Mechanism of action of ranolazine.
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Acetanilides↗
Biomedical subjects
Michael Sweeney
Publications and source records attributed to Michael Sweeney.
Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS).
OBJECTIVE: To ascertain remission rates in depressed youth participating in the Treatment for Adolescents With Depression Study (TADS), a multisite clinical trial that randomized 439 adolescents with major depressive disorder (MDD) to a 12-week treatment of fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO). METHOD: Using an end-of-treatment Children's Depression Rating Scale-Revised (CDRS-R) total score of 28 or below as the criterion for remission, rates of remission were examined with logistic regression, controlling for site. Loss of MDD diagnosis and residual symptoms in responders (defined as Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) were also examined across treatment groups. RESULTS: After 12 weeks of treatment, 102 (23%) of 439 youths had reached remission. The remission rate was significantly higher in the COMB group (37%) relative to the other treatment groups (FLX, 23%; CBT, 16%; PBO, 17%), with odds ratios of 2.1 for COMB versus FLX, 3.3 for COMB versus CBT, and 3.0 for COMB versus PBO. In addition, 71% of subjects across treatment groups no longer met criteria for MDD at the end of acute treatment. Fifty percent of the youths who responded by CGI-I criteria continued to have residual symptoms, such as sleep or mood disturbances, fatigue, and poor concentration. CONCLUSIONS: The combination of FLX and CBT was superior to both monotherapy and PBO in terms of remission rates, but overall rates of remission remain low and residual symptoms are common at the end of 12 weeks of treatment.
Adolescent↗
Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure.
Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p <0.002). Larger percentages of patients who received sildenafil reported improved erections (74%) and improved intercourse (68%) compared with patients who received placebo (18% and 16%, respectively). Intercourse success rates were 53% among patients who received sildenafil and 20% among those who received placebo. Patients who received sildenafil were highly satisfied with treatment and their sexual life compared with patients who received placebo. Sixty percent of patients who received sildenafil and 48% of patients who received placebo developed adverse events, including transient headache, facial flushing, respiratory tract infection, and asthenia. The incidence of events related to cardiovascular effects was low. Sildenafil is an effective and well-tolerated management of ED in men who have mild to moderate CHF.
Adult↗
Host immune responses in hepatitis C virus clearance.
BACKGROUND AND AIM: The factors that determine the outcome of hepatitis C virus (HCV) infection are not fully understood. An increased and broadly targeted/multispecific T-cell response is thought to be paramount to a favourable outcome. Human leucocyte antigen (HLA) genes, in particular DRB1 and DQB1, are also reported to influence outcome of infection. We have previously demonstrated strong associations between DRB10101 and spontaneous viral clearance. The aim of the current study was to investigate HCV-specific T-cell response and the influence of DRB10101 in patients with long-term history of HCV clearance as compared to patients that developed persistent HCV infection. METHODS: The proliferation of peripheral blood mononuclear cells stimulated with five non-structural and core HCV antigens and 20 synthesized HCV peptides, designed using T-cell epitope-predictive software, was determined by the incorporation of H-thymidine. RESULTS: Although HCV-specific T-cell responses were more frequently detected and a broader range of peptides were targeted in the viral clearance group, the magnitude and breadth of the responses were not significantly different to that in the viral persistence group. The magnitude and breadth of the T-cell response was significantly associated, however, with possession of DRB10101. Furthermore DRB10101 positive individuals with viral clearance had broader HCV-specific T-cell responses. CONCLUSION: These findings lend further credence to the importance of the host immune system to the outcome of HCV infection and provide a rationale for the role of DRB10101 in the resolution of HCV infection.
Cells, Cultured↗
Tooth whitening: tooth color changes following treatment by peroxide and light.
