratory study. Patients with newly diagnosed, previously untreated hypertension were treated for 12 months with valsartan 160 mg/d and compared with an equal number of healthy, untreated control subjects. Baseline and follow-up visits at 3, 6, and 12 months included physical examination, systolic BP (SBP) and diastolic BP (DBP) measurements, ECG, echocardiography, and NT-proBNP and PICP determination.Results: A total of 20 patients (mean [SD] age, 48.05 [7.29] years) were enrolled and compared with 20 healthy controls (age, 49-6 [6.95] years). Compared with baseline, valsartan was associated with reduced BP in the group with hypertension after 12 months of treatment (mean SBP, 150.05 [11.15] vs 120.00 [8.43] mm Hg, P < 0.001; DBP, 97.80 [8.36] vs 79-50 [4.26] mm Hg, P < 0.001). Compared with the control group, at baseline, the group with hypertension had significantly higher mean left ventricular mass index (LVMI) (119.88 [22.86] vs 87.31 [15.77] g/m²; P < 0.001), relative wall thickness (thickness/radius [h/r] ratio: 0.45 [0.08] vs 0.35 [0.07]; P = 0.001), and NT-proBNP (50.00 [32.01] vs 25.47 [9.69] pg/dL; P = 0.002). PICP was higher, but the difference was not statistically significant (46.10 [15.69] vs 37.50 [7.20] μg/L). After 12 months, treatment with valsartan was associated with significant reductions in all measured parameters compared with baseline (LVMI, 106.51 [17.12] g/m², P = 0.004; h/r, 0.41 [0.07], P = 0.026; NT-proBNP, 22.55 [13.52] pg/dL, P = 0.001; PICP, 35.20 [9-19] μg/L, P < 0.008). At 12 months, patients with hypertension treated with valsartan achieved NT-proBNP and PICP levels not statistically different from those of the healthy controls (NT-proBNP, 22.55 [13-52] vs 25.24 [8.43] pg/dL; PICP, 35.20 [9.19] vs 36.90 [6.41] μg/L).Conclusion: Patients treated with valsartan for 12 months had significant reductions in BP, LVMI, and indices of subclinical organ damage (NT-proBNP and PICP) compared with baseline.     

Linezolid compared with vancomycin for the prevention of methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis vascular graft infection in rats: A randomized, controlled, experimental study

Background: Graft infections are severe complications of vascular surgery that may result in amputation or mortality. Staphylococci are the most frequent cause of vascular graft infections.Objective: In this study we assessed the prophylactic efficacy of linezolid in comparison with vancomycin in preventing prosthetic vascular graft infection due to methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE).Methods: This randomized, controlled, experimental study using healthy adult (aged >5 months) male Wistar rats was conducted in the research laboratory of the Pamukkale University, Denizli, Turkey. The study consisted of an uncontaminated control group and 3 groups for both staphylococcal strains: a contaminated group that did not receive any antibiotic prophylaxis; a contaminated group that received preoperative intraperitoneal (IP) prophylaxis with vancomycin; and a contaminated group that received preoperative IP prophylaxis with linezolid. All rats received a vascular Dacron graft placed inside a subcutaneous pocket created on the right side of the median line. Sterile saline solution (1 mL), to which MRSA or MRSE at a concentration of 2 × 10⁷ colony-forming units per milliliter had been added, was inoculated onto the graft surface using a tuberculin syringe to fill the pocket. The grafts were explanted 7 days after implantation and assessed by quantitative culture.Results: Seventy rats (mean [SD]weight, 323.7 [17.9]g; mean [SD]age, 5.98 [0.64] months) were evenly divided between the 7 groups. Statistical analysis of the quantitative graft culture suggested that both vancomycin and linezolid were effective in significantly inhibiting bacterial growth when compared with the untreated contaminated groups (all, P < 0.001). However, a statistically significant difference was not observed between the bacteria count in the vancomycin and linezolid prophylaxis groups. When a comparison was made between the bacterial growth in the contaminated control groups, MRSA had significantly greater affinity to the Dacron prostheses than MRSE (all, P < 0.001).Conclusion: Our study found that linezolid was as effective as vancomycin in suppressing colony counts in MRSA- or MRSE-infected vascular Dacron grafts in rats.     

