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Effect of salicylic acid on the activity of betamethasone-17,21-dipropionate in the treatment of erythematous squamous dermatoses.

Forty adult out-patients with erythematous squamous dermatoses of the scalp were treated in this 21-day double-blind study with an alcohol base lotion containing either 0.05% betamethasone-17,21-dipropionate, 2% salicylic acid, 0.05% betamethasone-17,21-dipropionate + 2% salicylic acid or their respective placebo. The four treatments were assigned randomly to the patients according to a 2 x 2 orthogonal factorial design. Changes in severity of redness, scaling, pruritus and size of lesions were evaluated. Since very few patients presented with excoriation and lichenification, these symptoms could not be ascertained. Results were assessed for significance by covariance analysis where initial status was used as regressor. A potentiation of the betamethasone-17,21-dipropionate activity by salicylic acid was observed for scaling. An additive effect was noted for redness and pruritus. According to the physician's global evaluation, patients treated with the combination drug showed a better evolution than those treated with placebo. The results suggest that addition of a keratolytic agent enhances the corticosteroid effect in the treatment of erythematous squamous dermatoses.

Administration, Topical↗

Loratadine (SCH29851) 40 mg once daily versus terfenadine 60 mg twice daily in the treatment of seasonal allergic rhinitis.

Seventy patients received loratadine 40 mg once daily, terfenadine 60 mg twice daily, or placebo in a 14-day, double-blind, randomized study. Four nasal and four non-nasal symptoms associated with allergic rhinitis were evaluated. At the endpoint (the last evaluable visit), the mean total scores of combined nasal and non-nasal symptoms decreased (improved) from the baseline by 51.8% and 55.7% with loratadine and terfenadine, respectively, but increased (worsened) by 6.1% with placebo. There was a significant difference between both the loratadine and terfenadine treatment groups and the placebo group (P = 0.001) but not between the active medication groups (P = 0.608). Overall therapeutic response was good or excellent in 14 of the 23 patients given loratadine, in 18 of the 24 given terfenadine and in none of the 23 given placebo. The difference between each active medication group and the placebo group was significant (P less than or equal to 0.01) but there was no significant difference between the two active treatment groups (P greater than 0.35). No loratadine patient had any adverse side-effects. Sedating effects occurred in one terfenadine patient, headache in one placebo patient and two terfenadine patients (one terfenadine patient with severe headache discontinued treatment), and dyspepsia in two placebo patients. No anti-cholinergic effects occurred in this study. Loratadine 40 mg once daily was effective and safe in the relief of symptoms of allergic rhinitis.

Adolescent↗

Photic resetting of the human circadian pacemaker in the absence of conscious vision.

Ocular light exposure patterns are the primary stimuli for entraining the human circadian system to the local 24-h day. Many totally blind persons cannot use these stimuli and, therefore, have circadian rhythms that are not entrained. However, a few otherwise totally blind persons retain the ability to suppress plasma melatonin concentrations after ocular light exposure, probably using a neural pathway that includes the site of the human circadian pacemaker, suggesting that light information is reaching this site. To test definitively whether ocular light exposure could affect the circadian pacemaker of some blind persons and whether melatonin suppression in response to bright light correlates with light-induced phase shifts of thecircadian system, the authorsperformed experiments with 5 totally blind volunteers using a protocol known to induce phase shifts of the circadian pacemaker in sighted individuals. In the 2 blind individuals who maintained light-induced melatonin suppression, the circadian system was shifted by appropriately timed bright-light stimuli. These data demonstrate that light can affect the circadian pacemaker of some totally blind individuals--either by altering the phase of the circadian pacemaker or by affecting its amplitude. They are consistent with data from animal studies demonstrating that there are different neural pathways and retinal cells that relay photic information to the brain: one for conscious light perception and the other for non-image-forming functions.

Adult↗

The acute effect of methylphenidate in Brazilian male children and adolescents with ADHD: a randomized clinical trial.

