Influence of Electromagnetic Fields on Function of Automated External Defibrillators

Objectives: In this study, the authors tested whether electromagnetic interference (EMI) is able to impair correct electrocardiogram analysis and produce false‐positive shock advice from automated external defibrillators (AEDs) when the true rhythm is sinus. Methods: Nineteen healthy subjects were used to test five AEDs available on the Austrian market in a prospective, open, and sequence‐randomized study. The primary outcome variable was the absolute number of shocks advised in the presence of EMI. The secondary outcome was the number of impaired analyses caused by incorrectly detected patient movements or electrode failure. Results: Of 760 tests run, 18 (2.37%) cases of false‐positive results occurred, and two of five AEDs recommended shocks in the presence of sinus rhythm. Of 760 tests run, no electrode failures occurred. There were 27 occurrences (3.55%) of motion detected by an AED in the presence of strong electromagnetic fields. Conclusions: AED models differ in their response to EMI; it may be useful to consider specific safety requirements for areas with such fields present. Working personnel and emergency medical services staff should be informed about potential risks and the possible need for patient evacuation before AEDs are attached and shock recommendations are followed.     

Health lifestyles and self-direction in employment among American men: A test of the spillover effect

This paper examines whether American males with a high degree of control over their work situation pursue healthy lifestyles and rate their physical health more positively than those who score low on occupational self-direction. That is, are persons who control their work more likely to also try to control their health through living in a particularly healthy manner? We found that there was no support for a spillover effect from high occupational self-direction to enhanced participation in health lifestyles or more positive self-rated health. The findings suggest health lifestyles have spread throughout occupational work groups in the U.S. and support research that maintains such lifestyles have spread across social strata in America.     

Extended donor criteria for lung transplantation--a clinical reality.

OBJECTIVE: Standard lung donor criteria have been established on opinions and individual experiences rather than on existing evidence. Since the scarcity of donor organs is one of the major limitations to lung transplantation, extension of donor lung criteria might considerably increase the donor pool. This study therefore evaluates the outcome, achieved with the use of extended donors versus standard donors and aims to redefine lung donor criteria. METHODS: We performed a retrospective analysis of 98 consecutive primary lung transplantations from 94 donors from 1/2001 to 12/2002. Donors were classified as extended if they fulfilled at least one criteria: age >55 years, PaO(2) at FiO(2)/PEEP 5 <300mmHg, tobacco history >20 pack years, inhalative drug abuse, presence of infiltration on chest X-ray or purulent secretions at bronchoscopy. Recipients were stratified in two groups according to whether they received a 'standard' or 'extended' organ. Postoperative complications, extubation time, ICU and hospital stay and survival were compared. RESULTS: Twenty-three (24.5%) donors were extended. Twenty-six recipients (26.55%) received organs from extended donors. Differences in intubation times (12+/-2 days standard vs. 14+/-5 days extended, P=0.70), ICU stay (16+/-2 days standard vs. 18+/-5 days extended, P=0.74) and hospital stay (38+/-4 days standard vs. 40+/-6 days extended, P=0.71) were not statistically significant. Postoperative bleeding rates were comparable (n=14 standard vs. n=3 extended) as well as bronchial anastomotic complications (n=7 standard vs. n=3 extended). Three months survival was 88.89% in the standard group vs. 92.31% in the extended group. One year survival is comparable as well with 81.94 vs. 84.62%, respectively. CONCLUSIONS: The use of lung donors who fail to meet standard criteria does not impair short and medium term results compared to standard lung donors. The impact on long term development of BOS has yet to be evaluated. The strict application of standard lung donor criteria excludes a considerable number of lungs potentially suitable for transplantation, thus liberalisation of donor criteria might help to overcome donor shortage.     

