[A new treatment for androgenetic alopecia : platelet-rich plasma injections]. / Un nouveau traitement de l'alopécie androgéno-génétique : les injections dans le cuir chevelu de plasma riche en plaquettes (PRP) autologue.

Androgenic alopecia is a genetically determined and leads to a progressive hair loss of the vertex, affecting both men and women. It is related to an important psychological and social distress. Medical therapies include topical minoxidil, oral 5?-reductase inhibitors and oestroprogestative drugs with anti-androgen effects for women. The surgical option is autograft hair transplantation. Recently, phototherapy with low-level energy lasers became available. All these treatments may present adverse effects and their effectiveness is questionable. Subcutaneous injections of autologous platelet-rich plasma into the scalp represent an interesting alternative treatment for androgenetic alopecia, as monotherapy or as an adjuvant treatment. The methodology, the possible mechanisms of action and some initial clinical results of this treatment are presented.

L'alopécie androgéno-génétique se manifeste par une perte progressive des cheveux du sommet du cuir chevelu, touchant aussi bien l'homme que la femme. Ses impacts sociaux et psychologiques négatifs sont souvent très importants. Elle peut se traiter par des médicaments (minoxidil topique, inhibiteurs de la 5?-réductase per os, oestroprogestatifs à visée anti-androgénique chez la femme), par des techniques chirurgicales d'autogreffes capillaires, ou encore, par photothérapie avec des lasers de basse énergie. Tous ces traitements ne sont pas dénués d'effets indésirables et leur efficacité n'est pas constante. Les injections sous-cutanées de plasma riche en plaquettes autologue dans le cuir chevelu peuvent constituer un traitement efficace de l'alopécie androgéno-génétique, en monothérapie ou comme adjuvant. Les modalités techniques, les modes d'action potentiels et les principaux résultats cliniques obtenus à ce jour sont présentés.

High-resolution array-CGH analysis on 46,XX patients affected by early onset primary ovarian insufficiency discloses new genes involved in ovarian function.

STUDY QUESTION: Can high resolution array-CGH analysis on a cohort of women showing a primary ovarian insufficiency (POI) phenotype in young age identify copy number variants (CNVs) with a deleterious effect on ovarian function? SUMMARY ANSWER: This approach has proved effective to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms. WHAT IS KNOWN ALREADY: POI describes the progression toward the cessation of ovarian function before the age of 40 years. Genetic causes are highly heterogeneous and despite several genes being associated with ovarian failure, most of genetic basis of POI still needs to be elucidated. STUDY DESIGN, SIZE, DURATION: The current study included 67 46,XX patients with early onset POI (<19 years) and 134 control females recruited between 2012 and 2016 at the Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano. PARTICIPANTS/MATERIALS, SETTING, METHODS: High resolution array-CGH analysis was carried out on POI patients' DNA. Results of patients and female controls were analyzed to search for rare CNVs. All variants were validated and subjected to a gene content analysis and disease gene prioritization based on the present literature to find out new ovary candidate genes. Case-control study with statistical analysis was carried out to validate our approach and evaluate any ovary CNVs/gene enrichment. Characterization of particular CNVs with molecular and functional studies was performed to assess their pathogenic involvement in POI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 37 ovary-related CNVs involving 44 genes with a role in ovary in 32 patients. All except one of the selected CNVs were not observed in the control group. Possible involvement of the CNVs in POI pathogenesis was further corroborated by a case-control analysis that showed a significant enrichment of ovary-related CNVs/genes in patients (P = 0.0132; P = 0.0126). Disease gene prioritization identified both previously reported POI genes (e.g. BMP15, DIAPH2, CPEB1, BNC1) and new candidates supported by transcript and functional studies, such as TP63 with a role in oocyte genomic integrity and VLDLR which is involved in steroidogenesis. LARGE SCALE DATA: ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/); accession numbers SCV000787656 to SCV000787743. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis for almost all of the CNVs identified. Inheritance studies of CNVs in some non-familial sporadic cases was not performed as the parents' DNA samples were not available. Addionally, RT-qPCR analyses were carried out in few cases as RNA samples were not always available and the genes were not expressed in blood. WIDER IMPLICATIONS OF THE FINDINGS: Our array-CGH screening turned out to be efficient in identifying different CNVs possibly implicated in disease onset, thus supporting the extremely wide genetic heterogeneity of POI. Since almost 50% of cases are negative rare ovary-related CNVs, array-CGH together with next generation sequencing might represent the most suitable approach to obtain a comprehensive genetic characterization of POI patients. STUDY FUNDING/COMPETING INTEREST(S): Supported by Italian Ministry of Health grants 'Ricerca Corrente' (08C203_2012) and 'Ricerca Finalizzata' (GR-2011-02351636, BIOEFFECT) to IRCCS Istituto Auxologico Italiano.

