Atopic Dermatitis Phenotypes in Preschool and School-Age Children: A Latent Class Analysis.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in childhood. Few data are available about AD phenotypes and their nationwide distribution. METHODS: We performed a cross-sectional multicenter study involving some of the main Italian pediatric allergy centers from 9 Italian cities. A structured questionnaire was administered to 371 children with AD. Patients were divided in 2 groups: preschool children (aged ≤5 years) and schoolchildren (aged 6-14 years). A latent class analysis was used to detect AD phenotypes and to investigate their association with risk factors and other atopic diseases. RESULTS: Latent class analysis identified 5 AD phenotypes in preschoolers ("moderate-severe AD, high comorbidity", 8%; "moderatesevere AD, low comorbidity", 35%; "mild AD, low comorbidity", 20%; "mild AD, respiratory comorbidity", 32%; "mild AD, food-induced comorbidity", 5%) and 4 AD phenotypes in schoolchildren ("moderate-severe AD, high comorbidity", 24%; "moderate-severe AD, low comorbidity", 10%; "mild AD, low comorbidity", 16%; "mild AD, respiratory comorbidity", 49%). Parental history of asthma and eczema, early day-care attendance, and exposure to molds were significantly associated with the "moderate-severe AD, high comorbidity" phenotype in preschool children (P<.05). The "moderate-severe AD" phenotypes were also associated with the highest burden in terms of medication use and limitations in daily activities. CONCLUSIONS: The detection of different AD phenotypes highlights the need for a stratified approach to the management of this complex disease and for further studies to predict the course of AD and to develop more efficient therapeutic strategies.

Atopic dermatitis phenotypes in preschool and school-age children: a latent class analysis

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in childhood. Few data are available about AD phenotypes and their nationwide distribution. METHODS: We performed a cross-sectional multicenter study involving some of the main Italian pediatric allergy centers from 9 Italian cities. A structured questionnaire was administered to 371 children with AD. Patients were divided in 2 groups: preschool children (aged ≤5 years) and schoolchildren (aged 6-14 years). A latent class analysis was used to detect AD phenotypes and to investigate their association with risk factors and other atopic diseases. RESULTS: Latent class analysis identified 5 AD phenotypes in preschoolers ("moderate-severe AD, high comorbidity", 8%; "moderatesevere AD, low comorbidity", 35%; "mild AD, low comorbidity", 20%; "mild AD, respiratory comorbidity", 32%; "mild AD, food-induced comorbidity", 5%) and 4 AD phenotypes in schoolchildren ("moderate-severe AD, high comorbidity", 24%; "moderate-severe AD, low comorbidity", 10%; "mild AD, low comorbidity", 16%; "mild AD, respiratory comorbidity", 49%). Parental history of asthma and eczema, early day-care attendance, and exposure to molds were significantly associated with the "moderate-severe AD, high comorbidity" phenotype in preschool children (P<.05). The "moderate-severe AD" phenotypes were also associated with the highest burden in terms of medication use and limitations in daily activities. CONCLUSIONS: The detection of different AD phenotypes highlights the need for a stratified approach to the management of this complex disease and for further studies to predict the course of AD and to develop more efficient therapeutic strategies

