Methodological considerations for research in nocturnal home hemodialysis

Nocturnal hemodialysis (NHD) is a form of frequent, intensive renal replacement therapy, which has been suggested to offer multiple physiological benefits over conventional hemodialysis (CHD). Though the evidence supporting these advantages is steadily increasing, significant methodological challenges exist in conducting research in this area. Our review highlights these important considerations and potential biases within the present NHD literature and suggests future research opportunities.     

Mitogenic effect of interleukin-2 on unstimulated human T cells: an editorial review

The most salient feature of the lymphokine interleukin-2 (IL-2), a hormone-like protein, is its ability to sustain the proliferation of immunocompetent T cells. Results of initial studies characterizing IL-2 in vitro led investigators to conclude that IL-2 had no known effects on lymphocytes that had not been previously activated by exposure to a mitogen or antigen. Several groups postulated that T cell growth required two signals. The first signal, delivered by a mitogen or antigen, induced T cell activation. Resting T cells, which were thought to lack the membrane receptor for interleukin-2 (IL-2R), progressed from the G0-G1 phase to the S phase, during which time they converted from IL-2R- to IL-2R+ cells. Thereafter, the second signal, served by IL-2, induced T cell proliferation of the IL-2R+ cells. Recently, a number of investigators have demonstrated that highly purified preparations of both natural and recombinant IL-2 induced high levels of T cell proliferation in the absence of any known mitogens or antigens. Presented herein is a review of these studies and an overview of the hypotheses of the mechanisms whereby IL-2 alone induces T cell activation and proliferation.     

An analysis of response to nicotine infusion using an automated radiotelemetry system

Previous studies from our laboratory have demonstrated that chronic nicotine infusion evokes tolerance to nicotine injected IP several hours after withdrawal from chronic infusion. This method may introduce problems related to withdrawal reactions and to stress associated with handling of the animals. The studies reported here measured tolerance to nicotine in mice using an automated radiotelemetry system. DBA/2 mice were infused intravenously with saline for 4 days followed by infusion of a 4 mg/kg per h dose of nicotine for 7 days. After the nicotine treatment, the mice were infused with saline for 7 days. The nicotine was infused continuously or in four 1 mg/kg pulses, two 2 mg/kg pulses or one 4 mg/kg pulse each hour. Home cage activity and body temperature were measured throughout the treatment periods using a radiotelemetry system. Nicotine infusion produced an abrupt decrease in body temperature and activity, but this effect was totally reversed within 12 h in the continuously infused and four infusions/h treatment groups. Mice that received one or two infusions/h also showed a rapid response to nicotine that was reversed as treatment proceeded, but nicotine continued to produce a measurable effect for several days. After nicotine withdrawal, temperature and activity returned to predrug infusion values in all of the groups except those infused once per hour. This group showed depressed activity for a minimum of 3 days after nicotine treatment stopped. Thus, the kinetics of nicotine administration affected the intensity of response during continued treatment as well as activity after cessation of chronic treatment.     

Impact of prostaglandin and thromboxane synthesis blockade on disposition of group B streptococcus in lung and liver of intact piglet.

Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648-653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of 111In-labeled GBS (10(8) colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spiral magnetic resonance coronary angiography--direct comparison of 1.5 Tesla vs. 3 Tesla.

BACKGROUND: MR coronary angiography (MRCA) has been demonstrated successfully at 3 Tesla (T). However, the advantages remain unclear. No systematic comparison of MRCA between 1.5 T and 3 T has been performed. Therefore, anatomic coverage, image quality, signal-to-noise ratio (SNR), contrast-to-noise ration (CNR), and susceptibility artifacts were compared in 23 subjects. METHODS AND RESULTS: Identical real-time (RT) and high-resolution (HR) sequences were implemented on the GE 1.5 T (Signa Twinspeed) and 3.0 T (Signa VH/i) whole body systems (GE, Milwaukee, WI). Both scanners were equipped with high-performance gradient systems capable of 40 mT/m peak amplitude and 150 mT/m/ms slew rate. Real-time localization of the coronary arteries was followed by a cardiac-gated, breath-hold HR sequence. Twenty-three subjects were recruited consecutively and underwent both 3 T and 1.5 T MRCA within one week. Coronary coverage based on the number of coronary segments visualized, image quality using a grading scale, SNR, CNR, and presence of susceptibility artifacts were analyzed. A significant improvement in SNR (47%), CNR (30%), and image quality were seen in 3 T. However, a significant increase in susceptibility artifacts was also noted. CONCLUSION: MRCA at 3 T significantly improves SNR, CNR, and image quality at the expense of susceptibility artifacts. Further optimization of the imaging parameters at 3 T may facilitate clinical implementation of MRCA.     

