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Biomedical subjects

W J Manning

Publications and source records attributed to W J Manning.

At least 109 records · Page 6Linked to original sources

Cardioversion of nonrheumatic atrial fibrillation. Reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution.

BACKGROUND: The use of warfarin anticoagulation for several weeks before cardioversion results in a 90% reduction in the incidence of cardioversion-related thromboembolism. The mechanism of this benefit, however, is unknown; it has been widely attributed to organization and adherence of atrial thrombi, a finding observed among pathological studies of patients with rheumatic valvular disease. METHODS AND RESULTS: Serial transesophageal echocardiography was performed in 14 patients with nonrheumatic atrial fibrillation after identification of atrial thrombi on initial transesophageal study. All patients received warfarin anticoagulation and were followed clinically for signs of thromboembolism. Eighteen atrial thrombi were identified on initial transesophageal study, including 14 thrombi confined to the left atrial appendage, 2 in the body of the left atrium, 1 in the right atrial appendage, and 1 in the body of the right atrium. Thrombus size varied from 5 to 20 mm, and 6 were considered mobile. After a median of 4 weeks of warfarin, 16 of 18 atrial thrombi (89%; 95% CI, 73% to 100%) had completely resolved on transesophageal echocardiographic study. In addition, no new thrombi were identified on follow-up study, and no patient had a clinical thromboembolic event between studies. CONCLUSIONS: These data strongly support the hypothesis that among patients with nonrheumatic atrial fibrillation, the mechanism of clinical benefit with 3 to 4 weeks of warfarin before cardioversion is related to thrombus resolution and prevention of new thrombus formation rather than thrombus organization.

Aged↗

Climate change: potential effects of increased atmospheric carbon dioxide (CO2), ozone (O3), and ultraviolet-B (UV-B) radiation on plant diseases.

Continued world population growth results in increased emission of gases from agriculture, combustion of fossil fuels, and industrial processes. This causes changes in the chemical composition of the atmosphere. Evidence is emerging that increased solar ultraviolet-B (UV-B) radiation is reaching the earth's atmosphere, due to stratospheric ozone depletion. Carbon dioxide (CO(2)), ozone (O(3)) and UV-B are individual climate change factors that have direct biological effects on plants. Such effects may directly or indirectly affect the incidence and severity of plant diseases, caused by biotic agents. Carbon dioxide may increase plant canopy size and density, resulting in a greater biomass of high nutritional quality, combined with a much higher microclimate relative humidity. This would be likely to promote plant diseases such as rusts, powdery mildews, leaf spots and blights. Inoculum potential from greater overwintering crop debris would also be increased. Ozone is likely to have adverse effects on plant growth. Necrotrophic pathogens may colonize plants weakened by O(3) at an accelerated rate, while obligate biotroph infections may be lessened. Ozone is unlikely to have direct adverse effects on fungal pathogens. Ozone effects on plant diseases are host plant mediated. The principal effects of increased UV-B on plant diseases would be via alterations in host plants. Increased flavonoids could lead to increased diseased resistance. Reduced net photosynthesis and premature ripening and senescence could result in a decrease in diseases caused by biotrophs and an increase in those caused by necrotrophs. Microbial plant pathogens are less likely to be adversely affected by CO(2), O(3) and UV-B than are their corresponding host plants. Changes in host plants may result in expectable alterations of disease incidence, depending on host plant growth stages and type of pathogen. Given the importance of plant diseases in world food and fiber production, it is essential to begin studying the effects of increased CO(2), O(3) and UV-B (and other climate change factors) on plant diseases. We know very little about the actual impacts of climate change factors on disease epidemiology. Epidemiologists should be encouraged to consider CO(2), O(3) and UV-B as factors in their field studies.

Journal Article↗

Estimating the risks and benefits of pesticides: considering the agroecosystem and integrated pest management in the use of EBDC fungicides on apples.