ANTECEDENTES: La dermatitis atópica (DA) es la enfermedad crónica cutánea más frecuente en la infancia. Hay pocos datos disponibles sobre los diferentes fenotipos de DA y su distribución geográfica. MÉTODOS: Se realizó un estudio transversal multicéntrico en nueve de los principales centros italianos de alergia infantil. Se realizó un cuestionario a 371 con DA. Los pacientes fueron divididos en dos grupos: preescolares (<5 años) y escolares (6-14 años). Se empleó un análisis de clases latentes (ACL) para establecer los fenotipos de la DA y su asociación con factores de riesgo y otras enfermedades atópicas. RESULTADOS: El ACL identificó cinco fenotipos de DA en el grupo preescolar (8% DA moderada-severa con alta comorbilidad, 35% DA moderada-severa con baja comorbilidad, 20% DA leve con baja comorbilidad, 32% DA leve con patología respiratoria asociada, 5% DA leve con alergia alimentaria asociada) y cuatro fenotipos en escolares (24% DA moderada-severa con alta comorbilidad, 10% DA moderada-severa con baja comorbilidad, 16% DA leve con baja comorbilidad, 49% DA leve con patología respiratoria asociada). Los antecedentes familiares de asma y eccema, la asistencia temprana a guardería y la exposición a hongos se asociaron al fenotipo DA moderada-severa con alta comorbilidad en niños preescolares (p < 0,05). Los fenotipos moderados-severos requerían mayor uso de medicación y tenían mayores limitaciones para su actividad diaria. CONCLUSIONES: La clasificación de la DA en diferentes fenotipos implica la importancia de un tratamiento estratificado para esta compleja enfermedad así como la necesidad de estudios capaces de predecir el curso de la DA y con ello desarrollar estrategias de tratamiento más eficientes

Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study.

The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

Evaluation of heart rate recovery in relation to playing position in professional soccer players.

AIM: The aim of the study was the evaluation of the autonomic cardiac function in professional soccer players by heart rate recovery (HRR) measurement after 1' or 2' of active recovery (HRR1 or HRR2, respectively) from an exercise stress test. METHODS: Ninety-two adult professional soccer players (aged 25.27 ± 4.06 years). The exercise test was performed using a cycle ergometer with a ramp protocol. The subjects began with a load of 25W that was increased by 3W every 6 seconds, followed by an active recovery phase. We assessed the heart rate at rest (HRr), the PR interval, the QT and QTc intervals, the QRS axis, the QRS duration, the maximal heart rate, and the heart rate and heart rate recovery after 1 or 2 minutes from suspension of the load. RESULTS: The HRR1 was significantly slower (20.53 SD 6.67) among goalkeepers in comparison with other roles (HRR1 30.7 SD 6.62; P<0.01). There were also significant differences among the HRR1 values of forwards (27.11 SD 4.04), midfielders (HRR1 31.31 SD 7.43), and defenders (HRR1 32.10 SD 9.55). Goalkeepers had a significantly higher heart rate at rest (HRr, 65.69 SD 10.90) than other players (HRr 57.24 SD 6.21; P<0.01). CONCLUSION: These data show better autonomic function in roles with alternate aerobic-anaerobic activity compared to other roles. The results agree with the data in other literature about the positive action of intense aerobic-anaerobic physical activity on cardiovascular autonomic system adjustment.

V-Y Bilateral gluteus maximus myocutaneous advancement flap in the reconstruction of large perineal defects after resection of pelvic malignancies.

OBJECTIVE: To evaluate the role of the V-Y bilateral gluteus maximus myocutaneous flap (GLM) in the reconstruction of large perineal defects after wide surgical resections for pelvic malignancies. METHOD: Twelve consecutive patients (seven females and five males), of mean age 59 years (36-78), with primary or recurrent pelvic malignancies (rectal, anal and vulvar carcinoma), underwent either abdomino-perineal rectum excision with partial sacrectomy or total pelvic exenteration. The perineal defect was reconstructed by means of a GLM flap. Intra-operative blood loss, operative time, hospital stay, postoperative complications and long-term outcome were retrospectively assessed. RESULTS: One patient died postoperatively. All the remaining patients had at least one early and/or late complication. After a mean follow-up of 31.2 months, seven patients were alive. No major functional impairment in daily activities was observed. Five patients experienced a slight discomfort in either walking, sitting or cycling. CONCLUSION: Gluteus maximus myocutaneus flap is a useful technique for the repair of perineo-pelvic defects after abdomino-perineal rectum excision with partial sacrectomy.

Aerobic exercise and non-alcoholic fatty liver disease: a case report.

