Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with major complications. Ongoing research is focused on new pacing devices for alternative treatment of this disease. The objective of an AF registry is to store prospectively all relevant data covering clinical information, quality of life and device parameters and by this means provide a platform for long-term follow-up. For statistical analysis, categorical and numerical items are required, thus a high-granular data structure must be defined and implemented in the clinical setting. Facing the limits of formalization, we developed an XML-based documentation scheme consisting of 619 items in eight tables and implemented it with state-of-the-art Intranet technology. At present detailed information on 88 patients is recorded. The pacing device generates per patient and follow-up visit a file consisting of approximately 400-500 parameters provided on a floppy disk, which are transferred by means of a specific interface into the database. Success factors for integration of a complex research database into the routine workflow of a busy university hospital are interfaces between data sources to enable non-redundant data entry, intensive fine tuning by iterative software engineering and benefit for the clinical users in form of clinical reports and patient-specific summaries. Data quality must be assured by plausibility checks. To get an overview of this complex dataset we developed a dedicated visualization tool. Due to the high number of items a large patient collective must be recruited for statistical evaluation. Interinstitutional cooperation is required for a consensus on common minimal documentation schemes to enable pooling of data.

Atrial Fibrillation↗

PubMed2002

Monte Carlo transport model comparison with 1A GeV accelerated iron experiment: heavy-ion shielding evaluation of NASA space flight-crew foodstuff.

Deep-space manned flight as a reality depends on a viable solution to the radiation problem. Both acute and chronic radiation health threats are known to exist, with solar particle events as an example of the former and galactic cosmic rays (GCR) of the latter. In this experiment Iron ions of 1A GeV are used to simulate GCR and to determine the secondary radiation field created as the GCR-like particles interact with a thick target. A NASA prepared food pantry locker was subjected to the iron beam and the secondary fluence recorded. A modified version of the Monte Carlo heavy ion transport code developed by Zeitlin at LBNL is compared with experimental fluence. The foodstuff is modeled as mixed nuts as defined by the 71st edition of the Chemical Rubber Company (CRC) Handbook of Physics and Chemistry. The results indicate a good agreement between the experimental data and the model. The agreement between model and experiment is determined using a linear fit to ordered pairs of data. The intercept is forced to zero. The slope fit is 0.825 and the R2 value is 0.429 over the resolved fluence region. The removal of an outlier, Z=14, gives values of 0.888 and 0.705 for slope and R2 respectively.

Cosmic Radiation↗

PubMed2002

Rescue percutaneous coronary intervention for failed thrombolysis: results from a district general hospital.

OBJECTIVE: To assess the outcome of a policy of emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction and electrocardiographic (ECG) evidence of failed reperfusion after thrombolysis. DESIGN: Observational study. SETTING: District general hospital. PATIENTS: A total of 109 consecutive patients with acute myocardial infarction who underwent emergency angiography and angioplasty for failed reperfusion diagnosed on the basis of standard ECG criteria. MAIN OUTCOME MEASURES: In-hospital mortality; death, infarct territory reinfarction, and reintervention by PCI or coronary artery bypass graft (CABG) during follow up; in-lab resource utilisation. RESULTS: At initial angiography, 76 patients had Thrombolysis in Myocardial Infarction (TIMI) trial 0/1 flow and 33 had TIMI 2/3 flow. Fourteen patients were in cardiogenic shock. TIMI 3 flow was established or maintained in 93 patients (85%). Overall in-hospital mortality was 9%. It was 3% in non-shock patients, 50% in shocked patients, and 40% when the procedure was unsuccessful (TIMI 0/1 flow post-procedure). Over a mean follow up of 30 months (>12 months of follow up in all patients) there were 19 further events (one death, five reinfarctions, and 13 revascularisations (nine CABG and four PCI)). The cost of rescue PCI was not significantly higher than comparable elective interventions. CONCLUSION: A policy of emergency angiography and PCI for failed reperfusion in acute myocardial infarction can be carried out in a hospital without on-site surgical backup with good medium term clinical outcomes.

Angioplasty, Balloon, Coronary↗

PubMed2002

The response of a spherical tissue-equivalent proportional counter to iron particles from 200-1000 MeV/nucleon.

The radiation environment on board the space shuttle and the International Space Station includes high-Z and high-energy (HZE) particles that are part of the galactic cosmic radiation (GCR) spectrum. Iron-56 particles are considered to be one of the most biologically important parts of the GCR spectrum. Tissue-equivalent proportional counters (TEPCs) are used as active dosimeters on manned space flights. These TEPCs are further used to determine the average quality factor for each space mission. A TEPC simulating a 1-microm-diameter sphere of tissue was exposed as part of a particle spectrometer to (56)Fe particles at energies from 200-1000 MeV/nucleon. The response of TEPCs in terms of mean lineal energy, y(F), and dose mean lineal energy, y(D), as well as the energy deposited at different impact parameters through the detector was determined for six different incident energies of (56)Fe particles in this energy range. Calculations determined that charged-particle equilibrium was achieved for each of the six experiments. Energy depositions at different impact parameters were calculated using a radial dose distribution model, and the results were compared to experimental data.

