Environmentally superior technologies for swine waste management.

The high nitrogen content of animal waste provides opportunities for processing to marketable byproducts and challenges for proper management to avoid harmful impacts. Technologies are being developed to conserve and utilize nitrogen as well as other valuable constituents in animal waste. Advanced treatment technologies are also being developed for housing/waste management systems that address public concerns and protect soil, water and air quality. Smithfield Foods, Premium Standard Farms and Frontline Farmers have entered into an agreement with North Carolina to develop environmentally superior technologies that meet these goals. The 18 candidate technologies are identified and three with the longest operating period, and thus most data to date are discussed. Methods for distributing this information for implementation of cost-effective technologies through the Curriculum Project and the National Center for Manure and Animal Waste Management will be presented. This work supports priority goals to conserve and utilize valuable animal waste constituents while also protecting against negative impacts.

Current and emerging commercial optical biosensors.

The field of commercial optical biosensors is rapidly evolving, with new systems and detection methods being developed each year. This review outlines the currently available biosensor hardware and highlights unique features of each platform. Affinity-based biosensor technology, with its high sensitivity, wide versatility and high throughput, is playing a significant role in basic research, pharmaceutical development, and the food and environmental sciences. Likewise, the increasing popularity of biosensors is prompting manufacturers to develop new instrumentation for dedicated applications. We provide a preview of some of the emerging commercial systems that are dedicated to drug discovery, proteomics, clinical diagnostics and routine biomolecular interaction analysis.

G-protein signaling through tubby proteins.

Dysfunction of the tubby protein results in maturity-onset obesity in mice. Tubby has been implicated as a transcription regulator, but details of the molecular mechanism underlying its function remain unclear. Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxyl terminal "tubby domain." X-ray crystallography reveals the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidyl- inositol binding factors. Receptor-mediated activation of G protein alphaq (Galphaq) releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein 3 (TULP3) is similarly regulated. These data suggest that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G-protein signaling and the regulation of gene expression.

The ATPase reaction cycle of yeast DNA topoisomerase II. Slow rates of ATP resynthesis and P(i) release.

DNA topoisomerase II catalyzes the transport of one DNA duplex through a transient break in a second duplex using a complex ATP hydrolysis mechanism. Two key rates in the ATPase mechanism, ATP resynthesis and phosphate release, were investigated using 18O exchange and stopped-flow phosphate release experiments, respectively. The 18O exchange results showed that the rate of ATP resynthesis on the topoisomerase II active site was slow compared with the rate of phosphate release. When topoisomerase II was bound to DNA, phosphate was released slowly, with a lag. Since each of the preceding steps is known to occur rapidly, phosphate release is apparently a rate-determining step. The length of the lag phase was unaffected by etoposide, indicating that inhibiting DNA religation inhibits the ATPase reaction cycle at some step following phosphate release. By combining the 18O exchange and phosphate release results, the rate constant for ATP resynthesis can be calculated as approximately 0.5 s(-1). These data support the mechanism of sequential hydrolysis of two ATP by DNA topoisomerase II.

First-line treatment for osteoarthritis. Part 1: Pathophysiology, assessment, and pharmacologic interventions.

While surgical interventions often relieve severe pain for those with osteoarthritis (OA), there are thousands of patients with this common and disabling condition who do not receive surgery. Pharmacologic and nonpharmacologic interventions may offer a reduction in pain and improvement in physical functioning. To help patients with OA, nurses should conduct thorough assessments based on pathophysiology, and plan appropriate care with the patient. In this first article of a two-part series, the pathophysiology and classification of OA are presented. Assessment factors are discussed, and pharmacologic interventions are presented. Part 2 of this series, to run in the November/December issue, will focus on nonpharmacologic interventions and evaluation.

First-line treatment for osteoarthritis. Part 2: Nonpharmacologic interventions and evaluation.

Because of the chronic nature of osteoarthritis, nonpharmacologic interventions provide the client with self-care strategies that may lessen pain, improve physical functioning, and increase independence and sense of control. Nonpharmacologic interventions include exercise, rest and joint protection, heat and cold, hydrotherapy, therapeutic touch, acupuncture/acupressure, biofeedback, hypnotherapy, cognitive-behavioral techniques, activity and home maintenance modification, nutrition, and transportation interventions. Most of these therapies are very useful for nurses as independent interventions. Suggestions for evaluation of interventions are made.