OBJECTIVE: This study examined the use of color measurement to determine tooth color in a study of bleaching with peroxide and light used separately and in combination. Two measurement protocols were evaluated for their ability to reveal differences between treatments and confirm tooth shade evaluations. METHODOLOGY: Before and after treatment, 43 subjects were evaluated for tooth color using a shade guide and a chromameter. Two measurement procedures were used: one measured a single location on each tooth using a fabricated plastic stent, and the other measured nine locations across the buccal surface. Values from the two procedures were compared to each other, and to shade guide measurements. RESULTS: Tooth color, as measured by both procedures, significantly correlated with shade evaluation. Statistically significant differences between treatment groups were found more often with data from the multiple-site procedure than from the single-site procedure. Incisal-gingival color gradation on tooth surfaces was diminished as a result of whitening treatments. Chromameter measurement data showed that tooth whitening procedures reduced tooth yellowness (b) more reproducibly than they increased whiteness (L). CONCLUSION: When more sites per surface were measured, tooth color measurement by the chromameter more closely matched shade with less variability and greater statistical power. Chromameter-derived values can be used to estimate shade values to a reasonable level of accuracy. Decreasing yellowness, particularly at the gingival margin, was an important component of the tooth whitening effect. Following tooth whitening, teeth were more uniform in their color, and this may contribute substantially to the subjective patient recognition of whiter teeth.
Adolescent↗
Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease.
This was a double-blind, placebo-controlled, flexible-dose study of the efficacy and safety of sildenafil in men with erectile dysfunction (ED) and clinically stable coronary artery disease (CAD). Patients were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function (IIEF). Secondary outcomes included the other IIEF questions and functional domains, the Life Satisfaction Checklist, the Erectile Dysfunction Inventory of Treatment Satisfaction, 2 global efficacy assessment questions, and intercourse success rate. By week 12, sildenafil-treated patients (n = 70) showed significant improvements on questions 3 and 4 compared with placebo-treated patients (n = 72; p <0.01). Larger percentages of sildenafil-treated patients reported improved erections (64%) and improved intercourse (65%) compared with placebo-treated patients (21% and 19%, respectively). Sildenafil-treated patients were highly satisfied with treatment and their sexual life compared with placebo-treated patients. Forty-seven percent of sildenafil- and 32% of placebo-treated patients experienced adverse events, including transient headache, hypertension, flushing, and dyspepsia. There were no serious drug-related cardiovascular effects. Thus, sildenafil is an effective and well-tolerated treatment for ED in men with CAD. Sildenafil was not associated with additional safety risks in this patient population.
3',5'-Cyclic-GMP Phosphodiesterases↗
Effects of very low-fat diets on anginal symptoms.
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Acetanilides↗
Low inferior vena caval catheters for hemodynamic and pulmonary function monitoring in pediatric critical care patients.
OBJECTIVE: To assess the value of low inferior vena caval (LIVC) catheters for estimating central venous pressure in pediatric intensive care patients and to assess influences of intra-abdominal pressures and mean airway pressure on these measurements. DESIGN: Prospective cohort of consecutive patients. SETTING: Pediatric intensive care unit. PATIENTS: Thirty patients ranging in age (18, 0-1 yrs; four, 1-3 yrs; four, 3-10 yrs; four, > or =10 yrs). INTERVENTIONS: Interventions included catheterizations via internal jugular, subclavian, and common femoral veins, as well as direct right atrial catheterization during surgery; arterial catheter placement; airway pressure monitoring during mechanical ventilation; indirect intra-abdominal pressure monitoring via bladder catheter pressure readings; and arterial and central venous blood gas analysis. LIVC vein catheters were placed below the origin of the renal veins. MEASUREMENTS AND MAIN RESULTS: LIVC pressure was highly correlated with central venous pressure (n=30, r2=.965, p=.0001). LIVC pressure did not correlate with intra-abdominal pressure (n=18, r2=.000). Mean airway pressure did not correlate with central venous pressure (n=11, r2=.106). The pH of LIVC blood was similar to that of central venous blood (n=18, r2=.941, p=.0001). PCO2 values of inferior vena cava and central venous blood correlated (r2=.945, p=.0001). However, agreement between inferior vena cava and central venous PO2 and oxyhemoglobin saturation was poor (PO2, r2=.066; oxyhemoglobin saturation, r2=.000). CONCLUSIONS: LIVC catheters whose tips lie below the origin of the renal veins predict central venous pressure in pediatric intensive care unit patients. Intra-abdominal pressure and mean airway pressure do not affect this relationship, within the wide range of values for these variables included in this study. Blood samples drawn from femoral venous catheters can be used to monitor acid-base balance and partial pressure of carbon dioxide.
