Detection of Borrelia burgdorferi and Borrelia lonestari in birds in Tennessee.

Lyme disease in the United States is caused by the bacterial spirochete Borrelia burgdorferi s.s. (Johnson, Schmid, Hyde, Steigerwalt, and Brenner), which is transmitted by tick vectors Ixodes scapularis (Say) and I. pacificus (Cooley and Kohls). Borrelia lonestari, transmitted by the tick Amblyomma americanum L., may be associated with a related syndrome, southern tick-associated rash illness (STARI). Borrelia lonestari sequences, reported primarily in the southeastern states, have also been detected in ticks in northern states. It has been suggested that migratory birds may have a role in the spread of Lyme disease spirochetes. This study evaluated both migratory waterfowl and nonmigratory wild turkeys (Meleagris gallopavo silvestris, Eastern wild turkey) for B. burgdorferi and B. lonestari DNA sequences. A total of 389 avian blood samples (163 migratory birds representing six species, 125 wild turkeys harvested in habitats shared with migratory birds, 101 wild turkeys residing more distant from migratory flyways) were extracted, amplified, and probed to determine Borrelia presence and species identity. Ninety-one samples were positive for Borrelia spp. Among migratory birds and turkeys collected near migration routes, B. burgdorferi predominated. Among turkeys residing further away from flyways, detection of B. lonestari was more common. All A. americanum ticks collected from these areas were negative for Borrelia DNA; no I. scapularis were found. To our knowledge, this represents the first documentation of B. lonestari among any birds.

The nonhomologous end joining factor Artemis suppresses multi-tissue tumor formation and prevents loss of heterozygosity.

Nonhomologous end joining (NHEJ) is a critical DNA repair pathway, with proposed tumor suppression functions in many tissues. Mutations in the NHEJ factor ARTEMIS cause radiation-sensitive severe combined immunodeficiency in humans and may increase susceptibility to lymphoma in some settings. We now report that deficiency for Artemis (encoded by Dclre1c/Art in mouse) accelerates tumorigenesis in several tissues in a Trp53 heterozygous setting, revealing tumor suppression roles for NHEJ in lymphoid and non-lymphoid cells. We also show that B-lineage lymphomas in these mice undergo loss of Trp53 heterozygosity by allele replacement, but arise by mechanisms distinct from those in Art Trp53 double null mice. These findings demonstrate a general tumor suppression function for NHEJ, and reveal that interplay between NHEJ and Trp53 loss of heterozygosity influences the sequence of multi-hit oncogenesis. We present a model where p53 status at the time of tumor initiation is a key determinant of subsequent oncogenic mechanisms. Because Art deficient mice represent a model for radiation-sensitive severe combined immunodeficiency, our findings suggest that these patients may be at risk for both lymphoid and non-lymphoid cancers.

Estimating the exposure of small mammals at three sites within the Chernobyl exclusion zone--a test application of the ERICA Tool.

An essential step in the development of any modelling tool is the validation of its predictions. This paper describes a study conducted within the Chernobyl exclusion zone to acquire data to conduct an independent test of the predictions of the ERICA Tool which is designed for use in assessments of radiological risk to the environment. Small mammals were repeatedly trapped at three woodland sites between early July and mid-August 2005. Thermoluminescent dosimeters mounted on collars were fitted to Apodemus flavicollis, Clethrionomys glareolus and Microtus spp. to provide measurements of external dose rate. A total of 85 TLDs were recovered. All animals from which TLDs were recovered were live-monitored to determine (90)Sr and (137)Cs whole-body activity concentrations. A limited number of animals were also analysed to determine (239,240)Pu activity concentrations. Measurements of whole-body activity concentrations and dose rates recorded by the TLDs were compared to predictions of the ERICA-Tool. The predicted (90)Sr and (137)Cs mean activity concentrations were within an order of magnitude of the observed data means. Whilst there was some variation between sites in the agreement between measurements and predictions this was consistent with what would be expected from the differences in soil types at the sites. Given the uncertainties of conducting a study such as this, the agreement observed between the TLD results and the predicted external dose rates gives confidence to the predictions of the ERICA Tool.

