PubMed Health⌕ Search

Biomedical subjects

M Fadda

Publications and source records attributed to M Fadda.

At least 19 recordsLinked to original sources

Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B.

AIM: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. METHODS: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. RESULTS: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. CONCLUSION: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

Antiviral Agents↗

The use of the anti-tumour necrosis factor monoclonal antibody--infliximab--to treat ulcerative colitis: implications and trends beyond the available data.

The monoclonal antibody to the tumour necrosis factor--infliximab--has recently been added to the list of off-label therapeutic means for ulcerative colitis. We conducted a descriptive analysis of the results from studies on the use of the drug published so far. A total of 187 patients qualified for analysis. They were divided into four main categories, including steroid-refractory and responsive adults and children. The median frequencies of an early and a sustained response were 77 and 44.5%. These data suggest that adult non-steroid-refractory, and paediatric patients may respond with the highest frequency. While it is obligatory to wait for the yield of the ongoing controlled trials before any conclusion on these indications is drawn, the data provide seminal ideas to further investigations, including the hypothesis to inaugurate with infliximab a top-down strategy for the treatment of inflammatory bowel disease.

Antibodies, Monoclonal↗

Long-term efficacy of oral microemulsion cyclosporin for refractory ulcerative colitis.

AIM: The 60% bioavailable oral microemulsion formulation of cyclosporin (NEORAL ), has replaced the intravenous route to treat both organ transplant and immune-based disease. Its use for steroid-refractory ulcerative colitis (a recognized indication for intravenous cyclosporin) has been scanty. METHODS: Twenty-three consecutive patients (14 male/9 female, universal colitis 14/23) entered a 3-month course of NEORAL (initially dosed at 5 mg/kg/day) because of steroid-refractoriness (14 cases) and steroid-dependence (9 cases). Responders (at least showing a 50% reduction of a clinical activity score) were continued on azathioprine. The initial steroid dose was tapered on commencing NEORAL; patients requiring steroid resumption or increase in the follow-up were defined as relapsers. RESULTS: The target trough concentration of 200 ng/ml of whole blood was achieved without major titration in all but 1 patient. There were 7 non-responders (30%). Of the 16 responders (70%), 2 have not relapsed; the remaining 14 relapsed at the median time of 9.5 months (1.5-60) with 10 (71%) showing only 1 relapse. Five patients were colectomized 12 months after NEORAL (1.5-24), leaving 11 of the initial 23 (47%) with their colon. Of the 16, all but 1 had azathioprine; the median daily steroid needs fell from 32 to 5 mg. CONCLUSION: The rates of acute and chronic response of 70% and 47% achieved by NEORAL in this indication duplicate the figures achieved by the traditional schedules of cyclosporin administration.

Administration, Oral↗

[Need for hospital admission in patients with ulcerative colitis during maintenance with azathioprine].

AIM: The aim of this study is to analyse the clinical course of ulcerative colitis during maintenance therapy with azathioprine, a drug which is still not proved to be able to modify the natural history of the disease. METHODS: A retrospective study is made of data regarding the frequency of hospital admission for patients with ulcerative colitis referring to a gastroenterological Day-Hospital between 1991 and 2000. The disease history of these patients has been divided into 2 sections: one preceding and the other following an index-event, identified as the beginning of a maintenance regimen with azathioprine; this allowed to find possible differences in the clinical course after the index-event. Patients were controls of themselves. RESULTS: Seventeen patients qualified for analysis. Remission from an acute severe attack of ulcerative colitis was reached by intravenous or oral cyclosporine for 14 of them and by prednisone for 3 of them. The maintenance treatment with azathioprine, which started in all but 1 patient (intention-to-treat), showed a reduction in the number of hospital admissions, decreasing from a mean of 2.12+/-0.69 in the preceding 4.2+/-4.3 years to a mean of 0.12+/-0.33 in the following 5.8+/-2.5 years (p=0.000). CONCLUSIONS: Patients undergoing maintenance therapy with azathioprine showed face fewer relapses needing hospitalisation than those without azathioprine.