Non-alcoholic steatosis (non-alcoholic fatty liver disease [NAFLD]), now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma, can also be explained by physical inactivity and increased dietary fat intake. No established treatment exists for this potentially serious disorder. The authors present the case of a 29-year-old man with NALFD who followed a restricted diet and practiced aerobic exercise for 16 weeks. Outcome after a combination therapy of aerobic exercise and diet was good, suggesting that treatment with a restricted diet and physical exercise can improve blood biochemical values in patients with NAFLD. Moderate-intensity aerobic exercise may help to normalize liver enzyme values and the quality of life of patients with fatty liver diseases.

Endoscopic treatment of bilateral pheochromocytoma in MEN 2A syndrome: case report and review of the literature.

The benefits of laparoscopic adrenalectomy for single adrenal lesion have been well documented in literature; less experience though has been reported with simultaneous bilateral laparoscopic adrenalectomy. This operation is indicated in case of primary hypercortisolism caused by bilateral adrenocortical hyperfunction, Cushing's disease after failure of pituitary surgery, ectopic adrenocorticotropic hormone (ACTH) production by a tumour inaccessible for surgical intervention, and pheochromocytoma when it occurs bilaterally in case of multiple endocrine neoplasia type 2A and 2B. Different laparoscopic approaches have been described to perform this operation, such as the "anterior" approach (transperitoneal), the "lateral" approach (transperitoneal and retroperitoneal), and the "posterior" approach (retroperitoneal). We report a case of bilateral laparoscopic adrenalectomy in a 33 years old female affected with bilateral pheochromocytoma due to multiple endocrine neoplasia type 2A treated with a bilateral transperitoneal laparoscopic adrenalectomy and disease free after 18 months follow-up.

Culture of human skeletal muscle myoblasts: timing appearance and localization of dystrophin-glycoprotein complex and vinculin-talin-integrin complex.

The dystrophin-glycoprotein complex together with the vinculin-talin-integrin complex plays an important role in muscle function; in fact the mutations of their elements lead to diverse forms of muscular dystrophies. The relationship between the elements of dystrophin-glycoprotein complex and vinculin-talin-integrin and the time course of their formation are still not known in detail. In order to better understand this relationship we studied their expression during development in normal human skeletal muscle culture. Using a standardized muscle cell culture procedure, this study was performed to analyze the timing, appearance and the localization of some proteins of the dystrophin-glycoprotein complex and vinculin-talin-integrin complex during cellular proliferation (myoblast) and differentiation (4, 7, 15 and 21 days). The indirect immunofluorescence technique was used and cells were examined using a Meta Zeiss LSM510 confocal laser scanning inverted microscope. We examined the progressive appearance of the following proteins: alpha, beta, gamma, delta-sarcoglycans, beta-dystroglycan, dystrophin, talin, vinculin and integrin isoform alpha7/beta1. Immunofluorescence of these proteins, in satellite cells entering myogenic differentiation, revealed different patterns of localization depending on the time of culture. We showed that nondifferentiated cultures of human myoblasts expressed a perinuclear distribution of all proteins tested. During myoblast differentiation into myotubes (4 days) immunofluorescence gradually increased and was located in the whole cytoplasm. Subsequently, at day 7, a strong and homogeneous cytoplasmic labelling of all proteins was seen. At 15 days the distribution of the proteins was on the membrane. At this time some myotubes displayed a significant degree of precostameric banding pattern. As fusion proceeded at 21 days, the cytodistribution progressively changed and appeared along fibrillar longitudinal structures, and myotubes showed a clear periodic distribution (costameres). In conclusion, in normal human muscle cultures DGC and vinculin-talin-integrin proteins are first localized in the perinuclear region, then they diffuse in the cytoplasm and finally form at the plasma membrane into typical rib-like structures that are sarcolemma-associated.

Modulation of nicotinic acetylcholine receptor turnover by tyrosine phosphorylation in rat myotubes.

