Validation of bovine hoof slices as a model for infected human toenails: in vitro ciclopirox transungual permeation.

BACKGROUND: Topical therapy has recently been proposed for treating onychomycosis and other nail disturbances. However, the clinical outcome may be limited by the difficulty of active ingredients effectively penetrating the nail plate. Bovine hoof membranes have been widely used to predict in vitro efficacy of drug products in nail diseases. Many studies have compared bovine hooves with human healthy nails, considering the difference between healthy and unhealthy nails to be negligible. OBJECTIVES: To validate bovine hoof slices as a model for human unhealthy nails by investigating the transungual permeation/retention of ciclopirox (CPX) through bovine hoof slices and excised infected human toenails after application of a new film-forming formulation (P-3051). To investigate the ability of CPX to achieve fungicidal concentrations in and through infected toenails. METHODS: A new experimental technique based on a permeation unit allowed analysis by high-performance liquid chromatography of the amounts of CPX permeating through and retained in the membranes. The efficacy index was evaluated as follows: amount of permeated CPX/Trichophyton rubrum minimum inhibiting concentration. RESULTS: Extrapolated CPX flux through bovine hoof slices was about 14-fold higher than through infected human toenails, the difference being mainly due to the fourfold higher thickness of the toenails. In toenails, the CPX efficacy index for T. rubrum was positive (>1·0) soon after P-3051 application. CONCLUSIONS: This study confirms the validity of bovine hoof slices as a model for infected human nails, and suggests a substantial equivalence between the two models. Following P-3051 application, CPX reaches fungicidal concentrations in and through human infected toenails.

Hydrosoluble medicated nail lacquers: in vitro drug permeation and corresponding antimycotic activity.

BACKGROUND: Two nail lacquers, containing ciclopirox (CPX) or amorolfine (MRF), based on water-insoluble polymers are currently considered mainstays of topical treatment of onychomycosis. The present study aimed at evaluating the antimycotic activity of a new water-soluble nail lacquer containing CPX (CPX/sol), easily removable by washing with water and applicable to periungual skin. OBJECTIVES: To compare transungual permeation of CPX with that of MRF in the same hydroxypropyl chitosan-based nail lacquer (MRF/sol) and with a nonwater-soluble reference (Loceryl); Galderma International, La Défense, France), and to evaluate the antimycotic activity of CPX/sol and Loceryl against the most common fungal strains that cause onychomycosis. Methods In vitro drug permeation experiments with CPX/sol, MRF/sol and Loceryl were carried out through bovine hoof slices. Experimental permeates from CPX/sol and Loceryl underwent in vitro susceptibility testing against clinical isolates of dermatophytes, moulds and yeast. Results MRF transungual flux from MRF/sol lacquer was significantly higher when compared with Loceryl. CPX was able to permeate hoof membranes more easily compared with MRF. CPX and MRF concentrations in the subungual fluids collected after application of CPX/sol or Loceryl were sufficient to inhibit fungal growth, with the exception of Candida parapsilosis. Smaller amounts of fluid containing CPX were required for complete inhibition of fungal growth. Efficacy index values were significantly higher for CPX/sol. Conclusions Application of the CPX/sol nail lacquer allows rapid nail penetration of CPX, providing CPX levels sufficient to inhibit fungal growth for a prolonged period of time (30 h) after application of lacquer dose. CPX/sol nail lacquer appeared superior to the market reference Loceryl in terms of both vehicle (hydroxypropyl chitosan) and active ingredient (CPX) as witnessed by its higher efficacy on all nail pathogens.

In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer.

