Down-regulation of riα subunit of camp-dependent protein kinase induces growth inhibition of human mammary epithelial cells transformed by c-ha-ras and c-erbb-2 proto-oncogenes

MCF- 10A is a spontaneously immortalized, non-transformed human mammary epithelial cell line. We have recently obtained MCF- 10A clones (MCF- 1OA HE cells) that are transformed following over-expression of both a human point-mutated c-Ha-ras and the c-erbB-2 proto-oncogenes. Two isoforms of the cAMP-dependent protein kinase (cAK) have been described in mammalian cells. Enhanced levels of type-I cAK (cAKI) are generally found in tumor cells. To determine whether inhibition of cAKl expression may interfere with ras and erbB-2 oncogene-induced transformation of human mammary epithelial cells, we have tested the effects of 2 agents that specifically down-regulate cAKI, such as 8-chloro-cAMP and an anti-sense oligodeoxynucleotide targeted against the R1α regulatory subunit of cAKl on MCF-10A HE cells. Treatment of MCF-10A HE cells with 8-chloro-cAMP induces a dose-dependent growth inhibition under both monolayer and soft-agar growth conditions, that is correlated with an accumulation of MCF-10A HE cells in G₀/G, phases of the cell cycle and a reduction of the number of cells in S phase. In contrast, 8-chloro-cAMP has no effect on MCF-10A cell growth. Furthermore, 8-chloro-cAMP treatment of MCF-10A HE cells induces a 4- to 6-fold reduction in p185erbB-2 expression and brings p21 ras expression to levels comparable to those found in MCF-10A cells. Treatment of MCF-10A HE cells with an Rlα anti-sense oligodeoxynucleotide determines a comparable inhibition of both anchorage-dependent and anchorage-independent cell growth. Our results suggest that cAKl may act as a mediator of ras and erbB-2 oncogene action in human breast cells and that interference with cAKl action provides a potential tool for inhibiting the growth-promoting effects of these oncogenes.     

Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: Improved results and revised prognostic criteria

Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine. prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age >30 years, absolute blast count >15 × 10⁹/1, and CD10-negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara-C and VM-26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0·10) than those with normal karyotype or negative molecular study (probability 0·70), and those not studied or with insufficient methaphases (probability 0·50) (p<0·05 by log-rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management of adult ALL.     

Demystifying values assessment

The current climate of networking and restructuring among healthcare providers calls for measurable methods to assess an organization's adherence to its fundamental values. In response to that need, the SSM Health Care System (SSMHCS) prepared a guide to assessing values integration. This innovation tool has proven to be adaptable for many uses: it helps organizations examine the compatibility of potential partners' values, as well as their own progress toward integration of their stated mission, values, and philosophy. The guide outlines 10 key areas that serve to focus and define the values assessment: Vision. Serving the poor. Serving the community. Continuous quality improvement. Employment practices. Role of leaders. Stewardship Advocacy. Wellness. Church. The guide includes a discussion of the significance of each of these key areas: the implications of including each area; and key indicators, or standards statements, for assessment. Users' response to the guide has been overwhelmingly positive. This guide should provide valuable systemwide data and identify areas of strength or needed growth.     

Detection of Progression of Coronary Artery Disease in the Elderly

In order to assess the progression of coronary artery disease (CAD) in the elderly, we evaluated 91 patients aged 75 years or older who had undergone 2 consecutive angiograms without intervening revascularization. Progression was defined as an absolute increase in lumen narrowing by at least 20% with minimum stenosis of 50% at second angiogram, or progression to total occlusion of any preexisting lesion. Progression involving at least 1 vessel was observed in 63% of patients. Only 6% of initially normal or insignificantly diseased segments showed progression. In contrast, 72% of segments that progressed to total occlusion had shown an initial narrowing greater than 75%. Progression occurred in 100% of patients with an interval myocardial infarction, but in no patients with symptomatic valvular disease. No regression was observed, while 7 of 36 (19%) of initially occluded segments had recanalized. We conclude that progression of CAD in the elderly occurs at rates similar to those observed in a younger population; however no correlation could be found between the rate of progression and either risk factors or elapsed time between angiographic studies.     

The fate of small-size pericardial heart valve prostheses in an older patient population

Background

Structural valve deterioration (SVD) is the Achilles' heel of bioprostheses. Its correlation with younger age is well known. In recent years we exclusively reserved use of small-size Mitroflow valve prostheses (LivaNova, London, United Kingdom) to an older patient population with small aortic annuli. This study aimed to assess the incidence of SVD and its effect on patient survival and need for reoperation.

Effects of prolonged ischemia on human skeletal muscle microcirculation as assessed by near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) has been used to detect in vivo microvascular alterations by means of a vascular occlusion test. We sought to analyse by NIRS the microcirculatory profile of patients undergoing prolonged tourniquet-induced bloodless condition for extremity surgery, and compare the results with time of ischemia and comorbidities. We conducted a prospective observational study on 42 patients undergoing upper limb surgery. Regional anaesthesia was achieved and ischemia was induced by a tourniquet cuffed at 250 mmHg. The probe of a NIRS monitor (InSpectra 325, Hutchiston, USA) was placed on the brachial muscle, and muscle oxygen saturation (StO₂) was recorded continuously before anaesthesia, during and after surgery. The following variables were recorded: baseline StO₂, StO₂ desaturation slope during occlusion (dSlope, units/s), resaturation rate following ischemia (RR, units/s), hyperaemic peak (peak, units), and duration of the hyperaemic period following ischemia (hyperaemic time, s). Values of dSlope were similar among all patients. RR and hyperaemic time were significantly correlated with the duration of ischemia, but not with comorbidities [p = 0.007 CI (?35.64 to ?13.1), and p < 0.001 CI (0.049–0.159), respectively]. Grouping patients by duration of ischemia (30, 60, or 90 min), we found a significant decrease in RR after 60 and 90 min (p < 0.001 and p = 0.03, respectively). Hyperaemic peak was lower in the 90 min group (83.9 ± 6.8 vs. 91.2 ± 5.7 %, p = 0.02) whereas the hyperaemic time was significantly increased (595 ± 136 vs. 429 ± 107 min, p < 0.001). Alterations of skeletal muscle microcirculation were correlated with the duration of ischemia, but not with comorbidities. We observed an initial impairment of the microcirculatory recovery at 90 min of ischemia.     

Prognostic role of ΔMTV and ΔTLG in Burkitt lymphoma

Annals of Nuclear Medicine - Burkitt’s lymphoma (BL) is an aggressive lymphoma sub-type with high 18F-FDG avidity, but no well established evidence of PET/CT’s role in treatment...