OBJECTIVE: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. METHOD: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were evaluated pre- and posttreatment using the 10-item Conners Abbreviated Rating Scale (ABRS), the Children's Global Assessment Scale (CGAS), and a simplified version of the Continuous Performance Test (CPT). RESULTS: The MPH group had a significantly greater decrease in ABRS scores and a significantly higher increase in CGAS scores than the placebo group (p < 0.01). The MPH group showed also a significantly higher proportion of patients with a robust improvement (decrement of at least 50% in the ABRS score after the intervention) than the placebo group (p < 0.01). The MPH effect size for the ABRS was 1.05 (95% CI = 0.73-1.37). CONCLUSION: Our results extend the efficacy of MPH on the ADHD core symptoms extensively demonstrated in clinical trials with samples from some developed countries to a sample from a developing country where a diverse culture may modulate the clinical presentation of the disorder.

Adolescent↗

A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.

OBJECTIVES: To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression. RESEARCH DESIGN AND METHODS: A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60). OUTCOME MEASURES: Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed. RESULTS: Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery. CONCLUSIONS: This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances.

Adult↗

A general practice study to compare the efficacy and tolerability of a spray ('Otomize') versus a standard drop formulation ('Sofradex') in the treatment of patients with otitis externa.

In an open, multi-centre study in general practice, a comparison was made of the efficacy, tolerability and acceptability of a neomycin/dexamethasone preparation administered by metered-dose spray ('Otomize') and a framycetin/gramicidin/dexamethasone preparation ('Sofradex') administered as drops in 60 patients with otitis externa. Patients were allocated at random to receive one or other preparations 3-times daily for 10 days and were followed-up again 14 days after cessation of therapy. Clinical assessments were carried out under observer blind conditions on entry (Day 0) and on Days 10 and 24 of the severity of erythema, swelling and debris in the affected ear(s). A global assessment of clinical outcome was made by the doctor on Day 10. There were no significant differences in the two groups at the start of treatment. Significant improvement occurred in both groups from Day 0 to Day 10 and from Day 10 to Day 24 in all symptoms, with the proportion symptom-free in the 'Otomize' group significantly greater than in the 'Sofradex' group at 24 days, and approaching significance at 10 days. Significantly more patients in the 'Otomize' group were rated as having a good clinical outcome by the physician, and fewer patients experienced discomfort on application. Few side-effects were reported by either treatment group, none necessitating discontinuation of therapy.

Adolescent↗

A beta adrenergic stimulant (salbutamol) versus clomipramine in depression: a controlled study.

A controlled study comparing salbutamol (6 mg/day) to clomipramine (150 mg/day), both given by intravenous infusion, was performed on depressed inpatients (10 per group). The symptomatology was evaluated by two blind observers at days 0, 5, and 15 using the Hamilton Rating Scale. Both treatments were effective on the overall symptomatology but the onset of action of salbutamol was more rapid.

Adolescent↗

Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study.

BACKGROUND: Acamprosate is a newly registered drug that appears to reduce alcohol-drinking in both animal models and clinical conditions. METHOD: In order to assess the efficacy and safety of the drug in the treatment of detoxified alcoholics, we performed a 90-day double-blind trial comparing two dosages of acamprosate (1332 mg/day and 1998 mg/day). RESULTS: For all efficacy parameters, acamprosate appeared to be significantly superior to placebo, with a trend towards a better effect at the higher dosage. Furthermore, acamprosate appeared to be extremely safe. CONCLUSION: This study confirms that acamprosate could be an interesting adjuvant for maintaining abstinence in detoxified alcoholics.

Acamprosate↗

A torque-controlled device to measure passive abduction of the thumb carpometacarpal joint.

