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This multicenter, randomized, investigator-blinded study investigated the efficacy and tolerability of adapalene gel 0.1% plus clindamycin phosphate lotion 1%, compared with clindamycin plus vehicle for the treatment of mild to moderate acne vulgaris. A total of 249 patients applied clindamycin lotion twice daily and adapalene (125 patients) or vehicle gel (124 patients) once daily for 12 weeks. A significantly greater reduction of total (P

Background: The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance. Objective: We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen. Methods: A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12. Results: There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was −62% compared with −60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was −26% compared with −30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents. Conclusion: This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea. (J Am Acad Dermatol 2001;45:723-30.)

OBJECTIVE The high morbidity and mortality rates associated with dural sinus thrombosis may be heightened by a delay in diagnosis, which necessitates prompt and effective treatment. Traditional treatment consists of the initiation of systemic anticoagulation with heparin and, more recently, regional thrombolysis with direct endovascular infusion of thrombolytic agents. We report our experience in a series of five patients in whom we accomplished mechanical clot lysis with the combination of a rheolytic device and balloon catheters. METHODS Five patients with dural sinus thrombosis were treated with a combination of pharmacological and mechanical thrombolysis with the 5-French AngioJet rheolytic catheter (Possis Medical, Minneapolis, MN) and balloon catheters. The success of the procedure was determined by resolution of or improvement in the patient's neurological examination results and imaging features. RESULTS All five patients demonstrated immediate improvement as observed on imaging studies or in terms of neurological status. Three patients required more than one intervention, and all but one patient continued to improve after the final intervention. Two of the five patients continued to experience mild residual neurological deficits, and two patients experienced complete recovery. The fifth patient had a delayed recurrence of thrombosis that required multiple interventions, and the patient has significant neurological deficits. Navigation of the dural sinuses was possible in all patients with the use of a microcatheter and was possible to a variable degree with the rheolytic catheter. Known complications of the procedures included two pseudoaneurysms at the femoral puncture site. CONCLUSION Mechanical clot lysis is a powerful technique for immediate restoration of antegrade venous flow in dural sinus thrombosis. In most patients, the superior sagittal sinuses and contralateral transverse sinuses could be accessed with the 5-French rheolytic catheter.

Background: Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. Objective: This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). Methods: This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for ∼24 hours; the Friday patches were left in place over the weekend for ∼72 hours. Results: All 36 subjects (26 men, 10 women; age, 18–49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had ≥1 application discontinued prematurely on ≥1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25–1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products ( P Conclusions: Adapalene gel and cream were well tolerated, with possible benefits for compliance. Their low irritation potential should be considered when prescribing a topical retinoid for the treatment of acne vulgaris.

Increased endotracheal tube cuff pressure causes mucosal ischemia that can lead to necrosis, infection, and, eventually, tracheomalacia or tracheal stenosis. Endotracheally intubated patients frequently undergo portable chest radiography. In this study we explored the relationship of endotracheal tube cuff pressure and the appearance on the tracheal air columns on the portable chest radiograph. We measured the endotracheal tube cuff pressure of intensive care unit patients 124 times immediately before portable chest radiography. On 64 of these radiographs we measured the width of the tracheal air column below the tip of the endotracheal tube and at the maximal diameter of the endotracheal tube balloon. We then analyzed the relationship of cuff pressure to tracheal dilation. The results of ANOVA of tracheal dilation for three groups (safe, borderline, and unsafe cuff pressures) were significant. Large overlapping ranges existed in each group. Regression analysis confirmed a linear relationship between cuff pressure and tracheal dilation (r = 0.435, p < 0.001). Predicted tracheal expansion at 20 mm Hg was a poor screen for endotracheal tube cuff inflation safety; the sensitivity was only 56% and specificity only 71%. The differences in the capacity for tracheal distension between patients make these findings not unexpected. The portable chest radiograph is a poor screening tool for unsafe endotracheal tube cuff pressure. (Otolaryngol Head Neck Surg 1999;120:51-6.)

