Picture archiving and communication systems lead to sustained improvements in reporting times and productivity: results of a 5-year audit.

AIM: To evaluate the impact of picture archiving and communications systems (PACS) on reporting times and productivity in a large teaching hospital. MATERIALS AND METHODS: Reporting time, defined as the time taken from patient registration to report availability, and productivity, defined as the number of reports issued per whole time equivalent (WTE) radiologist per month, were studied for 2 years pre- and 3 years post-PACS installation. Mean reporting time was calculated for plain radiographs and specialist radiology techniques [computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine]. Productivity, total department workload, and unreported film rates were also assessed. Pre- and post-PACS findings were compared. RESULTS: Between 2002-2006 the number of radiological patient episodes increased by 30% from 11,531/month to 15,057/month. This was accompanied by a smaller increase in WTE reporting radiologists, from 32 to 37 (15%). Mean reporting times have improved substantially post-PACS, plain radiograph reporting time decreased by 26% (from 6.8 to 5 days; p=0.002) and specialty modalities by 24% (4.1 to 3.1 days; p<0.001). Radiologist productivity has increased by 18% (337 films to 407 films/WTE radiologist/month). Unreported films have decreased from 5 to 4% for plain radiographs and are steady for specialty modalities (< 1%). In most areas improvements have been sustained over a 3-year period. CONCLUSION: Since the introduction of PACS, reporting times have decreased by 25% and the productivity improved by 18%. Sustained improvements are felt to reflect the efficiencies and cultural change that accompanied the introduction of PACS and digital dictation.

Pharmacological characterization of NAADP-induced Ca2+ signals in starfish oocytes.

The recently discovered second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) is central to the onset of intracellular Ca2+ signals induced by several stimuli, including fertilization. The nature of the Ca2+ pool mobilized by NAADP is still controversial. Depending on the cell type, NAADP may target either an acidic compartment with lysosomal properties or ryanodine receptors (RyRs) on endoplasmic reticulum. In addition, NAADP elicits a robust Ca2+ influx into starfish oocytes by activating a Ca2+-mediated current across the plasma membrane. In the present study, we employed the single-electrode intracellular recording technique to assess the involvement of either acidic organelles or RyRs in NAADP-elicited Ca2+ entry. We found that neither drugs which interfere with acidic compartments nor inhibitors of RyRs affected NAADP-induced depolarization. These data further support the hypothesis that a yet unidentified plasma membrane Ca2+ channel is the target of NAADP in starfish oocytes.

A transport mechanism for NAADP in a rat basophilic cell line.

NAADP is a second messenger that releases Ca2+ from intracellular stores. Surprisingly, it has been recently shown that extracellular application of NAADP is capable of inducing intracellular Ca2+ release. This is particularly important since the only mammalian enzymes known to catalyze the synthesis of this second messenger are located extracellularly. In the present manuscript, we have investigated whether mammalian cells possess a transport system capable of transporting this highly charged molecule into cells. Indeed, in RBL-2H3 cells, a rat basophilic cell line, and in SK-N-BE cells, a neuroblastoma cell line, [32P]NAADP is efficiently transported inside cells. NAADP transport is Na+ and Ca2+ dependent, is partially blocked by dipyridamole, but is unaffected by nitrobenzylthioinosine. RBL-2H3 cells also transport [32P]cADPR, but the differences in the pharmacological profile suggest that NAADP transport proceeds by a novel mechanism. Lastly, extracellular application of NAADP, but not NADP, induced a raise in intracellular Ca2+. This is the first demonstration that NAADP is transported into cells and highlights the possibility that, alongside a second messenger, NAADP might also act as an autocrine/paracrine signal.

Sphingosine releases Ca2+ from intracellular stores via the ryanodine receptor in sea urchin egg homogenates.

