Characterization of NCI-H295R cells as an in vitro model of hyperaldosteronism.

In depth analysis of key molecular mechanisms involved in functional autonomy of aldosterone secretion is hampered by the lack of tumor cell lines that reflect functional characteristics of aldosterone producing adenomas. Herein, we describe the characteristics of the adrenocortical carcinoma cell line NCI-H295R and its suitability as a model of hyperaldosteronism in relation to different culture conditions. Steroid profiling revealed that NCI-H295R cells predominantly secrete cortisol, while aldosterone and other steroids are released at much lower concentrations. However, aldosterone output specifically increased in response to different stimuli such as ACTH and angiotensin II, and in particular to potassium in a dose dependent manner. NCI-H295R cells readily formed spheroids under specific culture conditions, a method widely used for the enrichment of progenitor cells. Unexpectedly, spheroid cells excelled with higher aldosterone concentration and higher expression levels of the steroidogenic enzymes StAR, 3ßHSD, CYP17, SF-1, and the MC2-receptor. Further investigations revealed that this phenomenon is mainly attributed to epithelial growth factor (EGF) and particularly fibroblast growth factor (FGF), which are both essential ingredients in the spheroid culture medium. Aldosterone release under the combinatory influence of EGF and FGF was not higher than the effect of FGF alone. Spheroid growth per se, therefore, does not ensure an enrichment of less differentiated cell types in this cell line.

Assessment of patient safety research from an organizational ergonomics and structural perspective.

The aim of this study is to review patient safety improvement initiatives within a conceptual framework that builds upon principles of organizational ergonomics and emphasizes structural factors that influence patient safety. The literature review included 131 English language published studies of patient safety improvement strategies extracted using Medline, Ovid Healthstar, PubMed and CINAHL searches. Keywords for the search included: 'patient safety'; 'medical errors'; 'adverse event'; 'iatrogenic'; and truncated options for 'improve'. The multilevel, hierarchical framework offered in this paper integrates quality management principles and organizational ergonomics theory and organizes patient safety initiatives according to sociotechnical system elements within three structural levels: health policies and associated health care organizations; health care delivery organizations; and health care microsystems. Utilizing the conceptual framework, this review of patient safety improvement initiatives highlights the need for consideration of the impact of all improvement proposals on each structural component within health care systems. The review also supports the need for patient safety research to evolve from exploratory, 1-D reporting to multi-level, integrated research.

Issues in the assessment of continuous quality improvement implementation in health care organizations.

OBJECTIVE: This paper has two primary aims. First, it examines the need for improved assessment of continuous quality improvement implementation. Second, it analyzes current worldwide measures and studies of continuous quality improvement implementation. METHOD: A comprehensive literature review was conducted which included all published (English language) studies of organization-wide continuous quality improvement implementation. RESULTS: Analysis of the content and research methods incorporated into current measures of continuous quality improvement implementation used worldwide supports a strong consensus regarding the major criteria that need to be addressed. However, there are still promising areas for future research, namely increased use of criteria other than the Baldrige categories, increased focus upon financial variables, improved measures of implementation stage/phase and the use of different types of respondents from multiple organizational levels. CONCLUSION: Increased understanding of the empirical benefits and costs of continuous quality improvement in health care organizations is heavily contingent upon the continued development and improvement of measures of continuous quality improvement implementation.

Acetylcholine receptor bars and transmitter release in frog neuromuscular junctions.

After labelling with rhodaminated alpha-bungarotoxin, acetylcholine receptors in cutaneous pectoris muscles of normal adult frogs (Rana temporaria) appear as brightly fluorescent straight bars, usually extending over the whole gutter. Here we investigated first whether receptor bars can undergo changes and secondly whether they would provide a structural correlate for the strength of a junction. Bars of low fluorescence intensity, as well as short or discontinuous receptor bars consisting of two or three segments, suggest plasticity at the receptor/active zone level. In order to elucidate this notion, receptor bars were studied at different seasons which have previously been shown to be associated with structural changes. In two groups of frogs kept under laboratory conditions simulating wintertime and summertime, respectively, the length and number of receptor bars and the amount of discontinuous bars were investigated. Synaptic contact length, which is the summed length of labelled synaptic branches, and the number and total length of receptor bars did not differ significantly. A clear difference between Group I ("winter" frogs) and Group II ("summer" frogs) was found in the number of discontinuous bars, which was almost twice as high in Group I compared with Group II (6.4 +/- 3.3% S.D. vs 3.4 +/- 1.3% S.D., n = 8 and 7 muscles, respectively, P < 0.05). In addition, the average length of individual bars was slightly longer in Group I frogs (2.16 +/- 0.7 micron S.D. vs 2.07 +/- 0.12 microns S.D., 0.1 < P < 0.05). Transmitter release has been shown to be different in these two groups--as determined from endplate potential measurements in tubocurarine-containing bathing solutions--although it was equal when measured in low Ca2+/high Mg2+ [Dorlöchter M. et al. (1991) Pflügers Arch. 418, Suppl. 1, R31]. We also investigated whether receptor bars would be a reasonable structural correlate of synaptic function by comparing different measures of transmitters release with different structural parameters in 19 identified junctions. The mean quantal content (m) of a junction was positively correlated with the number and total length of receptor bars, but not with synaptic contact area or length. Amplitudes of the first, maximum, and plateau endplate potentials (corrected for a common resting potential and apparent input resistance) at tetanic nerve stimulation (40 Hz for 2 s) in tubocurarine block were strongly correlated with both synaptic contact length and total receptor bar length (r = 0.90 for maximum endplate potential); correlations between m and any structural measure were significantly worse.(ABSTRACT TRUNCATED AT 400 WORDS)