The primary aim of this study was to design and then test the intrarater reliability of a torque-controlled method of measuring passive abduction of the thumb carpometacarpal (CMC) joint. A secondary aim was to quantify passive CMC abduction in patients with and without contracture. Initially, clinicians used subjective feel (without range of motion measurements) to identify 52 people with loss of passive thumb CMC abduction. All subjects had a neurological condition. Passive thumb CMC abduction was measured in both hands of these 52 people and the hands of another 20 healthy able-bodied individuals (total of 72 people and 144 hands). Passive thumb CMC abduction was measured using a newly designed torque-controlled device and the previously recommended caliper method. Repeat measurements were taken with both devices, two to three days later, by blinded assessors on a subgroup of 12 patients (24 hands). Median (interquartile range) CMC angle of thumbs deemed by clinicians to have contracture was 45 degrees (41-52 degrees) and that of subjects without contractures was 56 degrees (53-60 degrees). The intraclass correlation coefficient for the repeat measures attained with the torque-controlled device was 0.78 (95% confidence interval, 0.56-0.90). The torque-controlled device provides a way of standardizing torque when measuring passive thumb CMC abduction. The clear difference between passive CMC abduction of subjects with and without contracture confirms the ability of clinicians to use feel and subjective assessment to identify patients with contracture.

Carpal Joints↗

Effect of angiotensin-converting enzyme inhibition on pituitary hormone responses to insulin-induced hypoglycemia in humans.

Renin, angiotensin-II, and angiotensin-converting enzyme (ACE) have been found in the hypothalamus and pituitary in rats, and renin, angiotensinogen, and ACE have been found in human pituitary lactotrophs. To determine the physiological relevance of the renin-angiotensin system in the pituitary hormone response to stress in humans, we created significant inhibition of ACE by administering a clinically used dose (10 mg) of enalapril (E) 4 h before measuring the stress hormone responses to insulin-induced hypoglycemia. Eight fasting lean healthy males (aged 20-35 yr) were given either placebo (P) or E (10 mg, orally) in two studies separated by at least 5 days in a blinded study design. Glucose, ACTH, cortisol, PRL, and GH levels were measured before E or P and at 20-min intervals beginning 20 min before insulin administration. ACE levels were similar at baseline (E, 21.6 +/- 2.7; P, 22.4 +/- 2.4 mU/mL/min), but were significantly lower at the time of insulin injection with E treatment (E, 2.9 +/- 0.5; P, 20.9 +/- 2.5 mU/mL/min; P less than 0.001). The mean of the total area under the curve of PRL secretion was significantly lower for the E group (E, 3767.2 +/- 710.7; P, 4554.9 +/- 650.1 micrograms/L.min; P less than 0.05). Although the mean peak PRL levels were lower for the E group, this did not reach statistical significance (E, 53.0 +/- 9.7; P, 64.4 +/- 9.4 micrograms/L; 0.05 less than P less than 0.10). These differences in PRL responses appeared to be due primarily to substantial decreases in PRL responses with E in three of the eight subjects. No significant differences were found with ACTH, cortisol, or GH for basal levels, peak levels, or areas under the curve.

Adrenocorticotropic Hormone↗

Occlusion versus air exposure on full-thickness biopsy wounds.

The benefits of moisture-retaining dressings on wound healing are well documented in experimental animal models but not in humans. To examine the effect of occlusion, the effects of three brands of synthetic occlusive dressings (Comfeel Plus, DuoDerm CGF, OpSite) were compared with air exposure in epithelial resurfacing and proliferation in acute, full-thickness skin wounds in humans. In 10 healthy males, four 4 mm standardised wounds were made with a sterile punch biopsy on each lower extremity. Epithelialisation of the wounds was assessed histologically and blindly postwounding on days 7 and 14. Wound margin epidermal proliferation was evaluated immunohistochemically with Ki67. Epithelial percentage coverage increased significantly (p = 0.007) with the occlusive dressings (62 +/- 6%, mean +/- SEM), compared with air exposure, (39 +/- 7%) on day 7 but not on day 14 (p = 0.500). Epidermal cell proliferation showed no significant intergroup difference on either day. Treatment with occlusive dressings increased early epithelial migration of acute full-thickness biopsy wounds compared with air exposure in healthy men.