Calculating the risks and benefits of agricultural pesticides determines whether a pesticide will be registered for use on commodities. Historically, the US Environmental Protection Agency (EPA) has used very conservative estimates of health risks, particularly in the absence of data regarding actual use patterns of the pesticide and actual pesticide residue at the point of food purchase. However, when grower groups and manufacturers were faced with the problem of losing the ethylene bisdithiocarbamate (EBDC) fungicides, they approached EPA offering to provide hard data in place of estimates. Plant pathologists familiar with apple agroecosystems pointed out that different fungicides have highly specific uses in integrated pest management (IPM) programs, and that banning EBDC use on apples would probably raise total pesticide use in apples by compromising the pesticide reductions obtained under existing IPM programs. In addition, an early study showed that use-patterns could significantly reduce the amount of EBDC residue on apples. This approach led to a more realistic appraisal of both risks and benefits of the fungicides, lowering risks and raising benefits. The process ended with a registration prescribing use-patterns which result in minimal residue at harvest, thus providing valuable tools for use in IPM programs.

Journal Article↗

Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5-year study.

OBJECTIVES: We sought to validate the safety of transesophageal echocardiographically guided early cardioversion in conjunction with short-term anticoagulation as a strategy for guiding early cardioversion in hospitalized patients with atrial fibrillation. BACKGROUND: Because atrial thrombi are poorly seen by conventional imaging techniques, several weeks of prophylactic anticoagulation is routinely prescribed before cardioversion. Transesophageal echocardiography is a superior test for identifying atrial thrombi; preliminary feasibility studies have supported its use to guide early cardioversion for patients in whom no thrombus is observed, but safety has not been validated in any large series. METHODS: All patients admitted to hospital with atrial fibrillation during a 4.5-year period were screened. The inclusion criterion was a clinical duration of atrial fibrillation > 2 days or of unknown duration. Patients received anticoagulation with heparin/warfarin and underwent conventional transthoracic echocardiography followed by transesophageal study. Patients in whom transesophageal echocardiography revealed no atrial thrombus underwent pharmacologic or electrical cardioversion followed by warfarin therapy for 1 month. Cardioversion was deferred in patients with evidence of atrial thrombi, and they received prolonged warfarin treatment. RESULTS: Two hundred thirty-three patients (86% of those eligible) agreed to participate, and 230 underwent transesophageal echocardiography. Transesophageal echocardiography identified 40 atrial thrombi (left atrium 34, right atrium 6) in 34 patients (15%). One hundred eighty-six (95%) of 196 patients without thrombi had successful cardioversion to sinus rhythm, all without prolonged anticoagulation, and none (0%, 95% confidence interval 0% to 1.6%) experienced a clinical thromboembolic event. Eighteen patients with atrial thrombi underwent uneventful cardioversion after prolonged anticoagulation. CONCLUSIONS: Compared with smaller series that have shown only feasibility, this large prospective and consecutive study of patients undergoing transesophageal echocardiographically facilitated early cardioversion in conjunction with short-term anticoagulation validates the safety of this strategy. This treatment algorithm has a safety profile similar to conventional therapy and minimizes both the period of anticoagulation and the overall duration of atrial fibrillation.

Adult↗

Ambient ozone (O3) and adverse crop response: a unified view of cause and effect.

This paper presents a cohesive view of the dynamics of ambient O(3) exposure and adverse crop response relationships, coupling the properties of photochemical O(3) production, flux of O(3) from the atmosphere into crop canopies and the crop response per se. The results from two independent approaches ((a) statistical and (b) micrometeorological) were analyzed for understanding cause-effect relationships of the foliar injury responses of tobacco cv Bel-W3 to the exposure dynamics of ambient O(3) concentrations. Similarly, other results from two independent approaches were analyzed in: (1) establishing a micrometeorological relationship between hourly ambient O(3) concentrations and their vertical flux from the air into a natural grassland canopy; and (2) establishing a statistical relationship between hourly ambient O(3) concentrations in long-term, chronic exposures and crop yield reductions. Independent of the approach used, atmospheric conditions appeared to be most conducive and the crop response appeared to be best explained statistically by the cumulative frequency of hourly ambient O(3) concentrations between 50 ppb and 90 ppb (100 and 180 microg m(-3)). In general, this concentration range represents intermediate or moderately enhanced hourly O(3) values in a polluted environment. Further, the diurnal occurrence of this concentration range (often approximately between 0900 and 1600 h in a polluted, agricultural environment) coincided with the optimal CO(2) flux from the atmosphere into the crop canopy, thus high uptake. The frequency of occurrence of hourly O(3) concentrations > 90 ppb (180 microg m(-3)) appeared to be of little importance and such concentrations in general appeared to occur during atmospheric conditions which did not facilitate optimal vertical flux into the crop canopy, thus low uptake. Alternatively, when > 90 ppb (180 microg m(-3)) O(3) concentrations occurred during the 0900-1600 h window, their frequency of occurrence was low in comparison to the 50-90 ppb (100-180 microg m(-3)) range. Based on the overall results, we conclude that if the cumulative frequency of hourly ambient O(3) concentrations between 50-62 ppb (100-124 microg m(-3)) occurred during 53% of the growing season and the corresponding cumulative frequency of hourly O(3) concentrations between 50-74 ppb (100-148 microg m(-3)) occurred during 71% of the growing season, then yield reductions in sensitive crops could be expected, if other factors supporting growth, such as adequate soil moisture are not limiting.