Commercial antimycotic nail lacquers are commonly based on water-insoluble resins. The present study was aimed at evaluating a novel, experimental nail lacquer (P-3051, Polichem SA, Lugano, Switzerland) based on the water-soluble film-forming agent hydroxypropyl chitosan (HPCH). The in vitro permeation of ciclopirox (CPX) from P-3051 and from a commercial, water-insoluble lacquer based on a vinyl resin (Penlac, Aventis Pharma), was investigated using thin membranes obtained from bovine hooves, an accepted model for human nails. Similar CPX permeation fluxes at steady state through the membranes, but significantly different lag times were observed for P-3051 and Penlac, when these were tested as dry films. The formulations thus appeared to influence only the time required by CPX to saturate the membrane, and not the final drug concentration gradient in the membrane. Permeation experiments performed on the same membranes and on hairless mouse skin with P-3051 and with a similar, HPCH-free vehicle (ERV), both tested in liquid form, disproved the possibility that HPCH might act as a permeation enhancer for CPX in either substrate. The possible reasons for the greater efficiency of the HPCH vehicle in terms of CPX transfer from the vehicle itself to the keratin membrane are discussed. This effect might be tentatively attributed to a particular affinity of HPCH for the membrane, resulting in intimate contact and strong adhesion of the HPCH lacquer to the keratin substrate.

Effect of iontophoresis on transcorneal permeation 'in vitro' of two beta-blocking agents, and on corneal hydration.

Purpose of the present investigation was to examine the effect of iontophoresis on permeation of two beta-blocking agents, timolol maleate (TM) and betaxolol hydrochloride (BX) across rabbit corneas in vitro. Continuous or pulsed current of variable intensity and duration was applied, and possible corneal damage due to the electric treatment was assessed by measuring the corneal hydration level. The effect of iontophoresis on corneal permeation of the relatively more hydrophilic TM was much greater than the effect on the more lipophilic BX. It was found that for both drugs the iontophoretically driven transcorneal penetration is governed only by current density and overall time of treatment, irrespective of the type of treatment (single or repeated) and of current (constant or pulsed). For both drugs all significant permeation increases due to iontophoresis were invariably accompanied by a significant increased corneal hydration, indicative of damage to the corneal epithelium. Even if the present in vitro data cannot be extrapolated to an in vivo treatment, they confirm the potential risk associated with ocular iontophoresis.

Combined treatment with haloperidol and trazodone in patients with tic disorders.

The combination of haloperidol and trazodone was evaluated in an open-label trial in 10 patients with chronic tic and Tourette's syndrome. We found a mean reduction of symptoms of 58.9% on the Yale Global Tic Severity Scale, with a statistically significant difference (p < 0.001) between the baseline and endpoint treatment conditions. This approach significantly reduces clinical symptoms, with the advantage of a lower dose of haloperidol than usual, with no side effects reported by the patients.

[Tic disorders in children and adolescents. Clinical and genetic features, comorbidity]. / Disturbo da tic in età evolutiva. Aspetti clinici e genetici, comorbidità.

UNLABELLED: Tic disorders in children and adolescents. Clinical and genetic features, comorbidity. BACKGROUND: Aim of the study is to evaluate the clinical and genetic characteristics of tic disorders, in view of individuating similarities or differences relevant to the prognosis among different nosological groups. METHODS: A retrospective study of 79 children and adolescents (average age 9.3 yrs) was performed. The cases were diagnosed according to DSM-IV as: transitory tics (TT) 13 cases; chronic tics (CT) 50 cases; Tourette disease (TD) 16 cases. They were compared to a control group of 18 school age children without any neurological or psychiatric disturbance. The study included: semi-structured interviews focused on natural history of the disturbances, familiarity, presence of perinatal pathology, comorbidity; neurological examination, EEG, psychodiagnostic tests and investigation. RESULTS: Mean age of onset and type of first symptoms are the same in the three groups. Compared to the control group there is a significant increase in: familiarity for tics disturbances in TD; presence of perinatal pathological factors in the three groups of patients; comorbidity for obsessive-compulsive disorder (OCD) in CT and TD, comorbidity with ADHD in CT group. Three clinical cases are reported to exemplify the mixed features in the families and the different responsivity to the pharmacological treatment.

[Adolescents with scoliosis: psychological and psychopathological aspects]. / Adolescenti con scoliosi: aspetti psicologici e psicopatologici.

