Misbehaviour of XIST RNA in Breast Cancer Cells

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors.     

Pitfalls in CT diagnosis of appendicitis: Pictorial essay

Despite the high diagnostic accuracy of CT for appendicitis, numerous pitfalls exist that may result in a misdiagnosis. This pictorial review outlines the potential pitfalls in the CT diagnosis of appendicitis that includes atypical position of the appendix and coexisting pathologies. Various mimickers of appendicitis and clinical dilemmas will be highlighted. Upon completion, the reviewer should have an improved ability to recognise appendicitis mimickers and identify equivocal or atypical findings.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.     

Unrelated donor marrow transplantation in children

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA- mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Tetralogy of Fallot: MR findings

Surgical treatment of patients with tetralogy of Fallot requires accurate definition of all anatomic structures, particularly the central pulmonary arteries. Magnetic resonance (MR) images of 22 patients with tetralogy of Fallot were studied to assess their usefulness in providing information regarding the spectrum of anatomic abnormalities in this condition. MR findings were compared with information obtained at catheterization (in 16 patients) and at surgery (in nine patients), both of which were performed within 3 months of MR imaging. Ventricular chamber enlargement and wall hypertrophy were clearly delineated in most of the 17 patients who were examined before definitive surgical repair, and ventricular septal defects were visualized in all 17. Palliative systemic-to-pulmonary shunts were visualized in 11 patients and could be evaluated for patency. Most important, the morphology and size of the right ventricular outflow tract and central pulmonary arteries could be accurately assessed. Pulmonary artery measurements obtained from MR images demonstrated excellent correlation with angiographic measurements. In six patients examined after complete surgical repair, MR images accurately reflected changes in pulmonary artery outflow tract morphology and complications, such as residual pulmonary artery stenosis and thrombosis. The findings suggest that MR imaging can complement or obviate catheterization in the evaluation of tetralogy of Fallot with regard to suitability for definitive surgical repair.     

Craniosynostosis in X-linked hypophosphataemic rickets

A report of three cases of craniosynostosis in X-linked hypophosphataemic rickets (XLH) is presented. The literature is reviewed, suggesting that craniosynostosis is relatively common in XLH and that boys may be more at risk than girls. It is recommended that radiological screening be offered to all patients with XLH.     

The thoracic aorta studied by MR imaging

Thirty-three patients with a variety of disorders of the thoracic aorta (aneurysm, dissection, Marfan syndrome, coarctation/pseudocoarctation, L-transposition, and Takayasu disease) were evaluated with magnetic resonance (MR) imaging. MR imaging delineated the presence and extent of thoracic aortic aneurysms and showed the relationship of the aneurysm to arch vessels; it also demonstrated intimal flaps and individual lumina in types A and B aortic dissection. Dilation of the ascending aorta in Marfan syndrome and focal narrowing of the aorta in coarctation were well visualized. The anteroposterior and side-to-side relationships of the aorta and pulmonary artery in L-transposition were demonstrated, as were aortic wall thickening and branch vessel narrowing in Takayasu arteritis. Initial experience suggests that MR imaging may provide a noninvasive method for evaluating thoracic aortic disease. Limitations include inferior spatial resolution, occasional difficulty in imaging the entire region of interest in one section, lack of signal from calcifications, and inability to monitor critically ill patients.