Long-term efficacy of sertraline in the prevention of alcoholic relapses in alcohol-dependent patients: A single-center, double-blind, randomized, placebo-controlled, parallel-group study

Background: Alcoholism may be related to dysfunction of the serotonergic system in some patients. Therapy with a selective serotonin reuptake inhibitor (SSRI) may help to reduce alcohol consumption in these patients.Objective: The aim of this study was to examine the long-term efficacy of the SSRI sertraline in preventing alcoholic relapse and in increasing the number of abstinent days after alcohol withdrawal in alcohol-dependent patients.Methods: Male patients who met the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R) diagnostic criteria for alcohol dependence with no concurrent disorders on Axis I participated in this single-center, double-blind, randomized, placebo-controlled, parallel-group study. All of the patients had been withdrawn from alcohol for 7 to 21 days when included in the study during their inpatient treatment and were followed up for 6 months with monthly assessments. Patients were given either two 50-mg capsules of sertraline hydrochloride daily (100 mg/d) or 2 placebo capsules daily.Results: A total of 59 patients (mean [SD] age, 43.8 [8.5] years) were enrolled (30 in the sertraline group and 29 in the placebo group). The 2 groups differed significantly in terms of the mean (SD) number of abstinent days (sertraline, 125.5 [60.6] days; placebo, 91.9 [66.4] days; P = 0.047). Although the percentage of relapse was lower in the sertraline group in all monthly assessments, the difference in percentage of relapse between the 2 groups reached statistical significance only at month 4 (P = 0.027).Conclusions: Sertraline seems to increase the number of abstinent days and thus has a preventive effect on alcoholic relapse. However, this finding needs to be supported by further controlled studies.     

Effects of ezetimibe on glucose metabolism in patients with type 2 diabetes: A 12-week, open-label, uncontrolled, pilot study

Background: A potential effect of ezetimibe, a novel cholesterol-absorption inhibitor, on insulin resistance has been reported in an animal model.Objective: The aim of this study was to evaluate the effects of ezetimibe on glucose metabolism in patients with type 2 diabetes mellitus (T2DM).Methods: Between March and June 2008, outpatients with T2DM who were being treated at Yokohama Sakae Kyosai Hospital, Yokohama, Japan, were enrolled in this pilot study if they had not achieved the target lipid levels recommended by the Japan Atherosclerosis Society Guidelines despite diet and exercise or a statin therapy for ≥3 months. At baseline and at 4 and 12 weeks after open-label treatment with ezetimibe 10 mg/d, the levels of lipid parameters, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA_1c), and high-sensitivity C-reactive protein were measured. Adverse effects (AEs) were assessed at each study visit by patient interviews and laboratory testing.Results: A total of 21 consecutive patients (10 men, 11 women; mean [SD] age, 72 [9] years; weight, 63.4 [10.5] kg; body mass index, 25.5 [3.2] kg/m²) were enrolled in this study. The mean (SD) level of LDL-C decreased significantly from 146 (31) to 114 (27) mg/dL (−21%; P < 0.001) after 12 weeks of treatment with ezetimibe. The mean level of remnant-like particle cholesterol also decreased significantly from 6.5 (3.8) to 4.8 (2.2) mg/dL (−15%; P = 0.03). Treatment with ezetimibe was associated with a reduction in FPG level from 127 (31) to 119 (30) mg/dL (P = 0.02), and HbAlc from 6.3% (0.6%) to 6.1% (0.7%) (P = 0.003). No AEs were observed or reported during the study period.Conclusion: In this small, open-label, uncontrolled, pilot study, ezetimibe was associated with a significant decrease in lipid parameters and improvement in glucose metabolism in these patients with T2DM.     

Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine.Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice.Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29.Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 [0.16]; P < 0.05).Conclusion: Clozapine 10 mg/kg was associated with significant decreases in body weight and significant increases in fasting blood glucose and glucose tolerance in these male C57BL/6 mice.     

Body weight loss with phentermine alone versus phentermine and fenfluramine with very-low-calorie diet in an outpatient obesity management program: a retrospective study

Background: Obesity, which is epidemic in the United States, is associated with increased morbidity and mortality. The combination of diet, exercise, and a behavior-modification program often does not result in ideal body weight.Objective: The aim of this study was to determine the efficacy of phentermine (Phen) alone compared with phentermine plus fenfluramine (Phen-Fen), when used in combination with a very-low-calorie diet (VLCD) for weight loss in an outpatient obesity center.Methods: We analyzed data collected at the UCLA outpatient University Obesity Center between 1993 and 1999. Data for patients who attended the center for at least 12 weeks and at least 4 visits, who were taking Phen or Phen-Fen, and whose body mass index (BMI) was ≥30 kg/m² were included in this retrospective study.Results: During the study period, 3200 visits were recorded. Of 1133 potential participants, 446 patients were included in the analysis (309 women, 137 men; mean [SD] age, 46.7 [11.4] years; mean [SEM] body weight, 109.6 [26.7] kg; mean [SEM] BMI, 38.0 [7.6] kg/m²). Of these, 128 women and 60 men (mean [SEM] body weight at baseline, 103.4 [24.0] kg and 124.9 [28.2] kg, respectively) received Phen alone; 181 women and 77 men (mean [SEM] body weight at baseline, 102.5 [21.4] kg and 124.9 [30.2] kg, respectively) received Phen-Fen. No statistically significant differences were found between the Phen and Phen-Fen groups in mean age, body weight, or BMI for women or men at baseline. No significant differences in the time of weight loss were found when a VLCD was used with Phen alone compared with the Phen-Fen combination for either sex even at 12 weeks. For women, the mean total body weight loss was 7.4% in the Phen group and 8.7% in the Phen-Fen group, but these differences were not significant. For men, the mean total body weight loss was 7.8% in the Phen group and 8.2% in the Phen-Fen group, but these differences were not significant. No significant differences in BMI, severe adverse events, or dropout rate were found between the 2 treatment groups for men or women.Conclusions: This outpatient study did not detect any significant difference between adjunctive uses of Phen compared with Phen-Fen pharmacotherapy when used with VLCD over 12 weeks. Phen can be used to achieve significant weight loss when combined with VLCD. The tolerability and positive physical response further suggest that Phen is a valuable medication for obesity management in the outpatient setting.     

Effectiveness and tolerability of rosiglitazone on insulin resistance and body composition in nondiabetic Thai patients undergoing continuous ambulatory peritoneal dialysis: A 12-week pilot study