Critical review: nicotine for the fetus, the infant and the adolescent?

The recent expansion of Nicotine Replacement Therapy to pregnant women and children ignores the fact that nicotine impairs, disrupts, duplicates and/or interacts with essential physiological functions and is involved in tobacco-related carcinogenesis. The main concerns in the present context are its fetotoxicity and neuroteratogenicity that can cause cognitive, affective and behavioral disorders in children born to mothers exposed to nicotine during pregnancy, and the detrimental effects of nicotine on the growing organism. Hence, the use of nicotine, whose efficacy in treating nicotine addiction is controversial even in adults, must be strictly avoided in pregnancy, breastfeeding, childhood and adolescence.     

VERSE-guided numerical RF pulse design: a fast method for peak RF power control

In parallel excitation, the computational speed of numerical radiofrequency (RF) pulse design methods is critical when subject dependencies and system nonidealities need to be incorporated on-the-fly. One important concern with optimization-based methods is high peak RF power exceeding hardware or safety limits. Hence, online controllability of the peak RF power is essential. Variable-rate selective excitation pulse reshaping is ideally suited to this problem due to its simplicity and low computational cost. In this work, we first improve the fidelity of variable-rate selective excitation implementation for discrete-time waveforms through waveform oversampling such that variable-rate selective excitation can be robustly applied to numerically designed RF pulses. Then, a variable-rate selective excitation-guided numerical RF pulse design is suggested as an online RF pulse design framework, aiming to simultaneously control peak RF power and compensate for off-resonance.     

Equity in public health standards: a qualitative document analysis of policies from two Canadian provinces

ABSTRACT: INTRODUCTION: Promoting health equity is a key goal of many public health systems. However, little isknown about how equity is conceptualized in such systems, particularly as standards ofpractice are established. As part of a larger study examining the renewal of public health intwo Canadian provinces, Ontario and British Columbia (BC), we undertook an analysis ofrelevant public health documents related to equity. The aim of this paper is to discuss howequity is considered within documents that outline standards for public health. METHODS: A research team consisting of policymakers and academics identified key documents relatedto the public health renewal process in each province. The documents were analyzed usingconstant comparative analysis to identify key themes related to the conceptualization andintegration of health equity as part of public health renewal in Ontario and BC. Documentswere coded inductively with higher levels of abstraction achieved through multiple readings.Sets of questions were developed to guide the analysis throughout the process. RESULTS: In both sets of provincial documents health inequities were defined in a similar fashion, as theconsequence of unfair or unjust structural conditions. Reducing health inequities was anexplicit goal of the public health renewal process. In Ontario, addressing "prioritypopulations" was used as a proxy term for health equity and the focus was on existingprograms. In BC, the incorporation of an equity lens enhanced the identification of healthinequities, with a particular emphasis on the social determinants of health. In both, prioritywas given to reducing barriers to public health services and to forming partnerships withother sectors to reduce health inequities. Limits to the accountability of public health toreduce health inequities were identified in both provinces. CONCLUSION: This study contributes to understanding how health equity is conceptualized and incorporatedinto standards for local public health. As reflected in their policies, both provinces haveembraced the importance of reducing health inequities. Both conceptualized this as rooted instructural injustices and the social determinants of health. Differences in theconceptualization of health equity likely reflect contextual influences on the public healthrenewal processes in each jurisdiction.     

Moral Distress: Tensions as Springboards for Action

In the previous four papers in this series, individual versus structural or contextual factors have informed various understandings of moral distress. In this final paper, we summarize some of the key tensions raised in previous papers and use these tensions as springboards to identify directions for action among practitioners, educators, researchers, policymakers and others. In particular, we recognize the need to more explicitly politicize the concept of moral distress in order to understand how such distress arises from competing values within power dynamics across multiple interrelated contexts from interpersonal to international. We propose that the same socio-political values that tend to individualize and blame people for poor health without regard for social conditions in which health inequities proliferate, hold responsible, individualize and even blame health care providers for the problem of moral distress. Grounded in a critical theoretical perspective of context, definitions of moral distress are re-examined and refined. Finally, recommendations for action that emerge from a re-conceptualized understanding of moral distress are provided.