Pediatric Nail Disorders.

Background: Pediatric nail disorders encompass a broad range of conditions. This article aimed to consolidate current knowledge on pediatric nail disorders to enhance diagnostic proficiency and clinical management among healthcare professionals. Summary: Pediatric nail disorders present a diagnostic challenge due to their diverse nature. Non-syndromic congenital nail disorders encompass various anomalies such as anonychia/hyponychia, congenital malalignment of the great toenail, and racket thumbs, each with distinct clinical presentations and genetic associations. Syndromic congenital nail disorders, often part of complex syndromes, are characterized by unique features and associated abnormalities. Acquired nail diseases in children, like Beau's lines and onychomadesis, typically result from trauma or infection, while melanonychia, although rare in children, requires careful monitoring for potential malignant alterations, with consideration for biopsy in cases with concerning features. Key Messages: (1) Pediatric nail disorders may pose diagnostic challenges and require a comprehensive understanding of nail anatomy and development. (2) Congenital nail disorders encompass isolated anomalies and syndromic associations, necessitating thorough evaluation for associated systemic conditions. (3) Acquired nail diseases may indicate underlying trauma or systemic illness and require careful assessment.(4) Melanonychia in children requires ongoing monitoring and evaluation, emphasizing the importance of consistent follow-up and histopathological examination when necessary.

Trichoscopy of Discoid Lupus Erythematosus in Caucasian Scalp: A Review.

Background: Scalp discoid lupus erythematosus in Caucasians is still a rare disease with a variable clinical presentation. Its dermoscopic characteristics are poorly described in literature, especially in the white population. The aim of this review was to critically analyze published papers on this topic and summarize relevant features. Summary: A comprehensive search for eligible articles was conducted in the databases of MEDLINE/PubMed. Results were analyzed following dermoscopic patterns such as follicular openings, hair shafts, perifollicular surface, and vessel pattern. Key Messages: The most representative features appeared the absence of follicular openings and the presence of follicular keratotic plugs, along with yellow-brown and red dots. In long-lasting lesions with chronic stage, trichoscopy showed the absence of follicular openings, white or milky red cicatricial patches, white and brown structureless areas, and thick arborizing vessels.

Symmetrical cutaneous rash in two women.

Symmetrical drug-related intertriginous and flexural exanthema, commonly known as "baboon syndrome" due to its typical involvement of the gluteal area, is an erythematous symmetrical rash associated with systemic drug administration.

Dermoscopic Nail Changes in Psoriasis, Lichen Planus, and Lichen Striatus.

Background: Onychoscopy is a noninvasive method helpful in diagnosing nail disorders. The aim of the study was to review literature on the usability of onychoscopy in nail psoriasis, nail lichen planus, and nail lichen striatus. Summary: Onychoscopic features of nail psoriasis are pitting, onycholysis with erythematous border, salmon patches, splinter hemorrhages, dotted vessels in lateral and proximal folds, and hyponychium. Onychoscopic features of nail lichen planus are onychorrhexis, onycholysis, longitudinal melanonychia, and red lunula. The literature on the usability of onychoscopy in nail lichen striatus is scarce. Keynotes: Onychoscopy facilitates evaluation of nail abnormalities compared to the clinical examination. Lunular alterations, salmon patches, erythematous border of onycholysis as well as splinter hemorrhages in nail psoriasis are better visualized with onychoscopy compared to the naked eye. Onychoscopy enhances detection of melanonychia, dyschromia, and lunular changes in nail lichen planus. Onychoscopic features are different in fingernails and toenails.

Onychoscopy (nail dermoscopy) is a noninvasive method used in diagnosing of nail disorders. In this review, we evaluated if onychoscopy may be helpful in diagnosing inflammatory nail disorders such as psoriasis, lichen planus, and lichen striatus. Nail psoriasis can be characterized with the presence of pitting, salmon patches, splinter hemorrhages, onycholysis with or without erythematous border and dilated vessels in the hyponychium on onychoscopy. Onychoscopy of nail lichen planus shows the presence of longitudinal ridging and splitting (onychorrhexis), splinter hemorrhages, longitudinal melanonychia as well as red lunula (distal part of nail matrix). The data on onychoscopy in nail lichen striatus are scarce. Onychoscopy is a helpful tool in visualization of nail abnormalities, with most of the features better visualized with onychoscopy compared to the naked eye.

Nails Involvement in Winiwarter-Buerger Disease.

Introduction: Buerger disease, or thromboangiitis obliterans, is an inflammatory and occlusive process involving small and medium size arteries and veins, which generally affects the lower limbs of young adult male with the habit of smoking. Case Presentation: This paper reports 2 patients who developed nail lesions as the first sign of Buerger disease. Conclusion: Signs and symptoms of Buerger's disease are secondary to the inflammatory process and arterial occlusion which results in severe ischemia. Involvement of nails is not common, but we found 2 different clinical features which have not been previously reported in the literature: chronic paronychia, and proximal leukonychia or onycholysis and nail bed erosion.

