Sustained improvement of a girl affected with Devic's disease over 2 years of mycophenolate mofetil treatment.
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Brain↗
Biomedical subjects
S Trapani
Publications and source records attributed to S Trapani.
Apoptosis during chick inner ear development: some observations by TEM and TUNEL techniques.
In order to clarify the occurrence, distribution and possible role of apoptosis during inner ear development, the ultrastructural aspects (by TEM) (at 9-19 incubation day and 1 day after hatching) and the distribution of the apoptotic phenomenon (by the TdT-mediated dUTP nick end-labeling technique), were studied in the crista ampullaris of chick embryo at 5-19 days of incubation to hatching and of postnatal 1-day old chick. We found, in the sensorial epithelium, dark supporting cells in chick embryos and mainly dark hair cells in postnatal chicks, both with ultrastructural features consistent with those of apoptosis. The presence of apoptotic phenomena was confirmed by the TUNEL technique. According to our findings, it is hypothesized that apoptosis in the inner ear may be involved: 1) at first, in macroscopic remodelling of the membranous labyrinth in early developmental stages, 2) later, in the correct differentiation of the hair and of the supporting cells, leading to characteristic cellular pattern formation and 3) finally, in physiological cell turnover of the postnatal chicken sensorial epithelium of the crista.
Animals↗
Crystal structure of the dimeric phosphoenolpyruvate carboxykinase (PEPCK) from Trypanosoma cruzi at 2 A resolution.
ATP-dependent phosphoenolpyruvate carboxykinase (PEPCK) (ATP: oxaloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) is a key enzyme involved in the catabolism of glucose and amino acids in the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. Due to the significant differences in the amino acid sequence and substrate specificity of the human enzyme (PEPCK (GTP-dependent), EC 4.1.1.32), the parasite enzyme has been considered a good target for the development of new anti-chagasic drugs. We have solved the crystal structure of the recombinant PEPCK of T. cruzi up to 2.0 A resolution, characterised the dimeric organisation of the enzyme by solution small angle X-ray scattering (SAXS) and compared the enzyme structure with the known crystal structure of the monomeric PEPCK from Escherichia coli. The dimeric structure possesses 2-fold symmetry, with each monomer sharing a high degree of structural similarity with the monomeric structure of the E. coli PEPCK. Each monomer folds into two complex mixed alpha/beta domains, with the active site located in a deep cleft between the domains. The two active sites in the dimer are far apart from each other, in an arrangement that seems to permit an independent access of the substrates to the two active sites. All residues of the E. coli PEPCK structure that had been found to interact with substrates and metal cofactors have been found conserved and in a substantially equivalent spatial disposition in the T. cruzi PEPCK structure. No substrate or metal ion was present in the crystal structure. A sulphate ion from the crystallisation medium has been found bound to the active site. Solution SAXS data suggest that, in solutions with lower sulphate concentration than that used for the crystallisation experiments, the actual enzyme conformation may be slightly different from its conformation in the crystal structure. This could be due to a conformational transition upon sulphate binding, similar to the ATP-induced transition observed in the E. coli PEPCK, or to crystal packing effects. The present structure of the T. cruzi PEPCK will provide a good basis for the modelling of new anti-chagasic drug leads.
Amino Acid Sequence↗
Pulmonary involvement in juvenile dermatomyositis: a two-year longitudinal study.
OBJECTIVE: To investigate the prevalence and features of asymptomatic pulmonary involvement in juvenile dermatomyositis (JDM). METHODS: Twelve JDM patients underwent pulmonary function tests at baseline, 12 and 24 months. Disease activity, duration, serum lactate dehydrogenase (LDH) values and antinuclear antibody (ANA) titres were also evaluated. RESULTS: Five patients showed lung impairment at baseline and four at 12 and 24 months. Forced expiratory volume in 1s, forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and alveolar volume were the most frequently altered variables, indicating a restrictive pattern and impairment of diffusion. The prevalence and features of pulmonary alterations did not change during follow-up. FVC values were significantly lower in active JDM patients and were inversely related to LDH. DLCO values were significantly lower in ANA-positive patients. About half of the patients of this small case series of JDM had asymptomatic lung disease. CONCLUSIONS: We suggest that lung function should be evaluated at disease onset and regularly during follow-up, as pulmonary function tests can detect otherwise unpredictable pulmonary involvement.
Adolescent↗
Calcification processes in the chick otoconia and calcium binding proteins: patterns of tetracycline incorporation and calbindin-D28K distribution.