Background: Patients with chronic renal insufficiency, especially those undergoing continuous ambulatory peritoneal dialysis (CAPD), normally have insulin resistance due to deficiencies in insulin secretion and degradation, as well as tissue resistance to insulin at both receptor and postreceptor levels.Objective: The aim of this study was to investigate the effectiveness and tolerability of rosiglitazone on insulin resistance and body composition in patients without diabetes mellitus (DM) undergoing CAPD.Methods: This pilot study included a pretest and posttest with a repeated-measure design in a small number of patients. CAPD patients without DM received rosiglitazone 2-mg tablets BID for 12 weeks. Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) and bioelectrical impedance analysis (BIA) were used to assess insulin resistance and body composition, respectively. Tolerability was assessed using laboratory analyses as well as physical examination findings to evaluate peripheral edema. Peripheral edema was assessed by the study investigators.Results: Thirteen Thai patients (mean [SD] age, 54.17 [11.42] years [range, 35-85 years]; body mass index [BMI], >20 to <30 kg/m²; fasting blood glucose [FBG] concentration, <5.39 mmol/L) were included in the study. One patient was withdrawn due to illness unrelated to the study. No significant difference was found in FBG concentration between baseline and posttreatment (after 12 weeks of treatment) (5.45 [0.59] vs 5.24 [0.51] mmol/L), but fasting plasma insulin concentrations (28.50 [23.70] vs 10.15 [4.22] μIU/mL; P = 0.005) and HOMA-IR score (6.70 [5.23] vs 2.40 [1.15]; P = 0.011) were significantly lower. There were no significant changes in weight or BMI from baseline to posttreatment. Seven subjects (58.3%) experienced weight gain at week 4, while 2 patients (16.7%) still had weight gain after 12 weeks of treatment. A significant increase was found between baseline and posttreatment in total body water (38.03 [4.55] vs 42.44 [5.99] L; P = 0.018), extracellular fluid (20.24 [3.75] vs 26.22 [8.69] L; P = 0.005), plasma fluid (4.29 [0.80] vs 5.20 [0.93] L; P = 0.005), and interstitial fluid (14.99 [2.78] vs 17.68 [3.07] L; P = 0.040). Using BIA, no significant changes were observed in intracellular fluid, fat mass, or liver function. After 12 weeks of rosiglitazone administration, 2 patients (16.7%) had mild edema.Conclusions: Rosiglitazone 2 mg BID for 12 weeks was associated with significantly improved insulin resistance in this small group of nondiabetic Thai patients undergoing CAPD. There was a significant increase in total body water and extracellular fluid after administration of rosiglitazone for 12 weeks. There were no significant changes in FBG, weight, or BMI.     

Poster 41: Objectively measured personality traits in the prediction of early neurobehavioral symptoms after mild traumatic brain injury

Objective: To determine if objectively measured preinjury personality predicts early neurobehavioral symptoms after mild traumatic brain injury (TBI) compared with orthopedic injury. Design: Cohort study with matched controls; participants and significant others completed questionnaires of preinjury personality and early postinjury symptoms. Setting: Inpatient hospital and outpatient follow-up. Participants: 87 people hospitalized with mild TBI and 82 with orthopedic injury. Interventions: Not applicable. Main Outcome Measures: The NEO Personality Inventory-Revised (NEOPI-R) and Neurobehavioral Functioning Inventory (NFI). Results: For both mild TBI and orthopedic injury groups, personality traits were generally normal; concordance rates between self and significant others personality and symptoms scales were moderate. Self and significant others’ ratings of conscientiousness on the NEOPI-R were higher in the orthopedic injury than in the mild TBI group. Significant others’ reports of NFI somatic symptoms were higher in the orthopedic injury than in the mild TBI group. Stepwise linear regression showed that, in both groups, NEOPI-R agreeableness and neuroticism accounted for a significant proportion of aggressive symptoms (orthopedic injury group, R²=.56; mild TBI group, R²=.46; P<.01). In the mild TBI group, NEOPI-R neuroticism accounted for a significant proportion of depressive symptoms (R²=.44, P<.01). Unfortunately, significant findings appear to be the result of substantial content overlap between the NEOPI-R and the NFI, rather than reflecting predictive relationships. Conclusion: Objectively measured personality holds limited predictive value in understanding early neurobehavioral symptoms after mild TBI.     

Antioxidant effects of gliclazide, glibenclamide, and metformin in patients with type 2 diabetes mellitus

