Neuropeptide Y-like signalling and nutritionally mediated gene expression and behaviour in the honey bee.

Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether neuropeptide Y (NPY)-like signalling, a conserved pathway that regulates food-related behaviour, is involved in a derived, nutritionally-related trait, the division of labour in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared with younger bees performing brood care ('nurses'). A subset of these changes can be attributed to nutrition, but neuropeptide F peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labour and the related insulin-signalling pathway and suggest that some elements of molecular pathways associated with feeding behaviour may be more evolutionarily labile than others.

Development and evaluation of a Global Acne Severity Scale (GEA Scale) suitable for France and Europe.

BACKGROUND AND OBJECTIVE: Many acne grading methods exist; however, there is no agreed-upon standard. Our objective was to create and validate a reproducible acne assessment scale for rating the severity of juvenile facial acne suitable for use in France and Europe. METHODS: The scale we created described the different types of acne lesions in a manner similar to global assessment scales used in clinical trials. The scale was then validated by seven expert dermatologists in the field of acne [the Global Evaluation Acne (GEA) group] first on 34 photographic cases of Caucasian acne patients and second by clinical examination of 22 acne patients. RESULTS: There was good agreement in Investigators' assessments of acne both on photographs and patients (R = 0.8057; P < 0.0001, and R = 0.8437; P = 0.0015). CONCLUSION: The GEA Scale is a global scale validated both on photographs and acne patients which can be used either in clinical research or by the dermatologist in his office.

Bacterial resistance in French acne patients.

BACKGROUND: The percentage of strains of Propionibacterium acnes resistant to antibiotics in acne is increasing in many countries, raising the question of the risks associated with bacterial resistance. Numerous series of cases have been published on European populations of acne patients, but at the moment we still have very few data regarding France. OBJECTIVES: The aim of this study was to evaluate the prevalence of P. acnes resistant strains to erythromycin, tetracycline, and doxycycline in a population of French acne patients. METHODS: Specimens were collected from 273 patients in 43 centers located throughout France (12 hospitals and 31 private office practices). RESULTS: 75.1% of the patients were carriers of P. acnes strains resistant to erythromycin and 9.5% to tetracycline. One hundred percent of strains resistant to tetracycline were also resistant to doxycycline. There was no significant difference among the regions and between patients followed in hospital or private office. CONCLUSIONS: It clearly appears that the percentage of patients with P. acnes strains resistant to erythromycin is similar to that in other countries, but lower for tetracycline or doxycycline in comparison to other European countries.

Inter-observer agreement on acne severity based on facial photographs.

BACKGROUND: The three-grade acne classification (mild, moderate, severe) is widely used to define the licensed indications of acne treatments, and for therapeutic decision-making in clinical practice, but its reproducibility has never been assessed. METHODS: Ten photographs of facial acne were scored independently by eight experts using the three-grade acne classification. We conducted a descriptive analysis of the results, based on graphical representation of the scores for each photograph. RESULTS: Inter-observer agreement on acne severity based on the three-grade acne classification was very poor. CONCLUSION: The classical three-grade acne classification is poorly reproducible. A new rating tool accompanied by a clinical description of each severity level would be extremely useful.

Bioavailability of oral vitamin E formulations in adult volunteers and children with chronic cholestasis or cystic fibrosis.

PURPOSE: To test bioequivalence of oral vitamin E formulations, water-soluble tocofersolan (test) and water-miscible (reference), in healthy adult volunteers, and their bioavailability in children with chronic cholestasis or cystic fibrosis. METHODS: In a two-way open randomized single dose cross-over design, 1200 IU were administered in 12 healthy volunteers and 100 IU/kg in 12 children with chronic cholestasis or cystic fibrosis. RESULTS: In healthy volunteers, formulations were not bioequivalent with a higher exposure to tocofersolan. In cholestatic children tocofersolan bioavailability was significantly higher than reference formulation (maximum plasma concentration: P = 0.008 and AUC: P = 0.0026). Bioavailability was not statistically different in cystic fibrosis. CONCLUSIONS: Oral tocofersolan was more bioavailable than the reference formulation in children with chronic cholestasis and similarly bioavailable in cystic fibrosis. Tocofersolan may represent an alternative to painful intramuscular vitamin E injections in chronic cholestasis, or to other oral formulations in cystic fibrosis.