"Blind" testing of models for predicting the 90Sr activity concentration in river systems using post-Chernobyl monitoring data.

Two different models for predicting the time-dependent mobility of (90)Sr in river systems have been evaluated using post-Chernobyl monitoring data for five large Belarusian rivers (Dnieper, Pripyat, Sozh, Besed and Iput) in the period between 1990 and 2004. The results of model predictions are shown to be in good agreement (within a factor of 5) with the measurements of (90)Sr activity concentration in river waters over a long period of time after the accident. This verifies the relatively good accuracy of the generalised input parameters of these models which were derived primarily from measurements of (90)Sr deposited after atmospheric nuclear weapons testing (NWT). For the cases studied here, the simpler AQUASCOPE model performed just as well as the more complex "Global" model which used GIS-based catchment data as an input. The reasons for this are discussed. Exponential decay equations were also curve-fitted to the data for each river to help assess the uncertainties in the predictive models.

Factors contributing to radiocaesium variability in upland sheep flocks in west Cumbria (United Kingdom).

Following the Chernobyl accident in 1986, restrictions were placed on the movement and slaughter of sheep within upland areas of the UK because radiocaesium activity concentrations in their meat exceeded 1000 Bq kg(-1) fresh weight. Some farms remain under restriction in 2007. From 1991 to 1993 detailed studies were conducted on three sheep farms within the restricted area of west Cumbria to systematically assess the various parameters which may contribute to the observed variability in radiocaesium activity concentrations within sheep flocks. This paper reports the spatial variation in soil and vegetation activity concentrations across the grazed areas at these farms and determines the influence of grazing behaviour on variability in (137)Cs activity concentrations between individual sheep within the flocks. Together with previously reported results, these new data are used to draw conclusions on the factors determining variability within the three flocks. However, the factors are too site specific to be able to generalise the findings to other farms within the restricted areas of the UK.

Prediction of spatial variation in global fallout of 137Cs using precipitation.

Deposition from atmospheric nuclear weapons tests (termed global fallout) has been shown to be proportional to the rate of precipitation. Here we describe methods for using precipitation and radionuclide deposition information for a reference site to estimate global fallout at other locations. These methods have been used to estimate global fallout in Iceland, identified during the Arctic Monitoring and Assessment Programme (AMAP) by Wright et al. [Wright, S.M., Howard, B.J., Strand, P., Nylén, T., Sickel, M.A.K., 1999. Prediction of 137Cs deposition from atmospheric nuclear weapons tests within the Arctic. Environ Pollut 104, 131-143.] as one of the Arctic areas which received the highest global fallout, but where measurements of contamination were sparse, and difficult to obtain due to the remote and inaccessible terrain of much of the country. Measurements of global fallout 137Cs deposition have been made in Iceland at sites close to meteorological stations to ensure that precipitation data were of high quality. The AMAP modeling approach, based on measured precipitation and radionuclide deposition data, was applied using a reference monitoring station located close to Reykjavik. The availability of good precipitation data and locally based estimates of time dependent ratios of 137Cs deposition to precipitation during the fallout period gave a better correlation between predicted and measured 137Cs global fallout (r2=0.96) than that achieved using the much more heterogeneous set of data collected by AMAP over the whole of the Arctic. Having obtained satisfactory results with the model for a number of calibration sites alongside meteorological stations we then produced a map of estimated 137Cs deposition based on a model of estimated precipitation. This deposition map was then successfully validated (r2=0.85) for sites where 137Cs deposition was measured; the associated uncertainty in predictions was also estimated.

Patterns and inventories of radioactive contamination of island sites of the Yenisey River, Russia.

