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Background: On July 22, 2011, a single perpetrator killed 77 people in a car bomb attack and a shooting spree incident in Norway. This article describes the emergency medical service (EMS) response elicited by the two incidents., Methods: A retrospective and observational study was conducted based on data from the EMS systems involved and the public domain. The study was approved by the Data Protection Official and was defined as a quality improvement project., Results: We describe the timeline and logistics of the EMS response, focusing on alarm, dispatch, initial response, triage and evacuation. The scenes in the Oslo government district and at Utøya island are described separately., Conclusions: Many EMS units were activated and effectively used despite the occurrence of two geographically separate incidents within a short time frame. Important lessons were learned regarding triage and evacuation, patient flow and communication, the use of and need for emergency equipment and the coordination of helicopter EMS.

Background: During manual chest compressions for cardiac arrest the waveforms of chest compressions are generally sinusoidal, whereas mechanical chest compression devices can have different waveforms, including trapezoidal. We studied the haemodynamic differences of such waveforms in a porcine model of cardiac arrest., Methods: Eight domestic pigs (weight 31±3kg) were anaesthetised and instrumented to continuously monitor aortic (AP) and right atrial pressure (RAP), carotid (CF) and cerebral cortical microcirculation blood flow (CCF). Coronary perfusion pressure (CPP) was calculated as the maximal difference between AP and RAP during diastole or decompression phase. After 4 min of electrically induced ventricular fibrillation, mechanical chest compressions were performed with four different waveforms in a factorial design, and in randomized sequence for 3 min each. Resulting differences are presented as mean with 95% confidence intervals., Results: Mean AP and RAP were higher with trapezoid than sinusoid chest compressions, difference 5.7 (0.7, 11) and 6.3 (2.1, 11)mmHg, respectively. Flow measured as CF and CCF was also improved with trapezoidal waveform, difference 14 (2.8, 26)ml/min and 11 (5.6, 17)% of baseline, respectively, with a parallel, non-significant (P=0.08) trend for CPP. Active vs. passive decompression to zero level improved CF, but without even a trend for CPP., Conclusion: Trapezoid chest compressions and active decompression to zero level improved blood flow to the brain. The compression waveform is an additional factor to consider when comparing mechanical and manual chest compressions and when comparing different compression devices., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates. Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses. Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant., Experimental Design: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially. Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year. Clinical response was assessed by measuring lesion size. Biopsies were analyzed for HPV DNA and tumor-infiltrating lymphocytes including T regulatory cells., Results: The treatment was well-tolerated. There was an overall response rate of 55% by intention treat and 64% per protocol. The 52-week symptom response was 65% asymptomatic, compared with 5% at baseline. The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment., Conclusions: The response rates are clinically relevant, and the treatment regimen was feasible for the majority. Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity. The potential benefit of this treatment is its ability to treat multifocal disease.

Background: Undetected malpositioned or dislodged ventilation tubes during cardiac arrest have fatal consequences, and no single method can detect the tube position reliably during such low-flow states. We wanted to test the ability of impedance changes as measured across the chest via the standard defibrillation pads to distinguish between oesophageal and tracheal ventilations in non-circulated patients., Materials and Methods: After the end of futile resuscitation transthoracic impedance was measured with a prototype defibrillator, and ventilation variables were collected with a spirometer-capnography unit during tracheal ventilations and after repositioning of the tube; during oesophageal ventilations for paired comparisons., Results: We registered 123 oesophageal and 178 tracheal ventilations in nine patients. Transthoracic impedance changes associated with ventilations were always larger during tracheal than oesophageal ventilations (mean difference 1.3 ohms (95% CI 1.0, 1.5), P<0.001), and all such changes above 1.2 ohms were associated with tracheal ventilations, while changes below 0.4 ohms always were associated with oesophageal ventilations. By subtracting 0.5 ohms from the individual mean transthoracic change associated with tracheal ventilations, tube position was predicted with sensitivity 0.99 and specificity 0.97., Conclusion: Transthoracic impedance changes may be used to detect malpositioned and dislodged tubes also during situations without spontaneous circulation. Our predictive values must be retested in another population.