A tool to evaluate rapidly the quality of clinical trials on topical acne treatment.

Practicing dermatologists rarely evaluate therapeutic trials. This study was designed to build a simple evaluation tool, use it to evaluate the quality of published trials and thereby consider their applicability. Reports on 146 therapeutic trials, published from 1969 to 2004, were selected. A 50-item list was used for an initial assessment. After comparison with existing grids, a shortened nine-item list was established and used for this analysis. The results were analyzed item by item (logistic regression) and globally (principal component analysis). An index was then established and validated using Cronbach's coefficient alpha. The overall quality of trials was poor: 9% to 73% positive response range. This rate increased after 1990 for six items. Two factors explained almost 60% of the total variance: factor 1 summing six items concerning the formal content of the articles and factor 2 its underlying basis. Using the sum of these six variables, Cronbach's coefficient alpha reached 0.716; their mean sum improved from 1969 to 1970-2001-2005. The significantly improved quality of trials, based on the mean sum over time, supports well-founded basis of this tool. Regarding the application of evidence-based medicine in clinical practice, this tool is user friendly and should facilitate the updating of our knowledge.

[Lithium gluconate 8% in the treatment of seborrheic dermatitis]. / Gluconate de lithium gel à 8 p. 100 dans le traitement de la dermatite séborrhéique.

Seborrheic dermatitis is a chronic from of inflammatory dermatitis characterized by erythema and desquamation with predominant localization on the face (nasolabial folds, eyebrows, hair-line and ears). It appears to be caused by proliferation of Malassezia yeasts. Lithium gluconate 8% gel (Lithioderm 8% gel) is the only drug containing topical lithium salt commercially available in France for the treatment of seborrheic dermatitis. The mechanism of action of topical lithium is not well known; it may act through anti-inflammatory and antifungal action. Efficacy and safety were assessed in 2 clinical studies, one versus placebo and the other versus ketoconazole 2% foaming gel using the same principal criterion defined as the rate of patients showing complete remission after 2 months of treatment (complete disappearance of both erythema and desquamation). Lithium gluconate 8% was significantly more effective than placebo and than ketoconazole 2% foaming gel and was well tolerated. Adverse events observed were cutaneous (burning sensation, erythema and pruritus), for the most part of mild severity. No cutaneous side effects contributed to those reported with the use of systemic lithium in psychiatric disorders were noted. Pharmacokinetic studies have shown that systemic absorption after topical application is low. Lithioderm 8% gel is applied twice daily over a recommended period of 2 months. It constitutes a new alternative in the treatment of facial seborrheic dermatitis, regardless of severity.

Effect of selenium intake on the prevention of cutaneous epithelial lesions in organ transplant recipients.

Organ graft recipients have a high rate of pre-malignant and malignant epithelial lesions. Selenium directly influences the number of Langer-hans cells. In several studies selenium has shown its role in preventing various carcinomas, it was worth investigating whether it could prevent skin cancer linked to human papilloma virus (HPV). A multicentre, randomised, placebo-controlled, parallel group study in 184 recent organ transplant recipients was undertaken. Patients were treated for 3 years with 200 mug/day selenium (91 patients) or a matching placebo (93 patients), and then monitored for 2 years. Occurrence rates of warts and various keratoses (main criterion) and of skin cancers (secondary criterion) were compared in the two groups, using Kaplan-Meyer analyses. There was no difference between the two groups for the main criterion (odds-ratio 1.09, p = 0.72) or the secondary criterion (odds-ratio 3.08; p = 0.15). When both arms were pooled, phenotype and age were not found to be discriminatory factors, whereas a previous history of an actinic keratosis significantly increased the risk of developing a skin cancer by 17.5%. Safety was good and similar in both groups. Selenium was not shown to prevent the occurrence of skin lesions linked to HPV. The occurrence of skin cancer was higher if there had been a previous actinic keratosis, highlighting the importance of early dermatological follow-up of the transplanted population. This was demonstrated by the high rate of epithelial lesions detected, which was more than twice the rate usually reported in the literature.

[Efficacy and safety of 5% imiquimod cream in external genital warts: a 6 month follow-up evaluation]. / Efficacité et tolérance de l'imiquimod crème 5% dans le traitement des condylomes acuminés externes: résultats d'un suivi à 6 mois.

