The NORwegian study on DIstrict treatment of ST-elevation myocardial infarction (NORDISTEMI)

OBJECTIVES: Thrombolysis is the treatment of choice for patients with ST-elevation myocardial infarction (STEMI) living in rural areas with long transfer delays to percutaneous coronary intervention (PCI). This trial compares two different strategies following thrombolysis: to transfer all patients for immediate coronary angiography and intervention, or to manage the patients more conservatively. DESIGN: The NORwegian study on DIstrict treatment of STEMI (NORDISTEMI) is an open, prospective, randomized controlled trial in patients with STEMI of less than 6 hours of duration and more than 90 minutes expected time delay to PCI. A total of 266 patients will receive full-dose thrombolysis, preferably pre-hospital, and then be randomized to either strategy. Our primary endpoint is the one year combined incidence of death, reinfarction, stroke or new myocardial ischaemia. The study is registered with ClinicalTrials.gov, number NCT00161005. RESULTS: By April 2006, 109 patients have been randomized. Thrombolysis has been given pre-hospital to 52% of patients. The median transport distance from first medical contact to catheterization laboratory was 155 km (range 90-396 km). Results of the study are expected in 2008.     

Establishing Laparoscopic Roux-en-Y Gastric Bypass: Perioperative Outcome and Characteristics of the Learning Curve

Background  Bariatric surgery was established at several Norwegian hospitals in 2004. This study evaluates the perioperative outcome and the learning curves for two surgeons while introducing laparoscopic Roux-en-Y gastric bypass (LRYGB). Methods  Morbidly obese patients undergoing primary LRYGB were included. Lengths of surgery and postoperative hospital stay, and 30-day rates of morbidity, reoperations, and readmissions were set as indicators of the learning curve. Learning effects were evaluated by graphical analyses and comparing the first and last 40 procedures for both surgeons. Results  The 292 included patients had a mean age of 40.0 ± 9.5 years and a mean body mass index (BMI) of 46.7 ± 5.3 kg/m². The mean length of surgery was 101 ± 55 min. Complications occurred in 43 patients (14.7%), with no conversions to open surgery in the primary procedure and no mortality. Reoperations were performed in 14 patients (4.8%), of which five patients required open surgery. The median length of stay was 3 days (range 1–77), and 19 patients (6.5%) were readmitted. High patient age, but not high BMI, was associated with an increased risk of complication. For both surgeons, lengths of surgery and hospital stay were significantly reduced (p < 0.001), leveling out after 100 procedures. Reductions in the rates of morbidity, reoperations and readmissions were not found. Conclusion  LRYGB was introduced with an acceptable morbidity rate and no mortality. Only the length of surgery and postoperative hospital stay were suitable indicators of a learning curve, which comprised about 100 cases.     

Overestimation of Human Immunodeficiency Virus Type 1 Load Caused by the Presence of Cells in Plasma from Plasma Preparation Tubes

The human immunodeficiency virus type 1 (HIV-1) load is an important marker of disease progression and treatment efficacy in patients with HIV-1 infection. In recent years, an increase in the number of samples with detectable HIV-1 RNA has been reported among patients with previously suppressed viral loads, affecting clinical patient care and leading to repeat measurements of viral load and drug resistance. This rise seems to have coincided with the increased use of plasma preparation tubes (PPTs) for sample collection, and we have aimed to explain why PPTs might yield elevated HIV-1 RNA levels. The impacts of different sample-processing procedures on HIV-1 RNA levels were compared retrospectively. Prospectively, the presence of different cells and cell-associated HIV-1 nucleic acids in paired plasma samples from PPTs centrifuged before (PPT1) and after (PPT2) transportation to the laboratory was compared. A retrospective analysis of 4,049 patient samples with <1,000 HIV-1 RNA copies/ml showed elevated HIV-1 RNA levels in plasma from PPT1 compared with the levels from PPT2 and standard EDTA-containing tubes. Prospective data revealed cell-associated HIV-1 nucleic acids and abundant blood cells in plasma from PPT1 but not from the corresponding PPT2. The levels of HIV-1 RNA correlated with the lymphocyte counts in plasma in PPT1. Cells could be removed by the recentrifugation of PPT1 before analysis. In conclusion, the transportation of PPTs after centrifugation may render cells in the plasma fraction containing cell-associated HIV-1 nucleic acids that contribute significantly to the HIV-1 RNA copy numbers in patients with low viral loads.Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma is an essential tool in the clinical management of patients with HIV-1 infection and is used to monitor HIV-1 disease progression and the response to antiretroviral therapy (ART) (9, 12, 14, 15). It is also an important end point in most HIV-1 treatment clinical trials.Although intermittent low-level viremia is often reported among patients receiving seemingly effective ART (4, 13, 16, 23), the unexpected detection of HIV-1 RNA might have a clinical impact and lead to repeat quantification of HIV-1 RNA and testing for drug resistance. In recent years, several HIV-1 clinics and laboratories have reported an increased number of cases of detectable HIV-1 RNA in patients with previous suppressed viral loads, raising concerns about drug resistance and virologic failure (8, 17, 20). At the Oslo University Hospital, Ullevål, we have also experienced an unusual increase in the proportion of plasma samples with HIV-1 RNA levels in the range of 40 to 1,000 copies/ml. This seems to have coincided with a change in the routines for plasma sample collection, and here we present data providing an explanation for this phenomenon.It is recommended that blood samples for HIV-1 RNA quantification be collected in tubes with EDTA as an anticoagulant (3, 12). Standard EDTA-containing tubes require transfer of the plasma to a secondary tube within 6 h after sample collection to reduce the risk of RNA degradation (3). This is often inconvenient in a patient clinic, and as an alternative, plasma preparation tubes (PPTs; Becton Dickinson [BD], Franklin Lakes, NJ) are increasingly often used. Upon centrifugation of the PPTs, a gel barrier separates the plasma from most of the cellular elements, theoretically allowing transportation of the sample in the primary tube.The collection of samples in PPTs from patients receiving effective ART is reported to yield increased levels of HIV-1 RNA compared with the levels in plasma collected in standard EDTA-containing tubes (5, 6, 8, 17, 18, 20, 21). However, the reason for this discrepancy has remained unclear. Our data confirm the previous findings that PPTs generate significantly higher HIV-1 RNA levels in samples from patients with low-level viremia. Additionally, we have shown that the source of this overestimation is cell-associated HIV-1 nucleic acids. These findings necessitate a reconsideration of low-level viral load results in plasma obtained from PPTs not handled with care after centrifugation. Furthermore, we present a simple procedure that will circumvent the problem.     

