THE ACTION OF DRUGS ON RESPIRATION : II. ETHER,CHLOROFORM, CHLORAL,URETHANE, LUMINAL,MAGNESIUM, CAFFEINE,STRYCHNINE, AND ATROPINE.

1. The depressant drugs which have been studied in this series of experiments were found to resemble morphine and heroine in that they depressed expiration more than inspiration, but they acted only in narcotic doses and always depressed inspiration at the same time. Ether caused a sharp expiratory rhythm, persisting until narcosis was very deep, probably a result of irritation of the air passages. Chloroform sometimes caused dyspnea, even in very deep narcosis, probably because of circulatory depression. Hydrated chloral made respiration more rapid, but shallower. Urethane usually made expiration active, often with inspiratory pauses, such as may follow vagotomy. Magnesium seemed to produce the most uniform, uncomplicated depression of all the depressants tried. Luminal resembled morphine and heroine more closely than any of the general depressants, making expiration passive without depressing inspiration, but it acted only in narcotic doses, unlike morphine and heroine. 2. Caffeine and strychnine, whenever they caused acceleration after morphine, brought back active expiration. Atropine never stimulated, and commonly acted as a synergist to morphine. 3. It is suggested that the results outlined in this and the preceding paper point to the existence of a separate central mechanism for the control of each of the phases of respiration, and that, while each responds to the same chemical stimuli, the threshold of the expiratory is higher than that of the inspiratory. Evidence is presented to indicate that if expiration remains passive a marked increase in depth of breathing may slow the rate, and a respiratory mechanism that lacks active expiration may be so inefficient that a CO₂ concentration which stimulated when expiration was active may depress when it is passive.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.     

Current immunization practices. 1. Polio, diphtheria, tetanus, pertussis, measles, mumps, rubella, and influenza

When used appropriately, immunization can effectively prevent many infections and diseases. Some vaccines, such as that for polio, are believed to produce lifelong immunity. Others, such as those for tetanus and diphtheria, may require that a booster injection be given upon exposure to assure full immunity. Still others, such as that for influenza, confer immunity for only a limited time. Inoculation is not without risk, particularly in immunosuppressed, allergic, febrile, or pregnant patients. However, in otherwise healthy patients, serious sequelae are so rare that they are far overshadowed by the enormous benefits of immunization.     

BrainVoyager--past, present, future

BrainVoyager started as a simple fMRI analysis tool in the mid 1990s; the software was primarily created to fulfill the needs of its author and his colleagues to analyze anatomical and functional MRI data in a way that would be most appropriate for their research questions in visual and auditory perception. More specifically, the software was designed with three major goals in mind. First, it should allow analyses that would exploit optimally the high-resolution information available in fMRI data. Second, it should integrate volume-based analysis and cortex-based analysis including the possibility to visualize topographic activation data on flattened cortex representations. Third, it should combine hypothesis testing with data-driven analysis including interactive visualization tools that would make it as easy as possible to look at and explore data. A fourth guiding principle was to develop a software package that fulfilled the author's preference for elegant user interfaces, beautiful visualizations and high-performance computing. These major guiding principles from the beginning of BrainVoyager development are still noticeable in the most recent incarnations of the software that has grown from a small fMRI analysis tool on the Windows platform to a comprehensive cross-platform multi-modal software package integrating (real-time) fMRI, DWI/DTI, (i)EEG, MEG, TMS and fNIRS analyses.     

Between-groups study designs demand between-groups analyses: a response to hernandez-reif, shor-posner, baez, soto, mendoza, castillo, quintero, perez, and zhang

The most recent massage therapy (MT) study by Hernandez-Reif et al. displays flaws persistent in this area of research that are attributable to MT researchers' frequent mistake of using within-group analyses of dependent variables in studies that are purported to be randomized control trials. This practise violates the logic of using randomization to create treatment and control groups, and thereby fails to control for the validity threats of spontaneous remission, placebo effects, and statistical regression. The result is that a clear understanding of what MT can and cannot do is seriously hampered.     