In order to clarify the otoconia formation and turnover, tetracycline, an antibiotic that precipitates at calcifying fronts and serves as a fluorescent marker, was injected into eggs at different stages of chick embryonic development, as well as into postnatal chicken and into adult animals. The changes in the intensity, location patterns and time course of fluorescent labelling in each examined stage in the otolithic organs was studied. The presence and distribution of calbindin (CB)-D28K, one of the calcium-binding proteins constantly found in the mammalian and chicken cochlea and also in otolithic membrane of some adult mammals, was studied. Results in embryonal stages, postnatal and adult animals allow us to postulate that otoliths are mainly produced during the embryonal phase, but they may also be produced throughout the whole life span. Results also indicate that otoconia are dynamic structures which undergo turnover. The correspondence between the patterns of CB-D28K immunoreactivity and tetracycline fluorescence may indicate that CB-D28K participates in the formation of otoconia.
Aging↗
Incidence of occult cancer in children presenting with musculoskeletal symptoms: a 10-year survey in a pediatric rheumatology unit.
OBJECTIVES: To assess the frequency and types of cancer found in children presenting to our Unit with musculoskeletal symptoms over a 10-year period. METHODS: The medical records of patients with musculoskeletal symptoms and a final diagnosis of cancer were reviewed. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, provisional and final diagnoses, and time between clinical onset and correct diagnosis were reviewed. RESULTS: An underlying neoplasia was found in 10 of 1,254 patients (<1%) complaining of musculoskeletal symptoms. The types of malignancies found included acute lymphocytic leukemia (ALL) (6 cases), lymphoma (2 cases), neuroblastoma (1 case), and Ewing's sarcoma (1 case). The mean time between disease onset and final diagnosis was 3.2 months. The most common presenting feature was monoarthritis, involving the larger joints such as the elbows, knees or ankles. Juvenile idiopathic arthritis (JIA) was the most frequent provisional diagnosis. In the preliminary hematologic evaluation, eight patients had an increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) value. White blood cell (WBC) count was normal in almost all children, with a normal differential count. Lactic dehydrogenase (LDH) was raised in all children. Bone marrow aspirates and lymph node or bone biopsies were necessary to reach the final diagnosis. CONCLUSIONS: A malignancy should always be excluded in children with musculoskeletal symptoms, especially when the clinical pattern is not characteristic of a specific rheumatic disease. Routine laboratory tests may be misleading. The simultaneous presence of high LDH or alpha-hydroxybutyric dehydrogenase (alpha-HBDH) levels and raised ESR or CRP, even with normal blood cell counts, should lead to additional investigations. RELEVANCE: All patients presenting with arthritis or other musculoskeletal symptoms should have a thorough clinical examination. Disproportionate pain levels and an atypical pattern of "arthritis," especially in the presence of systemic manifestations, suggest a possible underlying malignancy.
Adolescent↗
Correlation between clinical and ultrasound assessment of the knee in children with mono-articular or pauci-articular juvenile rheumatoid arthritis.
BACKGROUND: Ultrasonography of the knee is a non-invasive, readily available and low-cost tool for demonstrating peri-articular tissues. OBJECTIVE: To correlate clinical features with US findings in the detection, quantification and follow-up of inflammatory signs of the knee in children with pauci-articular juvenile rheumatoid arthritis (JRA). MATERIALS AND METHODS: US of both knees was performed in 49 patients on the same day as the clinical examination. All joints were classified into two groups by clinical criteria: group A (active disease) or group B (quiescent disease). Thirteen patients underwent one or more follow-up examinations. US was performed with a small-parts, 7.5-MHz, electronic linear probe by using a technique previously reported. Quantitative assessment of any effusion and synovial thickening was evaluated at the level of the suprapatellar bursa. Wilcoxon and Spearman tests were employed to compare US findings between the two groups and to correlate clinical and US findings within each group, respectively. RESULTS: US demonstrated significant increase of effusion and synovial thickening in group A joints. US enabled visualisation of clinically undetected popliteal cysts in three patients. Correlation between clinical and US findings was significant in group A and positive, though not significant, in group B. CONCLUSIONS: US seems to be a sensitive and reliable method for the assessment and monitoring of knee joint involvement in pauci-articular JRA.
Adolescent↗
Human parvovirus B19 infection: its relationship with systemic lupus erythematosus.
OBJECTIVES: The clinical presentation and outcome of four cases of human parvovirus-B19 (HPV-B19) infection, initially diagnosed as systemic lupus erythematosus (SLE), were reviewed and compared with similar cases previously reported in the literature. The relationship between HPV-B19 infection and SLE is discussed. METHODS: The medical records of four patients with documented HPV-B19 infection, initially diagnosed as SLE, were reviewed and studied in detail. A Medline search from 1985 to 1997 was performed to identify other cases reported in the literature in which a relationship between HPV-B19 and SLE had been identified in both adults and children. RESULTS: In all of our cases, the clinical findings (fever, rash, arthritis and malaise) and hematologic data (leukopenia, thrombocytopenia, anemia, presence of autoantibodies, hypocomplementemia, etc.) had initially suggested a diagnosis of juvenile SLE. Subsequently, evidence of HPV-B19 infection at the time of clinical presentation was ascertained. In three of these cases, the disease course was self-limiting with complete clinical remission and normalization of hematologic abnormalities within 18 months; one case, however, had persistent disease activity and repeated exacerbations. CONCLUSIONS: The occurrence of HPV-B19 infection has been documented in patients with SLE, in particular in relation to disease onset. Similarities in clinical and immunological features of viral infections and SLE at presentation may hinder the differential diagnosis between these two conditions. The family history, a self-limiting disease course and certain disease specific clinical aspects may help the pediatrician formulate an accurate diagnosis. In our patients, HPV-B19 infection may have mimicked the onset of SLE in three cases, but triggered the disease in one.