Adult↗

Cost-effectiveness of enhancing primary care depression management on an ongoing basis.

PURPOSE: Although potentially costly, enhancing primary care depression management on an ongoing basis results in substantial long-term treatment effectiveness. The purpose of this article is to compare the cost-effectiveness of this approach with that of usual care. METHODS: The study was conducted in 12 community primary care practices randomized to enhanced or usual care after stratification by baseline practice patterns. Practices assigned to enhanced care encouraged depressed patients to engage in active treatment, using practice nurses to provide regularly scheduled care management during the course of 24 months. We analyze outcomes for 211 adults (73.4% of potential eligible patients) beginning a new treatment episode for major depression determined by previsit screening. Outcomes included blinded estimates of days free of depression impairment as well as health care costs for 2 years. RESULTS: Enhanced care significantly increased the number of days free of depression impairment for 2 years when compared with usual care (647.6 days vs 588.2 days, P <.01). The incremental cost-effectiveness ratio for enhanced care ranged from 9,592 dollars to 14,306 dollars per quality-adjusted life-year (QALY). The number of incremental days free of depression impairment increased between the first year and the second year (23.0 vs 36.4, respectively, P <.001) while incremental health plan costs decreased significantly (568 dollars vs -12 dollars, P <.001). CONCLUSIONS: Enhancing primary care depression management on an ongoing basis should be considered for adoption by policy and health plan leaders.

Adult↗

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients.

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1 +/- 3.2, placebo vs 103.3 +/- 3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2 +/- 0.2 vs 5.7 +/- 0.2 mmol/l, p < 0.01), serum insulin (168.0 +/- 14.5 vs 138.9 +/- 7.9 pmol/l, p < 0.05), serum C-peptide (0.68 +/- 0.03 vs 0.58 +/- 0.02 nmol/l, p < 0.05) and total serum cholesterol (6.07 +/- 0.41 vs 5.48 +/- 0.38 mmol/l, p < 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p < 0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p < 0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU.kg-1 x min-1) glucose disposal rate tended to be increased (18%, p = 0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

Adipose Tissue↗

Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular AAA repair? A randomized controlled pilot study.

PURPOSE: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as evidenced by changes in markers of renal function. METHODS: Twenty consecutive men (mean age 72 years, range 65-79) undergoing EVAR were randomized to receive standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg BID orally, 4 doses). Venous blood and urine were collected prior to the procedure and for 5 postoperative days and analyzed blindly for serum creatinine, urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR). RESULTS: There were no significant differences in baseline demographics between the groups. No patient developed acute renal failure. In both groups, urinary RBP rose significantly from baseline (median 15 microg/mmol to peak 699 microg/mmol in controls versus 17 to 648 microg/mmol in the treatment group, p<0.003). There were similar significant rises in ACR (p<0.02). There was, however, no significant difference in the postoperative RBP or ACR between the groups at any time point. CONCLUSION: EVAR causes significant acute renal injury in most patients. This was not attenuated by N-acetylcysteine. The causes of renal injury are probably multifactorial, the long-term clinical significance of which is unclear.

Acetylcysteine↗

Effect of N-acetyl-L-cysteine on lymphocyte apoptosis, lymphocyte viability, TNF-alpha and IL-8 in HIV-infected patients undergoing anti-retroviral treatment.