The distribution of radioactive contamination at three island sites downstream from the Krasnoyarsk Mining and Chemical Combine (KMCC) was studied with the objectives of mapping contamination levels, interpreting radionuclide distributions through consideration of alluvial processes and determining radionuclide inventories. Contamination was measured using in situ gamma spectrometry and landforms characterised using topographic surveying methods. Maximum (137)Cs contamination densities (700 kBq m(-2)) were found on low- and middle-level floodplains and low-lying interconnecting areas of Beriozovy Island (16 km from the KMCC). On Mikhin Island (180 km from the KMCC) maximum total (60)Co, (152)Eu and (154)Eu activity concentrations (30-40 kBq m(-2)) occur in low-lying areas inundated during flooding. Maximum (137)Cs and total (60)Co, (152)Eu and (154)Eu contamination densities on Cheriomukhov Island (250 km from the KMCC) were 390 and 50 kBq m(-2), respectively. Estimated (137)Cs inventories were 145, 148 and 16GBq for Beriozovy, Mikhin and Cheriomukhov Islands, respectively.

Biochemical RBC abnormalities in drug-free and lithium-treated manic patients.

RBCs from two lithium-free manic patients displayed lower choline transport and higher choline concentrations and methionine S-adenosyltransferase activity than those of controls. Lithium therapy decreased RBC methionine S-adenosyltransferase activity to normal, decreased choline transport further, and increased choline concentrations further.

Physician opinion about electronic publications.

PURPOSE: Many medical journals are currently offering physicians the option to subscribe electronically, allowing readers access by means of the Internet. However, physicians' opinions about this innovation are not known. This exploratory study was designed to learn more about physicians' opinions and attitudes regarding electronic publications. SUBJECTS AND METHODS: A three-page questionnaire was developed to survey all physicians (faculty and house officers) at a large university-affiliated teaching hospital in Baltimore, Maryland. The questionnaire explored many of the features that make electronic journals distinct from printed journals. RESULTS: Of the 314 physicians surveyed, 255 (81%) returned a completed questionnaire. The mean (+/- SD) age of the respondents was 41 +/- 10 years, 164 (65%) were male, and 50 (20%) were house officers. Twenty-six percent of respondents (n = 66) thought that electronic journals would lower the quality of the medical literature, and 25% (n = 63) believed that the prestige of authorship would be lessened. Seventy to eighty percent of physicians responded that electronic journals would decrease clutter in their offices and homes, be more environmentally friendly than the current system, make it easier to locate research reports that they had read, and offer the benefit of linkage to related articles. Seventy-four percent of physicians (n = 188) were concerned about losing the convenience of being able to read a printed journal anywhere. In multivariate analyses, female sex, being a faculty member (vs house officer), fewer publications, better computer skills, and more frequent use of the Internet were independently associated with positive attitudes toward various aspects of electronic journals. CONCLUSIONS: Physicians responded favorably to the many potential values and applications of electronic publications but were most concerned with the loss of the convenience that printed journals offer.

Comparison of outcomes of coronary stenting versus conventional coronary angioplasty in the department of veterans affairs medical centers.

Although the short-term benefits of stent deployment have been established, less is known about long-term outcomes. This study compares short- and long-term outcomes in veterans undergoing stenting and conventional coronary angioplasty. We used Department of Veterans Affairs databases to identify 27,224 veterans who had undergone percutaneous coronary intervention (PCI) in Veterans Affairs medical centers between October 1994 and September 1999. Patients were classified according to whether they had acute myocardial infarction (AMI) as the principal diagnosis. Baseline characteristics were similar in the stent and conventional groups. In AMI, hospital mortality was 2.9% for those with stents and 4.8% for those who underwent conventional coronary angioplasty (p <0.0001), whereas for patients without AMI, hospital mortality was similar (1.2% vs 1.4%, p = 0.12). For AMI, same-admission bypass surgery rates were lower in the stent group (0.7% vs 3.2%, p <0.0001) and in the group without AMI (1.2% vs 3.3%, p <0.0001). Two-year survival was better for stenting in veterans with (90% vs 88%, p = 0.006) and without (92% vs 91%, p = 0.008) AMI. For AMI, 2-year rehospitalization rates for PCI (10% vs 13%, p <0.0001), coronary artery bypass surgery (4% vs 6%, p <0.0001), and unstable angina (17% vs 23%) were lower for those who had stenting. In the no-AMI group, 2-year rehospitalization rates for PCI (14% vs 17%, p <0.0001), coronary artery bypass surgery (5% vs 8%, p <0.0001), and unstable angina (22% vs 29%, p <0.0001) were lower in the stent group. Veterans who underwent stenting had lower hospital mortality, reduced rates of same-admission bypass surgery, marginally better survival, and lower rates of rehospitalization than their counterparts who had conventional coronary angioplasty.