Cosmic Radiation↗

PubMed2001

Subcellular localization of presenilin 2 endoproteolytic C-terminal fragments.

Mutations in the genes that encode the presenilin 1 and 2 (PS1 and PS2) proteins cause the majority of familial Alzheimer's disease (FAD). Differential cleavage of the presenilins results in a generation of at least two C-terminal fragments (CTFs). An increase in the smaller of these two CTFs is one of the few changes in presenilin processing associated with FAD mutations in both PS1 and PS2. Interestingly, the phosphorylation of PS2 modulates the production of the smaller, caspase-derived PS2 CTF, which indicates that the generation of this fragment is a regulated, physiologic event. To date, there is no data concerning the subcellular distribution of the caspase-derived PS2 CTF. Because this fragment is normally present at levels that are difficult to detect, we have used cell lines in which the production of wild-type or N141I mutant PS2 is controlled by a tetracycline-regulated promoter in order to assess the subcellular localization of the caspase CTF in relation to the larger, constitutive PS2 CTF and to PS2 holoprotein. We have found that when levels of PS2 are low, the constitutive CTF colocalizes with markers consistent with localization in the early Golgi-ER-Golgi intermediate compartment (ERGIC) while the caspase CTF colocalizes with markers for the endoplasmic reticulum (ER). Following induction of wild-type or mutant PS2, when the levels of PS2 are high, the primary localization of the constitutive CTF appears to shift from the early Golgi-ERGIC in addition to the ER. Interestingly, while the induction of wild-type PS2 resulted in the localization of the caspase CTF primarily in the ER, the induction of mutant PS2 resulted in the localization of the caspase CTF to both the ER and the early Golgi-ERGIC. In summary, these data suggest that the two presenilin 2 CTFs have different patterns of subcellular localization and that the N141I PS2 mutation alters the localization pattern of the PS2 caspase fragment.

Alzheimer Disease↗

PubMed2001

Molecular mechanisms of IL-2 gene regulation following costimulation through LFA-1.

The integrin LFA-1 serves as an accessory molecule in T cell activation. In addition to its well-known role as an adhesion molecule, LFA-1 can contribute to T cell activation and up-regulation of IL-2 gene expression. However, the specific mechanisms by which LFA-1 influences T cell activation have not been elucidated. Therefore, we examined the impact of LFA-1:ICAM-1 interactions on transcriptional and posttranscriptional IL-2 gene regulation, using a costimulation-negative cell line transfected with MHC class II alone, or in combination with ICAM-1 or B7-1. IL-2 transcription was assessed utilizing transgenic mice expressing an IL-2 promoter luciferase reporter construct crossed to DO11.10 TCR-transgenic mice, and IL-2 mRNA stability was evaluated by real-time RT-PCR. Comparison of naive and previously activated T cells demonstrates a dramatic increase in IL-2-luciferase transcription in activated T cells that can, in part, be attributed to downstream signaling events. Costimulation through LFA-1 enhances transcription of the transgenic reporter construct across a wide Ag dose range, but does not affect IL-2 mRNA stability. In contrast, CD28 costimulation is clearly mediated through up-regulation of IL-2 transcription and through enhancement of mRNA stability. These results indicate that the primary pathway whereby engagement of LFA-1 through its ligand ICAM-1 up-regulates IL-2 gene expression is through enhanced IL-2 transcription, in the absence of any effect on IL-2 mRNA stabilization.

CD28 Antigens↗

PubMed2001

Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model.

BACKGROUND: Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. METHODS: Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group G0 (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. RESULTS: High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. CONCLUSION: Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

Animals↗

PubMed2001

A new system for grading recommendations in evidence based guidelines.

Explore the source record for details and available documents.

Evidence-Based Medicine↗

PubMed2001

Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center.

A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

Adult↗

PubMed2001

Intracellular transport of MHC class II and associated invariant chain in antigen presenting cells from AP-3-deficient mocha mice.

MHC class II-restricted antigen presentation requires trafficking of newly synthesized class II-invariant chain complexes from the trans-Golgi network to endosomal, peptide-loading compartments. This transport is mediated by dileucine-like motifs within the cytosolic tail of the invariant chain. Although these signals have been well characterized, the cytosolic proteins that interact with these dileucine signals and mediate Golgi sorting and endosomal transport have not been identified. Recently, an adaptor complex, AP-3, has been identified that interacts with dileucine motifs and mediates endosomal/lysosomal transport in yeast, Drosophila, and mammals. In this report, we have assessed class II-invariant chain trafficking in a strain of mice (mocha) which lacks expression of AP-3. Our studies demonstrate that the lack of AP-3 does not affect the kinetics of invariant chain degradation, the route of class II-invariant chain transport, or the rate and extent of class II-peptide binding as assessed by the generation of SDS-stable dimers. The possible role of other known or unknown adaptor complexes in class II-invariant chain transport is discussed.