Introduction: Quality of CPR performed by professionals has been reported to be substandard even with automated corrective feedback. Our hypothesis was that providing CPR performance evaluation (CPR-PE) to three ambulance services would facilitate local education and implementation of CPR guidelines and, consequently, improve CPR quality., Methods: Quality of CPR in 85 consecutive cases of adult out-of-hospital cardiac arrests after CPR-PE was compared to 39 cases prior to CPR-PE. Real-time automated verbal and visual feedback on CPR performance was given in all cases. No general implementation strategy was provided because the sites were expected to use the CPR-PEs in development of local strategies. Because the strategies were expected to vary, the sites were analyzed separately., Results: No significant improvement was seen in quality of CPR after CPR-PE. No chest compressions were given 40% of the time before versus 41% after CPR-PE. The median (95% confidence interval) percentage of chest compressions within the recommended depth range (38-51 mm) was 35% (27-57) before versus 51% (42-60) after CPR-PE (p = 0.12). In site-specific analysis, chest compressions within guideline depth increased from 31% to 61% after CPR-PE (p = 0.05) in one site., Conclusions: Overall our attempt to improve CPR-quality was unsuccessful. Quality improvement likely requires a full range of implementation strategies to change current attitudes and practices.

Background: Recent clinical studies reporting the high frequency of inadequate chest compression depth (<38 mm) during CPR, have prompted the question if adult human chest characteristics render it difficult to attain the recommended compression depth in certain patients., Material and Methods: Using a specially designed monitor/defibrillator equipped with a sternal pad fitted with an accelerometer and a pressure sensor, compression force and depth was measured during CPR in 91 adult out-of-hospital cardiac arrest patients., Results: There was a strong non-linear relationship between the force of compression and depth achieved. Mean applied force for all patients was 30.3+/-8.2 kg and mean absolute compression depth 42+/-8 mm. For 87 of 91 patients 38 mm compression depth was obtained with less than 50 kg. Stiffer chests were compressed more forcefully than softer chests (p<0.001), but softer chests were compressed more deeply than stiffer chests (p=0.001). The force needed to reach 38 mm compression depth (F38) and mean compression force were higher for males than for females: 29.8+/-14.5 kg versus 22.5+/-10.2 kg (p<0.02), and 32.0+/-8.3 kg versus 27.0+/-7.0 kg (p<0.01), respectively. There was no significant variation in F38 or compression depth with age, but a significant 1.5 kg mean decrease in applied force for each 10 years increase in age (p<0.05). Chest stiffness decreased significantly (p<0.0001) with an increasing number of compressions performed. Average residual force during decompression was 1.7+/-1.0 kg, corresponding to an average residual depth of 3+/-2 mm., Conclusion: In most out-of-hospital cardiac arrest victims adequate chest compression depth can be achieved by a force<50 kg, indicating that an average sized and fit rescuer should be able to perform effective CPR in most adult patients.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

Heterologous prime-boost vaccination schedules employing TA-HPV, a vaccinia virus encoding HPV 16/18 E6 and E7, in combination with TA-CIN, an HPV 16 L2E6E7 fusion protein, may offer advantages over the use of either agent alone for the immunotherapy of human papillomavirus (HPV) type 16-associated vulval intraepithelial neoplasia (VIN). In the present study, 10 women with HPV 16-positive high grade VIN, previously primed with TA-HPV, received three booster immunisations with TA-CIN. All but one demonstrated HPV 16-specific proliferative T-cell and/or serological responses following vaccination. Three patients additionally showed lesion shrinkage or symptom relief, but no direct correlation between clinical and immunological responses was seen.