A Biotin–Avidin-Based Enzyme Immunoassay for βh-Endorphin

An avidin–biotin enzyme-linked immunosorbent assay (ELISA) is described for _h-endorphin (_h-EP). Microtiter plates coated with commercially available antibodies were used together with _h-EP tracer derivatives that were biotinylated in positions 24, 28, and 29 via a C₆ spacer arm. Nonspecific binding of biotinylated derivatives to the microtiter plates was blocked with a mixture of 1% casein and 10% ethanolamine in 0.1 M NaHCO₃. A sequential saturation procedure using a high-affinity antiserum in combination with an avidin–alkaline phosphatase complex matched the sensitivity of reported radioimmunoassays (RIAs), with a detection limit of 0.5 fmol/assay. The intra- and interassay coefficients of variation were 5 and 12%, respectively. Results obtained by ELISA and RIA showed good correlations (r = 0.95). The -EP concentration in extracted rat plasma after high-performance liquid chromatographic (HPLC) fractionation was determined by this method to be 1600 fmol/ml.     

Effects of insulin-like growth factors and insulin-like growth factor binding protein-2 on the in vitro proliferation of peripheral blood mononuclear cells

Increasing evidence has implicated that insulin-like growth factors (IGFs), polypeptides structurally related to proinsulin, are involved in the function and development of the immune system. To probe the relevance of IGF binding protein 2 (IGFBP-2) in T-cell activation and proliferation, we studied the role of IGFBP-2 in anti-CD3 monoclonal antibody (mAb)-activated peripheral blood mononuclear cells (PBMCs). Secretion of IGF-I, IGF-II, and IGFBP-2 by PBMCs from healthy adult donors was determined by radioimmunoassays (RIAs). The PBMC proliferative response after stimulation with anti-CD3 mAb and exposure to increasing concentrations of IGF-I, IGF-II, IGFBP-2, and anti-IGFBP-2 were determined by bromodeoxyuridine enzyme-linked immunosorbent assay. Observations were tested for significance by paired t-tests. We demonstrate an increase in IGFBP-2 secretion associated with both activation of PBMC by anti-CD3 mAb and increasing cell density. Incubation with exogenous IGFBP-2 increased the proliferation of PBMCs, whereas anti-IGFBP-2 had an antiproliferative effect on PBMCs that was reversed by simultaneous exposure to IGFBP-2. The stimulatory activity of IGFBP-2 (1-10 ng/ml) on anti-CD3 mAb-activated PBMCs was similar to that of IGF-I and IGF-II (1-100 ng/ml), with the mean increase in PBMC proliferative response ranging between 150% and 160% for IGFBP-2 (p = 0.03), 150% and 170% for IGF-I (p < 0.01), 133%-161% for IGF-II (p < 0.01), and 157% and 175% for IGF-I + IGF-II (p < 0.01). Thus, our data strongly suggest a role for IGFBP-2 as a local growth factor contributing to the proliferation and activation of mononuclear cells.     

Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia

Mixed-lineage leukemia (MLL) fusion proteins are potent inducers of leukemia, but how these proteins generate aberrant gene expression programs is poorly understood. Here we show that the MLL-AF4 fusion protein occupies developmental regulatory genes important for hematopoietic stem cell identity and self-renewal in human leukemia cells. These MLL-AF4-bound regions have grossly altered chromatin structure, with histone modifications catalyzed by trithorax group proteins and DOT1 extending across large domains. Our results define direct targets of the MLL fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in cancer.     

Large picture archiving and communication systems of the world—Part 2

A survey of 82 institutions worldwide was done in 1995 to identify large picture archiving and communication systems (PACS) in clinical operation. A continuing strong trend toward the creation and operation of large PACS was identified. In the 15 months since the first such survey the number of clinical large PACS went from 13 to 23, almost a doubling in that short interval. New systems were added in Asia, Europe, and North America. A strong move to primary interpretation from soft copy was identified, and filmless radiology has become a reality. Workstations for interpretation reside mainly within radiology, but one–third of reporting PACS have more than 20 workstations out-side of radiology. Fiber distributed data interface networks were the most numerous, but a variety of networks was reported to be in use. Replies on various display times showed surprisingly good, albeit diverse, speeds. The planned archive length of many systems was 60 months, with usually more than 1 year of data on-line. The main large archive and off-line storage media for these systems were optical disks and magneto-optical disks. Compression was not used before interpretation in most cases, but many systems used 2.5∶1 compression for on-line, interpreted cases and 10∶1 compression for longer-term archiving. A move to digital imaging and communication in medicine interface usage was identified.     