[Vitamin D anti-cancer activities: observations, doubts and certainties]. / LES ACTIVITÉS ANTI-CANCÉREUSES DE LA VITAMINE D: les observations, les doutes et les certitudes.

The importance of vitamin D in bone and phosphocalcic status is well recognized by the scientific and medical communities; however, recently identified properties of this cholesterol derived molecule, such as immunomodulator and anticancer activities, are yet discussed. Actually, the debate is not so much about the new vitamin D properties, but rather about the optimal concentration required to reach these properties. The difficulty in determining the norms is rendered even more complex by the existence of a vitamin D receptor gene polymorphism. The body pool of this vitamin depends essentially on its endogenous synthesis, but also on its dietary intakes. Many epidemiological studies interested in Vitamin D serum level and cancer suggest a relation between low Vitamin D level and cancer risk, especially in breast and colon adenocarcinomas. In vitro, many studies showed, in different human and animal malignant cell lines, that this molecule exerts anticancer activities: it induces apoptosis and cell differentiation as well as it inhibits proliferation and angiogenesis. This review tries to update the current knowledge on vitamin D and, more particularly, the potential interest of this molecule in cancer prevention and management.

Herpes zoster in patients treated with biologicals.

BACKGROUND: The incidence and severity of herpes zoster (HZ) appear increased in patients receiving tumor necrosis factor-α antagonists. OBJECTIVE: To study the incidence and clinical features of HZ in 1,220 patients (4,206 patient-years) receiving either adalimumab, etanercept, infliximab, rituximab or ustekinumab. RESULTS: Twenty-two HZ cases were identified [1.26% of total cohort; adalimumab: 11/1,546 patient-years, incidence rate (IR) 7.1; etanercept: 4/789 patient-years, IR 5.1; rituximab: 1/168 patient-years, IR 5.2; ustekinumab: 2/37 patient-years, IR 53.5; infliximab: 4/1,666 patient-years, IR 2.4]. The time to event varied widely (1.5- 108 months). Extensive HZ was reported in 45 and 32% of the cases, respectively. Persistent postzoster neuralgia (PHN; >6 months) was observed in 5/20 patients. CONCLUSIONS: The HZ incidence was 2.1-fold higher among patients over 60 years, compared with a reference population, although not statistically significant. Severe, multidermatomal HZ and persistent PHN were common.

Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems.

Although the interaction between sleep and pain is generating considerable interest (NIH Technology Assessment Panel, 1996), it is still unknown if chronic pain is the cause or effect of poor sleep. To further this understanding, subjects free of pain and sleep problems need to be studied in order to assess their response to pain during sleep, defined as a behavioral and a physiological state in which sensory processing is altered. (For example, while auditory perception remains active, other sensory inputs are facilitated, attenuated, or suppressed (Velluti, 199746 degrees C) was statistically greater in the lighter sleep stage 2 (48.3%) than in the deeper stages 3&4 (27.9%). A nocifensive behavioral-motor response was associated with only 2.5% of the 351 heat pain stimuli. Two other markers of sleep quality-sleep stage shift and awakening-were not influenced by the thermal stimuli. None of the subjects demonstrated any burns in the morning following the thermal stimulations applied during sleep. We conclude that the processing of nociceptive inputs is attenuated across sleep stages.

Structured psychiatric interview and ambulatory sleep monitoring in young psychophysiological insomniacs.