Therapy of experimental murine brucellosis with streptomycin, co-trimoxazole, ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin.

Mice infected with Brucella melitensis were treated with streptomycin, co-trimoxazole, ciprofloxacin, doxycycline, and rifampin intraperitoneally and with ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin orally for 14 to 21 days. Doxycycline- and rifampin-treated animals (either route) demonstrated a cure rate significantly better than that of controls. Longer therapy periods were associated with a significantly better outcome. Therapy failure was observed in all mice treated with ciprofloxacin, ofloxacin, and pefloxacin administered orally as well as in mice treated intraperitoneally with ciprofloxacin. Our findings demonstrate that treatment of experimental brucellosis in mice with doxycycline and rifampin yields therapeutic results that are superior to those yielded by treatment with quinolones.     

Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: history and perspective

Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.     

Monitoring, past, present, future

Summary A little over 40 years ago, anesthesiology in the United States became recognized as a specialty. At that time, its practice was largely that of an art, the science of which was yet to come. A finger on the pulse, observation of color, skin turgor, perspiration, and perhaps a blood pressure cuff in adults, and an estimation of the reflex signs of anesthesia were the standards for the assessment of the patient status and the depth of anesthesia. How far have we come in the intervening years? The journey, as reflected in the experience of one physician, will be held up to the looking-glass; easily as astounding as that through which Alice passed.Caught as we are in the socio-economic climate of the present, how shall we react? Has the gadgetry and electronics of this day given us a meaningful cost-effective handle on a decreased morbidity and mortality? What impact is there on decision-making and outcome? What indeed is the contribution of the machine versus the newer agents, techniques, and the advanced educational milieu.The first attempts at monitoring were clearly directed toward the cardiovascular system. The devices developed were simple and non-invasive. The Riva-rocci method of measuring blood pressure was first applied in anesthesia by Harvey Cushing at the turn of the century. But it was 40 years before the electrocardiogram was introduced as an instrument of potential importance. It took another 25 years for it to have general acceptance, and even later for the anesthesiologist to become comfortable with it as a diagnostic tool. In the early 40s, Peterson, at Pennsylvania, began the applications of invasive blood pressure monitoring for clinical purposes. Subsequently, the use of the central venous catheter, and finally the Swan-Ganz catheter, became acceptable. The application for the technology of cardiac output was a long time in gaining clinical credence. However, this last link surely depended on the computer to make it a clinically useful instrument. The measurement of the cardiovascular system was first, because the means were there.The assessment of respiratory function was more cumbersome, and while the pneumotachygraph was available 40 years ago, its vagaries made it a research tool. Meters for respiration also were available, but too cumbersome for clinical use. The integration of respiratory measurements and blood gas analysis have gone hand-in-hand, the latter far outstripping the former in clinical utility. Shall it be invasive or non-invasive, what is the price? Lastly, our technology has introduced the means for what is a meaningful clinical measurement of neurological and neuromuscular activity. Nerve-muscle stimulators, electromyography, processed electroencephalogram, and the evoked potential as devices for assessment are only the beginning. In all this technological advance there is the black box and the electronic marvels that are part of this age. While invasive techniques surely have a place, the utilization of non-invasive techniques like the measurement of oxygen, carbon dioxide, and all the agents that we employ have changed forever the nature of our practice. Finally, the need to document the anesthesia course objectively will, and has already begun, to impact on our practice. How did we get where we are and where are we going will be explored in this personal journey.     

