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The ambulatory surgery unit as a learning experience.

Today's graduate nurses are expected to enter the work environment at increased levels of competence. Skills are expected to be ingrained, and health care administrators expect new graduates to be able to think critically. Nurse educators often are looking for new and creative ways to educate students. The ambulatory surgery setting can provide a plethora of clinical tasks and situations that teach students how to gather information, make judgments, prioritize, handle multiple demands and patients, and perform clinical skills quickly and efficiently. This article describes a pilot project in which eight nursing students learned valuable clinical and critical thinking skills in the fast-paced world of ambulatory care.

Ambulatory Surgical Procedures↗

Dynamics of effective oral presentations. Strategies for nurse educators.

Oral presentations can and should be exciting events for learners and educators. Inservice faculty members who are new educators have a plethora of sources that they can use to develop and refine their presentation skills. Just as individuals learn to read by reading and write by writing, staff instructors learn to teach well by teaching. Focus on developing your teaching versatility by combining strategies, because varying methods will appeal to learners' different learning styles. Whether you are a novice or seasoned teacher, you can constantly improve your teaching skills. When you execute an effective presentation, everyone wins. You experience and enjoy your own professional growth, and learners benefit from quality educational experiences. The most important benefit of effective presentations is that surgical patients receive competent care from well-informed, up-to-date clinicians.

Education, Nursing↗

Nuclear medicine instrumentation. Historic perspective.

Recording the chronology of nuclear medicine instrumentation poses some difficult decisions as does the determination of the "father" of nuclear medicine?. Historians can agree on well-defined dates and events, but many of them are subjective and reside in the memories of those of us who were fortunate to experience the formative years of our field. We all search for the historical truth. The highlights of this story may begin with John Lawrence and phosphorus-32 therapy at Berkeley and continue with Enrico Fermi's sustained nuclear reaction, which lead to the Manhattan Project, then the Atomic Energy Commission, and finally, Sam Seidlin's treatment of thyroid metastases with iodine-131. The rectilinear scanner came to us from Benedict Cassen and was followed by Hal O. Anger and his gamma scintillation camera, one of the most pivotal developments in the field. A plethora of cameras followed: Merrill Benders's digital autofluroscope, Dave Kuhl's efforts for tomographic imaging, and then on to single photon emission computed tomography. Finally, we come back to Hal O. Anger, who suggested and worked with the idea of a positron camera, with positron emission tomography becoming commercially available in 1985. Ours is a variegated history, and I hope that this account speaks the historical truth.

History, 20th Century↗

Carotid endarterectomy: what is its current status?

The plethora of recent articles regarding carotid endarterectomy has tended to confuse rather than clarify its indications, efficacy, and acceptability. The National Institutes of Health has recently funded two large multicenter controlled clinical trials, one including asymptomatic persons with carotid stenoses, and the other, patients having transient ischemic episodes or minor strokes. Eight academic professors of neurology (four), neurosurgery (two), and vascular surgery (two) with a long and abiding interest in cerebrovascular disease prepared a statement delineating acceptable levels of mortality and morbidity from this procedure. These might serve as guidelines until the large trials have been completed.

Arteriosclerosis↗

Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease.

Recent evidence supports a role for estrogens in both normal neural development and neuronal maintenance throughout life. Women spend 25-33% of their life in an estrogen-deprived state and retrospective studies have shown an inverse correlation between dose and duration of estrogen replacement therapy (ERT) and incidence of Alzheimer's disease (AD), suggesting a role for estrogen in the prevention and/or treatment of neurodegenerative diseases. To explore these observations further, an animal model was developed using ovariectomy (OVX) and ovariectomy with estradiol replacement (E2) in female Sprague-Dawley rats to mimic postmenopausal changes. Using an active-avoidance paradigm and a spatial memory task, the effects of estrogen deprivation were tested on memory-related behaviors. OVX caused a decline in avoidance behavior, and estrogen replacement normalized the response. In the Morris water task of spatial memory, OVX animals showed normal spatial learning but were deficient in spatial memory, an effect that was prevented by estrogen treatment. Together these data indicate that OVX in rats results in an estrogen-reversible impairment of learning/memory behavior. Because a plethora of information has been generated that links decline in memory-related behavior to dysfunction of cholinergic neurons, the effects of estrogens on cholinergic neurons were tested. We demonstrated that OVX causes a decrease in high affinity choline uptake and choline acetyltransferase activity in the hippocampus and frontal cortex; ERT reverses this effect. Further, we showed that estrogens promote the expression of mRNA for brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), 2 neurotrophic substances that have been shown to ameliorate the effects of age and injury on cholinergic neurons. Tissue culture models were used to evaluate whether estrogen treatment increases the survival of neurons when exposed to a variety of insults. 17-beta-Estradiol (beta-E2) protects cells from the neurotoxic effects of serum deprivation and hypoglycemia in human neuroblastoma cell lines. We have also observed that 17-alpha-estradiol (alpha-E2), a weak estrogen, shows neuroprotective efficacy in the SK-N-SH cell line at concentrations equivalent to beta-E2. Finally, we have observed that tamoxifen, a classic estrogen antagonist, blocks only one-third of the neuroprotective effects of either alpha-E2 or beta-E2. Collectively, these results indicate that estrogen is behaviorally active in tests of learning/ memory; activates basal forebrain cholinergic neurons and neurotrophin expression; and is neuroprotective for human neuronal cultures. We conclude that estrogen may be a useful therapy for AD and other neurodegenerative diseases.