BACKGROUND: The present study focuses on psychological and psychopathological aspects in children and adolescents with scoliosis. METHODS: The case series included 28 subjects with scoliosis (7 males, 21 females; range 9-25 years; mean age 15.8 years) admitted to the Dept. of Orthopaedics of Gaslini Institute and referred to our observation. Psychological approach included semi-structured interviews focused on the evolution of scoliosis and based on questions about consciousness of illness, family and patient emotional reactions during treatment; familial, social and school adaptation; body image; onset of psychopathological disorders. Family relational and educational attitudes were also considered. The following psychological tests were also performed: Raven Progressive Matrices; "Draw-a-Person" test; Sacks' battery of incomplete sentences to evaluate cognitive aspects, body image, familial and social relationships, interactive aspects. RESULTS: During adolescence consciousness of illness appeared concomitantly with the beginning of treatment. Most subjects presented intellectual-relational compensation strategies, but in a reasonable number of cases they showed insecurity and inferiority feelings. On a conscious level, body image appeared normal in most cases, but unconsciously (in 45% of cases) there were anguish aspects related to feelings of body deterioration. During long-term treatments anxious reactions, sometimes temporary, (in 36% of cases) and depressive aspects (in 9% of cases) were observed. CONCLUSIONS: The results obtained stress the importance of the family and the medical staff in providing a reassuring and firm support, in order to face difficulties related to the patient's illness.

Long-term outcome of children and adolescents with anorexia nervosa: study of comorbidity.

Eighty-seven children and adolescents with anorexia nervosa, admitted to the Gaslini Department of Child Neurology and Psychiatry between 1976 and 1990, were followed up after a mean of 9.6 years. Outcome measures included the Morgan Russell Outcome Schedule as modified by Jeammet. Outcome was good in 43 (53%) cases, intermediate in 27 (34%) cases, and negative in 11 (14%) cases. No deaths occurred. Based on the Jeammet assessment schedule, the most significant items predicting outcome were insight; sexual, familial, and social relationships; and mental state. Gender of patients and early disease onset did not seem to be predictive measures. Poor outcome was associated with a severe initial clinical picture and length of in-patient treatment. In regard to comorbidity, mood and personality disorders seemed to be negative prognostic indicators, whereas anxiety disorders did not show prognostic value.

[Juvenile fibromyalgia syndrome: 2 clinical cases]. / Sindrome fibromialgica giovanile: due casi clinici.

We report two cases (F. 11 years, M. 7 years) with juvenile fibro-myalgic syndrome, diagnosed because of the presence of musculo-skeletal pain, tender points and associated symptoms, and after exclusion of any other known etiology. Both patients improved after treatment with antidepressant serotoninergic (amitriptyline, trazodone).

[Suicidal behavior among adolescents]. / Comportamenti suicidari negli adolescenti.

Some data from the literature on adolescent suicidal behaviour are reported: incidence, employed methods, warning signs, risk factors, some psychodynamic aspects. The purpose of this work is to contribute to the study on this matter by a research on 33 adolescents (12 males, 21 females: mean age 14 years, range 11.2-17 years) examined because of suicidal behaviour. The study method includes: anamnesis, psychodiagnostic inquiry, family and environmental investigation, psychiatric evaluation. Suicidal behaviour is characterized by low levels of determined self-elimination intent ("suicidal gestures") in 36% of cases (1 male, 11 females). Relapses are found in 35% of cases, with death in 1 case. The most frequently used methods is drug poisoning (65%). Most common place where suicidal behaviour takes place is at home (82%). Most show warning signs especially verbal threats. Some problem in the family situation (conflicts in the parental couple or between parents and children, psychopathologic disturbances in the parents) and frequent difficulties in school and social adjustment are evident. In 45% a depressed state was noted, in the other cases several psychopathologic disturbances have been found: hysteric neurosis, borderline personality, psychosis. In 30% of cases symptoms coexist with a self-injuring meanings (nervous anorexia, pseudo-epileptic seizures). Prevalent psychodynamic characteristics are: vulnerability in facing frustrating situations and research of support from inadequate parental figures: displacement from hetero-direct aggressive drives to an expiratory or revengeful self wounding behaviour. Some criteria for an emergency care and for a middle to long term treatment are mentioned, and the opportunity for collaboration between pediatricians and psychotherapists is suggested.