Adolescent↗
Pulmonary function in children affected by juvenile spondyloarthropathy.
OBJECTIVE: Pleuropulmonary involvement in adult spondyloarthropathy (SpA) has been thoroughly investigated. SpA is usually detected by conventional radiology as fibrosis of the upper lobes in about 30% of asymptomatic patients. Pulmonary function tests (PFT) reveal decreased vital capacity and total lung capacity, as well as increased residual volume. Juvenile SpA (JSpA) is a rare clinical condition, and no extensive investigations have been carried out on pulmonary involvement in JSpA. We studied prevalence and features of PFT alterations in patients with JSpA over a 2 year followup and analyzed the relationship between PFT and disease duration, disease activity, and chest and spine mobility. METHODS: Eighteen patients with JSpA, with no clinical signs of lung disease and normal chest radiographs, underwent PFT--static and dynamic volumes, diffusing capacity for carbon monoxide (DLCO), at enrollment (T0), at 12 months (T1), and at 24 months later (T2). Disease activity was defined at each investigation by clinical and hematological data. RESULTS: Significant functional lung impairment was detected in 33% of patients (reduced forced vital capacity in 22% and DLCO in 11%). No significant change in the prevalence and features of PFT alterations was detected at T1 and T2; no relationship was found between PFT and duration, activity, and clinical scores of the disease. CONCLUSION: Thirty-three percent of JSpA patients without clinical symptoms and no radiological findings of lung involvement show PFT alterations, mainly characterized by a restrictive pattern. No progression or modification in PFT developed over 2 years. No correlation was found between PFT and disease duration, activity, and clinical scores.
Adolescent↗
Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis.
We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the therapy (group A = 14 patients, treated with a low dose of MTX and NSAIDs; group B = 13 patients, treated with NSAIDs alone). Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time 0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC, FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone.
Adolescent↗
Osteoporosis in juvenile systemic lupus erythematosus: a longitudinal study on the effect of steroids on bone mineral density.
Peak bone mass is an important determinant of future bone mass and of the risk of osteoporosis and subsequent fractures. Although some information concerning bone mineral density (BMD) in adults affected with systemic lupus erythematosus (SLE) is available, few data on children and adolescents have been reported. Many variables, such as duration and activity of the disease, reduced sun exposure, and steroid therapy have been suggested as risk factors in the pathogenesis of osteoporosis in SLE. In this study, we longitudinally evaluated, by dual energy X-ray absorptiometry (DEXA), the BMD of 20 young patients affected with juvenile SLE (JSLE), in order to establish the degree of osteoporosis and the influence of steroid treatment, among other clinical variables. At baseline, the mean BMD in JSLE patients was 0.978 g/cm2 and in controls 1.038 g/cm2 (P = 0.31). At 1 year (time 2), this value became 0.947 g/cm2 in JSLE children; the mean individual difference was 0.28 g/cm2 (3.4%). Only in those patients aged 19-25 years BMD was significantly lower than in controls, both at baseline and at time 2. Considering the steroid treatment, no significant difference between the two groups was found either at baseline or at time 2; however, the mean yearly BMD loss in the steroid patients was 0.031 g/cm2 (3.5%) vs. 0.005 g/cm2 (0.5%) in those who had not taken steroids. A significantly inverse correlation between BMD and the cumulative dosage of corticosteroids has been detected. BMD produced a significantly inverse correlation to the cumulative dosage of corticosteroids; no significant correlation has been found between BMD and disease activity or duration.
Absorptiometry, Photon↗
Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease.
Pleuro-pulmonary involvement has been well recognized in adults affected with systemic lupus erythematosus (SLE), but few studies have been carried out in children. A longitudinal study on a group of 15 children affected with juvenile SLE (JSLE), asymptomatic for lung disease, was performed, and the prevalence and the features of respiratory function alterations, over a period of 12 months, were analysed. Moreover, a possible correlation between any pulmonary function test (PFT) and disease duration, disease activity, visceral involvement and immunological pattern was evaluated. At baseline, a significant functional lung impairment was present in 40% of patients, with a significantly reduced FVC, VA and DLCO in 26% of them; in 60% of patients at 6 months and in 33% of patients at 12 months. At 6 and 12 months, our data did not show any significant modification in PFTs and the restrictive pattern, observed at baseline, remained unchanged. No correlation between altered PFTs and disease duration, activity and/or immunological findings was found. At baseline, the presence of neurological involvement was the only extra-pulmonary feature correlated to reduced FVC.