This study assessed the immunological and clinical responses of women with human papillomavirus (HPV) 16-associated high-grade vulval intraepithelial neoplasia (VIN) vaccinated with TA-HPV, a recombinant vaccinia virus encoding modified HPV 16 and 18 E6 and E7. Eighteen women with HPV 16-positive high-grade VIN were vaccinated with TA-HPV. The extent of their baseline disease was compared after 24 weeks by lesion measurements and histological analysis. Viral load was assessed pre- and postvaccination by real time PCR. Cell-mediated immunity to HPV 16 E6 and/or E7 peptides (HLA-A2 epitopes) or vaccinia-infected cell lysates was determined by IFN-gamma enzyme-linked immunospot (ELISPOT) and T cell proliferation using an HPV 16 L2E6E7 fusion protein. Antibodies were measured by ELISA using vaccinia-infected cell lysates or HPV 16 and 18 E6 and E7 glutathione S-transferase-fusion proteins. Lesion-infiltrating CD4(+), CD8(+), CD1a(+), and CD68(+) immune cells were assessed by immunohistochemistry. The single vaccination with TA-HPV was well tolerated, and all patients showed an increased ELISPOT and/or antibody response to vaccinia. There were significant differences in HPV-16 E7-specific ELISPOT and L2E6E7 proliferative responses in the patients at one or more time points postvaccination as compared with the prevaccination status; two patients showed transient increased antibody responses. Overall, 13 women showed an increased HPV 16-specific immune response by one or more methodologies after immunization. Eight patients demonstrated a reduction in lesion diameter of at least 50% and a further four patients showed significant symptom relief. Viral load was reduced or cleared in six of eight lesion responders but also in six of ten nonresponders. Before vaccination, clinical responders had significantly higher levels of lesion-associated CD4(+), CD8(+), and CD1a(+)-immune cells than nonresponders. There were no differences in CD68 (macrophages) between responders and nonresponders before or after vaccination. Nonresponders did show a significant increase in CD4(+)- and CD8(+)- but not CD1a(+)-immune cells postvaccination but at lower levels overall than responder patients. Local immune infiltration may be a critical factor in potential responsiveness to vaccine therapy in HPV-associated neoplasia and should be carefully monitored in future placebo-controlled trials of immunotherapy for VIN.

1. The receptors which mediate the effects of calcitonin gene-related peptide (CGRP), amylin and adrenomedullin on the guinea-pig vas deferens have been investigated. 2. All three peptides cause concentration dependant inhibitions of the electrically stimulated twitch response (pD2s for CGRP, amylin and adrenomedullin of 7.90+/-0.11, 7.70+/-0.19 and 7.25+/-0.10 respectively). 3. CGRP8-37 (1 microM) and AC187 (10 microM) showed little antagonist activity against adrenomedullin. 4. Adrenomedullin22-52 by itself inhibited the electrically stimulated contractions of the vas deferens and also antagonized the responses to CGRP, amylin and adrenomedullin. 5. [125I]-adrenomedullin labelled a single population of binding sites in vas deferens membranes with a pIC50 of 8.91 and a capacity of 643 fmol mg(-1). Its selectivity profile was adrenomedullin> AC187>CGRP=amylin. It was clearly distinct from a site labelled by [125I]-CGRP (pIC50=8.73, capacity=114 fmol mg(-1), selectivity CGRP>amylin=AC187>adrenomedullin). [125I]-amylin bound to two sites with a total capacity of 882 fmol mg(-1). 6. Although CGRP has been shown to act at a CGRP2 receptor on the vas deferens with low sensitivity to CGRP8-37, this antagonist displaced [125I]-CGRP with high affinity from vas deferens membranes. This affinity was unaltered by increasing the temperature from 4 degrees C to 25 degrees C, suggesting the anomalous behaviour of CGRP8-37 is not due to temperature differences between binding and functional assays.