Treatment goals for atopic dermatitis consist of attempting to eliminate inflammation and infection, hydrating the skin, controlling pruritus, and avoiding exacerbative factors. The aim of this study was to evaluate the effects of adding a moisturizing regimen to a low-potency topical corticosteroid lotion regimen in the treatment of atopic dermatitis. This controlled, randomized, investigator-masked 3-week study was undertaken to compare twice-daily applications of desonide lotion 0.05% alone with twice-daily applications of desonide lotion 0.05% plus three-times-daily applications of a moisturizing cream. The efficacy variables assessed included erythema, dryness or scaling, pruritus, excoriations, lichenification, oozing or crusting, and induration or papules. Administration of desonide lotion alone created statistically significant improvement in total sign and symptom scores. The addition of a moisturizer to the treatment regimen produced additional statistically significant improvement in total sign and symptom scores, physicians' global assessments of improvement, and most of the individual efficacy variables. Results of this study suggest that the addition of a moisturizer to a low-potency corticosteroid lotion in separate regimens was effective in treating the signs and symptoms of mild-to-moderate atopic dermatitis.

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available.

Background: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. Objective: The study was designed to compare the efficacy and safety of adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to III facial acne vulgaris. Methods: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2, 4, 8, and 12. Efficacy was determined by investigator counts of non-inflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. Results: Starting at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follows: 49% versus 37% for total lesions ( p p = 0.02); 48% versus 38% for inflammatory lesions ( p = 0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. Conclusion: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Background: The effectiveness of prophylactic knee bracing in preventing knee injuries during sports has been evaluated; however, because of the variability in study conclusions, the topic remains controversial. Despite a paucity of data, the authors believe that prophylactic knee bracing is frequently used in off-road motorcycling.Hypothesis: No statistically significant difference exists in the frequency and types of knee injuries incurred between braced and nonbraced riders using commercially available knee braces in off-road motorcycling.Study Design: Descriptive epidemiology study.Methods: Data from 2115 off-road motorcycle riders was obtained using an Internet-based survey over a 1-year period. Participants were grouped by use or nonuse of prophylactic knee bracing, and an incidence rate ratio was used for injury rate comparison.Results: Participants recorded 39 611 riding hours over the study period. A total of 57 riders (2.7%) sustained at least 1 knee injury, for a total of 89 injuries. The most common injuries involved the anterior cruciate ligament, menisci, and medial collateral ligament. There was a significantly higher rate of overall injuries in the nonbraced group versus the braced group (3.675 vs 1.587 per 1000 rider hours, P < .001). Significantly higher incidence rates of anterior cruciate ligament rupture (1.518 vs 0.701 per 1000 rider hours, P = .0274) and medial collateral ligament injury (0.799 vs 0.111 per 1000 rider hours, P = .002) were found among nonbraced riders compared with braced riders.Conclusion: The most common knee injuries in off-road motorcycling involve the anterior cruciate ligament, menisci, and medial collateral ligament. The use of prophylactic knee bracing appears to have a beneficial effect in preventing medial collateral ligament and anterior cruciate ligament injuries as well as overall knee injury occurrence. These findings may be applicable to other sports that involve similar forces and mechanics.

A new lotion formulation of 0.05% desonide was compared with 0.05% desonide cream in a single (investigator)-blind, randomized, paired bilateral comparison study in the treatment of eczematous dermatitis. Eighteen patients with bilateral dermatitis, who would normally be treated with a low- to mid-potency topical corticosteroid, were eligible for entry into the study. A 7-day washout period was required for any potentially interfering therapy. Both treatments were given three times daily for up to 3 weeks. Patients were seen at study entry (baseline), and at 1, 2, and 3 weeks of treatment. Fifteen (83%) of the 18 patients completed the study. Of those, 12 patients completed all 3 weeks of treatment and 3 patients cleared bilaterally before week 3. Two patients were lost to follow-up and 1 patient whose condition worsened was dropped from the study early in order to receive alternative treatment. The overall mean severity score was significantly decreased ( P = 0.0002) for both the lotion and the cream from moderate at baseline to mild, with no statistically significant differences between the two treatments. Few patients experienced stinging or burning (4 of 18) or general irritation (2 of 18). Based on the results of this study, we conclude that desonide lotion is a safe and effective medication for treating the signs and symptoms of eczematous dermatitis and is equal in efficacy to desonide in a cream formulation.