N-acetyl-L-cysteine (NAC) has been proposed as an additional therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated CD4+ lymphocytes, and it ameliorates immunological reactivity. In a randomized, 180-day, double-blind, placebo-controlled trial performed with HIV-infected patients classified as A2 and A3 according to the criteria of the Center for Disease Control and Prevention, we investigated the effects of oral administration of NAC on HIV-infected patients undergoing their first anti-retroviral therapy; viral load, CD4+ lymphocyte, lymphocyte viability and apoptosis, and TNF-alpha and IL-8 levels were determined. Sixteen patients who received anti-retroviral therapy plus a placebo formed the control group and the study group consisted of 14 patients who received anti-retroviral therapy and NAC supplementation. A significant decrease was seen in viral load, TNF-alpha and IL-8 levels, and lymphocyte apoptosis, and a significant increase was found in levels of CD4+ lymphocytes and lymphocyte viability in both groups after anti-retroviral treatment, but no measurable benefits of anti-retroviral therapy plus NAC oral supplementation (600 mg/day) were found in relation to anti-retroviral therapy alone, and the baseline levels of cysteine and glutathione in plasma were not recovered by this treatment. In conclusion, the daily doses of NAC necessary for the total recuperation of plasma cysteine and glutathione levels in HIV-infected patients and the additional benefits following the supplementation of NAC in patients submitted to anti-retroviral therapy, need to be studied further.

Acetylcysteine↗

Centric relation registration: intra- and interexaminer agreement after a calibration program.

Centric relation (CR) has been considered a maxillomandibular position of choice for some dental and prosthetic procedures. Although regarded as a fully reproducible relation, there is great controversy about its clinical use and recording technique, especially in patients with signs and symptoms of temporomandibular disorders (TMD). This study aimed at evaluating the effectiveness of a training program on intra- and interexaminer agreement when determining the clinical record of the CR position. Forty individuals constituted the sample, divided into symptomatic (TMD) and asymptomatic groups. Three previously calibrated examiners performed the initial assessment and the second evaluation after 30 days in a blind design, using Dawson s bilateral manipulation technique with and without an anterior stop. The amount of frontal and sagittal deviations in relation to intercuspal position, the presence of pain and discomfort during manipulation, and the first occlusal contact in CR were analyzed. Kendall and Kappa tests with a 5% level of significance were used to determine agreement. Values for both intra- and interexaminer agreement were deemed good. The best results were obtained for frontal deviations and assessment of pain (or absence of it) during manipulation. Sagittal deviations showed the lowest agreement in both examinations. The authors concluded that a calibration program could be effective for intra- and interexaminer agreement when recording centric relation. However, caution is recommended when analyzing some isolated items.

Brazil↗

The effects of a dentifrice containing zinc citrate and 2,4,4' trichloro-2'-hydroxydiphenyl ether.

The effects of a dentifrice which contained 1% zinc citrate and 0.5% of a nonionic antimicrobial agent, 2,4,4' trichloro-2'-hydroxydiphenyl ether on plaque and gingival health have been investigated. In a 4-day nonbrushing study in which dentifrices were used as slurries, this dentifrice inhibited plaque accumulation significantly more than dentifrices which contained either zinc citrate or Triclosan separately. In a 28-day double-blind cross-over study, a significant reduction in plaque accumulation and improvement in gingival health was demonstrated for the test dentifrice compared to the placebo. The effect was demonstrated with a group of well motivated volunteers who had a good standard of oral health. Analysis of the data suggested that the benefit might be extended to a less motivated population.

Adult↗

Effect of pinitol treatment on insulin action in subjects with insulin resistance.

OBJECTIVE: Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl-D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of insulin. We tested the hypothesis that oral administration of soybean-derived pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2) with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%). RESEARCH DESIGN AND METHODS: There were 22 subjects randomized to receive either pinitol 20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded trial. RESULTS: No toxicity due to the pinitol was observed during the study The sensitivity of glucose and lipid metabolism to insulin were assessed by measurement of whole-body glucose, palmitate, and glycerol kinetics during basal conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were made at baseline and again at the end of the study Final plasma levels of pinitol were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro-inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001) greater in the pinitol group compared with placebo. CONCLUSIONS: Four weeks of pinitol treatment did not alter baseline glucose production, insulin-mediated glucose disposal, or rates of appearance of free fatty acids and glycerol in plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are very responsive to pinitol ingestion, but insulin sensitivity does not increase after pinitol treatment in individuals with obesity and mild type 2 diabetes.

Blood Glucose↗