Various reports have demonstrated that the sphingolipids sphingosine and sphingosine-1-phosphate are able to induce Ca2+ release from intracellular stores in a similar way to second messengers. Here, we have used the sea urchin egg homogenate, a model system for the study of intracellular Ca2+ release mechanisms, to investigate the effect of these sphingolipids. While ceramide and sphingosine-1-phosphate did not display the ability to release Ca2+, sphingosine stimulated transient Ca2+ release from thapsigargin-sensitive intracellular stores. This release was inhibited by ryanodine receptor blockers (high concentrations of ryanodine, Mg2+, and procaine) but not by pre-treatment of homogenates with cADPR, 8-bromo-cADPR or blockers of other intracellular Ca2+ channels. However, sphingosine rendered the ryanodine receptor refractory to cADPR. We propose that, in the sea urchin egg, sphingosine is able to activate the ryanodine receptor via a mechanism distinct from that used by cADPR.

Role of the nicotinic acid group in NAADP receptor selectivity.

Nicotinic acid adenine dinucleotide phosphate (NAADP) has been shown to be an intracellular Ca2+-releasing messenger in a wide variety of systems to date. Its actions are both potent and highly specific despite differing structurally from the endogenous cellular co-factor and its precursor, NADP, only in the substitution of a hydroxyl for the amine group at the 3' position of the pyridine ring. This substitution allows NAADP to bind to a membrane-localized binding site in sea urchin egg homogenates with an IC50 at least 1000-fold greater than that of NADP as measured by competition radioligand binding assays. This suggests that the NAADP receptor protein must include certain features in the NAADP binding site that regulate this specificity. In order to investigate this interaction, we synthesised a series of NAADP analogues differing from NAADP at the 3' position of the pyridine ring that included both simple carboxylic acid analogues as well as a series of chemical isosters. We then investigated both their affinity for the NAADP binding site in sea urchin egg homogenates and their ability to activate the NAADP sensitive Ca2+ channel. We hereby show that a negative charge at the 3' position is an important determinant of affinity but the protein displays a large tolerance for the size of the group. Furthermore, the protein does not easily accommodate multiple charged groups or large uncharged groups.

NAADP receptors are present and functional in the heart.

Alongside the well-studied inositol 1,4,5 trisphosphate and ryanodine receptors, evidence is gathering that a new intracellular release mechanism, gated by the pyridine nucleotide nicotinic acid adenine dinucleotide phosphate (NAADP), is present in numerous organisms, ranging from plant to mammalian cells (reviewed in [1]). Most cells have been shown to express at least two Ca(2+)-release mechanisms controlled by different messengers, and this can lead to redundancy, convergence, or divergence of responses. One exception appears to be muscle and heart contractile tissues. Here, it is thought that the dominant intracellular channel is the ryanodine receptor, while IP(3) receptors are poorly expressed and their role appears to be negligible. We now report that NAADP receptors are functional and abundant in cardiac microsomes. NAADP binds specifically and with high affinity (130 pM and 4 nM) to two sites on cardiac microsomes and releases Ca(2+) with an apparent EC(50) of 323 +/- 14 nM. Furthermore, binding experiments show that this receptor displays both positive and negative cooperativity, a peculiarity unique among intracellular Ca(2+) channels. Therefore, we show that the heart possesses multiple mechanisms to increase the complexity of Ca(2+) signaling and that NAADP may be integral in the functioning of this organ.

Characterization of NAADP(+) binding in sea urchin eggs.

Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is a pyridine nucleotide which has been shown to release Ca(2+) from intracellular membranes in echinoderms, Ascidiae, mammals, and plants. NAADP releases Ca(2+) via a mechanism independent of ryanodine and inositol 1,4,5-trisphosphate (IP(3)) receptors and the NAADP(+) receptor is likely to be located on a separate organelle. We have investigated the binding characteristics of NAADP(+) to its receptor in sea urchin egg homogenates. NAADP(+) binds to a saturable membrane-bound site with high affinity (K(d) = 193 +/- 35. 7 pM). NAADP(+) associates to its receptor with a t(1/2) of approximately 7 min while dissociation does not occur during the time course of the experiment. Furthermore, NAD(+), NAAD(+), ADP, or ATP cannot displace NAADP(+) binding. The structurally related molecules NADP(+) and NADPH displayed a markedly lower affinity for the binding site with K(d)'s 500- and 25,000-fold higher than NAADP(+), respectively. This discrepancy between oxidized and reduced forms of NADP(+) might suggest that NAADP(+) signaling is itself regulated by the redox state of the cell.