Background: Hyperglycemia increases oxygen-reactive species generation and reduces the protective capabilities of antioxidant defense systems. In patients with type 1 or 2 diabetes mellitus (DM), the increased production of oxygen free radicals may be linked to the development of chronic complications of diabetes. In vitro studies have demonstrated that oral antidiabetic drugs have antioxidant effects that might be secondary to an inhibiting role in lipid peroxidation.Objective: The purpose of this study was to determine the effects of 3 common oral antidiabetic agents on oxidized anti-low-density lipoprotein antibody (o-LAb) plasma levels and on total antioxidant status (TAS).Methods: We studied in vivo patients with type 2 DM treated with long-term gliclazide, glibenclamide, or metformin therapy along with healthy control subjects. The diabetic patients were randomized to the following treatment groups: group 1, gliclazide 80 to 240 mg/d; group 2, glibenclamide 10 to 15 mg/d; and group 3, metformin 1500 mg/d.Results: Ninety-two patients with type 2 DM (group 1, 18 females, 15 males [mean age, 62.8 ± 9.5 years]; group 2, 19 females, 11 males [mean age, 63.2 ± 8.8 years]; group 3, 16 females, 13 males [mean age, 62.0 ± 5.3 years]) and 28 age- and sex-matched healthy control subjects (18 females, 10 males; mean age, 59.1 ± 5.3 years) were enrolled. In group 1, both the o-LAb level and TAS were similar to those of the control group. The o-LAb level was highest and the total antioxidant plasma level was lowest in group 3, whereas intermediate levels were found in group 2. Multivariate analysis using stepwise regression showed that the type of oral antidiabetic agent was independently associated with o-LAb and total antioxidant levels, as well as with sex, age, and type of antidiabetic agent.Conclusion: In the patients with type 2 DM in this study, gliclazide had a positive effect on the oxidation-reduction system.     

The Effects of a Standardized Herbal Remedy Made from a Subtype of Rosa canina in Patients with Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Background: A standardized rose-hip powder produced from the seeds and husks of fruit from a subtype of Rosa canina has been reported to inhibit leukocyte functions that cause cell injury in osteoarthritis.Objective: The aim of this study was to assess the impact of standardized rose-hip powder on mobility of the hip and knee joints, activities of daily living, quality of life, and pain in patients with osteoarthritis.Methods: Patients with a diagnosis of osteoarthritis of either the hip or knee, verified on radiography, participated in this randomized, placebo-controlled, double-blind study. Half of the patients were given five 0.5-g capsules of standardized rose-hip powder twice daily for 4 months, and the other half received identical placebo capsules twice daily for the same period. Mobility of the hip or knee was measured in both groups after the initial screening and again after 4 months of therapy.Results: One hundred patients (65 women, 35 men; mean [SD] age, 65.2 [11.1] years) were divided into 2 treatment groups of 50 patients each. Hip joint mobility improved significantly in the treatment group compared with the placebo group (P = 0.033). Similarly, pain decreased significantly in the treatment group compared with the placebo group (P = 0.035). Two patients (4%) from each group withdrew during the early stages of the trial for reasons not related to treatment.Conclusions: In this study population, standardized rose-hip powder reduced symptoms of osteoarthritis, as 64.6% of patients reported at least some reduction of pain while receiving treatment. Standardized rose-hip powder may improve hip flexion and reduce pain in patients with osteoarthritis.     

Comparison of methimazole/hydrocortisone ointment with oral methimazole in patients with graves disease: A prospective, randomized, open-label, parallel-group, 18-month study

Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT).Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD).Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen.Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completed the 18-month treatment period. Compared with the MMI group (n 76), the CATO- treated group (n 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12-150] vs 22 [7-60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1%] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%] person-time; P < 0.001), and a higher remission rate (year 1:46/69 [66.7%] vs 65/72 [90.3%] patients, P 0.001; year 2:40/69 [58.0%] vs 60/72 [83.3%] patients, P - 0.001; year 3:34/69 [49.3%] vs 57/72 [79.2%] patients, P < 0.001; and year 4:30/69 [43.5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reported in the CATO group.Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients.     

Use of adjunctive mitomycin C in external dacryocystorhinostomy surgery compared with surgery alone in patients with nasolacrimal duct obstruction: A prospective, double-masked, randomized, controlled trial

