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BACKGROUND Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography- guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P=0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography- guided PCI group. CONCLUSIONS Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. [ABSTRACT FROM AUTHOR]

Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA. Methods and results: Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively. Conclusion: Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation. [ABSTRACT FROM AUTHOR]

Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD) may reduce unnecessary invasive coronary angiographies (ICAs). However, the diagnostic accuracy of perfusion scans after primary CCTA is unknown. The aim of this study was to determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve (FFR) in patients suspected of CAD by CCTA., Methods and Results: Included were consecutive patients (1675) referred to CCTA with symptoms of CAD and low/intermediate risk profile. Patients with suspected CAD based on CCTA were randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was defined as FFR ≤ 0.80 or > 90% diameter stenosis by visual assessment. After initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS. Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76], respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68% [59-76], respectively., Conclusion: Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.

Coronary stent thromboses are characterized as early, if they occur within one month of the index PCI. Late stent thromboses (LST) have an occurrence after one month. Both early and late stent thromboses are a major concern in PCI, because of their clinical presentation as acute myocardial infarction and sudden cardiac death. Early stent thromboses are seen following implantation with bare metal (BMS) and drug eluting (DES) stents. Late occurring stent thromboses (LST) are rare but usually severe events and primarily seen after DES implantation. A number of pathogenetic mechanisms seem to be operating and there will probably be major differences between different types DES and the risk of LST. While early stent thrombosis is primarily related to stent implantation techniques, lesion characteristics and the effect of double platelet therapy, there is emerging evidence that very late stent thrombosis, occurring more than one year after the implantation may be caused by local tissue reaction to the polymers of sirolimus and paclitaxel eluting stents. It is likely that the use of new generations DES with tissue friendly polymers or bioabsorbable polymers will reduce the risk of late stent thrombosis.

The objective of this study was to assess the intra- and inter-investigator variation in the analysis of pressure-flow studies that were performed in men with lower urinary tract symptoms. Two hospitals were involved in this study. In each hospital 100 PFS were selected. Photocopies of printouts of all PFS were analyzed manually by six experienced investigators, including determination of P(detQmax) and Q(max). Afterward, all 200 PFS were analyzed again in a different order. For each P(detQmax) and accompanying Q(max) the AG-number was calculated. With these AG numbers, the intra-investigator SD, the inter-investigator SD and the intra- and inter-investigator SD combined were calculated. The intra- and inter-investigator SD combined was 10.7. This implies that if one investigator analyzes a PFS once and determines an AG number of 40, another investigator may determine an AG number between 40 +/- 2. 77*10.7 = 10-70, using a 95% confidence interval. The inter-investigator SD was 10.0 and the intra-investigator SD was 3.7. The reproducibility of the manual analysis of urodynamic studies is moderate owing to a considerable intra- and inter- investigator variation. This is mostly caused by the substantial intra-investigator variation.

Ultrastructural investigation of detrusor muscle cells in biopsies from 13 patients (8 interstitial cystitis (IC) and 5 controls) was performed. In all IC-patients and in one control a varying number of smooth muscle cells revealed a characteristic oak leaf pattern with protrusions of the sarcolemma. The alterations may express degeneration of smooth muscle cells. Although most probably non-specific yet highly characteristic, the ultrastructural detrusor changes may be important in diagnosing IC.

The neurotrophins are signaling factors that are essential for survival and differentiation of distinct neuronal populations during the development and regeneration of the nervous system. The long-term effects of neurotrophins have been studied in detail, but little is known about their acute effects on neuronal activity. Here we use permeabilized whole-cell patch clamp to demonstrate that neurotrophin-3 (NT-3) and nerve growth factor activate calcium-dependent, paxilline-sensitive potassium channels (BK channels) in cortical neurons. Application of NT-3 or nerve growth factor produced a rapid and gradual rise in BK current that was sustained for 30-50 min; brain-derived neurotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor-1 had no significant effect. The response to NT-3 was blocked by inhibitors of protein kinases, phospholipase C, and serine/threonine protein phosphatase 1 and 2a. Omission of Ca2+ from the extracellular medium prevented the NT-3 effect. Our results indicate that NT-3 stimulates BK channel activity in cortical neurons through a signaling pathway that involves Trk tyrosine kinase, phospholipase C, and protein dephosphorylation and is calcium-dependent. Activation of BK channels may be a major mechanism by which neurotrophins acutely regulate neuronal activity.

We assessed the symptomatic outcome of transurethral prostatectomy with the newly developed self-administered questionnaire, Danish Prostate Symptom Score (DAN-PSS-1), in men suffering from uncomplicated benign prostatic hyperplasia (BPH). The questionnaire was filled in adequately by 53 men, median age 69 (range 52-82), preoperatively and 2, 4 and 6 months after transurethral prostatectomy (TUR-P). The DAN-PSS-1 symptom score showed a high degree of sensitivity as the preoperative total score was median 20 (quartiles 14-36) and decreased to 4, 0 and 1 (quartiles from 0-4) at the 2, 4, and 6-month control respectively. The symptoms related to voiding were relieved totally after 2 months while symptoms related to storage were first relieved completely at 4-month control. Bother from symptoms was relieved after 2 months, although some symptoms still remained. The questionnaire was internally consistent with a reliability coefficient, Cronbach's alpha (alphaCr), of 0.73. We conclude that the DAN-PSS-1 questionnaire is an efficient tool among others in the indication and evaluation of treatment of uncomplicated BPH.