INTRODUCTION: One of the main issues raised by the management of external genital warts is their potential risk of recurrence. However, nearly all studies assessing recurrences have been conducted with a 3 month follow-up. Since the latency of the human papillomavirus is long, such 3 month follow-up might be too short to detect the true recurrence rate. We therefore conducted a study evaluating patients with external genital warts, treated with an immune response modifier, 5% imiquimod cream, and followed up to 6 months after total clearance. METHODS: This was an open, non comparative, multicenter study conducted in 51 private or hospital practices in France. 5% imiquimod cream was applied 3 times per week until the clearance of external genital warts, with a maximum application period of 16 weeks. Patients were followed-up for 6 months after complete clearance. RESULTS: One hundred ninety-one patients (103 males and 88 females), with a mean age of 31.4 years (18.1-70.4) were included in this study, between November 29 1999 and February 1st 2001. Complete clearance of external genital warts was noted in the ITT analysis in 103/191 cases (54 p. 100; CI95 p. 100: 40-61). Fifteen out of 92 (16 p. 100; CI95 p. 100: 9.4-25.5) had a recurrence within the 6 months follow-up period, 13 of these 15 recurrences were noted at the 3 month follow-up visit. CONCLUSION: The rate of recurrence of external genital warts at 6 months was similar to the rate noted at 3 months, suggesting that after the 3-month period, the risk of developing a recurrence was low. The mode of action of imiquimod through the induction of cytokines and the stimulation of the local immune response could explain these results.

[Acoustic hearing aid with an integrated noise generator in hearing-impaired subjects with tinnitus]. / Prothèse acoustique et bruiteur conjoint pour des sujets hypoacousiques et acouphéniques.

INTRODUCTION: Sound therapy has been studied in a group of 30 patients experiencing hearing loss and tinnitus. MATERIAL AND METHODS: Patients wore a BTE hearing-aid (TCI-COMBI by Siemens), which, in addition to acoustic amplification, can generate a broadband noise. Comparison of self-questionnaires completed by the patients during a 12 week period with amplification alone to a 12 week period with amplification and noise. RESULTS AND CONCLUSIONS: His study demonstrates that the level of suffering is significantly reduced during the period with added noise.

Lithium gluconate 8% vs ketoconazole 2% in the treatment of seborrhoeic dermatitis: a multicentre, randomized study.

BACKGROUND: Lithium significantly improved seborrhoeic dermatitis symptoms in comparison with placebo. Objectives This randomized controlled trial was designed to show a non-inferiority of 15% (primary end-point) of lithium gluconate 8% ointment compared with ketoconazole 2% emulsion. METHODS: The study population comprised out-patients who had facial seborrhoeic dermatitis for at least 2 months, with moderate to severe erythema and desquamation at inclusion. The primary end-point was complete remission, defined as the disappearance of both erythema and desquamation. The non-inferiority of lithium was assessed on the 95% confidence interval (CI) of the difference between treatments. RESULTS: The intent-to-treat analysis (ITT) involved 288 patients and the per protocol (PP) analysis 269 patients. Treatment groups were comparable at baseline on age, sex, disease duration and symptoms. For the main criterion, the success rate was 52.0% (lithium) vs. 30.1% (ketoconazole) in the ITT population and 53.2% (lithium) vs. 30.7% (ketoconazole) in the PP population. The non-inferiority of lithium was demonstrated with differences of 21.9% (95% CI 10.0-33.7%) and 22.5% (95% CI 10.2-34.8%), respectively, in the ITT and PP population. As the lower limit of the 95% CI was > 0, the superiority of lithium was shown. Lithium also showed better results on other symptoms: burning and dryness. Adverse events were reported by 26.3% (lithium) and 25% (ketoconazole) of patients. CONCLUSIONS: Lithium was 22% more effective than ketoconazole in giving complete remission of seborrhoeic dermatitis, with comparable safety.

Erythromycin-resistance of cutaneous bacterial flora in acne.

