Search

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

Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7 as a specific marker of a rare subpopulation of A(single) spermatogonia in mice. PAX7+ cells were present in the testis at birth. Compared with the adult testis, PAX7+ cells constituted a much higher percentage of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7+ spermatogonia self-maintained and produced expanding clones that gave rise to mature spermatozoa. Interestingly, in mice subjected to chemotherapy and radiotherapy, both of which damage the vast majority of germ cells and can result in sterility, PAX7+ spermatogonia selectively survived, and their subsequent expansion contributed to the recovery of spermatogenesis. Finally, PAX7+ spermatogonia were present in the testes of a diverse set of mammals. Our data indicate that the PAX7+ subset of A(single) spermatogonia functions as robust testis stem cells that maintain fertility in normal spermatogenesis in healthy mice and mediate recovery after severe germline injury, such as occurs after cancer therapy.

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.

NSCLC (non-small cell lung cancer) often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.

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.

The past ten years have seen a dramatic increase in the empirical investigation of psychopathic characteristics in children and adolescents. In general, the focus of this research has been on the validation of assessment instruments to evaluate psychopathy as well as concurrent and predictive validity. Little attention has been directed toward elucidating the core characteristics of this construct. The current study expands on previous research by asking juvenile justice personnel (424 juvenile detention and probation officers) to identify the core characteristics of the construct via prototypical analysis for both male and female adolescents. Results of separate factor analyses by gender revealed five identifiable dimensions: juvenile delinquency, serious/violent conduct problems, narcissistic/manipulation of others, impulsivity/acting out, and family problems. The results suggest that juvenile justice personnel focus on a wide range of behavioral indicators as indicative of adolescent psychopathy in addition to affective and interpersonal characteristics typically viewed as crucial to the construct by clinicians.

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.

Lung cancer is the leading cause of cancer-related deaths, with the majority of deaths due to failed therapy from tumor drug resistance. Third-generation chemotherapeutic agents represent the standard first-line treatment for advanced small cell (SCLC) and non-small cell (NSCLC) lung cancer patients. Response rates are poor (20-40%) with a median survival of 8-10 months. In an unbiased and comprehensive approach, we have combined a high-throughput screening platform with a library of chemically synthesized microRNA mimics and inhibitors. We have used this platform to identify mimics and inhibitors that reduce cell viability in general, and those that specifically sensitize cells to taxanes. We have identified several miRNAs for which over-expression or inhibition has a dramatic and selective effect on cell viability or drug response. We have demonstrated that miR-337-3p mimic sensitizes NSCLC cells to taxanes. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p by enhancing taxane-induced arrest in the G2 phase of the cell cycle. We have identified an inhibitor of miR-139-5p as a potent and selective regulator of SCLC cell viability. Inhibiting miR-139-5p decreases SCLC cell viability by over 80%, but has a minimal cytotoxic effect on that of NSCLCs or immortalized human bronchial epithelial cells. We are currently investigating the targets of miR-139-5p that mediate its effect on SCLC cell viability. We also identified miR-10a inhibitor as increasing cell viability, with the converse observed for miR-10a mimic, suggesting that miR-10a acts as a tumor suppressor gene by directly decreasing expression of gene(s) that promote cell survival and growth. Manipulation of miR-10a levels also resulted in significant changes in both mRNA and protein levels of its predicted target, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which has been shown to play a major role in proliferation and survival in a number of human cancers and is a significant therapeutic target. We have identified miR-337-3p as a regulator of taxane sensitivity, and miR-10a and miR-139-5p as modulators of cell viability. Increasing levels of miR-337-3p and inhibiting miR-10a and miR-139-5p may therefore provide novel therapeutic tools for the treatment of NSCLC and SCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 140. doi:1538-7445.AM2012-140

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.