Adolescent↗

[The team approach].

Teamwork is emerging like a model of prevailing reference in many working fields: the interaction and, above all, integration between several persons can be an instrument to empower the individual skills, allowing to reach different and higher levels of creativity and efficiency than the sum of the single members' capacities. However, the capacity of interaction, tolerance, and focusing on the problem is required to the members who also need training for this way of working. After a brief historical summary of some ''creative groups'' experiences in the fields of literature, science and arts, a vast review of theoretical model references is presented. Starting from specific North-American guidelines, a hypothesis of nutritional teamwork is introduced. This hypothesis aims at optimizing therapeutic interventions, at the critical review of the provided services and at a greater care for the cost-benefit ratio.

English Abstract↗

Expression and antigenic characterization of recombinant Mycoplasma agalactiae P48 major surface protein.

The gene encoding the P48 major surface lipoprotein of M. agalactiae has been recently characterised. Since its product plays an important role in the immune response of infected animals, in this study we analysed a recombinant P48 expressed in E. coli. Multiple point mutations were introduced by site directed mutagenesis in order to convert four tryptophan TGA codons, which are a typical feature of the mycoplasma genetic code, into the standard TGG. The mutated p48 gene was subcloned into pGex-2T and expressed in fusion with glutathione-S transferase. Following purification steps, P48 was eluted from carrier protein by thrombin digestion and used in Western blot and indirect ELISA using well-characterised sheep sera. Results demonstrate that specific antibodies against P48 are detected 3 weeks after onset of clinical disease and the recombinant P48 is a diagnostically relevant marker of M. agalactiae infection.

Animals↗

P48 major surface antigen of Mycoplasma agalactiae is homologous to a malp product of Mycoplasma fermentans and belongs to a selected family of bacterial lipoproteins.

A major surface antigenic lipoprotein of Mycoplasma agalactiae, promptly recognized by the host's immune system, was characterized. The mature product, P48, showed significant similarity and shared conserved amino acid motifs with lipoproteins or predicted lipoproteins from Mycoplasma fermentans, Mycoplasma hyorhinis, relapsing fever Borrelia spp., Bacillus subtilis, and Treponema pallidum.

Amino Acid Motifs↗

Minimally invasive 3D data registration in computer and robot assisted total knee arthroplasty.

Computer and robot assisted surgery is concerned with the improvements achievable by using computer methods and robotic devices to plan and execute surgical interventions. The registration of different coordinate frames, often achieved through the matching of 3D data sets, represents a crucial step connecting planning and execution. Orthopaedic surgery already features a number of functioning applications which include registration routines relying on presurgically implanted fiducial markers. Replacing such invasive routine with non-fiducial registration procedures is regarded as a necessary step towards a minimisation of surgical invasiveness. A minimally invasive registration technique based on the iterative closest point algorithm is presented and conceived for a specific computer and robot assisted orthopaedic reconstructive intervention, namely total knee arthroplasty. The whole surgical protocol is examined in detail and the experimental results, relative to tests performed on synthetic and animal specimens, are thoroughly reported and discussed. The authors indicate that the proposed registration approach is well-suited for the relevant application and appropriate for in vivo testing.

Algorithms↗

Use of a biocompatible fiducial marker in evaluating the accuracy of computed tomography image registration.

RATIONALE AND OBJECTIVES: Accurate registration of computed tomography (CT) images to the patient is crucial for computer-assisted surgery. Markers used in roentgen stereo-grammetric analysis (RSA) can be located in a CT scan using a novel approach and also can be located physically. Roentgen stereo-grammetric analysis data act as "ground truth" for the three-dimensional marker locations. METHODS: Two foam-bone phantoms were marked. The markers were scanned seven times with RSA, three times with axial CT, and contacted four times with a coordinate measuring arm. Root-mean-square (RMS) errors were derived for the registrations. RESULTS: Computed tomography and RSA data register to 0.15 mm RMS error. Computed tomography and arm data register to 0.25 mm. The markers are biocompatible, and the coordinate measuring arm is usable in an operating room. CONCLUSIONS: Typical in vitro registration errors are approximately 2 mm. The authors have developed a marker that provides superior registration, and a procedure that can be used for in vivo studies.