Blood Gas Analysis↗
Microbiological changes associated with dental prophylaxis.
BACKGROUND: Despite the common application of dental prophylaxis as part of patient therapy, there is little reported that describes the microbiological impact of this treatment. METHODS: The authors gave 20 healthy college-aged subjects three dental prophylaxes with a fluoride-containing prophylaxis paste during a two-week period and instructed them in oral hygiene. They evaluated the microbiological composition of dental plaque samples collected before and after treatment using DNA probe analysis. They analyzed 40 representative bacterial species in seven bacterial complexes by checkerboard DNA-DNA hybridization assay techniques. RESULTS: After three dental prophylaxes, the patients' mean Gingival Index score decreased from 0.82 to 0.77, the mean Plaque Index score decreased from 0.72 to zero, and the total number of bacteria per tooth decreased to approximately one-third of the original number. The authors computed two different measures of bacterial presence. The reduction in bacterial numbers was statistically significant and occurred in many species. Bacterial proportion (DNA percentage or percentage of the bacteria per tooth) did not change significantly. Greater reductions in bacterial count occurred in species that showed high numbers before treatment. The total bacterial count decreased by approximately 72 percent of its original level before prophylaxis was initiated. CONCLUSIONS: Professional dental prophylaxis did not target any particular bacteria or bacterial groups but removed bacteria nonspecifically and in proportion to their initial numbers. CLINICAL IMPLICATIONS: Repeated dental prophylaxes effect a reduction in bacterial amount that is commensurate with the initial amount, but they do does not alter composition. This suggests that mild gingivitis may be a bacterially nonspecific effect of plaque accumulation and emphasizes the need for regular plaque removal to maintain optimal gingival health.
Adolescent↗
Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.
OBJECTIVES: To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia. METHODS: In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint. RESULTS: An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated. CONCLUSIONS: Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.
5-alpha Reductase Inhibitors↗
Treatment responsiveness of the Self-Esteem And Relationship questionnaire in erectile dysfunction.
OBJECTIVES: To determine the treatment responsiveness of the disease-specific Self-Esteem And Relationship (SEAR) questionnaire in erectile dysfunction. METHODS: The SEAR questionnaire was administered at baseline and at the end of the study in 93 patients with erectile dysfunction enrolled in a 10-week, open-label, flexible-dose (50-mg sildenafil, adjustable to 25 mg or 100 mg) trial. Changes from the baseline score were analyzed using the paired t test. The correlation between the changes from baseline on the SEAR questionnaire and the Erectile Function domain of the International Index of Erectile Function was examined. RESULTS: Significant and meaningful differences (P = 0.0001) from baseline were observed in the two primary domains (Sexual Relationship and Confidence) and the two Confidence domain subscales (Self-Esteem and Overall Relationship). The magnitude of the change was quite high for most aspects (Sexual Relationship, effect size [ES] = 1.6; Confidence, ES = 1.0; Self-Esteem, ES = 1.1) and moderate for one (Overall Relationship, ES = 0.6). Changes in Erectile Function domain score correlated moderately with changes in the SEAR domain and subscale scores (Sexual Relationship, r = 0.69; Confidence, r = 0.48; Self-Esteem, r = 0.47; and Overall Relationship, r = 0.35; P <or=0.001). CONCLUSIONS: The SEAR questionnaire is responsive to effective treatment of erectile dysfunction. These data suggest that the SEAR questionnaire is a valid instrument for detecting psychosocial gains from beneficial intervention.
Adult↗
Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders.
OBJECTIVE: To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. METHOD: The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. RESULTS: No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement. CONCLUSIONS: In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.
Adolescent↗
Treatment of pediatric anxiety disorders: an open-label extension of the research units on pediatric psychopharmacology anxiety study.