Medical management of significant coronary angiographic stenoses: outcome of 60 patients observed for 433 patient years.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become routine in the management of patients with stable angina pectoris and significant coronary stenoses, while medical management of such patients has declined. HYPOTHESIS: The purpose of the present study was to evaluate the outcome of 60 patients at the Virginia Heart Institute with stable angina pectoris, observed between 1976 and 1997, who had documented evidence of severe angiographic disease but were elected to be monitored and managed in an outpatient pharmacologic rehabilitation program. METHODS: Sixty patients with significant stenoses by coronary angiography (21 with single-vessel, 26 with double-vessel, and 13 with triple-vessel) without impaired ventricular function, exercise-induced ischemia or hypotension, limited exercise performance, malignant arrhythmias, or drug intolerance were enrolled in a program of pharmacologic rehabilitation and observed for an average of 7.2 years. RESULTS: Among the 60 patients, there were 6 deaths at a mean interval of 8.3 years. Two deaths were in patients ineligible for revascularization. Another patient who died had refused revascularization after new-onset left ventricular dysfunction, and another died intraoperatively during abdominal aortic aneurysm repair. Two patients died while exercising. Thirteen patients underwent follow-up catheterization for worsening angina; 11 of 13 showed progression, predominantly from new lesions. Four of 11 were referred for revascularization; 7 of 11 continued medical treatment; 49 patients were stable on medical therapy throughout the period of observation. CONCLUSION: Medical management of selected patients with significant coronary stenoses is safe and effective.

Conversion of supra-ventricular tachycardia by catheter manipulation of the right atrium.

A case is described by which the right heart catheter was utilized to convert mechanically an episode of supraventricular tachycardia.

Steady-state and rapid kinetic analysis of topoisomerase II trapped as the closed-clamp intermediate by ICRF-193.

DNA topoisomerase II uses a complex, sequential mechanism of ATP hydrolysis to catalyze the transport of one DNA duplex through a transient break in another. ICRF-193 is a catalytic inhibitor of topoisomerase II that is known to trap a closed-clamp intermediate form of the enzyme. Using steady-state and rapid kinetic ATPase and DNA transport assays, we have analyzed how trapping this intermediate by the drug perturbs the topoisomerase II mechanism. The drug has no effect on the rate of the first turnover of decatenation but potently inhibits subsequent turnovers with an IC(50) of 6.5 +/- 1 microM for the Saccharomyces cerevisiae enzyme. This drug inhibits the ATPase activity of topoisomerase II by an unusual, mixed-type mechanism; the drug is not a competitive inhibitor of ATP, and even at saturating concentrations of drug, the enzyme continues to hydrolyze ATP, albeit at a reduced rate. Topoisomerase II that was specifically isolated in the drug-bound, closed-clamp form continues to hydrolyze ATP, indicating that the enzyme clamp does not need to re-open to bind and hydrolyze ATP. When rapid-quench ATPase assays were initiated by the addition of ATP, the drug had no effect on the sequential hydrolysis of either the first or second ATP. By contrast, when the drug was prebound, the enzyme hydrolyzed one labeled ATP at the uninhibited rate but did not hydrolyze a second ATP. These results are interpreted in terms of the catalytic mechanism for topoisomerase II and suggest that ICRF-193 interacts with the enzyme bound to one ADP.

Living with hurting and difficulty doing: older women with osteoarthritis.

Osteoarthritis (OA) is the most common rheumatologic health problem of older adults. Developing a greater understanding of what it is like to live with this chronic, progressive, and frequently unsuccessfully treated condition is necessary to improve evidence-based nursing care to support independent living. Eighteen women aged 65 to 92 years participated in narrative descriptive research based on naturalistic-framework and qualitative-analysis methods. Data were the transcribed narratives of the participants, field notes of observations and impressions, theoretical memos, coded units of the narratives, and categories noted. Deconstructions and reconstructions of the narratives led to the meaning of "Being With OA," with intermediate categories, "Living With Hurting" and "Living With Difficulty Doing." Recommendations included nursing interventions based on individual problems and strengths and further studies of older adults with chronic health problems.

Topoisomerase II drives DNA transport by hydrolyzing one ATP.

