Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes

In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS). A clinical trial was performed to evaluate whether a combination of these agents was effective in relieving the cytopenias associated with MDS. Twenty-seven patients with low- or intermediate-risk MDS were enrolled in a 12-week study. ATRA was administered orally at the dose of 80 mg/m(2) per day in 2 divided doses for 7 consecutive days every other week. Recombinant human EPO was given subcutaneously 3 times a week. The EPO dose was initiated at 150 U/kg and was increased to 300 U/kg if after 6 weeks there was no or there was suboptimal erythroid response. Patients who responded to therapy were continued on ATRA and EPO at the same doses for 6 additional months (extension phase). Further treatment was given to patients with a continued response. Clinically significant erythroid responses with increases of hemoglobin levels of at least 1 g/dL or reduction of transfusion needs were seen in 13 (48%) patients, with 4 showing improved responses after dose escalation of EPO. Ten (37%) patients displayed continued responses during 6 months of extended treatment, and 7 (26%) are still responsive after a follow-up period of 13 months. Neutrophil responses were observed in 5 of 12 patients with neutropenia, and platelet responses were observed in 6 of 9 patients with thrombocytopenia. Three patients displayed trilineage responses that were sustained during continuation therapy. Side effects were observed in all patients but were of mild entity and did not require discontinuation of therapy. It is concluded that the combination ATRA + EPO is an effective and well-tolerated treatment for patients with low- and intermediate-risk MDS. The optimal ATRA and EPO schedule and the role of maintenance treatment remain to be determined and warrant further investigation.     

Physeal fractures of the distal radius and ulna: long-term prognosis

OBJECTIVES: The long-term prognosis of injuries to the distal physis of forearm bones, including complications such as radioulnar length discrepancy and styloid nonunion, has not been extensively studied. Reliable radiographic prognostic criteria to predict physeal disturbance at trauma are also lacking. The aim of this study is to investigate both issues. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS/PARTICIPANTS: One hundred sixty-three lesions to the distal physis of the forearm bones in 157 patients were available for a long-term follow-up. Seventy-seven injuries of the distal radial physis were radiographically isolated, 54 were associated with a fracture of the ulnar styloid, and 26 with a fracture of the distal ulnar metaphysis. Of the six injuries of the distal ulnar physis, five were associated with a fracture of the distal radial metaphysis, and one was an isolated injury of the distal ulnar physis. INTERVENTION: Treatment consisted of wrist immobilization in a long-arm plaster cast for 6 weeks. Dorsal or volar displacement was reduced using general anesthesia. MAIN OUTCOME MEASUREMENTS: All patients had both clinical and radiographic evaluation, with an average follow-up of 25.5 years (range 14-46 years). The average age of the patients at injury was 11.6 years (range 5-17 years), whereas their average age at follow-up was 35.5 years (range 22-56 years). Both the Salter and Harris and the Ogden classifications were used to classify physeal injuries. RESULTS: According to Salter and Harris, of the 157 radial lesions, 18 were type 1 and 139 type 2. According to Ogden, 14 were type 1A, 4 type 1C, 84 type 2A, 13 type 2B, 17 type 2C, and 25 type 2D. Of the 6 ulnar lesions, 2 were Salter and Harris type 1 (Ogden type 1A), 3 type 2 (Ogden type 2A), and 1 type 4 (Ogden type 4A). Fifty-four radiographically evident fractures of the ulnar styloid associated with injuries of the distal radial physis were classified as Ogden type 7A. At follow-up, all of our patients were fully asymptomatic, except for those who had forearm bone growth failure of more than 1 cm. Shortening of the previously injured forearm bones ranging from 1 to 6.5 cm was observed in 2 open and subsequently infected lesions as well as in 5 uncomplicated lesions of the 157 distal radial physeal injuries (4.4%), and in 3 of the 6 distal ulnar physeal injuries (50%). Shortening of 1 cm or more was observed in the uncomplicated lesions of radial physeal injury with Ogden type 1C, 2B, and 2D lesions, and in ulnar physeal injuries Ogden type 1A, 2A, and 4A. Thirty-eight additional patients had radioulnar length discrepancy that ranged from 2 to 9 mm, and 53 patients had styloid nonunion, but all of them were asymptomatic. CONCLUSIONS: None of the patients reviewed at follow-up, including those with radioulnar length discrepancy of less than 1 cm and those with styloid nonunion, complained of any symptom related to their previous injury, not even those engaged in heavy manual labor. Of the 10 patients with either radial or ulnar shortening of more than 1 cm, only 2 with radial growth arrest and marked radioulnar length discrepancy had severe functional problems. Growth disturbances of more than 1 cm following distal radial physeal injury occurred only in Ogden type 1C, 2B, and 2D lesions, whereas in distal ulnar physeal injuries, growth disturbances occurred regardless of the Ogden classification type.     