BACKGROUND: The presence of psychiatric disorders (according to DSM-III-R), the discriminating power of a psychiatric structured interview, and sleep monitoring were investigated in psychophysiological insomnia. METHOD: Forty young (20-40 years old) patients, selected for putative psychophysiological insomnia, underwent a psychiatric structured interview and home ambulatory sleep monitoring for 2 nights. The results were compared with those of a group of nine young normal sleepers. RESULTS: 48% of the insomniacs showed some psychiatric disorders, while 52% did not meet DSM-III-R criteria for a psychiatric diagnosis. Both groups, but not the controls, showed a slight first-night effect in the sleep analysis. The sleep structure of all insomniacs was found to be disturbed, mainly in sleep continuity, but essentially the two groups showed no significant differences. When we used a stepwise logistic regression analysis, the number of sleep stage shifts (indicating sleep instability) was the best variable in discriminating the insomniacs from controls, but not the patients with psychiatric disturbances from those without psychopathologies. CONCLUSION: The evaluation of young insomniacs with a structured psychiatric interview rather than with ambulatory sleep monitoring seems to be most useful in discriminating between patients with only psychophysiological insomnia and patients with both insomnia and an associated diagnosis of another mental disorder.

Physiological and behavioral responses to minor stressors in offspring of patients with panic disorder.

Nineteen children born to patients with panic disorder and a comparison group of 16 children born to unaffected, non-psychiatric patient subjects exposed to novel and mildly stressful situations (visiting an unfamiliar place and watching a movie containing anxiogenic scenes) were assessed for their behaviors, heart rate, respiratory rate and salivary cortisol secretion. At arrival children born to patients with panic disorder had significantly longer latency of first spontaneous verbal comment, fewer prosocial behavior, and increased distress and attachment behavior. During the projection of the movie, children of the two groups differed for attachment, distress, and exploration behaviors. During the anxiogenic scenes children born to patients with panic disorder showed increased behavioral inhibition and higher heart rate. Autonomic modulation, respiratory rates and cortisol secretion were similar in the two groups. Some distinct psychophysiological patterns may constitute early manifestations of the transmitted liability to panic disorder.

EEG arousal pattern in habitual snorers with and without obstructive sleep apnoea (OSA).

This study evaluated the arousal pattern and sleep fragmentation in the sleep microstructure of heavy snorers and obstructive sleep apnoea (OSA) patients. Fifteen snorers [Group A, (A + H I) 10 30) were studied retrospectively analysing the number, duration and type of arousals according to scoring rules concerning definition (including delta bursts) and length (from 2 to 60 s) of phasic arousal events. The number of arousals per hour of sleep related to respiratory events was higher in Groups B and C, whilst in Group A there was a number of arousals not related to apnoea or hypopnoea. Daytime sleepiness, present in all three groups and measured by a subjective evaluation, correlated with both the number and EEG type of arousal, but not with the duration. Statistical analysis indicated that arousal index related to apnoea or hypopnoea was the best variable for determining the sleepiness risk in OSA and snorers. Sleep microstructure analysis seems a good scoring method for the detection of sleep fragmentation and arousals in relation to abnormal respiratory events.

Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP).

The aims of this study were to assess cognitive function in obstructive sleep apnea (OSA) patients and to evaluate the effect of short- and long-term treatment with continuous positive airway pressure treatment (CPAP). A battery of neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck Inventory Scale were administered to 23 patients with severe OSA (age: 56.5+/-6.13; AHI: 54.9+/-13.37) and to 23 age- and education-matched controls. The OSA patients were evaluated in a baseline condition and in two follow-up treatment sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA patients had a significant impairment, compared to controls, in tests of sustained attention, visuospatial learning, executive function, motor performance, and constructional abilities. The longitudinal evaluation showed that after a 15-days CPAP treatment attentive, visuospatial learning, and motor performances returned to normal levels. A 4-months CPAP treatment did not result in any further improvement in cognitive tests. Performance on tests evaluating executive functions and constructional abilities was not affected by short- and long-term treatment with CPAP. The findings of this study confirm the hypothesis of partial reversibility of cognitive dysfunction in OSA patients after CPAP.

Validity of diurnal sleep recording performed by an ambulatory device in the diagnosis of obstructive sleep apnoea.