Adolescent↗
Methotrexate-associated appearance and rapid progression of rheumatoid nodules in systemic-onset juvenile rheumatoid arthritis.
Rheumatoid nodules are a rare extraarticular manifestation of juvenile rheumatoid arthritis (JRA), usually detected in patients with polyarticular-onset disease and positive rheumatoid factor (RF). To date, there has not been a published report of rheumatoid nodules in systemic-onset JRA. Low-dose methotrexate (MTX) is generally considered to be the most useful second-line drug in the treatment of polyarticular JRA. In adult RA, MTX has been shown to be associated with appearance and progression of rheumatoid nodules. This report describes a 3-year-old girl with RF-negative, antinuclear antibody-negative systemic JRA who developed multiple rheumatoid nodules on the scalp and trunk during MTX therapy. The first nodule developed on the scalp 6 months after MTX treatment was initiated. Previous treatment with azathioprine was not associated with nodulosis. This represents an atypical case of MTX-associated accelerated nodulosis in systemic JRA, and raises the problem of treatment plan modification in the presence of this side effect.
Antirheumatic Agents↗
Catastrophic antiphospholipid antibody syndrome in pediatric systemic lupus erythematosus.
Catastrophic antiphospholipid antibody syndrome, reported in a minority of patients with circulating antiphospholipid antibodies, is characterized by widespread vascular occlusions. The term "catastrophic" has been used to describe the severity of symptomatology, sometimes leading to death. We describe a girl aged 11 years, fulfilling diagnostic criteria for systemic lupus erythematosus, with recurrent episodes of thromboembolic phenomena involving lung and skin, complicated with disseminated intravascular coagulation. Treatment with warfarin ultimately resulted in effective control of the disease.
Anticoagulants↗
Intravenous administration of alendronate counteracts the in vivo effects of glucocorticoids on bone remodeling.
The purpose of the investigation was to test the use of alendronate in the therapy of children affected by chronic rheumatic diseases and symptomatic drug-induced osteoporosis. Two courses of alendronate were intravenously administered to four girls with vertebral fractures that were glucocorticoid induced. Improvement of back pain and bone mineral density increase evaluated by DXA and conventional spine X-rays were observed. Our study supports the ABD-induced improvement of the negative effects of long-term therapy on bone mineral density in children with chronic rheumatic diseases.
Adolescent↗
The primary role of steroids on the osteoporosis in juvenile rheumatoid patients evaluated by dual energy X-ray absorptiometry.
Osteoporosis, a common clinical feature in children affected with Juvenile Rheumatoid Arthritis (JRA), is generally divided into two forms, a localized juxta-articular osteoporosis of the single joints and a generalized reduction of bone mass due to the disease itself, joint involvement and steroid treatment. Recently Dual Energy X-ray Absorptiometry (DEXA) has been suggested for Bone Mineral Density (BMD) measurement. In the present study DEXA has been used to investigate the lumbar spine BMD in JRA patients as compared to healthy children. Our results showed that BMD is reduced in JRA patients (BMD 0.685 g/cm2) when compared to healthy children (BMD 0.722 g/cm2), and it is significantly lower in the group of patients treated with steroids (BMD 0.623 g/cm2) when compared to those treated with nonsteroidal antiinflammatory drugs (BMD 0.710 g/cm2). The analysis of all risk factors of bone loss indicated that steroids represent the only parameter of significant negative correlation with BMD.
Absorptiometry, Photon↗
Growth patterns and gravitropic curvature of radish hypocotyls.
The rapid growth rate of radish cells makes the hypocotyl particularly valuable in research on growth phenomena and gravitropism. An examination of mean data regarding the growth of aetiolated radish seedlings not subjected to gravitropic stimulation showed that there was an increase in the growth rate from day 3 to day 5. When the hypocotyl was placed horizontally all zones showed an increase in growth of the lower surface of the hypocotyl and generally a decrease in the growth rate in the upper surface. The upper apical part of the gravistimulated hypocotyl grew almost the same as controls. In some cases, in both 4- and 5-day-old seedlings, in the upper median part there was a lower growth rate than in controls. The zones of growth during the development of the hypocotyl were different. Analysis of curvature showed that the growth rate of the different zones was a function of their location in the hypocotyl and that the rate of curvature was different in various parts of the hypocotyl.
Brassicaceae↗
Deflazacort in pediatric rheumatic diseases needs a frequent follow-up of bone densitometry.
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Anti-Inflammatory Agents↗