Toxicity and adaptive immune response to intracellular transgenes delivered by helper-dependent vs. first generation adenoviral vectors

The host immune response to intracellular transgenes delivered by helper-dependent (HDV) vs. first generation (FGV) adenoviral vectors has been relatively unstudied. Previous studies showed short-term correction of bovine and murine argininosuccinate synthetase (ASS) deficiency after first generation adenoviral-mediated liver gene therapy. To determine whether the host adaptive immune response against the intracellular transgene human ASS (hASS) contributed to loss of gene expression in this setting, the same vector (FGV-CAG-hASS) was injected into Rag-/- (immunodeficient) mice. As in wild-type C57BL/6 (B6) mice, Rag-/- mice also showed significant loss of hASS expression and vector by week 4 post-injection, with concomitant elevation of liver enzymes and disruption of liver architecture. Therefore, direct toxicity due to vector rather than adaptive immune response against hASS primarily accounted for loss of expression with FGVs. In contrast to hASS, beta-galactosidase is strongly immunogenic and activates the host adaptive immune response. Loss of transgene expression was observed in B6 mice with either a FGV or a HDV expressing beta-galactosidase. However, the drop in gene expression observed with the HDV was primarily due to the adaptive immune response, since both beta-galactosidase expression and vector genome were sustained in immunodeficient mice treated with HDV. As expected, with weakly immunogenic hASS, vector genome and hASS expression were sustained with a HDV in spite of ubiquitous expression of the transgene. Therefore, viral gene expression is a primary determinant of intermediate and chronic toxicities at day 3 and week 4 post-injection. However, even in the absence of viral gene expression, strongly immunogenic intracellular transgenes can stimulate clearance of transduced hepatocytes.     

Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6

Pseudoxanthoma elasticum (PXE) is a systemic heritable disorder that affects the elastic tissue in the skin, eye, and cardiovascular system. Mutations in the ABCC6 gene cause PXE. We performed a mutation screen in ABCC6 using haplotype analysis in conjunction with direct sequencing to achieve a mutation detection rate of 97%. This screen consisted of 170 PXE chromosomes in 81 families, and detected 59 distinct mutations (32 missense, eight nonsense, and six likely splice-site point mutations; one small insertion; and seven small and five large deletions). Forty-three of these mutations are novel variants, which increases the total number of PXE mutations to 121. While most mutations are rare, three nonsense mutations, a splice donor site mutation, and the large deletion comprising exons 23-29 (c.2996_4208del) were identified as relatively frequent PXE mutations at 26%, 5%, 3.5%, 3%, and 11%, respectively. Chromosomal haplotyping with two proximal and two distal polymorphic markers flanking ABCC6 demonstrated that most chromosomes that carry these relatively frequent PXE mutations have related haplotypes specific for these mutations, which suggests that these chromosomes originate from single founder mutations. The types of mutations found support loss-of-function as the molecular mechanism for the PXE phenotype. In 76 of the 81 families, the affected individuals were either homozygous for the same mutation or compound heterozygous for two mutations. In the remaining five families with one uncovered mutation, affected showed allelic compound heterozygosity for the cosegregating PXE haplotype. This demonstrates pseudo-dominance as the relevant inheritance mechanism, since disease transmission to the next generation always requires one mutant allelic variant from each parent. In contrast to other previous clinical and molecular claims, our results show evidence only for recessive PXE. This has profound consequences for the genetic counseling of families with PXE.