Inherited autoinflammatory syndromes: an expanding new group of chronic inflammatory diseases.
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Biomedical subjects
Publications and source records attributed to A Martini.
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OBJECTIVE: To compare the responsiveness of clinical measures in the assessment of disease flare in patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical records of all consecutive patients with JIA who were diagnosed between 1995 and 2000 were retrospectively reviewed. In each patient, all visits made during follow-up were analyzed and those meeting the criteria for disease flare were recorded. The definition of flare was based on the therapeutic alterations made by the attending physician. Responsiveness of JIA clinical measures to relevant increase in disease activity (a flare) was evaluated by assessing the score change of each measure from a visit made 6 (+/- 3) months before a flare and the flare visit. Responsiveness statistics included the standardized response mean (SRM) and the effect size (ES). RESULTS: A total of 115 patients, who were followed for 0.5 to 6.2 years (mean 2.8 years), were studied. During follow-up, 51 patients (44%) experienced 1 or more disease flares, with the total number of flares being 75. Strong responsiveness (ES and SRM > or = 0.8) to increase in disease activity was demonstrated by the physician's and parent's global assessments, the global articular severity score, and the morning stiffness. The active, swollen and painful joint counts, the swelling, pain on motion/tenderness and limited range of motion (LROM) scores, and the erythrocyte sedimentation rate revealed moderate responsiveness (ES and SRM > or = 0.5). The poorest performances (ES and/or SRM < 0.5) were provided by the parent's assessment of pain, the functional ability tool, the number of joints with LROM, the LROM score, the C-reactive protein, the white blood cell and platelet count, and the hemoglobin level. CONCLUSION: Our analysis suggests that the swollen or painful joint counts are better suited than the count of joints with LROM for the assessment of disease flare in patients with JIA.
PURPOSE: Pseudoseizures or nonepileptic seizures (NES) are termed "nonepileptic psychogenic seizures" and account for approximately 20% of all intractable seizure disorders. These seizures are often misdiagnosed as true epilepsy, resulting in inappropriate, ineffective and costly treatment of many patients. Nowadays video-EEG monitoring have greatly improved the ability of specialists to correctly distinguish NES from epilepsy. Nevertheless, patients with NES do not always demonstrate obvious psychopathology. The aim of this study is to examine the complexity and severity of psychopathological features of patients with NES, in order to optimize strategies of intervention and appropriate long-term psychological and psychopharmacological treatment for these patients. MATERIALS AND METHODS: We evaluated three samples: patients with NES, patients with epilepsy and a control sample. Subjects with pseudoseizures and epileptic seizures have been randomly recruited from the Epilepsy Centre at the Neurology Institute of Catholic University of Sacred Heart of Rome. Seizures have been documented by the recording of spontaneous events with video-EEG, EEG, clinical observation and ictal examination. Each sample of patients has been tested using the Hamilton Rating Scale for Depression (HDRS), Dissociative Experience Scale (DES), Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Short Form Health Survey 36 (SF-36). RESULTS: 17 (4 M; 13 F) patients with NES, 13 (3 M; 10 F) patients with epilepsy and 16 (4 M; 12 F) control subjects were recruited. Our preliminary results confirm previous researches showing that NES typically manifest between 20 and 30 years of age and that approximately a three-quarters of all patients are women. Besides, they confirm that psychosocial, environmental and intrapsychic mechanisms interact in the aetiology of NES: in particular, our preliminary results are consistent with the hypothesis that traumatic experiences are important precursors to the development and expression of NES. CONCLUSIONS: This study has yielded promising results and confirm the necessity to improve our knowledge about psychopathology of patients with NES. Psychiatrists and neurologists should work in equipe to guarantee an adequate treatment for a pathology too long set aside and almost ignored from clinical research.
Until recently, no uniform and widely accepted criteria for defining remission in juvenile idiopathic arthritis (JIA) were available. In recent years, a set of preliminary criteria for clinical remission in JIA was developed through an international collaborative effort. These criteria enable the classification of patients in the states of inactive disease, clinical remission with medication, and clinical remission without medication. The first phase of the validation process of the criteria, which was accomplished recently, established that they are feasible and have good face, content and construct validity, and strong discriminant properties. A few studies have applied the new remission criteria in series of patients with JIA, with results that concur with those of previous surveys in showing that only a few patients with JIA have a chance of remaining in long-term remission status without medications. These findings highlight the critical need for therapies that have the capacity to induce sustained complete disease control of JIA.
OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.
Increased intestinal permeability secondary to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and raised levels of anti-gliadin antibodies (AGA) have been reported in adults with rheumatoid arthritis. We have therefore retrospectively investigated the presence of serum AGA of the IgA and IgG classes in 70 patients with juvenile chronic arthritis (JCA). Serum IgA (but not IgG) AGA were found to be higher in JCA patients than in controls (6.2 +/- 8.7 vs 2.1 +/- 1.5 AU/ml; p less than 0.0001). This finding was observed independently of the JCA onset subtype or disease activity; however, lower levels of IgA AGA were found in patients with pauciarticular JCA and in those in remission. No significant differences in IgA AGA serum levels were observed between untreated patients and patients treated with NSAIDs. Five patients who presented the highest levels of IgA AGA were further studied a second time; serum IgA AGA were found to be markedly reduced or normalized and no clinical or laboratory evidence of coexistent coeliac disease was observed. In conclusion, our results suggest that the elevation of IgA AGA seen in our patients is secondary to non-specific immune stimulation rather than to an NSAID-induced increase in intestinal permeability.
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The Authors studied 21 patients affected by Juvenilis Rheumatoid Arthritis. The TMJ compromission was evaluated by un objective, clinical and radiographic examination. A teleradiographic with cephalometric analysis was also performed to all subjects. The results show a greater TMJ compromission in earlier arisen disease subjects.
Juvenile dermatomyositis (JDM) is a chronic multisystem inflammatory disease that primarily involves skin and muscles. The clinical picture is mainly characterized by the typical cutaneous rash and by skeletal muscle weakness. Nevertheless the vasculitic process may extend in some cases to other organs such as lung, joints or gastrointestinal system. Calcinosis represents a relatively frequent complication of JDM and occurs in most cases during the late stage of the disease. Usually serum levels of muscle enzymes are elevated and electromyography shows signs of myositis. Muscle biopsy is generally performed only in doubtful cases. JDM should be differentiated from the muscle involvement of other diffuse inflammatory connective tissue diseases and from non inflammatory myopathies. The treatment is mainly based on steroids, whose dosage and regimen depend on disease severity. Steroid therapy has greatly improved the prognosis of JDM.
In most patients tympanic membrane perforation spontaneously repairs itself. Nonetheless, in several cases the perforation persists due either to traumatic or phlogistic damage. Although the membrane perforation healing process has been under study for over a century there are still two contrasting theories. One of these theories asserts that repair takes place through the growth of granulation tissue while the other believes that epithelial migration is at the basis of healing. In the present study an experimental animal model (rat) was used in order to assess the staging of the natural evolution of post-traumatic membrane perforation and to characterize, from a morphological and sub-microscopic point of view, the cellular population and microstructural aspects of the extracellular matrix. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were employed to evaluate the progress in tympanic membrane healing and to make a comparison with the most recent theories. Eighteen Sprague-Dawley rats weighing 230-260 gr of the same age (10 weeks) were used in the study. The animals were anesthetized by intraperitoneal injections of Na-pentobarbital (NembutalR) (45 mg/Kg) and, under operating microscope, bilateral perforation of the upper rear quadrant of the pars tensa was performed with a myringotomy lancet. The animals were subjected to periodic follow-ups over next 30 days. Three animals were sacrificed during each control and the tympanic membrane was removed for TEM and SEM study. On the basis of the present study the following conclusions can be drawn: a) primary healing of the lesion is through granulation tissue; b) the healed T.M. is composed of three normal layers as is the normal T.M.; c) the presence of fibroblasts in the intermediate neoformed fibrous layer leads one to conclude that its extracellular matrix is produced and organized "in situ"; d) the neoformed lamina propria has a disorganized, fibrous structure.