Journal Article↗

Studies of Gd-DTPA relaxivity and proton exchange rates in tissue.

The image intensity in many contrast agent perfusion studies is designed to be a function of bulk tissue T1, which is, in turn, a function of the compartmental (vascular, interstitial, and cellular) T1s, and the rate of proton exchange between the compartments. The goal of this study was to characterize the compartmental tissue Gd-DTPA relaxivities and to determine the proton exchange rate between the compartments. Expressing [Gd-DTPA] as mmol/liter tissue water, the relaxivities at 8.45 T and room temperature were: saline, 3.87 +/- 0.06 (mM.s)-1 (mean +/- SE; n = 29); plasma, 3.98 +/- 0.05 (mM.s)-1 (n = 6); and control cartilage (primarily an interstitium), 4.08 +/- 0.08 (mM.s)-1 (n = 17), none of which are significantly different. The relaxivity of cartilage did not change with compression, trypsinization, or equilibration in plasma, suggesting relaxivity is not influenced by interstitial solid matrix density, charge, or the presence of plasma proteins. T1 relaxation studies on isolated perfused hearts demonstrated that the cellular-interstitial water exchange rate is between 8 and 27 Hz, while the interstitial-vascular water exchange rate is less than 7 Hz. Thus, for Gd-DTPA concentrations, which would be used clinically, the T1 relaxation rate behavior of intact hearts can be modeled as being in the fast exchange regime for cellular-interstitial exchange but slow exchange for interstitial-vascular exchange. A measured relaxivity of 3.82 +/- 0.05 (mM.s)-1 (n = 8) for whole blood (red blood cells and plasma) and 4.16 +/- 0.02 (mM.s)-1 (n = 3) for frog heart tissue (cells and interstitium) (with T1 and Gd-DTPA concentration defined from the total tissue water volume) supports the conclusion of fast cellular-extracellular exchange. Knowledge of the Gd-DTPA relaxivity and maintaining Gd-DTPA concentration in the range so as to maintain fast cellular-interstitial exchange allows for calculation of bulk Gd-DTPA concentration from bulk tissue T1 within a calculable error due to slow vascular exchange.

Animals↗

Impaired left atrial mechanical function after cardioversion: relation to the duration of atrial fibrillation.

OBJECTIVES: We hypothesized that the time course of the recovery of atrial systolic function may be related to the duration of atrial fibrillation before cardioversion and sought to study noninvasively the recovery of left atrial mechanical function utilizing serial transthoracic Doppler studies. BACKGROUND: Recovery of atrial mechanical function may be delayed for several weeks after successful cardioversion of atrial fibrillation to sinus rhythm. METHODS: After successful cardioversion, 60 patients with atrial fibrillation of brief (< or = 2 weeks, 17 patients), moderate (> 2 to 6 weeks, 22 patients) or prolonged (> 6 weeks, 21 patients) duration were followed up with serial transmitral pulsed Doppler echocardiography immediately (60 patients) and at 24 h (45 patients), 1 week (41 patients), 1 month (31 patients) and > 3 months (30 patients) after cardioversion. RESULTS: Atrial mechanical function is greater immediately and at 24 h and 1 week after cardioversion in patients with "brief" compared with "prolonged" atrial fibrillation. In all groups, atrial mechanical function increases over time, ultimately achieving similar levels. Full recovery of atrial mechanical function, however, is achieved within 24 h in patients with brief atrial fibrillation, within 1 week in patients with moderate-duration atrial fibrillation and within 1 month in patients with prolonged atrial fibrillation. CONCLUSIONS: Recovery of left atrial mechanical function is related to the duration of atrial fibrillation before cardioversion. These findings have important implications for assessing the early hemodynamic benefit of successful cardioversion.