Background: The most common cause for the failure of external dacryocystorhinostomy (DCR) surgery is the formation of granulation tissue at the osteotomy site or common canaliculus.Objectives: The aims of this study were to assess the efficacy of intraoperative adjunctive mitomycin C (MMC) treatment in external DCR surgery and to compare this procedure with the standard DCR procedure alone in the long term (1 year).Methods: In this prospective, double-masked, randomized, controlled trial, patients with primary acquired nasolacrimal duct obstruction were randomized (using a random number table) into 2 groups based on surgical procedure. In the MMC group, intraoperative adjunctive MMC 0.2 mg/mL was applied to the osteotomy site for 30 minutes. The control group underwent standard DCR procedure only. The results of the DCR surgeries were assessed using objective findings (eg, cessation of excessive tearing via nasolacrimal duct irrigation and the improvement in height of tear meniscus) and subjective symptoms (asking patients to describe the degree of tearing improvement). Both the patients and the researchers who were assessing the study outcomes were masked to treatment group.Results: One hundred eyes of 100 Turkish patients were assessed and equally randomized to the MMC (27 women, 23 men; mean [SD] age, 47.0 [7.6] years) and control (26 women, 24 men; mean age, 46.6 [8.8] years) groups. The follow-up period was not significantly different between the MMC and the control groups (13.1 [1.1] vs 13.2 [1.4] months). Significantly more eyes in the MMC group than the control group remained symptom-free throughout the 1-year follow-up period (45/50 [90%] vs 33/50 [66%]; P=0.005). Significantly more patients in the control group than the MMC group had an improvement in symptoms at the 1-year follow-up (8/50 [16%] vs 2/50 [4%] eyes; P=0.005). Based on the patency of the drainage system, the success rate was significantly greater in the MMC group than the control group (48/50 [96%] vs 42/50 [84%]; P=0.005). Based on nasolacrimal duct irrigation, significantly fewer patients in the MMC group than the control group had an enclosed naso-lacrimal duct (2/50 [4%] vs 8/50 [16%]). No adverse effects (eg, abnormal nasal bleeding, mucosal necrosis, infection) or any other surgical adverse events were observed.Conclusions: In the management of these patients with primary acquired nasolacrimal duct obstruction, adjunctive intraoperative MMC application with standard DCR surgery had a significantly higher success rate than did standard DCR surgery alone. Further large, double-masked, randomized studies are needed to confirm these findings.     

An observational study of the effect of two thiazolidinediones on blood lipid levels: Rosiglitazone and pioglitazone in routine clinical practice

Background: Rosiglitazone maleate and pioglitazone hydrochloride are established antihyperglycemic agents that are effective when used as monotherapy or in combination with other medications. However, the data regarding the effects of these agents on blood lipid levels are contradictory.Objective: The aim of this study was to determine whether the use of rosiglitazone and pioglitazone in clinical practice is associated with any changes in blood lipid levels.Methods: A retrospective chart review using electronic medical record data was conducted of patients with type 2 diabetes mellitus who were newly treated with either rosiglitazone or pioglitazone and had 1 lipid measurement within 6 months prior to and 12 months following initial thiazolidinedione (TZD) therapy. Outcome measures were mean changes in low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively). To control for differences in baseline characteristics and/or selection bias, the treatment cohorts were compared using multivariate statistical techniques.Results: A total of 371 patients were included in the study; the pioglitazone cohort comprised 148 patients (82 women, 66 men; mean [SD] age, 64.9 [10.8] years) and the rosiglitazone cohort comprised 223 patients (113 men, 110 women; mean [SD] age, 66.1 [11.9] years). Pioglitazone-treated patients had a statistically higher mean baseline LDL-C compared with rosiglitazone-treated patients (125.0 mg/dL vs 116.6 mg/dL; P = 0.04). On average, LDL-C levels decreased over the study period, with no significant differences between the 2 cohorts (9.9 mg/dL vs 4.3 mg/dL for pioglitazone and rosiglitazone, respectively), although changes in both cohorts were statistically significant (P < 0.001).Conclusions: TZD therapy appears to be associated with a small decrease in LDL-C within the first 6 months after initiation. No differences in changes in LDL-C or HDL-C could be discerned between patients treated with rosiglitazone compared with pioglitazone.     