Liposome encapsulated MnCl2 as a liver specific contrast agent for magnetic resonance imaging.

We examined the usefulness of MnCl2 entrapped in liposomes as a liver specific contrast agent for magnetic resonance imaging. Toxicity experiments showed that the effective dose for imaging experiments was 7 to 11 times lower than the LD50 of free MnCl2. In rats with implanted liver tumors, liposome encapsulated MnCl2 caused a two- to three-fold increase in the relaxation rate of the liver while having little effect on the relaxation rate of tumor tissue. T1 weighted, magnetic resonance images obtained at 0.5 T of an R3230 adenocarcinoma implanted in the liver showed an increase in the signal intensity of both normal liver and tumor tissue after the injection of free MnCl2 (25 mumole/kg). However, after the injection of liposome encapsulated MnCl2 (40 mumole/kg) the liver exhibited a marked increase in signal intensity with little change in the signal intensity of the tumor tissue. These results suggest that liposome encapsulated MnCl2 has excellent potential as a liver specific contrast agent for the improved detection of liver metastases.

Biomedical research in the nursing home: methodological issues and subject recruitment results.

Although nursing homes are potentially important sites for geriatric research, previous reports have identified impediments to subject recruitment in this setting. We are conducting five simultaneous clinical studies in a 725-bed nursing home. Utilizing a systematic subject recruitment methodology designed to minimize patient and staff burden, we have recruited over 100 subjects. The average recruitment rate over two years from nursing home residents meeting study entry criteria was 43%. The rate was highest (81%) for a study of urinary incontinence offering direct benefit to participants, and lowest (28% and 14% respectively) for physiologic studies of vasopressin regulation and dermal vitamin D production, offering no direct benefit. Studies of syncope and dementia which benefitted groups affected by these problems but not controls, had intermediate recruitment rates (46 and 44%, respectively, P less than .002 compared to incontinence). Thus, clinically relevant projects, sensitive to the needs of the patient and institution, can recruit subjects from the nursing home.

Production of endothelin by cultured human endothelial cells following exposure to nicotine or caffeine.

This study evaluated endothelin production by endothelial cells after exposure to nicotine or caffeine. Vasoconstrictive properties have been attributed to both nicotine and caffeine. The presence of endothelin, a potent vasoconstrictor itself, was determined using a radioimmunoassay. The optimal stimulatory doses for nicotine and caffeine were determined to be 1.0 micromol/L and 1.0 mmol/L, respectively. When endothelin production was evaluated over time after exposure to the optimal dose of each agent, it was determined that nicotine stimulated maximum endothelin production within 5 minutes. Caffeine failed to cause a distinct peak of endothelin production within 20 minutes. These results suggest that nicotine may have a possible acute and short-lived effect on the vasoconstrictive response associated with endothelin, while caffeine-induced endothelin release may require more long-term exposure.

Altered airway surfactant phospholipid composition and reduced lung function in asthma.