This study evaluated the sexual function in an unselected population referred to hospital for treatment of clinical BPH. 401 patients filled in the DAN-PSS questionnaire including 3 questions concerning sexuality (erection, ejaculation volume and pain/discomfort during eja culation). The patients were divided into four age groups (< 50; 50-59; 60-69 and > 69 years). The answers were analyzed for severity of symptoms and the related bothersomeness. The proportion of patients with erectile dysfunction increased with increasing age, and the related bother was much higher in the young males. Fiftyfour percent noticed that the amount of semen had decreased, and a correlation between increasing age and smaller ejaculation volume was observed. However, the related botherfactor was low. There was an age independent occurrence of about 15% of patients experiencing pain/discomfort during ejaculation and the bother factor is high. This study shows that the questions concerning sexuality in the DAN-PSS score system are formulated in a way that most patients can understand, and are willing to fill in the form.

The high-conductance Ca(2+)-activated K channel (BK channel) is not only regulated by a number of physiological stimuli, but it is also sensitive to pharmacological modulation. We have stably expressed the alpha-subunit of the human BK channel, hslo, in HEK 293 cells and studied by patch-clamp technique how its gating is modulated by the channel activator NS 1608, by the selective channel blocker paxilline, as well as by changes in [Ca2+]i and Vm. The cells expressed 200-800 hslo channels per patch. The channel activity was determined by tail current analysis, and the activation curves were fitted to single Boltzmann functions, from which a gating charge for the hslo channel of 1.2 elementary charges was deduced. The hslo channel was very sensitive to changes in [Ca2+]i within the physiological range, whereas Ca(2+)-independent openings were seen at Ca2+ concentrations of 15 nM or below. NS 1608 shifted the hslo channel activation curve towards negative membrane potentials with an EC50 of 2.1 microM and a maximal shift of -74 mV. The channels activated by NS 1608 were sensitive to block by paxilline, but the two molecules apparently did not interact within the same site, since paxilline reduced the size of the tail current at all voltages, whereas NS 1608 shifted the activation curve along the voltage axis. Further, the effect of paxilline was Ca(2+)-sensitive, whereas NS 1608 elicited identical effects in the presence of either < 0.5 nM or 500 nM [Ca2+]i. NS 1608 hyperpolarized the cells by -50 to -70 mV, and paxilline depolarized them towards 0 mV. In addition to the effects on the steady state current NS 1608 also significantly influenced the non-stationary channel kinetics. In the presence of NS 1608 the time constants for deactivation of tail currents were more than tripled at all potentials. We have shown, that NS 1608 modulates steady-state BK currents and channel gating kinetics through a Ca(2+)-independent interaction with the alpha-subunit of the channel.

It is disputed whether fibrosis of the detrusor is a consequence of obstruction or ageing. In the present study, bladder wall morphology was analyzed semiquantitatively in biopsies from "normal" young persons, infravesically obstructed and non-obstructed elderly persons. Fibrosis occurring around and inside muscle fascicles was demonstrated to the same degree with obstruction as well as ageing. Our results give rise to the question whether "prostatism" is related to obstruction per se or to ageing or both.

The gene expression of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) has previously been demonstrated in rat and human choroid plexus by in situ hybridization analysis. In the present study we have characterized IGF-II and IGFBP-2 transcripts and proteins in primary cultures of epithelial cells from lateral choroid plexus of sheep brain. Northern blot analysis of total RNA showed one major IGF-II mRNA of 4.8 kb and four minor IGF-II transcripts of 1.5, 2.0, 3.0 and 6.0 kb as well as one IGFBP-2 transcript of 1.7 kb. Radioreceptor assay of conditioned medium from the cultured choroid plexus epithelial cells showed inhibition of [125I]IGF-I and [125I]IGF-II binding to mouse NIH 3T3 fibroblasts, the displacement curves being identical to that of unlabelled IGF-II. The conditioned medium was fractionated by gel filtration on a Bio-Gel P-60 column, and analysis by IGF-II radioreceptor assay showed two peaks of IGF-II-binding inhibitory activity of M(r) 7.5-10 and 25 kDa, suggesting the presence of both IGF-II, and an IGFBP. Western immunoblot analysis of conditioned medium with antibodies toward IGF-II and IGFBP-2 demonstrated proteins with M(r) 6 kDa and 32 kDa, respectively. Protein binding assays of the conditioned medium with [125I]IGF-I or [125]IGF-II demonstrated that the IGFBP present in the conditioned medium preferentially binds IGF-II. In conclusion, cultured sheep choroid plexus epithelial cells synthesize and secrete IGF-II and IGFBP-2, suggesting that the choroid plexus epithelium is the main source of these polypeptides in the cerebrospinal fluid.

In order to estimate the specificity of the clinical diagnosis of acute appendicitis, case records of 148 patients, who underwent appendectomy or who were diagnosed as having periappendicular abscess during one year at a regional hospital in Denmark were analyzed. Operations without finding acute appendicitis occurred in 25.4 per cent of the patients. The group of women in the fertile age (12-50 years) was prone to unnecessary surgery (51.9 per cent in this group had a normal appendix). In children, men and non-fertile women only a few patients had unnecessary surgery. Belated diagnoses (perforation and/or abscess) were found truly in 10.7 per cent of the cases, and, with a significant higher incidence, in elderly patients (age greater than 50 years). The possibilities of diminishing the incidence of unnecessary surgery and belated diagnoses are discussed.