Treatment of chronic myeloid leukemia with autologous transplantation using peripheral blood stem cells or bone marrow cultured in IL-2 followed by IL-2, GM-CSF,and IFN-alpha administration

Interleukin-2 (IL-2) is able to generate nonspecific cytotoxic effectors from hematopoietic precursors. We evaluated the feasibility and efficacy of chronic myeloid leukemia (CML) treatment with autologous hematopoietic stem cell transplantation (HSCT) using grafts cultured in IL-2 followed by immunotherapy with IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-α. Eight patients with CML were enrolled: five in an accelerated phase and three in a chronic phase. They received peripheral blood stem cells (PBSC) or bone marrow (BM) cultured in a medium containing IL-2 for 24 h. A median of 1.29 × 10⁶ CD34+ cells/kg were infused after conditioning with busulfan (12–16 mg/kg) in PBSC recipients. BM was infused without prior myeloablative therapy. The engraftment occurred with a median of 15 d. Engraftment failure developed in one patient. The transplantation was followed by a 1-mo regimen of IL-2 (0.5 × 10⁶ IU/m² daily) and GM-CSF, and 6 mo of IFN-α. One complete and one transient minor cytogenetic remission were observed. At 24 mo after transplantation, two patients had died of progressive disease and one of infection. Five patients had stable disease in the chronic phase. Autologous transplantation using IL-2-activated graft is feasible and the subsequent IL-2, GM-CSF, and IFN-α administration has acceptable toxicity. However, no benefits in comparison with conventional autologous transplantation for CML were identified in our study. Tissue Bank, University Hospital Brno, Czech Republic     

Geographic variation in health services use in Nova Scotia

To further our understanding of factors underlying geographic variation in health and the potential role of availability of and access to health services, we sought to quantify the geographic variation in health services use in the province of Nova Scotia. For the period 1996 to 1999 we examined the variation in the use of health services across 64 geographic areas in conjunction with health and socio-economic factors, using multilevel methods and empirical Bayesian estimates based on provincial physician billings and hospital separation records. We revealed moderate geographic variation in the use of family physician services and large variation in specialist and hospital services. In the two urban centres, Metropolitan Halifax and the Cape Breton Regional Municipality, use of specialist services was respectively 26.24% and 15.59% higher than the provincial average, and use of hospital services was respectively 21.55% and 37.67% higher. Geographic areas in which residents had better health were characterized by more use of family physician services and reduced use of specialist and hospital services. These associations seem to support policy strategies that aim to improve health and to reduce health care costs by investing in prevention and primary health care, and they highlight the potential implications of the shortage of family physicians across Canada.     

Outcomes of bail-out stenting for suboptimal balloon angioplasty during primary intervention in acute myocardial infarction (The CADILLAC trial)

The results of bail-out stenting after unsuccessful primary balloon angioplasty compared with routine stenting or successful balloon angioplasty in acute myocardial infarction are unknown. In the CADILLAC trial, 168 of 1,044 patients (16.1%) randomized to balloon angioplasty crossed over to stenting after unsuccessful dilatation. Event-free survival was similar after bail-out and routine stenting, and was greater than after successful balloon angioplasty.     

Accuracy of Determining Nodal Negativity in Colorectal Cancer on the Basis of the Number of Nodes Retrieved on Resection

Background: Correct determination of nodal status is pivotal to accurate staging and predicting survival.Methods: This is a secondary analysis of INT0089, an intergroup trial of adjuvant chemotherapy for high-risk stage II and III colon cancer. A subset of patients was studied who underwent right or left hemicolectomy and from whom at least 10 lymph nodes were examined. A mathematical model was created to estimate the probability of a true negative result on the basis of the number of nodes examined. The number of nodes needed to predict nodal negativity with 85%, 50%, and 25% probability on the basis of tumor stage was calculated.Results: In this analysis, 1585 patients were studied. The average number of nodes removed at surgery was comparable between treatment groups at 18.5 (median of 16 in all groups). With this model, when 18 nodes are removed at resection, there is a <25% probability of true node negativity in T1/T2 tumors, whereas <10 nodes need to be examined in T3 and T4 tumors to achieve the same probability.Conclusions: Tumor stage and the number of nodes retrieved at resection influence the accuracy of determining nodal status in colon cancer. Most patients are understaged. Underestimating nodal stage may influence decisions regarding adjuvant therapy, as well as overall prognosis.     