The muscle nicotinic acetylcholine receptor (AChR) turns over at different rates depending on stage of synaptogenesis and innervation. Tyrosine phosphorylation modulates desensitization, interaction with cytoskeleton and lateral mobility in the membrane of AChR. To determine whether tyrosine phosphorylation also modulates the turnover of AChR, myotubes in vitro were exposed to the tyrosine phosphatase inhibitor pervanadate. Our data indicate that a transient increase of phosphotyrosine levels stabilized a fraction of AChRs. The effects were limited to the non-epsilon subunit-containing AChRs already present in the membrane. Tyrosine phosphorylation of the receptor occurred on the beta subunit, was transient and stable molecules were not selectively tyrosine phosphorylated. The data indicate that modulation of phosphotyrosine levels in muscle cells provides signals to control AChR metabolic stability.

Role of subunit composition in determining acetylcholine receptor degradation rates in rat myotubes.

During neuromuscular junction maturation, the rapidly degrading receptors (Rr; t1/2 approximately equal to 1 day) are replaced by metabolically stable molecules (Rs; t1/2 approximately equal to 10 days). Rr and Rs do not interconvert, are differently regulated after denervation in adult muscle and are endowed of unique responses to stabilizing agents. In cultured rat myotubes all the epsilon subunit-containing acetylcholine receptors (epsilon-AchRs) are of the Rs type. In the present study we show that Rs exist also in absence of epsilon-AChR and that nonepsilon-(presumably gamma-)AChRs can be included in the Rs pool when epsilon-AChR expression is low. The data indicate that Rs metabolic properties are independent of AChR subunit composition and that epsilon subunit is a signal to efficiently sort AChR molecules to the Rs pool.

A possible role of the plasmalemmal cytoskeleton, nitric oxide synthase, and innervation in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study.

In reference to a possible neuropathy in the pathogenesis of infantile hypertrophic pyloric stenosis (IHPS), previous studies have described alterations in peptidergic transmission while others have recently attributed an important role to nitrinergic activity. Little attention has been given to the organization of the extracellular matrix (ECM) and the constituent cytoskeleton and subsarcolemma of the pyloric smooth-muscle cell. To study a possible relationship between neuronal and muscular elements in IHPS, 9 biopsies from patients with IHPS and 5 biopsies of normal pylorus were examined using immunohistochemical techniques with regard to the distribution of nerve cells and fibers (bNOS and PGP 9.5) and the ECM (laminin) and cytoskeleton (talin, vinculin, dystrophin, alpha-smooth iso-actin, desmin) components of the pyloric muscle. Our results showed anti-protein gene product 9.5 and b-nitric oxide synthase immunoreaction respectively reduced or absent in nerve fibers with a positive reaction inside the ganglion cells. An uneven distribution of the ECM component laminin was evident, together with a negative immunoreaction to talin and dystrophin. The imunolocalization of vinculin, alpha-smooth iso-actin, and desmin was similar to the controls. Our findings suggest that there is a close relationship between the nerve and muscle elements in the pathophysiology of IHPS and that non-alteration of some elements of cytoskeleton organization can play an important role in regaining pyloric function after pyloromyotomy.

Effects of naringin on experimental ulcer in rats.

The effects of chronic intragastric administration of naringin (200 mg/kg) on experimental acetylsalicylic acid (ASA)-induced ulcer were studied in rat. The ulcer index and histological mucosa regeneration were evaluated. The ulcer index significantly decreased after treatment with naringin (200 mg/kg) once daily for seven days. Microscopic observations confirm these results.

Immunolocalization of the costameres in human skeletal muscle fibers: confocal scanning laser microscope investigations.