Pulmonary surfactant in bronchoalveolar lavage fluid (BALF) and induced sputum from adults with stable asthma (n = 36) and healthy controls (n = 12) was analyzed for phospholipid and protein compositions and function. Asthmatic subjects were graded as mild, moderate, or severe. Phospholipid compositions of BALF and sputum from control subjects were similar and characteristic of surfactant. For asthmatic subjects, the proportion of dipalmitoyl phosphatidylcholine (16:0/16:0PC), the major phospholipid in surfactant, decreased in sputum (P < 0.05) but not in BALF. In BALF, mole percent 16:0/16:0PC correlated with surfactant function measured in a capillary surfactometer, and sputum mole percent 16:0/16:0PC correlated with lung function (forced expiratory volume in 1 s). Neither surfactant protein A nor total protein concentration in either BALF or sputum was altered in asthma. These results suggest altered phospholipid composition and function of airway (sputum) but not alveolar (BALF) surfactant in stable asthma. Such underlying surfactant dysfunction may predispose asthmatic subjects to further surfactant inhibition by proteins or aeroallergens in acute asthma episodes and contribute to airway closure in asthma. Consequently, administration of an appropriate therapeutic surfactant could provide clinical benefit in asthma.

Effects of bipolar affective disorder and lithium administration on the cholinergic system in human blood.

Several processes relating to the cholinergic system that are present in human blood were measured in samples obtained from patients with bipolar affective disorder, both before and during treatment with lithium, and from controls. The biochemical measurements include RBC and plasma choline concentrations, the kinetics of RBC choline uptake, plasma non-specific cholinesterase and RBC and plasma acetylcholinesterase. The RBC choline level is increased and the Vmax of the RBC choline uptake system is decreased in samples from lithium-free bipolar patients during manic episodes. There are no differences from control in the plasma choline levels or in the acetylcholinesterase enzyme activities in blood samples from the lithium-free or lithium-treated patients. Plasma non-specific cholinesterase is below control levels in all patients. Lithium treatment increases the RBC choline concentration to more than ten-times control levels and reduces the Vmax and the affinity for choline of the RBC choline transport system. In vitro addition of lithium does not replicate the effects of in vivo administration of lithium. Possible mechanisms for these effects of lithium are discussed.

Recovery of erythrocyte Li+/Na+ countertransport and choline transport from lithium therapy.

Li+/Na+ countertransport, choline transport, and intracellular Li+ and choline were measured in the RBC of a manic-depressive subject as a function of time after termination of Li+ therapy. Countertransport recovered from its inhibition by Li+ in 10 days. This recovery involved a decrease in the Michaelis-Menten parameter Km, without change in Vmax. RBC choline decreased, and choline influx rose, much more slowly back towards pre-Li+ values over the course of two months. Thus, choline transport was still inhibited long after Li+ levels in RBC and plasma had become undetectable. Measurements on age-separated RBC fractions showed that recovery of choline transport was mainly in the young-cell fraction. Hence inhibition of choline transport by Li+ may be irreversible at the level of the individual RBC.

Availability of cardiac technology: trends in procedure use and outcomes for patients with acute myocardial infarction.

This study examines temporal trends in the use and outcomes of cardiac procedures for patients hospitalized with acute myocardial infarction in Department of Veterans Affairs (VA) hospitals with and without invasive cardiac services. Between 1988 and 1994, there was striking overall growth in the use of cardiac procedures in the VA. Over this time period, the authors found persistent variation in the use of cardiac procedures but diminished differences in patient survival among patients admitted to different types of hospitals. Growth of cardiac procedure use and improvements in patient survival were most significant in hospitals without on-site invasive cardiac services. We were unable to determine whether survival gains were associated with increased procedure use or unmeasured improvements in the process of care. These trends raise intriguing questions about access to and outcomes of cardiac procedures in health systems composed of hospitals with and without a full complement of on-site invasive cardiac services.

Where do elderly veterans obtain care for acute myocardial infarction: Department of Veterans Affairs or Medicare?