Some studies have raised the problem of an increase of bacterial resistance in acne patients. This study was carried out in France, where no previous studies about resistance to erythromycin has been performed, on 40 patients with mild to moderately severe acne. Microbiological samples were obtained by using Williamson and Kligman method. This study showed that the prevalence of bacterial resistance to erythromycin was 95% for Staphylococcus epidermidis strains and 52% for Propionibacterium acnes strains. Resistant strains were more frequent in patients with predominantly inflammatory lesions (papules and pustules). The influence of previous or current treatment with erythromycin was also studied and showed that even patients without any previous use of erythromycin had resistant strains for Propionibacterium acnes (42%). In addition the minimum inhibitory concentrations (MIC) for zinc were evaluated. All the Propionibacterium acnes strains tested were inhibited at concentrations less or equal to 512 mug/ml of zinc. However, zinc combined with erythromycin in vitro did not modify the erythromycin MIC. This first French study on bacterial resistance to erythromycin in acne patients confirms the results of studies performed in other countries.

Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of zinc gluconate versus minocycline hydrochloride in the treatment of inflammatory acne vulgaris.

BACKGROUND: In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne. OBJECTIVE: To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris. METHODS: Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules). RESULTS: This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline). CONCLUSION: Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.

Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes.

BACKGROUND: Common carotid artery intima-media thickness (IMT) progression was compared between 4 years of treatment with nifedipine and diuretic. METHODS AND RESULTS: This study, ancillary to the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), involved nifedipine 30 mg or co-amilozide (hydrochlorothiazide 25 mg and amiloride 2.5 mg) with optional subsequent titration. Among 439 randomized hypertensive patients, 324 had >/=1 year of follow-up (intent-to-treat group), and 242 completed follow-up (until-end-of-study group). Ultrasonography was performed at baseline, 4 months later, and then every year. Central computerized reading provided far-wall IMT, diameter, and cross-sectional area IMT (CSA-IMT). The primary outcome was IMT progression rate (slope of IMT-time regression). Secondary outcomes were changes from baseline (Delta) in IMT, diameter, and CSA-IMT. In the until-end-of-study population, between-treatment differences existed in IMT progression rate (P=0.002), Delta IMT (P=0.001), and Delta CSA-IMT (P=0.006), because IMT progressed on co-amilozide but not on nifedipine. In the intent-to-treat population, treatment differences existed in Delta IMT (P=0.004) and Delta CSA-IMT (P=0.04) but not in IMT progression rate (P=0.09). Patients with >/=2, 3, or 4 years of follow-up showed treatment differences in IMT progression rate (P=0.04, 0.004, 0.007, respectively), Delta IMT (P=0.005, 0.001, 0.005), and Delta CSA-IMT (P=0.025, 0.013, 0.015). Diameter decreased more on co-amilozide than on nifedipine in the intent-to-treat population (P<0.05), whereas blood pressure decreased similarly on both treatments. CONCLUSIONS: A difference in early carotid wall changes is shown between 2 equally effective antihypertensive treatments.

[Per os desensitization in nickel contact eczema: a double-blind placebo-controlled clinico-biological study]. / Désensibilisation per os dans l'eczéma de contact au nickel: étude clinico-biologique en double insu contre placebo.

BACKGROUND: Ingestion of nickel (Ni) has been demonstrated to induce a specific state of tolerance in the guinea pig and mouse. In a pilot study conducted in 10 patients, we demonstrated that per os administration of Ni leads to reduced proliferation of specific lymphocytes and a lower number of responding lymphocytes in blood. The aim of this study was to evaluate the clinical and biological changes induced by the ingestion of Ni in a double-blinded placebo-controlled study. PATIENTS AND METHODS: Patients with nickel contact hypersensitivity were given a capsule of nickel sulfate containing 5 mg Ni (group A) or an identical placebo (group B) once a week for 7 weeks. Clinical criteria were assessed 49 days after study onset: objective measurement of lesion extent and intensity and quantitative patch tests at concentrations 2.4-0.8-0.2 and 0.05 p. 100. Likewise stimulation of specific lymphocyte proliferation and the number of circulating lymphocytes responding to Ni at limit dilutions were determined. RESULTS: Thirty patients with nickel contact eczema were included in the study, 28 women and 2 men. There was no statistical difference between the two groups for the intensity of skin lesions or their clinical course, quantitative patch tests and lymphocyte stimulation tests. Conversely, the number of circulating lymphocytes responding to Ni was significantly lower in group A than in group B at study end (p < 0.05). DISCUSSION: This double-blind placebo-controlled study confirmed that per os nickel can induce a significant reduction in the number of circulating lymphocytes responding to Ni. No other effect could be demonstrated for the clinical and biological parameters studied. These preliminary results should prompt a multicentric controlled trial including a larger number of patients with more severe lesions at inclusion and with a longer treatment duration.

Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy.

UNLABELLED: Alterations of cardiac sympathetic innervation are likely to contribute to fatal outcomes in patients with heart failure. These alterations can be evaluated noninvasively by 123I-metaiodoben-zylguanidine (MIBG) imaging. METHODS: The hypothesis that impaired cardiac sympathetic innervation, as assessed using MIBG imaging, is related to adverse outcomes was tested in 112 patients with heart failure resulting from idiopathic cardiomyopathy. Main inclusion criteria were New York Heart Association classes II-IV and radionuclide left ventricular ejection fraction (LVEF) < 40%. Patients were assessed for cardiac MIBG uptake, circulating norepinephrine concentration, LVEF, peak Vo2, x-ray cardiothoracic ratio, M-mode echographic end-diastolic diameter and right-sided heart catheterization parameters. RESULTS: During a mean follow-up of 27 +/- 20 mo, 19 patients had transplants, 25 died of cardiac death (8 sudden deaths), 2 died of noncardiac death and 66 survived without transplantation. The only independent predictors for mortality were low MIBG uptake (P < 0.001) and LVEF (P = 0.02) when using multivariate discriminant analysis. Moreover, MIBG uptake (P < 0.001) and circulating norepinephrine concentration (P = 0.001) were the only independent predictors for life duration when using multivariate life table analysis. CONCLUSION: Impaired cardiac adrenergic innervation as assessed by MIBG imaging is strongly related to mortality. MIBG imaging may help risk stratify patients with heart failure resulting from idiopathic dilated cardiomyopathy.

[Treatment of adjustment disorder with anxiety: efficacy and tolerance of etifoxine in a double-blind controlled study]. / Traitement du trouble de l'adaptation avec anxiété: évaluation de l'efficacité et de la tolérance de l'étifoxine par un essai en double aveugle contre produit de référence.

Adjustment disorder with anxiety is defined as a clinically significant anxiety that occurs within 3 months after the onset of an identifiable psychological stressor. Recent studies indicate that this disorder is not uncommon and must be quickly identified and treated. However, few therapeutic trials have been done in relation with this disorder. According to the criteria set by DSM IV, 170 patients with a primary diagnosis of adjustment disorder with anxiety have been enrolled in a double blind multicenter controlled trial. Patients were treated for 4 weeks with etifoxine (150-200 mg/d), or buspirone (15-20 mg/d). Also both etifoxine and buspirone show clinical efficacy and safety, the two treatments are not equivalent. The global improvement score and the efficacy index are significantly improved in the etifoxine group. These results show the interest of using etifoxine in the treatment of adjustment disorder with anxiety and should be confirmed by further studies.

Saccharomyces boulardii prevents diarrhea in critically ill tube-fed patients. A multicenter, randomized, double-blind placebo-controlled trial.

OBJECTIVE: To assess the preventive effect of Saccharomyces boulardii on diarrhea in critically ill tube-fed patients and to evaluate risk factors for diarrhea. DESIGN: Prospective, multicenter, randomized, double-blind placebo-controlled study. SETTING: Eleven intensive care units in teaching and general hospitals. PATIENTS: Critically ill patients whose need for enteral nutrition was expected to exceed 6 days. INTERVENTION: S. boulardii 500 mg four times a day versus placebo. MEASUREMENTS AND RESULTS: Diarrhea was defined by a semiquantitative score based on the volume and consistency of stools. A total of 128 patients were studied, 64 in each group. Treatment with S. boulardii reduced the mean percentage of days with diarrhea per feeding days from 18.9 to 14.2% [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.50-0.90, P = 0.0069]. In the control group, nine risk factors were significantly associated with diarrhea: nonsterile administration of nutrients in open containers, previous suspension of oral feeding, malnutrition, hypoalbuminemia, sepsis syndrome, multiple organ failure, presence of an infection site, fever or hypothermia, and use of antibiotics. Five independent factors were associated with diarrhea in a multivariate analysis: fever or hypothermia, malnutrition, hypoalbuminemia, previous suspension of oral feeding, and presence of an infection site. After adjustment for these factors, the preventive effect of S. boulardii on diarrhea was even more significant (OR = 0.61, 95% CI = 0.44-0.84, P < 0.0023). CONCLUSIONS: S. boulardii prevents diarrhea in critically ill tube-fed patients, especially in patients with risk factors for diarrhea.