Bone metastases in the hip region: surgical treatment

Subjective factors of the patient such as age, weight, occupation, expectations, etc. must be carefully evaluated in terms of surgery. It is always important to remember life expectancy, and the choice of a surgical procedure must be based on it. Limited survival and possible radiation therapy must eliminate methods that require long healing times: we no longer use bone grafts because the risk of healing time taking up too much of the time left for the patient is too high. Reconstructions must have an immediate solidity allowing early use of the limb. Thus, in the proximal femur, we above all use protheses (traditional or modular RPS); in acetabular lesions that do not involve the joint surface, our treatment of choice is curettage with liquid nitrogen and cement, armed with screws and nails. Prostheses, which are always cemented, are assembled using bipolar cups; cases where lysis is so wide on the cotyloid side as to require THR are rare. The cotyles, in cases such as these, are those that allow for anchoring with several sites (Octopus type), the McMinn or, at times, common cotyles in PE.     

Resection of the proximal humerus for metastases and replacement with RPS prosthesis

In the surgical treatment of metastatic lesions of the proximal humerus it is important to find solutions that eliminate pain and solve the mechanical problem in a short time and with reduced costs. In 90% of cases, intralesional curettage, freezing with liquid nitrogen and cement enhanced intramedullary instrumentation is capable of brilliantly solving the problems of these patients. When, instead, osteolysis involves the greater tuberosity and/or the joint region, resection of the proximal humerus followed by reconstruction with a modular prosthesis is indicated. Of those available on the market, the RPS system (LIMA) has features that make it equivalent to others, but at costs considerably lower. However, in reconstructions with prostheses, active abduction is significantly limited. A personal series of 20 patients is presented.     

Novel antitenascin antibody with increased tumour localisation for Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT)

The Pretargeted Antibody-Guided RadioImmunoTherapy (PAGRIT) method is based on intravenous, sequential administration of a biotinylated antibody, avidin/streptavidin and (90)Y-labelled biotin. The hybridoma clone producing the monoclonal antitenascin antibody BC4, previously used for clinical applications, was found not suitable for further development because of the production of an additional, nonfunctional light chain. In order to solve this problem, the new cST2146 hybridoma clone was generated. The monoclonal antibody ST2146, produced by this hybridoma, having the same specificity as BC4 but lacking the nonfunctional light chain, was characterised. ST2146 was found able to bind human tenascin at an epitope strictly related, if not identical, to the antigenic epitope of BC4. It showed, compared to BC4, higher affinity and immunoreactivity and similar selectivity by immunohistochemistry. Biodistribution studies of biotinylated ST2146 and three other monoclonal antitenascin antibodies showed for ST2146 the highest and more specific tumour localisation in HT29-grafted nude mice. On the overall, ST2146 appears to be a good alternative to BC4 for further clinical development of PAGRIT.     

Prevention of experimental autoimmune encephalomyelitis by encephalitogenic epitope sequence simplified derivatives

The encephalitogenic epitope P81-100 from mouse myelin basic protein was used to generate two simplified derivatives with glycine substitutions in alternating positions which were tested for their biological activity in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis. While both derivatives were unable to induce in mice the disease at the same parent peptide P81-100 dosage, T cell proliferation assays demonstrated their ability to compete with the parental peptide in a dose related manner. Experiments of cell surface binding and T cell tolerance revealed a different behavior of the two derivatives, suggesting different roles in the MHC blockade or T cell tolerance. On induction of encephalomyelitis in animals by P81-100 treatment, one variant proved in vivo to be very effective in protecting from the disease.     

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

BACKGROUND: Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. METHODS: The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. RESULTS: In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. CONCLUSIONS: The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.     

Morfologia comparata del muscolo ?tensor tympani?

Con 19 figure nel testo.