Sub-lethal dosing of azaspiracid-1 in female NMRI mice

The main aim of this study was to examine absorption and pathological effects of a single sub-lethal dose of the marine biotoxin azaspiracid-1 (AZA1) in mice after oral intubation. When the mice received AZA1 at doses of 100, 200 or 300 μg/kg body weight (b.w.), the toxin was absorbed dose-dependently. Highest concentrations after 24 h were detected in kidneys, spleen and lungs, followed by liver and heart. Only trace amounts were seen in the brain. After seven days, the toxin level had dropped significantly in all organs except for the kidneys. The amount of toxin absorbed was highest in the liver, followed by kidneys, lungs, spleen and heart and the total amount of toxin in the internal organs analysed after 24 h was estimated to be only about 2% of the total amount given for all three dose groups. Pathological changes were only detected in the upper part of the small intestine (duodenum), consisting of mild cellular detachment in the tips of the villi, expansion of the crypts and necrotic changes in lamina propria. In a previous study very long persistence of damage to the gastrointestinal tract by repeated exposures to AZA toxins was reported. In our study, full recovery from the pathological changes was observed seven days after a single exposure to AZA1 at the doses applied.     

Beyond the EPR: Complementary roles of the hospital-wide electronic health record and clinical departmental systems

Background  

Many hospital departments have implemented small clinical departmental systems (CDSs) to collect and use patient data for documentation as well as for other department-specific purposes. As hospitals are implementing institution-wide electronic patient records (EPRs), the EPR is thought to be integrated with, and gradually substitute the smaller systems. Many EPR systems however fail to support important clinical workflows. Also, successful integration of systems has proven hard to achieve. As a result, CDSs are still in widespread use. This study was conducted to see which tasks are supported by CDSs and to compare this to the support offered by the EPR.     

The antimicrobial peptide, lactoferricin B, is cytotoxic to neuroblastoma cells in vitro and inhibits xenograft growth in vivo

Antimicrobial peptides have been shown to exert cytotoxic activity towards cancer cells through their ability to interact with negatively charged cell membranes. In this study the cytotoxic effect of the antimicrobial peptide, LfcinB was tested in a panel of human neuroblastoma cell lines. LfcinB displayed a selective cytotoxic activity against both MYCN-amplified and non-MYCN-amplified cell lines. Non-transformed fibroblasts were not substantially affected by LfcinB. Treatment of neuroblastoma cells with LfcinB induced rapid destabilization of the cytoplasmic membrane and formation of membrane blebs. Depolarization of the mitochondria membranes and irreversible changes in the mitochondria morphology was also evident. Immuno- and fluorescence-labeled LfcinB revealed that the peptide co-localized with mitochondria. Furthermore, treatment of neuroblastoma cells with LfcinB induced cleavage of caspase-6, -7 and -9 followed by cell death. However, neither addition of the pan-caspase inhibitor, zVAD-fmk, or specific caspase inhibitors could reverse the cytotoxic effect induced by LfcinB. Treatment of established SH-SY-5Y neuroblastoma xenografts with repeated injections of LfcinB resulted in significant tumor growth inhibition. These results revealed a selective destabilizing effect of LfcinB on two important targets in the neuroblastoma cells, the cytoplasmic- and the mitochondria membrane.