1. The aim of this study was to determine the conditions under which the alpha2-adrenoceptor agonist UK14304 produces vasoconstriction in the porcine isolated ear artery. 2. UK14304 (0.3 microM) produced a small contraction of porcine isolated ear arteries which was 7.8+/-3.3% of the response to 60 mM KCl. Similar sized contractions were obtained after precontraction with either 30 nM angiotensin II, or 0.1 microM U46619 (8.2+/-1.8% and 10.2+/-2.6% of 60 mM KCl response, respectively). However, an enhanced alpha2-adrenoceptor response was uncovered if the tissue was precontracted with U46619, and relaxed back to baseline with 1-2 microM forskolin before the addition of UK14304 (46.9+/-9.6% of 60 mM KCl response). 3. The enhanced responses to UK14304 in the presence of U46619 and forskolin were not inhibited by the alpha1-adrenoceptor antagonist prazosin (0.1 microM), but were inhibited by the alpha2-adrenoceptor antagonist rauwolscine (1 microM), indicating that the enhanced responses were mediated via postjunctional alpha2-adrenoceptors. 4. In the presence of 0.1 microM U46619 and 1 mM isobutylmethylxanthine (IBMX), 1 microM forskolin produced an increase in [3H]-cyclic AMP levels in porcine isolated ear arteries. Addition of 0.3 microM UK14304 prevented this increase. 5. The enhanced UK14304 response was dependent upon the agent used to relax the tissue. After relaxation of ear arteries precontracted with 10 nM U46619 and relaxed with forskolin the UK14304 response was 46.9+/-9.6% of the 60 mM KCl response, and after relaxation with sodium nitroprusside (SNP) the response was 24.8+3.3%. However, after relaxation of the tissue with levcromakalim the UK14304 response was only 8.2+/-1.7%, which was not different from the control response in the same tissues (12.2+/-5.6%). An enhanced contraction was also obtained after relaxation of the tissue with the cyclic AMP analogue dibutyryl cyclic AMP (23.2+/-1.3%) indicating that at least part of the enhanced response to UK14304 is independent of the ability of the agonist to inhibit cyclic AMP production. 6. Relaxation of U46619 contracted ear arteries with SNP could be inhibited by the NO-sensitive guanylyl-cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) indicating that production of cyclic GMP is necessary for the relaxant effect of SNP. However, ODQ had no effect on the relaxation of tissue by forskolin, suggesting that this compound does not act via production of cyclic GMP. Biochemical studies showed that while forskolin increases the levels of cyclic AMP in the tissues, SNP had no effect on the levels of this cyclic nucleotide. 7. In conclusion, enhanced contractions to the alpha2-adrenoceptor agonist UK14304 can be uncovered in porcine isolated ear arteries by precontracting the tissue with U46619, followed by relaxation back to baseline with forskolin, SNP or dibutyryl cyclic AMP before addition of UK14304. There was a greater contractile response to UK14304 after relaxation with forskolin than with SNP or dibutyryl cyclic AMP, suggesting that cyclic AMP-dependent and- independent mechanisms are involved in the enhancement of the UK14304 response.

1. The responses of the electrically stimulated guinea-pig ileum and vas deferens to human and rat calcitonin gene-related peptide (CGRP) and amylin were investigated. 2. The inhibition of contraction of the ileum produced by human alpha CGRP was antagonized by human alpha CGRP8-37 (apparent pA2 estimated at 7.15 +/- 0.23) > human alpha CGRP19-37 (apparent pA2 estimated as 6.67 +/- 0.33) > [Tyr0]-human alpha CGRP28-37. The amylin antagonist, AC187, was three fold less potent than CGRP8-37 in antagonizing human alpha CGRP. 3. Both human beta- and rat alpha CGRP inhibited contractions of the ileum, but this was less sensitive to inhibition by CGRP8-37 than the effect of human alpha CGRP. However, CGRP19-37 was twenty times more effective in inhibiting the response to rat alpha CGRP (apparent pA2 estimated as 8.0 +/- 0.1) compared to human alpha CGRP. 4. Rat amylin inhibited contractions in about 10% of ileal preparations; this effect was not antagonized by any CGRP fragment. Human amylin had no action on this preparation. 5. Both human and rat alpha CGRP inhibited electrically stimulated contractions of the vas deferens, which were not antagonized by 3 microM CGRP8-37 or 10 microM AC187. 6. Rat amylin inhibited the stimulated contractions of the vas deferens (EC50 = 77 +/- 9 nM); human amylin was less potent (EC50 = 213 +/- 22 nM). The response to rat amylin was antagonized by 10 microM CGRP8-37 (EC50 = 242 +/- 25 nM) and 10 microM AC187 (EC50 = 610 +/- 22 nM). 7. It is concluded that human alpha CGRP relaxes the guinea-pig ileum via CGRP1-like receptors, but that human beta CGRP and rat alpha CGRP may use additional receptors. These are distinct CGRP2-like and amylin receptors on guinea-pig vas deferens.