Adult↗

In vivo assessment of LV mass in mice using high-frequency cardiac ultrasound: necropsy validation.

Left ventricular (LV) mass is an important descriptor of cardiac status that increases with normal aging and may be affected by a variety of disease processes. There are currently limited noninvasive techniques that permit accurate determination of in vivo LV mass in very small animals, such as the mouse, a frequently used model for cardiac research. We sought to evaluate the ability of high-frequency (7.0 or 7.5 MHz), two-dimensional (2-D) guided M-mode echocardiography to estimate in vivo LV mass in the mouse. Fifteen adult mice weighing 22-45 g were studied, including six young adult (2- to 3-mo-old), two adult (12- to 14-mo-old), and seven senescent (18- to 20-mo-old) animals. Resting heart rate varied up to 450 beats/min. Anterior wall, inferior wall, and end-diastolic dimensions were measured, and echocardiographic LV mass (LVMe) was calculated using an uncorrected cube approximation. Autopsy LV mass was determined within 4 h of echocardiographic examination. Autopsy LV mass ranged from 88 to 211 mg. LV chamber dimensions included anterior wall (1.0 +/- 0.2 mm), inferior wall (1.1 +/- 0.3 mm), and end-diastolic dimension (3.7 +/- 0.5 mm). There was a very good correlation between LVMe (x) and autopsy LV mass (y):y = 0.96x - 7, r = 0.94, standard error of the estimate = 18 mg, P < 0.001. This correlation was stronger than that for autopsy LV mass and body weight (r = 0.70) or age (r = 0.74), indexes which until now were the only noninvasive correlates available for this very small animal model. We conclude that, despite the rapid heart rate and small size of the mouse heart, these results demonstrate the potential of high-frequency 2-D guided M-mode transthoracic echocardiography for the in vivo assessment of LV dimensions and mass in the mouse and may prove useful for cardiac research on aging and cardiomyopathies.

Aging↗

Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.

The effect of basic fibroblast growth factor (bFGF) administration on regional myocardial function and blood flow in chronically ischemic hearts was studied in 26 pigs instrumented with proximal circumflex coronary artery (LCX) ameroid constrictors. In 13 animals bFGF was administered extraluminally to the proximal left anterior descending (LAD) and LCX arteries with heparin-alginate beads and 13 other animal served as controls. bFGF-treated pigs showed a fourfold reduction in left ventricular infarct size compared to untreated controls (infarct size: 1.2 +/- 0.4% vs. 5.1 +/- 1.3% of LV mass, mean +/- SEM, P < 0.05). Percent fractional shortening (% FS) in the LCX area at rest was reduced compared with the LAD region in both bFGF and control pigs. However, there was better recovery in the LCX area after rapid pacing in bFGF-treated pigs (% FSLCX/% FSLAD, 22.9 +/- 7.3%-->30.5 +/- 8.5%, P < 0.05 vs. prepacing) than in controls (16.0 +/- 7.8%-->14.3 +/- 7.0%, P = NS). Furthermore, LV end-diastolic pressure rise with rapid pacing was less in bFGF-treated than control pigs (pre-pacing; pacing; post-pacing, 10 +/- 1; 17 +/- 3; 11 +/- 1* mmHg vs 10 +/- 1; 24 +/- 4; 15 +/- 1 mmHg, *P < 0.05 vs. control). Coronary blood flow in the LCX territory (normalized for LAD flow) was also better during pacing in bFGF-treated pigs than in controls. Thus, periadventitial administration of bFGF in a gradual coronary occlusion model in pigs results in improvement of coronary flow and reduction in infarct size in the compromised territory as well as in prevention of pacing-induced hemodynamic deterioration.

Animals↗