Plasma-exchange in the treatment of systemic rheumatic diseases: past and present experience

La terapia con plasma-exchange (PEx) e stata utilizzata sin dagli anni Settanta per la cura di molteplici malattie, nella cui patogenesi fattori umorali si riteneva potessero giocare un ruolo di rilievo. Questa modalita di trattamento comporta la rimozione di autoanticorpi, immunocomplessi circolanti, molecole di adesione, citochine, chemochine ed altri mediatori solubili implicati nello sviluppo del danno tissutale (1). Nel 1993 l'American Society of Apheresis (ASFA) ha per la prima volta pubblicato un elenco di applicazioni cliniche delle diverse tecniche di aferesi terapeutica, fra le quali di gran lunga la piu utilizzata era, allora come oggi, il PEx (2). Questo elenco comprendeva malattie autoimmuni, malattie ematologiche ed oncologiche, disordini metabolici, malattie neurologiche e malattie renali. Fra le malattie autoimmuni figuravano molte forme morbose di pertinenza reumatologica..

Anti-Hepatitis C Virus Serology in Immune Thrombocytopenia: A Retrospective Analysis in 101 Patients.

Hepatitis C virus (HCV), an RNA virus, is known to be the major cause of post-transfusion non-A, non-B hepatitis. HCV can induce several expressions of autoimmunity, including both serological abnormalities and clinical disorders. The relationship between the HCV infection and anti-platelet autoimmunity has been occasionally described, but is still far from well-defined. We retrospectively analysed 101 serum specimens, collected between 1988 and 1994, from patients with immune thrombocytopenia (ITP) for the presence of anti-HCV antibodies. Eighty-seven patients were classified as having idiopathic, and 14 secondary ITP (4 systemic lupus erythematosus, 9 non-Hodgkin's lymphoma and 1 Evan's syndrome). Anti-HCV antibodies were determined by second generation tests (ELISA + RIBA). A specimen was considered positive for HCV antibodies in the presence of ELISA reactivity (sample optical density/cut-off > 1.00) accompanied by RIBA reactivity to at least one HCV specific antigen. 20 sera (20%) were positive, with a prevalence higher in secondary than in idiopathic ITP (43% vs. 16%, p < 0.05). No differences were found between anti-HCV positive and negative patients regarding gender, platelet count, platelet associated immunoglobulins, hepatitis B virus serology and liver enzyme profile. On the contrary, mean age was higher in the HCV positive vs HCV negative ones (58±18SD vs. 44±20yrs, p < 0.01), in keeping with the increasing prevalence of HCV infection with ageing. HCV positive patients, showed a poor response to treatment (platelet count lower than 50,000/μl after conventional medical therapy for immune thrombocytopenia) compared to anti-HCV negative ones, (50% versus 7.3%, p < 0.001). When we excluded patients who were exposed to risk factors for HCV infection after ITP diagnosis and before the serum collection, the prevalence of anti-HCV antibodies was not very different (17.6%) from that found in the series as a whole (19.8%). Our results seem to indicate that HCV infection may play a role in triggering several cases ITP, and moreover might constitute a negative prognostic factor for therapy response

L^2 stability estimates for shock solutions of scalar conservation laws using the relative entropy method

We consider scalar nonviscous conservation laws with strictly convex flux in one spatial dimension, and we investigate the behavior of bounded L^2 perturbations of shock wave solutions to the Riemann problem using the relative entropy method. We show that up to a time-dependent translation of the shock, the L^2 norm of a perturbed solution relative to the shock wave is bounded above by the L^2 norm of the initial perturbation.Comment: 17 page

Oxcarbazepine add‐on for drug‐resistant partial epilepsy

Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and tolerability of oxcarbazepine when used as an add‐on treatment for patients with drug‐resistant partial epilepsy

Gravity, Geoid, Isostasy and Moho Depth in the Ross Sea, Antarctica

In the framework of several international research projects performed in Ross Sea (Antarctica) in the last years marine gravity data, high resolution reflection seismic line sand deep seismic sounding profiles have been acquired. The gravity data set has been used to compute maps of Bouguer anomaly, isostatic anomaly, isostatic correction and local geoid undulations. Forward modelling of seismic and gravity data has been also used to compute the depths of the Crust-Mantle discontinuity

Different patterns of pelvic ureteral endometriosis. What is the best treatment? Results of a retrospective analysis

Objective. Endometriosis is an estrogendependent disease. The incidence of urinary tract endometriosis (UE) increased during the last few years and, nowadays, it ranges from 0.3 to 12% of all women affected by the disease. The ureter is the second most common site affected. The ureteral endometriosis is classified in extrinsic and intrinsic. The aim of this study is to individuate the best treatments for each subset of ureteral endometriosis. Materials and Methods. 32 patients diagnosed with surgically treated UE were retrospectively reviewed. The patients were divided into 3 subsets (intrinsic UE, extrinsic UE with and without obstruction). The patients with intrinsic UE (n = 10) were treated with laser endoureterotomy. The patients with extrinsic UE (n = 22) were divided in two subsets with (n = 16) and without (n = 6) hydronephrosis. All the patients underwent ureteral stenting, and resection and reimplantation was performed in the first group, and when the mass was &gt; 2.5 cm (n = 3) Boari flap was performed. Laparoscopic ureterolysis (shaving) was performed in the second group. Results. In the extrinsic subset of UE, we obtained an high therapeutic success (84%). Conversely, in the intrinsic subset there was a recurrence rate of the disease in 6/10 of the patients (60%). Conclusions. Ureterolysis seems to be a good treatment in extrinsic UE without obstruction. Resection and reimplantation allows excellent results in the extrinsic UE with obstruction. In the intrinsic subset, the endoureterotomy approach is inadequate

Population pharmacokinetic study of benznidazole in pediatric chagas disease suggests efficacy despite lower plasma concentrations than in adults

Introduction: Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce. Patients and Methods: Prospective population pharmacokinetic (PK) cohort study in children 2-12 years old with Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387). Results: Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs). Discussion: Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted. Trial Registration: ClinicalTrails.gov NCT00699387.Facultad de Ciencias Exacta