Branching Dilated Vessels: A Possible Trichoscopic Clue for Diagnosis of Erosive Pustular Dermatosis of the Scalp in Children.

Introduction: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory scalp condition that usually affects the elderly, while only few cases have been reported in childhood. In children, it may mimic fungal or bacterial infections, especially kerion. Case Presentation: We describe the usefulness of trichoscopy as a supportive diagnostic tool in 2 cases of pediatric EPDS. Discussion: Clinical distinction between EPDS and different types of alopecia in children is difficult, with a significant likelihood of diagnostic errors and delay in therapy. Trichoscopy may provide a noninvasive option that can help avoid invasive diagnostic procedures in children.

Recurrent Onychomadesis of the Toenails in Children and Adults: A Case Series.

INTRODUCTION: Onychomadesis occurs when the nail plate separates from the nail matrix and nail bed, eventually leading to shedding of the nail. This condition has been attributed to viral infections, autoimmune disorders, drug side effects, and physical trauma. A subset of patients has a recurrent form of onychomadesis without a clear trigger; this phenomenon is not well characterized in the literature. CASE PRESENTATION: We present a case series of pediatric and adult patients with recurrent toenail onychomadesis in order to better characterize the disorder and explore possible etiologies, risk factors, and treatments. DISCUSSION/CONCLUSION: For the cases herein, we propose microtrauma associated with footwear as the underlying etiology given the periodicity of nail shedding, exclusion of other etiological factors, and presence of predisposing risk factors in certain patients. Many patients saw improvement with application of urea 40% cream, suggesting this can be a valuable part of a treatment strategy, in addition to minimizing injury to involved digits.

Trichodynia Revisited.

Trichodynia refers to the painful sensation of the scalp related to the complaint of hair loss. Originally suggested to be distinguishing for telogen effluvium and related to hair loss activity and follicular inflammation, further studies have found trichodynia to be common in androgenetic alopecia as well and coexisting with psychopathologic findings. The respective studies failed to demonstrate correlations between trichodynia and quantifiable hair loss activity, nor histopathologic evidence for follicular inflammation. A symptomatic scalp is a frequent condition in specific dermatological conditions of the scalp. By definition of exclusion, we are not dealing with trichodynia in these cases. It is conceivable that neuropeptides are key players between the central nervous system and the skin immune and microvascular system. Such mechanisms would explain the noxious effects of both external stimuli and emotional distress in eliciting cutaneous nociception. Since we have begun to understand the diverse etiologies of trichodynia, and a single term does not measure up to this circumstance, it may be wiser to describe the condition depending on the type of scalp sensation and its specific disease association. Further studies are warranted into the neural/endothelial/follicular interactions both in hair growth and shedding and the psychosomatic diseases of the hair and scalp.

2D-QSAR and 3D-QSAR/CoMFA analyses of the N-terminal substituted anthranilic acid based CCK(1) receptor antagonists: 'Hic Rhodus, hic saltus'.

A research is presented on quantitative structure-activity relationship (QSAR) studies on the more recent class of non-peptidic CCK(1) receptor antagonists. Our results suggest that the balance of hydrophobicity and volume dependent polarizability term plays a key role in the antagonism of CCK(1) receptor. The size of the substitution of ligands at particular position which induce steric fit is crucial as well as their hydrophobic contribution. Indicator variables were used after the best model was found to account for the usual structural features. The CoMFA results show a good variance explanation and the best self-predictivity is slightly lower than 60% with both leave-one-out and random-group methods. The CoMFA molecular fields showed the importance of steric hindrance of the substituent. From the GRIND models it can be deduced that the shape differences of the molecules are secondary in the regulation of the activity, or better, that their polar substituents are capable of occupying the same zones of the space in the most of the cases.

Anthranilic acid based CCK1 receptor antagonists: blocking the receptor with the same 'words' of the endogenous ligand.

The anthranilic acid diamides represent the more recent class of nonpeptide CCK(1) receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK(1) receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C-terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK(1) receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK(1) receptor affinity diorthosis.

Enhanced sensitivity to quipazine in the genetically dystonic rat (dt).

Both normal and genetically dystonic (dt) rats show a high-frequency forepaw tremor in response to systemic administration of the serotonin (5-HT) agonist quipazine at 8 days of age. The response declines with age in normal, but not dystonic, rats. By 16 days of age and after the development of a generalized movement disorder, the dystonic rat exhibits enhanced sensitivity to the tremorogenic effects of the drug in comparison with normal rats. Tremor was blocked by pretreatment with ketanserin, suggesting that it is mediated by 5-HT2 receptors. The dystonic rat has previously been shown to be insensitive to the tremorogenic effects of harmaline, a drug presumed to act indirectly through serotonergic neurons. This finding, coupled with the increased sensitivity to quipazine, suggests the presence of an abnormality in serotonergic systems in the mutants. Since there is evidence of abnormality in the olivo-cerebellar system in the dystonic rat, the alternative hypothesis that a nonserotonergic defect in the olivo-cerebellar system accounts for both the failure of behavioral response to harmaline and the persistent expression of a response to quipazine is also discussed.