OBJECTIVE: To examine Department of Veterans Affairs (VA) and Medicare hospitalizations for elderly veterans with acute myocardial infarction (AMI), their use of cardiac procedures in both systems, and patient mortality. DATA SOURCES: Merging of inpatient discharge abstracts obtained from VA Patient Treatment Files (PTF) and Medicare MedPAR Part A files. STUDY DESIGN: A retrospective cohort study of male veterans 65 years or older who were prior users of the VA medical system (veteran-users) and who were initially admitted to a VA or Medicare hospital with a primary diagnosis of AMI at some time from January 1, 1988 through December 31, 1990 (N = 25,312). We examined the use of cardiac catheterization, coronary bypass surgery, and percutaneous transluminal coronary angioplasty in the 90 days after initial admission for AMI in both VA and Medicare systems, and survival at 30 days, 90 days, and one year. Other key measures included patient age, race, marital status, comorbidities, cardiac complications, prior utilization, and the availability of cardiac technology at the admitting hospital. PRINCIPAL FINDINGS: More than half of veteran-users (54 percent) were initially hospitalized in a Medicare hospital when they suffered an AMI. These Medicare index patients were more likely to receive cardiac catheterization (OR 1.24, 95% C.I. 1.17-1.32), coronary bypass surgery (OR 2.01, 95% C.I. 1.83-2.20), and percutaneous transluminal coronary angioplasty (OR 2.56, 95% C.I. 2.30-2.85) than VA index patients. Small proportions of patients crossed over between systems of care for catheterization procedures (VA to Medicare = 3.3%, and Medicare to VA = 5.1%). Many VA index patients crossed over to Medicare hospitals to obtain bypass surgery (27.6 percent) or coronary angioplasty (12.1 percent). Mortality was not significantly different between veteran-users who were initially admitted to VA versus Medicare hospitals. CONCLUSIONS: Dual-system utilization highlights the need to look at both systems of care when evaluating access, costs, and quality either in VA or in Medicare systems. Policy changes that affect access to and utilization of one system may lead to unpredictable results in the other.

When should learning about hospitalized patients end? Providing housestaff with post-discharge follow-up information.

PURPOSE: As hospital stays grow shorter, many patients are discharged to follow up with their primary care physicians before their diagnoses and responses to treatment are clear. The authors studied the value and feasibility of providing housestaff with follow-up information about their former inpatients. METHOD: Patients included in the study (1) had been admitted to the housestaff service during the study period (January to March 1997), (2) had received follow-up care from a primary care physician in the Johns Hopkins Bayview Physicians' Professional Association, and (3) had been hospitalized for at least three days. The primary care physician completed a single-page follow-up form four to six weeks after the patient's discharge from the hospital; that form was given to the house officers who had cared for that patient. RESULTS: Responses to a preintervention questionnaire completed by 28 of 39 house officers (72%) showed that 92% felt it to be important or extremely important to get follow-up information about inpatients; 86% indicated that they rarely or never receive such information. During the study period, house officers were sent follow-up information for 65 of 76 eligible patients (85%). In their responses to a post-intervention questionnaire (response rate 73%), the house officers most valued learning about the accuracy of the discharge diagnosis, the results of additional diagnostic tests, and information about the patient's quality of life since discharge. Housestaff's satisfaction with the follow-up information received about inpatients improved (p = .001). CONCLUSIONS: Providing follow-up information was a feasible intervention that was valued by housestaff.

Feedback control of the nuclear magnetization state: modeling and control design.

Magnetic resonance (MR) images are obtained by observing the fluctuations in nuclear magnetization produced by sequences of RF pulses and applied magnetic field gradients. The design of a pulse sequence is based on the expected response of the nuclear magnetization. Currently, all pulse sequence parameters are loaded into the pulse programmer before the start of the sequence and remain unchanged until the completion of the sequence. A fundamentally different approach is considered, whereby the sequence parameters are adjusted between successive RF excitation pulses. In this manner, the nuclear magnetization is regulated to a desired state by using measurements of the magnetization to adjust the amplitude and duration of the RF pulses. Feedback control of the nuclear magnetization state may be advantageous in certain types of MR experiments, for example those requiring a repeated spin-echo or gated MR image acquisition. As a first step in developing this approach a simple scheme for regulating the angle between the bulk magnetization and the axis applied static magnetic field is presented. The behavior of the closed-loop system is explored using computer simulations.