The objective of this study was to compare the results of oxygen desaturations and sleep apnoea during a daytime nap (D) versus nocturnal sleep (N) evaluation, recorded by a portable multichannel monitoring device in patients with a clinical suspicion of obstructive sleep apnoea (OSA). Two polysomnographic studies were performed, by means of the Healthdyne NightWatch System, in 82 subjects (mean age 57.9 years). No difference was found in the apnoea + hypopnoea index (AHI) and mean SaO2 between D and N recordings. At an AHI threshold of 20, in the D recordings, compared to the N ones, the sensitivity was 91% and the specificity 100%. A good correlation was found for AHI and oxygen desaturation index (ODI) between the two experimental conditions (r = 0.89 and 0.79, respectively). Our study shows that D recordings seem to be accurate for OSA diagnosis in the majority of patients with a clinical suspicion of sleep apnoea syndrome.

Triazolam and melatonin effects on cardiac autonomic function during sleep.

After benzodiazepine (BDZ) administration, a decrease in cardiac vagal tone has been described during wakefulness, but data on cardiac autonomic function during sleep are lacking. Melatonin (MLT), reported to have hypnotic properties, caused an increase in vagal tone in animals. The aim of this study was to evaluate heart rate (HR) variability during sleep after a single bedtime dose of triazolam (TRI, 0.125 mg) and MLT (100 mg) in six healthy young subjects. We evaluated tonic (vagal activity) HR modifications in relation to sleep as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during rapid-eye-movement (REM) and non-REM (NREM) sleep. No significant change in sympathetic activity was observed after TRI and MLT in comparison with placebo, whereas TRI caused a significant decrease in vagal tone during sleep. Our nocturnal study seems to confirm previous diurnal findings about a decrease in vagal tone by BDZs.

Epidemiology of obstructive sleep apnea syndrome.

The association of obstructive sleep apnea (OSA) syndrome with obesity, hypertension and cardiovascular disease has highlighted the broad public health importance of this condition. OSA affects at least 9% to 15% of middle-aged adults. Both epidemiological and sleep clinic-based studies indicate that OSA is more common in men than in women. However, the ratio of men to women with OSA in clinical studies appears to be considerably higher than in the community: up to 8:1 versus 2 to 3:1. Cross sectional studies on OSA prevalence showed effects of age, independently from the unfortunate propensity for a rising body mass index (BMI) with age: an approximate doubling of apnea-hypopnea index (AHI) every 10 years has been reported. A recent prospective study with 4-year follow-up showed that a 10% weight gain predicted a 32% increase in AHI, whereas a 10% loss in weight predicted a 26% decrease in AHI. Another 5-year prospective study found that longitudinal change in AHI varies nonuniformly with age, sex and weight: older heavier may experience the highest rate of AHI increase over time and, thus, may benefit most from prospective monitoring.

Effects of continuous positive airway pressure on cognitition and neuroimaging data in sleep apnea.

Obstructive sleep apnea (OSA) has been associated with a broad range of neurocognitive difficulties. The current view is that the neurocognitive impairment in OSA is due to the adverse effects of sleep fragmentation and/or intermittent hypoxia. The overall picture of cognitive deficits in OSA is complex. On balance, there appears to be negative effects of OSA on cognition, most likely in the domains of attention/vigilance, verbal and visual delayed long-term memory, visuospatial/constructional abilities, and executive dysfunction. Continuous positive airway pressure (CPAP) is the most effective and widely used treatment of OSA. In the majority of studies of OSA patients treated with CPAP, attention/vigilance improved, but changes in global functioning, executive functioning, and memory improved in about half of the studies. This may be due, in part, to variability in study design and sampling methodology across studies. Structural volume changes have been demonstrated in brain regions of OSA patients including areas that regulate memory and executive function (e.g., frontal cortex, anterior cingulate, and hippocampus). Growing evidence suggests that the OSA-related changes in brain morphology may improve with CPAP treatment. Neuroimaging studies performed during cognitive testing have provided insight into CPAP's effect on function of neuroanatomical circuits in the brain. Although neuroimaging can provide important insights into the structural and functional differences associated with OSA, one of the challenges is to interpret the findings in light of comorbid conditions that also cause neural injury. The purpose of this article is to provide a narrative review of the publications on cognition and neuroimaging in OSA before and after CPAP treatment.