[Surveillance of adverse reactions of drugs and monitoring of drug prescriptions as routine in hospital activities]. / La sorveglianza delle reazioni avverse da farmaci e il monitoraggio delle prescrizioni mediche come attività "normali" di reparti ospedalieri.

Since January 1988 is taking place a multicentre experience on pharmaco-epidemiology named ARIES (Adverse Reaction Identification Evaluation System), with two primary aims: surveillance of drug adverse reactions and monitoring of medical prescriptions. At present 5 departments of internal medicine are involved in the study. The factual cooperation of the departmental doctors depends on the evaluation of benefits and costs of the study. The benefits for doctor are: (a) the possibility of contributing to the research in a field which has not been systematically investigated in a hospital setting; b) the acquisition of skill in monitoring adverse reactions: to facilitate doctors cooperation an algorithm has been developed to select the events to be entered into the system; c) the possibility of evaluating and improving the prescription habits. At present, data on 9,000 patients and 60,000 prescriptions are available. As an example of utilization study, we report a research on antibiotics prescribed for bronchopneumonia in two departments involved in the ARIES project. The remarkable differences in the prescription settings lead to some rethinking on the strategies of such different prescription choices. In each department, the contribution of doctors is integrated by a monitor, entering additional information on drugs and patients into the system. Thanks to the cooperation of doctors and contribution of monitors, the pharmaco-epidemiology research may become a "normal" component of the hospital activities, thus allowing to systematically retrieve and process some basic knowledges, which are not routinely used, derived from the daily activity of the departmental doctor.

New anthranilic acid based antagonists with high affinity and selectivity for the human cholecystokinin receptor 1 (hCCK1-R).

The anthranilic acid diamides represent the most recent class of nonpeptide CCK(1) receptor (CCK(1)-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK(1)-R affinity and 15-fold for the human CCK(1)-R relative to the reference compound 12 (VL-0395). The eutomer of 2 (6) exhibited a nanomolar range affinity toward the human CCK(1)-R and was at least 400-fold selective for the CCK(1)-R over the CCK(2)-R. Molecular docking in the modeled CCK(1)-R and its validation by site-directed mutagenesis experiments showed that the 6 binding site overlaps that occupied by the C-terminal bioactive region of the natural agonist CCK. Owing to their interesting properties, new compounds provided by this study represent a solid basis for further advances aimed at synthesis of clinically valuable CCK(1)-R antagonists.

The gating paradigm: effects of presentation format on spoken word recognition by children and adults.

This study focused on the impact of stimulus presentation format in the gating paradigm with age. Two presentation formats were employed--the standard, successive format and a duration-blocked one, in which gates from word onset were blocked by duration (i.e., gates for the same word were not temporally adjacent). In Experiment 1, the effect of presentation format on adults' recognition was assessed as a function of response format (written vs. oral). In Experiment 2, the effect of presentation format on kindergarteners', first graders', and adults' recognition was assessed with an oral response format only. Performance was typically poorer for the successive format than for the duration-blocked one. The role of response perseveration and negative feedback in producing this effect is considered, as is the effect of word frequency and cohort size on recognition. Although the successive format yields a conservative picture of recognition, presentation format did not have a markedly different effect across the three age levels studied. Thus, the gating paradigm would seem to be an appropriate one for making developmental comparisons of spoken word recognition.

Abnormal cerebellar output in rats with an inherited movement disorder.

Biochemical and metabolic mapping techniques have consistently identified the deep cerebellar nuclei (DCN) of the genetically dystonic rat as a site of abnormality. Extracellular single-unit recording techniques were used to assess the functional significance of these findings in affected rats and normal littermates between 16 and 25 days of age. Cells in the medial nucleus of the mutant rats had significantly increased spontaneous firing rates in comparison with cells from normal rats. In both the medial and the interpositus nuclei, cells from the mutants fired more rhythmically than those from the normal rats. When harmaline was administered systemically to activate the olivo-cerebellar system, in normal rats, increased firing rate and bursting patterns of activity were seen. There was no reliable change in the average firing rate or rhythmicity of cells in the medial nucleus of the dystonic rats, although previous studies have shown that harmaline activates neurons in the inferior olive in the mutants. It is likely that naturally stimulated olivary activity also fails to modulate cerebellar output in this model of inherited movement disorder. Anatomical studies did not reveal any consistent changes in the number of Purkinje cells, the volume of the DCN, or the soma size of DCN neurons. Since the electrophysiological findings cannot be ascribed to a loss of the Purkinje cells that normally provide an inhibitory input to the cerebellar nuclei, the results of this study indicate the presence of a functional defect in the control of cerebellar output in the dystonic rat that accounts for the failure of these animals to display harmaline tremor and which may be critical to the motor syndrome.