BACKGROUND: The costameres in skeletal muscle fibers were first described by Pardo et al. (1983a) and have been defined as transverse circumferential elements of the cytoskeleton associated to the sarcolemma. Specific immunostaining for vinculin shows that the costameres overlie I bands. However, an exact correlation between the costameres and the Z line is uncertain, although approximately 10 proteins so far have been localized in the costameres. To define the exact localization of costameres in human skeletal muscle fibers, we carried out an immunofluorescence study using confocal scanning laser microscopy on the fascia lata muscle of adult males. METHODS: Samples were fixed in 3% paraformaldehyde; frozen sections were treated with antivinculin, antitalin, antidesmin, and anti-alpha-actinin, then immunostained with TRITC. For double localization, the TRITC-streptavidin, as a marker for vinculin and FITC-streptavidin a marker for desmin, were used. RESULTS: The distance between two subsequent transverse lines of actininf indicated that muscle fibers were well stretched. Processing, with different software functions of the images obtained using CLSM, shows that vinculin and talin are only present in the sarcolemmal lattice. Immunostaining for vinculin and double immunostaining for vinculin and desmin demonstrate that costameres superimpose underlying I bands without interruption at the Z line. Immunostaining for talin showed that the protein is located in correspondence with the I band and M line. CONCLUSIONS: We believe that costameres are "proteic machinery." The findings of the present study suggest that it is possible to determine the width and the period of each proteic component. In addition, we indicate that costameres are present in correspondence with M line.

[Morphological variations of the human gastric mucosa after omeprazole treatment: a scanning electron microscopic study]. / Variazioni morfologiche della mucosa gastrica umana dopo trattamento con omeprazolo: studio al microscopio elettronico a scansione.

Numerous studies have been performed on the effects of omeprazole, a powerful inhibitor of gastric acid secretion, on the various morphotypes of oxyntic mucosa, whilst scant attention has been paid to modifications induced by this drug on surface epithelial mucosa. The authors carried out a SEM study on bioptic fragments removed at gastric level from 15 patients receiving omeprazole treatment for duodenal ulcer and/or reflux esophagitis, but apparently free from lesions to the mucosa of the body of the stomach. Biopsies were performed before the start, after two months and after seven-ten months of treatment. The results of basal biopsies showed an hypersecretive trend in surface epithelial cells, with frequent dissolution of the apical plasmalemma and emptying of cell bodies. After two months of treatment the hypersecretive phenomena regressed, whereas the mucosa appeared hypertrophic and presented typical cell polymorphism in some areas. After seventeen months of treatment the mucosa showed normal characteristics, except in one case in which there was a trend towards atrophy. In conclusion, the authors attribute the hypertrophic-dysplastic modifications observed after medium-term treatment to hypergastrinemia, secondary to treatment, and suggest careful morphological control follow-up during the course of treatment so as to obtain an early diagnosis of a possible deviation towards intestinal metaplasia.

Psoriasis and cyclosporin: immunohistochemical aspects of the basement membrane.

We have demonstrated both in vivo and in vitro that Cyclosporin (CsA) treatment during psoriasis induced a regression of typical keratinocyte alterations and normalization of the basement membrane (BM). It is also known that the structure of BM implies cohesion between the networks formed by laminin and type IV collagen and that these components positively influence the cytomorphosis processes of keratinocytes. According to these results, we have evaluated, by immunohistochemical study, the behaviour of laminin and type IV collagen on psoriatic skin prior to the therapy and at the end of pharmacological treatment with CsA. This study was carried out on biopsies of involved skin taken from 12 patients with severe psoriasis and with PASI between 50 and 70. Our results can be summed up as follows: Untreated psoriasis: absence of laminin within BM; modest staining in basal keratinocytes; intense staining in suprabasal keratinocytes; discontinuous staining of Type IV collagen in the BM. After treatment: evident and continuous staining of laminin and Type IV collagen within the BM. The obtained results confirm the positive effect of immunomodulation determined by CsA in the regulation of the functional activity of cells implicated in BM component production. In conclusion, the authors discuss the pathogenesis of the disease.