Biocompatible Materials↗

Ultrastructural appearance of chondroblastoma.

The ultrastructural appearance of two chondroblastoma were examined by scanning and transmission electron microscopy. The polygonal basal cells, with a scanty pericellular matrix, show a poorly developed endoplasmic reticulum and many Golgi bodies. The highly differentiated chondroid cells are assembled in isogenous clusters and show intracytoplasmic inclusions of glycogen and lipids, numerous mitochondria and superficial secretion vesicles arising from a well developed rough endoplasmic reticulum. Clusters of crystals, in close contact with the matrix collagen fibres are found near to the tumour cells. These ultrastructural characteristics, together with the basal undifferentiated cells that proliferate and differentiate into cartilaginous tissue, distinguish this neoplasm from chondroma, mesenchymal chondrosarcoma and chondromyxoid fibroma and confirm its chondroid origin.

Adolescent↗

Scanning electron microscopy of osteoid osteoma.

We have examined the organic components of the nidus of an osteoid osteoma in 4 patients using scanning electron microscopy. Different organisation of the osteoblastic cells and of the fibrous structures of the osteoid matrix in different zones was demonstrated. These findings indicated a greater degree of immaturity in the centre, as compared with the peripheral area where the process of differentiation was more evident.

Adolescent↗

Dermatophilosis in sheep: first report in Italy, experimental reproduction and evaluation of immune response.

A severe exudative-crustous and proliferous dermatitis in a 2 year old sheep caused by Dermatophilus congolensis (observed for the first time in Italy), is reported. The disease was reproduced experimentally in sheep, goats, rabbits and guinea pigs, whose skin was treated in different ways before infection. E.L.I.S.A. and Immunoblotting tests carried out in experimentally infected sheep, showed the antigenic complexity of the pathogen and the existence of cross-immunity to the protein components. Intradermoreaction tests were carried out in all animals. The development of a positive reaction only in rabbits and guinea pigs, confirmed that these animals have a cellular immunity against Dermatophilus congolensis.

Actinomycetales↗

Morphological aspects of the synovial membrane and femoral epiphyseal cartilage in experimentally induced chronic anemia.

The authors describe the microscopic and ultrastructural changes in the synovial membrane and femoral growth cartilage in experimentally induced chronic anemia. The reiterated anoxic stimulus is responsible for premature morphologic changes which become progressively worse and then appear to stabilize after 30 days. The series of events at the completion of the experiment are characterized by the following: 1) villous hyperplasia-hypertrophy with an increase of the secretory vesicles of type B synoviocytes in the intima and lymphoplasmacellular infiltrates in the sub-intima of the synovial membrane with fragmentation of the bony trabeculae, 2) areas of premature closure of the growth cartilage, 3) irregularity of the profile, thickness, and structure of the articular cartilage. The authors propose a biologic correlation between the above osteoarticular changes and the typical features of certain disorders of this anatomical region (hemopathies, Legg-Calvé-Perthes disease).

Anemia↗

Peripheral chondrosarcoma: ultrastructural investigation by transmission and scanning electron microscopy.

Ultrastructural analysis by transmission and scanning electron microscopy was performed on two grade 1 peripheral chondrosarcomas which had arisen from a preexisting osteochondroma. This analysis allowed us to determine the morphologic changes in both the cell and the matrix and suggested a low grade of malignancy. We emphasize that ultrastructural analysis with scanning and electron microscopy is only valid when conducted on representative areas of the tumor.

Adult↗