Adaptor Proteins, Vesicular Transport↗

PubMed2001

The outbreak of West Nile virus infection in the New York City area in 1999.

BACKGROUND: In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. METHODS: Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. RESULTS: Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). CONCLUSIONS: This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

Adolescent↗

PubMed2001

Six-year clinical effect of donor bone marrow infusions in renal transplant patients.

BACKGROUND: To date, several single- and multicenter clinical trials have attempted to induce specific immunological unresponsiveness using donor bone marrow cell infusions to augment solid organ transplantation, but the outcomes have not been definitive. METHODS: Between September 1994 and May 1998, 63 cadaver (CAD) renal transplant recipients of either one or two postoperative donor bone marrow cell (DBMC) infusions were prospectively compared with 219 non-infused controls given equivalent immunosuppression. There was at least a 1 HLA DR antigen match present between donors and recipients. The immunosuppressive regimen included a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. A total 7.01x10(8)+/-1.9x10(8) (SD) DBMC/kg was infused into the CAD recipients on either days 4 and 11 (n=42) or one half of that dose on day 4 (n=21) postoperatively. Clinical follow-up has ranged from 2.9 to 6.3 years (mean, 4.7 years). Studies were also performed of humoral immunity and quantitative cellular chimerism. RESULTS: There is clear-cut equivalence in immunosuppressive dosaging and in the other major demographic variables in both groups. However, only 2/63 DBMC recipients had biopsy-proven chronic rejection, whereas 41/219 showed chronic rejection in the controls (P = <0.01). In both groups, mortality was not associated with rejection. The actuarial graft survival at 6.3 years in the CAD DBMC group was 84.3% compared with 72.2% in the control group (not statistically significant). However, if death with a functioning graft was excluded, graft survival was 94.1% in the DBMC group and 79.8% in the controls (P=0.039). Forty patients in the control group continue to have deteriorating renal function (increasing serum creatinine concentrations to 2 mg/dl and higher), compared with 2 patients in the DBMC group (P=0.04). In the DBMC group, chimerism in iliac crest marrow aspirates has increased 3-fold in yearly sequential measurements between 1 and 4 years postoperatively averaging 1.3+/-0.36% (SE) most recently. This has not occurred in the controls. CONCLUSIONS: There now appears to be more solid long-term evidence, in kidney transplant recipients prospectively receiving DBMC infusions, of an improvement in long-term graft survival, and of the degree of chimerism positively correlating with the absence of graft loss.

Adolescent↗

PubMed2001

Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy.

BACKGROUND: Osteopenia has been associated with antiretroviral therapy, particularly with protease inhibitors. Osteopenia in HIV-uninfected men is associated with mitochondrial defects. METHODS: Bone density was assessed by dual-energy X-ray absorptiometry (DEXA) in 221 HIV-infected men (mean age 43 years) recruited to a lipodystrophy prevalence survey. Additional parameters assessed were demographics, exercise, smoking, type(s) and duration of all antiretroviral therapy, lipodystrophy (overall and by region), CD4 counts, HIV RNA, fasting metabolic parameters (lipid, glycaemic, lactate, liver enzymes, testosterone) and regional body fat and lean mass (DEXA and L4 abdominal computed tomographic scan). RESULTS: Thirty-two patients were drug-naive; 42 were receiving nucleoside analogue reverse transcriptase inhibitors (NRTI) and 147 were receiving these plus protease inhibitors. Osteoporosis (t-score < -2.5 SD below normal) was found in seven (3%) and osteopenia (t-score -1.0 to -2.5 SD) in 44 (22%). No patient had had a fracture since being infected with HIV. The only factors independently associated on logistic regression with osteopenia or osteoporosis were higher lactate levels, even if asymptomatic [odds ratio (OR) 2.39 per 1 mmol/l increase; 95% confidence interval (CI) 1.39-4.11; P = 0.002), and lower weight prior to commencing antiretroviral therapy (OR 1.06 per 1 kg decrease; 95% CI 1.02-1.11; P = 0.006). There was no independent association with any other parameter, including type or duration of antiretroviral therapy and lipodystrophy at any site. Lower total bone mineral density was associated with lower weight prior to commencing antiretroviral therapy whereas lower spinal bone mineral density was associated mostly with higher lactate. CONCLUSION: Osteopenia in HIV-infected men is common, asymptomatic and is associated with asymptomatic NRTI-related lactic acidemia and lower weight pre-antiretroviral therapy.

Absorptiometry, Photon↗