A new lotion formulation of 0.05% desonide was compared with its vehicle and with 0.05% desonide cream in a double-blind, randomized, parallel study in the treatment of psoriasis. Eighty patients with mild to moderate psoriasis, normally treatable with a low-potency topical corticosteroid, were enrolled in the study. All treatments were applied three times daily for up to 3 weeks, with weekly examinations. In both the lotion and cream treatment groups, 93% of patients completed the study. Only 75% of patients in the vehicle group completed the study. There was no statistically significant difference between the lotion and the cream at any of the three visits. Both treatments were well tolerated by the patients. Only 3 of 80 patients reported mild irritation, consisting of two cases of transient stinging and one of erythema without symptoms. Both active treatment groups showed significant improvement from baseline and over the vehicle group, reached a global improvement of 50% to 75% by weeks 2 and 3 compared with

Thirty patients with seborrheic dermatitis of the scalp were evaluated in this double-blind, randomized, bilateral study comparing 0.05% desonide cream with 1.0% hydrocortisone cream. Postauricular areas were treated twice daily for 8 weeks. Clinical evaluations at 1, 2, 4, 6, and 8 weeks included a quantitative assessment of telangiectasia; gradings of epidermal thinning, striae, and shiny surface appearance; and notation of presence or absence of hair loss, muscle waste, fat waste, loss of elasticity or skin markings, and purpura or bruising. No statistical differences were detected between the two products at the end of the 8-week treatment period. There were no signs of atrophy caused by either corticosteroid. The total number of telangiectasia, while few in number, was greater on the hydrocortisone-treated sites than on the desonide-treated sites.

Adapalene is a new naphthoic acid derivative developed for the topical treatment of acne vulgaris.We describe the results of a combined safety analysis of two multicenter trials conducted in the U.S. and Europe in which adapalene 0.1% gel was compared with tretinoin 0.025% gel in the treatment of mild to moderate acne vulgaris.A total of 591 acne patients were enrolled in these investigator-masked, randomized, controlled, parallel group studies. In the two studies, each patient was randomly assigned to receive topical adapalene 0.1% gel or tretinoin 0.025% gel once daily at bedtime, for 12 weeks. In addition to assessments of efficacy and facial skin tolerance, data on adverse events were recorded at each visit or at any other time the patient reported problems. We extracted data concerning adverse reactions (i.e., adverse events judged to be related to the study treatment) from both studies and combined the results to obtain a global comparison of safety of the two products.A total of 15 of 296 patients (5.1%) reported 19 adverse reactions in the adapalene-treated groups, compared with 27 of 295 patients (9.1%) reporting 39 adverse reactions in the tretinoin-treated groups (p0.05). The number of patients discontinuing the study because of adverse events was approximately twice as low with adapalene (1.3% compared with 2.4%). Most adverse reactions for both products were related to skin irritation. No systemic adverse reactions were reported.The results of these two multicenter clinical studies indicate that adapalene gel is better tolerated than tretinoin gel.

Pneumothorax ex vacuo is a little-known complication of lobar collapse. In this condition, acute bronchial obstruction from mucous plugs, aspirated foreign bodies, or malpositioned endotracheal tubes causes acute lobar collapse and a marked increase in negative intrapleural pressure around the collapsed lobe. As a result, gas is drawn into the pleural space around the collapsed lobe while the seal between the visceral and parietal pleura of the adjacent lobe or lobes remains intact. The pneumothorax spontaneously resolves when the bronchial obstruction is relieved and the lobe reexpands. Recognition of pneumothorax ex vacuo is crucial in directing treatment to relieve the bronchial obstruction rather than inserting a chest tube into the pleural space.