BACKGROUND: An 8-week placebo-controlled study, the Research Units on Pediatric Psychopharmacology Anxiety Study, documented beneficial effects of fluvoxamine in the treatment of pediatric social anxiety, separation anxiety, or generalized anxiety disorders. Following completion of this study, participants were invited to enter a 6-month open-label treatment phase designed to examine three issues: (a) long-term maintenance of response in fluvoxamine responders, (b) acute response to fluoxetine in fluvoxamine nonresponders, and (c) acute response to fluvoxamine in placebo nonresponders. METHODS: Participants aged 6-17 years meeting criteria for social anxiety, separation anxiety, or generalized anxiety disorders previously treated in an 8-week placebo-controlled trial (n = 128) were offered open treatment. Changes in symptoms of anxiety during open treatment were assessed in three groups: (a) fluvoxamine responders maintained on fluvoxamine, (b) fluvoxamine nonresponders changed to fluoxetine, and (c) placebo nonresponders changed to fluvoxamine. Response was defined based on Clinical Global Impression criteria. RESULTS: During 6 months of continued open treatment, anxiety symptoms remained low in 33 of 35 (94%) subjects who initially responded to fluvoxamine. Among 14 fluvoxamine nonresponders switched to fluoxetine, anxiety symptoms appeared significantly improved in 10 (71%) subjects. Finally, among 48 placebo nonresponders, 27 (56%) showed clinically significant improvement in anxiety on fluvoxamine. CONCLUSION: The current findings concerning extended treatment of pediatric anxiety disorders are only preliminary, because treatment was uncontrolled. Results suggest that an initial fluvoxamine response is likely to be retained with continued treatment, that some fluvoxamine nonresponders may respond to fluoxetine, and that some placebo nonresponders may respond to fluvoxamine.
Adolescent↗
Identification and characterization of the allergenic proteins of Bahia grass (Paspalum notatum) pollen.
BACKGROUND: Pollen of Bahia grass (Paspalum notatum) represents a major cause of type I allergy in diverse geographical areas, particularly in the southeastern coastal plain area of the United States. The aqueous protein extract of Bahia grass pollen contains the allergenically active components that produce skin-test-positive reactions in sensitive patients. OBJECTIVE: The emphasis of this study included the identification and characterization of the allergenic proteins present in the crude protein aqueous extract of Bahia grass pollen. METHODS: The crude extract of Bahia grass pollen, partially purified by isoelectric focusing and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was electroblotted onto nitrocellulose membranes, probed with sera from patients skin test positive to Bahia grass and detected using anti-human IgE conjugated peroxidase. RESULTS: Four allergenic proteins of Bahia grass pollen with estimated molecular weights of 45, 33, 31 and 28 kD were identified and characterized. Following treatments with deglycosylation enzymes, the 4 allergens retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. CONCLUSION: The crude extract of Bahia grass pollen contains many proteins but only 4 have allergenic reactivity. Following deglycosylation treatment, Bahia grass allergenic proteins have retained their antigenic reactivity with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies. Four proteins reactive with IgE were detected, but the 33-kD protein (pI of 6.59) was the most reactive.
Allergens↗
Continuous propofol infusion in 142 critically ill children.
OBJECTIVE: In recent years, continuous intravenous propofol infusion has been widely used in pediatric intensive care units. Several case reports have raised concerns about its safety. The objective of this study was to report our experience with continuous intravenous propofol in consecutive patients during an 18-month period. METHODS: The study design was a retrospective review of a case series. Case was defined as a critically ill child who was treated with continuous intravenous propofol. The attending physician staff agreed to prescribe propofol via continuous intravenous infusion at a dose not to exceed 50 microg/kg/min. The protocol allowed for each patient to receive an additional intravenous bolus of propofol at a dose of 1 mg/kg no more than once per hour. The study entailed data collection from consecutive patients who were prescribed a continuous infusion of propofol in either the pediatric intensive care unit or bone marrow transplant unit. RESULTS: Data from 142 patients were analyzed. Each patient enrolled was adequately sedated. Administration of propofol via continuous intravenous infusion was not associated with metabolic acidosis or hemodynamic compromise. No patient in the study group was inadvertently extubated or had a central venous catheter accidentally discontinued. CONCLUSIONS: Propofol can be safely and effectively used to provide sedation to critically ill infants and children. We speculate that continuous infusion of propofol for extended periods of time should not exceed 67 microg/kg/min.
Acidosis↗