Preparedness for hospital practice among graduates of a problem-based,graduate-entry medical program

OBJECTIVE: To compare preparedness for hospital practice between graduates from a problem-based, graduate-entry medical program and those from other programs (undergraduate problem-based and traditional). DESIGN: Survey of graduates (by mailed questionnaire) and organisers of clinical training (by semistructured interview); results were compared with published results of surveys of graduates from other programs. SETTING AND PARTICIPANTS: All graduates of the first intake of the University of Sydney graduate-entry medical program were surveyed at the end of their first intern year (2001), along with the director of clinical training or intern manager at each of the New South Wales hospitals that employed the graduates. MAIN OUTCOME MEASURES: Graduates' self-reported level of preparedness in the eight domains of the Preparation for Hospital Practice Questionnaire; and organisers' opinions of their strengths and weaknesses. RESULTS: 76 of 108 graduates from the graduate-entry program (70%) and organisers of clinical training at all 17 hospitals participated. Graduates from the program felt more prepared than did those from other programs in five of the eight domains assessed (interpersonal skills, confidence, collaboration, holistic care, and self-directed learning) and no less prepared in any domain. Organisers rated the graduates highly, especially in clinical competence, confidence, communication and professional skills. Opinions of interns' knowledge of basic sciences conflicted, with strengths and weaknesses mentioned with equal frequency. CONCLUSION: Graduates from the graduate-entry, problem-based program are at least as well prepared for their intern year as graduates from traditional and undergraduate problem-based programs.     

Sensitivity and specificity of different staining methods to monitor apoptosis induced by oxidative stress in adherent cells

Anincreasingscopeofbiologicalinvestigationsfocussesonthebiologicalimpactofapoptosisinducedbyoxidativestressespeciallyinartheriosclerosisresearch A greatvarietyofmethodshavebeenintroducedtodetectandquantifyapoptosisincludingTUNEL reaction ,1 4 　 poly (ADP ribose ) polymerase (PARP ) cleavage ,5,6Apo2 7 expression ,7 9　single stranded DNA staining(ssDNA) ,10 12 　AnnexinV binding ,13 15　demonstationofDNA ladder,16 ,17　andcleavageofspecificsubstratesbycertaincaspases,18,19　respe…     

Dimensions of working memory dysfunction in schizophrenia

The aim of this study was to investigate the underlying structure of eight working memory tests used to assess prefrontal dysfunction in schizophrenia research [Letter-Number Span (LNS), Digit-Symbol Test (DST), Trail-Making Test B (TMT-B), Delayed Response Task (DRT) for spatial working memory, Subject Ordered Pointing Task (SOPT), Dual Tasking (DUAL), Continuous Performance Test (CPT)-Identical Pairs, Wisconsin Card Sorting Test (WCST)]. Sixty-six patients with schizophrenia showed significant working memory performance deficits in all tests when compared with 45 healthy controls. Performance was not systematically related to psychopathology. When differences in IQ were controlled, working memory deficits remained stable except in the WCST. Principal components analyses yielded three components for healthy controls: a comparator function of the central executive defined by a comparison of working memory content with information from the environment, an allocation of attentional resources function, and a maximum storage capacity function. The comparator and maximum storage functions could be replicated in the schizophrenia sample. However, the allocation function did not emerge as an independent component and was replaced by a component defined by the WCST. These findings suggest that working memory is not a unitary concept but rather should be conceptually differentiated as functions of transient storage/active rehearsal capacity and central executive manipulation supporting a previous suggestion proposed by Perry et al. [Schizophr. Bull. 27 (2001) 157].