[Early autism and congenital muscular dystrophy: a clinical case]. / Autismo precoce e distrofia muscolare congenita: un caso clinico.

The authors describe the case of a twelve-year-old patient presenting early autism associated with congenital muscular dystrophy--subtype IV, according to the subclassification of Fukuyama (slight mental retardation, ability to walk, muscle pseudohypertrophy). To our knowledge, this association has never been reported. Several factors may have played a causative role in the development of an autistic disorder in the patient. The authors suggest the following as the most significant ones: disharmonious personality, weak emotional structure, inadequate primary relation with the mother, poor environmental influences, frustrations encountered because of the muscular disorder.

[Children and adolescents with epilepsy. Cognitive abilities, learning disorders and depression]. / Bambini e adolescenti con epilessia. Abilità cognitive, disturbi di apprendimento, depressione.

The authors studied some psychological and psychopathological problems in epileptic children and adolescents. 47 cases (range 6.6-16 ys), with well controlled seizures and learning difficulties, have been examined and compared with 80 children and adolescents with learning disorders. The analysis of anamnestic data about early minimal brain damage (MBD) differentiated 4 groups: with an without epilepsy, with and without MBD. Psychodiagnostic evaluation showed: normal cognitive abilities and sectorial neuropsychological dysfunction connected with MBD, more evident if epilepsy is associated with MBD. Depression is frequently noticed: 74% of epileptic patients, 52% of non-epileptic patients. The depression symptoms are similar in these 2 groups and above all sustained by psychogenic pathogenesis. The authors conclude with a critical reflection on prejudices regarding children and adolescents with epilepsy.

[Language disorders in children: diagnostic, pathogenetic and developmental aspects]. / Disturbi del linguaggio nell'infanzia: aspetti diagnostici, patogenetici ed evolutivi.

Several Authors report the pathogenetic factors of developmental language disorders, some clinical features, the evaluation criteria, the treatment prospects aimed also at learning disorders. 163 children with language disorders have been examined: M98, F65; range 2.8-6.2 ys, mean 5.1 ys. The study of verbal comprehension and production and the evaluation of cognitive level, of language function, of communicative abilities, of handedness was performed. The diagnostic evaluation results: uncomplicated language retardation (31.2%), developmental dysphasia (7.4%), acquired aphasia (0.6%), dysphasia/cognitive retardation (36.8%), language retardation/deafness (10.4%), stuttering (6.8%), relational disorders (6.8%). The pathogenetic features are the following: organic factors (early brain damage 51%, early otopathies 10%), environment factors (24%, partly as joined factors), emotive disorders (11%), familiarity (10%), no determinable etiology (2%). The Author remarks some therapeutic strategies and evolution prospects of the different language disorders. In order to attain early diagnosis and treatment it seems advisable to increase cognitive-linguistic examination in preschool age and to start rehabilitation services at nursery-school.

[Anorexia nervosa in adolescents. Clinical aspects of the diagnosis and a follow-up]. / Anoressia mentale in età evolutiva. Aspetti clinici alla diagnosi e ad un follow-up.

In a brief review of the literature, the diagnostic, prognostic and therapeutic criteria of anorexia nervosa in adolescence are considered. An interdisciplinary approach (child neuropsychiatrists, clinical psychologists, auxological pediatricians) was adopted in 52 cases with a diagnosis of anorexia nervosa (46 females, 6 males; mean age 14). The results of the analysis of somatic disturbances (weight loss, anomalous sexual maturation), psychological aspects (cognitive level, organization of the personality), environmental implications (familial, social and school adjustment; mother-child relationship; pedagogic modalities; social and economic factors) are reported. The data from a follow-up of 29 patients (26 females, 3 males; mean age 19) are reported, and the degree of recovery assessed as follows: 1) clinical recovery at somatic-adjustment level (79% complete, 17% with atypical characteristics); 2) achievement of a harmonic organization of the personality (48%). The paper concludes with some remarks on the treatment, prognosis and prospects for prevention of the condition.