We describe two children with an otherwise unexplained deep vein thrombosis associated with high titer anticardiolipin antibodies (ACA) of the IgG class and circulating lupus anticoagulant (LAC). One of these patients had persistent proteinuria but neither had systemic lupus erythematosus. Our observation suggests that ACA and LAC assays should be performed in children with thromboembolic disease even when no underlying autoimmune disease can be found.
We evaluated the effect of 47 serum samples obtained from 34 children with juvenile chronic arthritis (JCA) on mitogen-induced proliferation of normal peripheral blood lymphocytes (nPBL). We found that sera from patients with active disease, and particularly those with the systemic form, inhibited significantly PHA-induced proliferation of nPBL at all the PHA concentrations tested. This inhibitory activity was independent of the treatment and was correlated with the value of the erythrocyte sedimentation rate. Part of the JCA sera inhibitory effect could be reversed by the addition of exogenous interleukin 2 (IL-2), but not of interleukin 1 (IL-1) or interferon-gamma, moreover, JCA sera were able to partially inhibit the IL-2 dependent proliferation of CTLL. When we tested serum fractions obtained by Sephadex G-200 chromatography for their inhibitory activity, we observed that: a) two major peaks of inhibitory activity on PHA-induced proliferation were present: peak 1 with MW less than 600,000 and peak 2 with MW between 70,000 and 35,000; b) the inhibitory activity present in the high MW peak was in part IL-2 related; and c) both peaks contained elevated levels of acute phase proteins (APP) which are known to inhibit mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. This activity is due to the presence of multiple inhibitors, one of which appears to be IL-2 related; at least part of the inhibitory activity may be due to elevated serum levels of APP.
15 patients with chronic progressive Multiple Sclerosis were treated with Hyperbaric Oxygen Therapy at 2.0 atmospheres absolute for a total of 20 daily exposures followed by 2 exposures every month. The treatment was carried out for a 24 months follow-up. No objective benefit resulted from Hyperbaric Oxygen Therapy at the completion of the study while a subjective improvement in bladder control was reported in the short and in the long-term follow-up by 8 and by 5 patients respectively. No significant variations in the electrophysiological results were observed after the first 20 consecutive exposures. It is concluded from this trial that a long-term Hyperbaric Oxygen Treatment cannot moderate the progression of Multiple Sclerosis. However, an improvement in the quality of life can be obtained in some patients resulting from a better control of bladder function.
Unstimulated and pokeweed mitogen (PWM)-stimulated "in vitro" IgM synthesis by peripheral blood lymphocytes has been evaluated by an ELISA method in 33 patients with juvenile rheumatoid arthritis (JRA). Lymphocyte PWM responses were significantly reduced in patients with JRA compared with healthy controls. When patients were divided according to disease activity, a significant increase of stimulation index (ratio of IgM synthesis with over that without PWM) has been observed in patients with disease remission compared with those with active disease. These findings confirm the defect in PWM-induced IgM synthesis by peripheral blood lymphocytes of patients with JRA and suggest that these abnormalities may be related to disease activity.
Fourteen patients with juvenile dermatomyositis (JDM) have been investigated for the presence of several serum autoantibodies: antinuclear (ANA), anti-single-stranded and double-stranded DNA, anti-histones, anti-Sm, anti-ribonucleoprotein, anti-SSA/SSB, anti-PM-1, anti-Jo-1, anti-mitochondrial, anti-smooth muscle, anti-gastric parietal cells, anti-cardiolipin (ACA) antibodies and rheumatoid factor. Patients were negative for all autoantibodies except for ANA and ACA. ANA were detected in 50% of the patients when tested on rat liver, but the percentage of positivity rose to 86% when HEp-2 cells were used as substrate. This finding suggests that HEp-2 cells represent a more sensitive substrate than rat liver for the detection of ANA in JDM. Three patients were positive for ACA; two of these presented vascular complications, thus suggesting a possible relationship between ACA and vascular involvement in JDM.
Recent technological developments have led in the the last years to the isolation and characterization of a group of polypeptides, generally termed cytokines, which are produced by cells of the immune system, and by other cell types; these peptides regulate the immune response and the inflammatory reaction, and, in general, cellular growth and differentiation. Because of the availability of large quantities of these cytokines, produced with recombinant DNA techniques, their use in therapy is now possible; promising results have been obtained in some diseases.
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