Drafting a diversity,equity, and inclusion textbook inventory: Assumptions,concepts, conceptual framework

Nursing education programs have the sole responsibility to graduate future nurses prepared to care for their patients, families, and communities holistically in a way that is just and equitable, meeting their needs while centering their desires and goals for care. An implicit part of the nurse educator role is to promote efforts to build a more equitable, antiracist, and welcoming world. To this end, we recognize the critical part textbooks play as foundational components of most nursing educational programs. This article outlines the rationale for the development of a textbook inventory for assessing dimensions of diversity, equity, and inclusion in nursing textbooks. Next steps and a robust discussion around future directions are presented to demonstrate our commitment to creating a schema for evaluating nursing texts to ensure that what nursing students are taught is aligned with nursing values, including human dignity, cultural respect, and social justice. Our hope is that the textbook inventory will provide a first step to transforming nursing curriculum in a way that is tangible, making nursing curriculum more welcoming to students while laying groundwork for more robust capacity to care for folks from a wide array of backgrounds.     

Smoking, Nicotine, Nicotine Replacement, and Cardiovascular Disease

Cigarette smoking is a major risk factor for the development of coronary artery disease and its complications. Nicotine is one of the major substances that contributes to the pharmacologic activity of cigarette smoke, its toxicity, as well as its addictive nature. Strategies have been developed that utilize nicotine as a replacement substance in motivated patients who wish to stop smoking. Studies have shown that nicotine replacement therapy can be used safely in patients with known coronary artery disease.     

Preparation, premedication, and surveillance

The main criteria for assessing conscious sedation (perhaps now more correctly termed "moderate sedation/analgesia") continue to be patient satisfaction and comfort, short duration, amnesia, and above all, patient safety. The problems reviewed last year - including the increasing pressure on endoscopy units to perform yet more procedures, reduce costs, and achieve shorter patient turn-around times - certainly have not gone away. Studies reviewed this year suggest that although many endoscopic procedures, such as oesophagogastroduodenoscopy (OGD), colonoscopy, and endoscopic ultrasonography (EUS) can indeed be performed without intravenous sedation, many patients still prefer to be sedated. Further papers on the possible role of ultrathin endoscopes in unsedated OGD are reviewed here. A study in Italy comparing virtual computed-tomographic (CT) colonography and conventional colonoscopy suggests that unsedated colonoscopy is unlikely to meet with wide acceptance. Audits of colonoscopy in both the United States and the United Kingdom suggest that there is still a long way to go before caecal intubation rates of more than 90 % are regularly attained. The evidence suggests that some endoscopists are using larger doses of a midazolam and pethidine combination than are generally recommended (particularly in elderly patients), and sedation-related deaths are still occurring. Impressively large clinical studies, particularly those from Switzerland, on the use of propofol administered by nonanaesthetists are leading to reconsideration of the earlier view that propofol should only be used by anaesthetists. If propofol is to be used more widely and become an agent administered by endoscopists (or nursing staff), then considerable improvements in the standard of airways management will be needed. Several new studies relating to bowel-cleansing agents and the use of a carbohydrate/electrolyte "cholera mixture" to prevent the associated intravascular volume contraction have been published. Warm water is a cheap and effective way of reducing colonic spasm during colonoscopy, and intraluminal peppermint oil is a good antispasmodic in the stomach as well as the colon. Sedation should still be regarded as one part of an overall "endoscopy package". Finally, more attention needs to be given to patients' complaints regarding what are often considered by endoscopists to be "trivial complications" if the patients are to have a positive experience of their examination that will lead to them being prepared to come back a second time.     

Self-Compassion,Self-Injury,and Pain

We conducted an experiment to examine self-compassion and responses to pain among undergraduate women with and without histories of self-injury. After a writing task that has been shown to increase self-compassion in a values-affirming condition relative to a neutral control condition, participants completed a self-report measure of state self-compassion and the cold pressor task. As predicted, participants with a history of self-injury reported lower trait self-compassion than those without such a history, and participants in the values-affirming condition reported significantly higher state self-compassion than those in the control condition. Moreover, participants with a history of self-injury demonstrated significantly less insensitivity to pain in the values-affirming condition than the control condition. Future research should investigate the possibility that interventions involving self-compassion and/or affirmation of values may help correct high-risk responses to pain among those who self-injure.     