Comparison of candesartan and felodipine alone and combined in the treatment of hypertension: a single-center, double-blind, randomized, crossover trial

Background: In the past decade, many studies have indicated that the combination of low doses of different classes of antihypertensive agents may be more efficacious than monotherapy while minimizing the likelihood of dose-dependent adverse effects (AEs).Objective: The aim of this study was to determine whether combination therapy with lower doses of candesartan and a calcium antagonist, felodipine, would be more effective and tolerable in controlling mild to moderate hypertension compared with either drug used alone.Methods: In this 18-week, single-center, double-blind, crossover study, patients with mild to moderate essential hypertension were randomized to 1 of 2 treatment groups after a 2-week placebo washout period. Patients in group 1 received candesartan 16 mg once daily and patients in group 2 received felodipine 5 mg once daily, for 6 weeks. All patients then received half-dose combination therapy (candesartan 8 mg plus felodipine 2.5 mg, once daily) for 6 weeks. Finally, patients received 6 weeks of monotherapy with the alternate medication (group 1 received felodipine 5 mg once daily and group 2 received candesartan 16 mg once daily).Results: Thirty patients (18 men, 12 women; mean [SD] age, 54.0 [4.9] years; range, 39-62 years) were included in the study. During both monotherapy periods, candesartan and felodipine significantly reduced blood pressure (BP) (both P<0.001). BP further decreased with combination therapy (P<0.001 in both groups). Overall, 90.0% (27/30) of the patients achieved the target BP at the end of combination therapy. The incidence of AEs was similar with combination therapy compared with either monotherapy.Conclusions: In this study population, candesartan and felodipine had additive effects when used in combination, even at low doses, in the treatment of hypertension. Therefore, the combination of candesartan and felodipine is an effective alternative to that of candesartan and hydrochlorothiazide.     

Effects of dibutyryl cyclic adenosine monophosphate on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs

Background: Hypercapnia is associated with diaphragm muscle dysfunction that causes a reduction of diaphragmatic force generated for a constant elective myographic activity. No published data are available concerning hypercapnic depression of diaphragmatic contractility during dibutyryl cyclic adenosine monophospate (DBcAMP) administration.Objective: The aim of this study was to assess the effects of DBcAMP on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.Methods: This experimental study was conducted from July to December 2008 at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Adult (aged >5 years) mongrel dogs weighing 10 to 15 kg were randomly divided into 3 equal groups. Hypercapnia (80-90 mm Hg) was induced with 10% carbon dioxide added to the inspired gas. When hypercapnia was established, group 1 was infused with low-dose DBcAMP (0.05 mg/kg/min); group 2 was infused with high-dose DBcAMP (0.2 mg/kg/min); and group 3 received placebo (saline). Study drug was administered intravenously for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at baseline, induction of hypercapnia, and study drug administration.Results: Twenty-one dogs were divided into 3 groups of 7. There were no significant differences observed at baseline. In the presence of hypercapnia, Pdi (mean [SD], cm H₂O) at low- (20-Hz) and high-frequency (100-Hz) stimulation was significantly decreased from baseline in each group (all, P = 0.001). In groups 1 and 2, Pdi at both stimuli was significantly increased during DBcAMP administration compared with hypercapnia-induced values (group 1: 20-Hz, 13.5 [2.2] vs 15.0 [2.4], respectively, P = 0.001, 100-Hz, 21.2 [1.6] vs 22.5 [1.6], P = 0.001; group 2: 20-Hz, 13.7 [1.4] vs 19.2 [1.7], P = 0.001, 100-Hz, 21.0 [2.4] vs 27.2 [2.5], P = 0.001). The Pdi at both stimuli during DBcAMP administration was significantly higher in group 2 than in group 1 (20-Hz, 19.2 [1.7] vs 15.0 [2.4], P = 0.001, 100-Hz, 27.2 [2.5] vs 22.5 [1.6], P = 0.003). In group 3, Pdi did not significantly change in regard to either stimulus from hypercapnia-induced values.Conclusion: DBcAMP, in a dose-dependent manner, was associated with improved hypercapnic depression of diaphragmatic contractility in these pentobarbital-anesthetized dogs.