Viral infections of the pubis.

There are no demographic data published on those with viral infections of the pubis (VIPs). We conducted a two-year prospective study to collect demographic information on patients with VIPs. Data were gathered on age, sex, diagnosis, low (≤10) or high (>10) lesion number, symptoms, how the patient discovered the lesions, localization, lesions beyond the pubis, risk factors, shaving habits, human papillomavirus (HPV) vaccination status and treatment. In a total of 61 patients, molluscum contagiosum (MC) was identified in 71%, condylomata acuminata (CA) in 11%, concomitant MC and CA infections in 11% and herpes simplex virus (HSV) infection in 4.8%. Shaving represented a risk factor for a high lesion number, but not for the extension beyond the pubis. MC, CA and HSV infections affecting the pubis are uncommon and often asymptomatic. As they may represent a hidden source of infection we recommend thorough inspection of the pubis during routine skin examination.

[The Cri du Chat syndrome: a study on the quality of care]. / Sindrome del Cri du Chat: indagine sulla qualità dell' assistenza.

AIM: The Cri du Chat syndrome (SCdC / [OMIM #123450]) is a rare disease characterized by the deletion of the short arm of chromosome 5. The typical clinical features are the cat-like cry, microcephaly, a distinct facial phenotype and a severe psychomotor and mental retardation. The aim of this study was to provide an analysis on the data concerning the life quality and families assistance to whom have a child affected by Cri du Chat syndrome such as: the life's change of parents after the child's birth, the frequency of treatments, the collaboration between family and center of reference. METHODS: We have also analyzed the improvement obtained, the type of school attended, the aide and the time spent at home in postprimary education. Through a questionnaire sent to 100 families, we have been picked up information on 76 patients. RESULTS: These families have to adapt to the reality of a child with a rare genetic disorder for which there are no pharmacological or surgical therapies. CONCLUSION: Therefore, it seems important to give information and tips for dealing with the disease and the early start of rehabilitation and educational therapy.

Nocturnal frontal lobe epilepsy misdiagnosed as sleep apnea syndrome.

Some clinical features as the awakenings with feeling of choking, the abnormal motor activity during sleep and the excessive daytime sleepiness are relatively common both in obstructive sleep apnea syndrome and in nocturnal frontal lobe epilepsy. In these cases, a full-night video-polysomnographic monitoring is of the utmost importance to provide a differential diagnosis between the two conditions, and to verify, in the case of the co-existence of the two disorders, which is the one responsible for sleep disruption. In the present case reports, we described 2 patients referred to our Sleep Disorders Center with the above mentioned clinical features and with a previous clinical diagnosis of obstructive sleep apnea syndrome. After the recording of them, by means of full-night video-polysomnography, they were both diagnosed as having nocturnal frontal lobe epilepsy as the main sleep disorder and then successfully treated with carbamazepine.

Craniofacial modifications in children with habitual snoring and obstructive sleep apnoea: a case-control study.

Habitual snoring and obstructive sleep apnoea in children, which are frequently associated with adenotonsillar hypertrophy, may begin early in life and in relation with orocraniofacial features. The aim of this study was to detect the presence of early bone craniofacial modifications in young children with a long history of habitual snoring. Twenty-six habitually snoring children (mean age 4.6 yrs) were studied by nocturnal portable recording or diurnal polysomnography, cephalometry and orthodontic evaluation. A comparison of cephalometric findings was made between the studied group and 26 age-matched children (mean age 5.1 yrs) with no history of snoring or respiratory problems during sleep. The cephalometric analyses showed a significant increase in craniomandibular intermaxillar, lower and upper goniac angles with a retroposition and posterior rotation of the mandible (high angle face) and a reduction in the rhinopharynx space caused by higher thickness of adenoids in habitually snoring children compared with controls. Cross-bites and labial incompetence as well as daytime symptoms and familiarity for habitual snoring were found in most of the studied group of snorers compared with controls. The results indicate that upper airway obstruction during sleep is associated with mild but significant cephalometric and craniofacial modifications in children complaining of habitual snoring. Whether this skeletal conformation is genetically determined or influenced by the early onset of habitual snoring remains to be assessed.