Background: Desonide, a class 6 nonfluorinated topical corticosteroid, has been available for more than two decades. Hydrocortisone is widely used in the treatment of dermatoses in children. Objective: Our purpose was to compare the safety and efficacy of desonide ointment and 1.0% hydrocortisone ointment in children with atopic dermatitis. Methods: One hundred thirteen children (mean age, 4.8 years) with mild to moderate atopic dermatitis were enrolled in a multicenter, randomized, investigator-masked, parallel-group study. Treatments were applied twice daily for 5 weeks and extended to 6 months in 36 of the patients. Signs of atrophy were evaluated. Efficacy was determined by measuring global improvement, erythema, lichenification, excoriations, oozing or crusting, pruritus, and induration. Results: No differences in safety were observed between hydrocortisone and desonide. The investigator's global assessment of improvement significantly favored desonide over hydrocortisone during 3 months of treatment ( p Conclusion: Desonide ointment showed greater efficacy, produced more rapid improvement, and demonstrated an equivalent cutaneous safety profile when compared with 1% hydrocortisone ointment for up to 6 months.

We are addressing the questions of whether microRNAs (miRNAs) play a functional role in modulating drug sensitivity of lung cancer cells, and whether miRNA expression levels can be manipulated to increase drug sensitivity in lung cancer treatment. Using a combination of in silico and in vitro approaches, we identified miR-337-3p as a modulator of paclitaxel sensitivity in NSCLC cell lines where over-expression of miR-337-3p sensitizes NSCLC NCI-H1155 cells to paclitaxel (>2 fold) and docetaxel (>10 fold) by enhancing taxane-induced mitotic arrest. Of several possible targets of miR-337-3p we found that Stat3 and Rap1A are the direct targets responsible for mediating miR-337-3p sensitization to paclitaxel. In studies of multiple NSCLC lines we found that miR-337-3p can, in general, sensitize NSCLC lines to paclitaxel, and that Stat3 expression is significantly correlated with paclitaxel resistance in NSCLC lines, suggesting that tumor Stat3 expression is an intrinsic determinant and biomarker for paclitaxel response. We conclude we have discovered a novel pathway modulating NSCLC paclitaxel sensitivity, which involves the down-regulation of Stat3 and Rap1A expression by miR-337-3p. These findings have prompted: our ongoing studies of patient samples annotated for miR-337-3p, Stat3, and Rap1A expression and response to taxane therapy; preclinical testing of a miR-337-3p mimic as an adjuvant to taxanes for NSCLC therapy; and further tests of this pathway to provide both new therapeutic targets and biomarkers predictive of response for NSCLC taxane based therapy. This research was supported by NIH R01 CA129632 from the National Cancer Institute and by P50 CA70907 from the UT Southwestern/MD Anderson Cancer Center Lung Specialized Program of Research Excellence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4709. doi:10.1158/1538-7445.AM2011-4709

RATIONALE AND OBJECTIVES To evaluate the use of a new thrombus-specific ultrasound contrast agent, MRX-408, in the ultrasonic detection of thrombus in arteriovenous (AV) fistulae. METHODS Six purpose-bred mongrels with two AV fistulae each were imaged with gray-scale ultrasound 7 weeks after graft implantation before and after the intravenous bolus injection of MRX-408 (a GPIIb receptor-targeted ultrasound contrast agent). Pre- and postcontrast videotaped segments were randomized and reviewed by four radiologists blinded to the presence of thrombus in the grafts. RESULTS After the use of MRX-408, there was improved visualization of thrombus within the grafts (P < 0.0001). This was due to the enhancement of the thrombus (P < 0.0001). The improved visualization and contrast enhancement were more marked in the grafts that contained thrombus nonhyperechoic to surrounding soft tissues. CONCLUSIONS MRX-408 demonstrated better visualization of thrombus within AV fistulae. This was shown in both patent and occluded grafts. These results are encouraging and suggest that this contrast agent merits further development.

The authors studied the antipruritic effects of 10% crotamiton lotion in 31 patients with bilaterally symmetrical pruritic dermatoses. In this double-blind, paired-comparison clinical trial, there was no significant difference in relief of pruritus between the crotamiton lotion and its vehicle. The study does not confirm the results of previous uncontrolled studies indicating that crotamiton has an antipruritic effect.