DNA topoisomerase II is a homodimeric molecular machine that couples ATP usage to the transport of one DNA segment through a transient break in another segment. In the presence of a nonhydrolyzable ATP analog, the enzyme is known to promote a single turnover of DNA transport. Current models for the enzyme's mechanism based on this result have hydrolysis of two ATPs as the last step, used only to reset the enzyme for another round of reaction. Using rapid-quench techniques, topoisomerase II recently was shown to hydrolyze its two bound ATPs in a strictly sequential manner. This result is incongruous with the models based on the nonhydrolyzable ATP analog data. Here we present evidence that hydrolysis of one ATP by topoisomerase II precedes, and accelerates, DNA transport. These results indicate that important features of this enzyme's mechanism previously have been overlooked because of the reliance on nonhydrolyzable analogs for studying a single reaction turnover. A model for the mechanism of topoisomerase II is presented to show how hydrolysis of one ATP could drive DNA transport.

Gender influence on perceptions of hostile environment sexual harassment.

Perceptions of sexual harassment were investigated as a function of perpetrators' and recipients' gender. Undergraduate students (100 women, 98 men) were presented 34 scenarios of men and women interacting at work. Participants were asked to read carefully each scenario and indicate on a scale anchored by 1 (strongly disagree) and 7 (strongly agree) their opinions as to whether the scenario represented an incident of sexual harassment. Analysis indicated that women rated "hostile environment" scenarios as more harassing than men, and male perpetrators were rated as more harassing than female perpetrators. Even though some scenarios were rated as more harassing than others, the full range of the 7-point scale was used on every scenario, indicating a lack of agreement on what constitutes harassment. This lack of agreement highlights the debate within the legal community about whether the "reasonable person" or the "reasonable woman" standard should be used to judge sexual harassment in the workplace.

Place attachment, isolation, and the power of a window in a hospital environment: a case study.

This paper describes the relevance of the literature on environmental psychology to the coping strategies a leukemia patient used in adapting to psychological and physical isolation on a hospital bone marrow transplant unit and oncology unit. The case study describes the difficulty of place attachment on the isolation unit and its evolution on the oncology unit. The power of a window with a natural view--including a view of a cemetery--was especially evident even as the disease became terminal.

Outpatient cardiac catheterization: its role in managed care.

Cardiac catheterization, as developed by Dr. Sones, has revolutionized the practice of ischemic heart disease. I personally appreciate his support on behalf of the development of outpatient cardiac catheterization, as he counseled me over the years in regards to this methodology. I believe its appropriate use, both in certified ambulatory facilities as well as in expanded hospital programs, would lower the death rate in those who experience sudden death as well as myocardial infarction. Cardiovascular administrators must now position themselves in the outpatient area in order to coordinate not only outpatient catheterization, but also noninvasive assessment. They also must provide support for managed care, which utilizes low-cost programs such as: outpatient cardiac rehabilitation for drug selection, assessment of ischemia, appropriate management (rather than relying on sudden death and myocardial infarction as a satisfactory method of identifying patients with heart disease).

Efficacy and safety of oral nadolol for exercise-induced ventricular arrhythmias.

Sixty-four patients with reproducible exercise-induced ventricular arrhythmias were enrolled in an open-label, multicenter study to assess the efficacy and safety of oral nadolol therapy. There were 53 men and 11 women ranging in age from 19 to 75 years (mean 53.9). The severity of arrhythmias varied from frequent ventricular premature beats to nonsustained and sustained ventricular tachycardias. Using serial treadmill exercise tests, patients underwent dose titration for 1 month and were followed up for 3 to 6 months. Depending on drug tolerance and response to treadmill exercise testing, the single daily required dose of oral nadolol ranged from 20 to 240 mg (average 66). Twenty-three (36%) of the patients experienced a total of 30 adverse effects of nadolol therapy; however, only 9 (14%) patients had to be withdrawn from the study. The adverse effects observed were those commonly associated with beta-adrenergic blocking agents, and all were dose-dependent and reversible. At the last patient visit, the severity of exercise-induced ventricular arrhythmias was significantly decreased compared with pretreatment in 36 (75%) of 48 evaluable patients. Eighteen (38%) of the patients demonstrated total suppression of arrhythmias. This was accompanied by significant increases from pretreatment in both the mean duration of symptom-limited exercise (+1.02 +/- 0.41 minutes, p less than 0.05) and the mean time of exercise required for arrhythmia induction (+1.80 +/- 0.66 minutes, p less than 0.01), a significant decrease from pretreatment in the mean peak exercise double-product (-4,775, p less than 0.001) and a decrease in the incidence of exercise-induced ST-segment depression (-33%).(ABSTRACT TRUNCATED AT 250 WORDS)