Antibiotics--TAZ/PIPC, synercid, linezolid, everninomicin

The increasing resistance among Gram-positive cocci have been accompanied by their increasing frequency as cause of severe infection. Thus new antimicrobial agents, TAZ/PIPC, synercid and linezolid, are in various stages of development. TAZ/PIPC, a combination drug of a new beta-lactamase inhibitor tazobactam and piperacillin at ratio in 1 to 4 has a broad spectrum of antimicrobial activity. Evidence from randomized clinical trials in adults in Japan has shown that TAZ/PIPC is superior to PIPC as a drug for complicated urinary tract infection. Synercid is a streptogramin antibiotic. The spectrum of activity of synercid is similar to vancomycin. Furthermore, most of E. faecium were susceptible. The efficacy of synercid in clinical trials in patients infected with VREF was 65-70%. Linezolid is a member of the oxazolidinones. The antimicrobial spectrum of linezolid is similar to that of vancomycin. In the US, patients with significant infection caused by resistant Gram-positive organisms(mostly VREF) were treated with linezolid. The efficacy of linezolid was about 75%. The clinical trials for everninomicin had been discontinued because of insufficient clinical data supporting its efficacy and safety.     

Disposition of caspofungin, a novel antifungal agent, in mice, rats, rabbits, and monkeys

The metabolism, excretion, and pharmacokinetics of caspofungin (Cancidas; Merck & Co., Inc.) were investigated after administration of a single intravenous dose to mice, rats, rabbits, and monkeys. Caspofungin had a low plasma clearance (0.29 to 1.05 ml/min/kg) and a long terminal elimination half-life (11.7 h to 59.7 h) in all preclinical species. The elimination kinetics of caspofungin were multiphasic and displayed an initial distribution phase followed by a dominant beta-elimination phase. The presence of low levels of prolonged radioactivity in plasma was observed and was partially attributable to the chemical degradation product M0. Excretion studies with [(3)H]caspofungin indicated that the hepatic and renal routes play an important role in the elimination of caspofungin, as a large percentage of the radiolabeled dose was recovered in urine and feces. Excretion of radioactivity in all species studied was slow, and low levels of radioactivity were detected in daily urine and fecal samples throughout a prolonged collection period. Although urinary profiles indicated the presence of several metabolites (M0, M1, M2, M3, M4, M5, and M6), the majority of the total radioactivity was associated with the polar metabolites M1 [4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine] and M2 [N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-L-threonine]. Caspofungin was thus primarily eliminated by metabolic transformation; however, the rate of metabolism was slow. These results suggest that distribution plays a prominent role in determining the plasma pharmacokinetics and disposition of caspofungin, as very little excretion or biotransformation occurred during the early days after dose administration, a period during which concentrations in plasma fell substantially. The disposition of caspofungin in preclinical species was similar to that reported previously in humans.     

Worry, Procrastination, and Perfectionism: Differentiating Amount of Worry, Pathological Worry, Anxiety, and Depression

This study investigates features that differentiate worry from somatic anxiety and depression. Theoretical models of the worry process suggest that worry is closely related to procrastination. In addition, research on worry and elevated evidence requirements proposes a relationship between worry and perfectionism. Perfectionism, however, is multidimensional in nature. Moreover, previous research has linked procrastination and perfectionism mainly to anxiety and depression. Therefore, the relationship among worry, procrastination, and dimensions of perfectionism was investigated in a sample of 180 students, controlling for anxiety and depression. Results show that worry had substantial correlations with procrastination and perfectionism, particularly with perfectionist concern over mistakes and doubts. Moreover, worry was related to parental criticism and expectations, but unrelated to excessively high personal standards. Instead, high-worriers reported to lower standards under stress. Partial correlations indicated that these correlations were specific for amount of worry, thus differentiating amount of worry, pathological worry, anxiety, and depression.     

Public policy,federalism, and AIDS

Abstract

The AIDS epidemic poses important challenges to the American political system. In the context of AIDS, relationships between the public and private sectors as well as those among federal, state, and local governments have had a significant impact in shaping the nations response to the epidemic. The character of health policy in the United States has in large part been determined by uncertainty regarding the appropriate role of the public sector and by persistent beliefs that the best solutions are private sector ones. Similarly, relationships across levels of government are clouded by concerns about the presumed excesses of centralized (federal) government and the widespread conviction that the most appropriate solutions are state and local ones. AIDS emerged as a public health issue at a point in the early 1980s when a new federal administration was calling for a reduction in public sector and federal responsibility for addressing health and social needs. Since that time, stronger public and federal leadership appears to be developing, and both are essential to forging the policy partnerships between the public and private sectors and across levels of government that are essential to the development of a comprehensive policy response to the AIDS epidemic.     

Carpal tunnel syndrome, diabetic neuropathy, fibromyalgia, glucosamine and chondroitin, hypnosis in pain management, marijuana for pain

This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are carpel tunnel syndrome, fibromyalgia, glucosamine and chondroitin, hypnosis, marijuana.     

Low fermentable oligosaccharides,disaccharides, monosaccharides,and polyols diet in children

Irritable bowel syndrome (IBS) is a lifelong condition with a high prevalence among children and adults. As the diet is a frequent factor that triggers the symptoms, it has been assumed that by avoiding the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP), the symptoms might be improved. Therefore, in the past decade, low FODMAP diet has been intensively investigated in the management of IBS. The capacity of FODMAPs to trigger the symptoms in patients with IBS was related to the stimulation of mechanoreceptors in the small and large intestine. This stimulation appears as a response to a combination of increased luminal water (the osmotic effect) and the release of gases (carbon dioxide and hydrogen) due to the fermentation of oligosaccharides and malabsorption of fructose, lactose and polyols. Numerous studies have been published regarding the efficacy of a low FODMAP diet compared to a traditional diet in releasing the IBS symptoms in adults, but there are only a few studies in the juvenile population. The aim of this review is to analyze the current data on both low FODMAP diet in children with IBS and the effects on their nutritional status and physiological development, given the fact that it is a restrictive diet.     

Anxiety,Arousal, and the Self-Concept

Too often, theories of emotions in humans are simple extensions of theories of emotions in subhuman animals. Though it is reasonable to extend our knowledge of emotions from lower to higher order animals, there is one major difference between man and other animals that imposes a serious limitation on this procedure. The difference is that man has a highly developed conceptual system that not only structures the content of what he fears, but itself must be defended against threat. Expressed otherwise, fears in animals are primarily a consequence of threats to life and limb, while in humans they are primarily a consequence of threats to ego. There are essentially two basic types of threat to ego, threats to the assimilative capacity of an individual's conceptual system, and threats to his self-esteem.     

Public policy, federalism, and AIDS

The AIDS epidemic poses important challenges to the American political system. In the context of AIDS, relationships between the public and private sectors as well as those among federal, state, and local governments have had a significant impact in shaping the nations response to the epidemic. The character of health policy in the United States has in large part been determined by uncertainty regarding the appropriate role of the public sector and by persistent beliefs that the best solutions are private sector ones. Similarly, relationships across levels of government are clouded by concerns about the presumed excesses of centralized (federal) government and the widespread conviction that the most appropriate solutions are state and local ones. AIDS emerged as a public health issue at a point in the early 1980s when a new federal administration was calling for a reduction in public sector and federal responsibility for addressing health and social needs. Since that time, stronger public and federal leadership appears to be developing, and both are essential to forging the policy partnerships between the public and private sectors and across levels of government that are essential to the development of a comprehensive policy response to the AIDS epidemic.