Alzheimer Disease↗

Thirty-year experience with repair of pectus deformities in adults.

BACKGROUND: A plethora of studies have described repair of pectus deformities in children, but only few reports have described this repair in adults. The purpose of this study was to review our 30-year experience with surgical repair of pectus deformities in adults. METHODS: A retrospective review of all adult patients (> 16 years old) who underwent repair of congenital pectus deformities from 1971 through 2001. RESULTS: There were 77 patients, 64 men and 13 women. Sixty-eight patients underwent surgery for pectus excavatum and 9 for pectus carinatum; median age was 22 years old (range, 16 to 68 years old). Indication for repair was medical concerns in all patients. Preoperative symptoms were dyspnea on exertion in 43 patients, shortness of breath at rest in 22 patients, chest pain in 8 patients, and palpitations in 8 patients. Preoperative electrocardiogram findings included right bundle branch block in 9 patients, sinus bradycardia in 8 patients, left atrial enlargement in 6 patients, and right atrial dilatation in 5 patients. Patterns of the pectus defect were symmetric and localized in 29 patients, symmetric and diffuse in 21, asymmetric and localized in 18, and asymmetric and diffuse in 9 patients. Intraoperative classifications were severe in 38 patients, moderate in 33 patients, and mild in 6 patients. There were no operative deaths. Complications occurred in 11 patients (14.3%). Mean hospital stay was 4 days (range, 2 to 8 days). Mean follow-up was 12 +/- 7 years (range, 4 months old to 24 years old); 1 patient (1.3%) required reoperation for recurrent pectus excavatum. Patient satisfaction and relief of medical symptoms was excellent in 70 patients (90.9%), good in 6 patients, and fair in 1 patient. CONCLUSIONS: Repair of congenital defects of the sternum in adults can be performed safely with low morbidity and no mortality. Long-term results are excellent with requirement for reoperation rare.

Adult↗

Surgical treatment of the ruptured aneurysm of the aortic sinuses.

Over the past 11 years, 51 patients (36 male, 15 female) underwent operation to correct ruptured sinus of Valsalva at the Shanghai Chest Hospital. Associated lesions were present in 36 patients. All patients had cardiac enlargement, pulmonary plethora, and prominence of the main pulmonary arterial trunk. Preoperative arterial pressure averaged 135/46 mm Hg (range, 200-96/95-0 mm Hg). At operation the cardiac chamber into which the ruptured aneurysm emptied was opened. The projecting aneurysmal sac was resected at its base, leaving a fringe of 2 to 3 mm for suturing. A double-layer suture closure was used, first a row of figure-of-eight sutures, followed by a row of buttressed mattress sutures. Forty-five patients survived operation; 6 died shortly after operation, a perioperative mortality of 11.8%. Follow-up averaged 4 to 8 months. Thirty-eight patients were symptom free and working; 7 had returned to part-time work. There were no late deaths. A grade II systolic murmur persists in 2 patients, and in 1 of them a loud continuous murmur and thrill were both noted. All patients who survived have shown remarkable reduction in cardiothoracic ratio and improvement in symptoms. These results justify early surgical intervention.

Adolescent↗

Biochemical implications of sequence comparisons of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is both of medical significance in humans and of interest with regard to osmoregulation in aquatic organisms. CFTR is composed of five domains: two membrane-spanning domains, two nucleotide-binding domains, and a regulatory domain. Notwithstanding the plethora of information concerning the structure and function of CFTR, the biochemistry of many facets of CFTR are not completely understood. In this regard, we have performed a sequence alignment of representative vertebrate CFTR with the aim of generating hypotheses on the functional significance of conserved and variable residues. Postulates on function common to all organisms are: (i) Thr338 in the sixth transmembrane segment could have a function related to that of the pore-lining residue Lys335, and it is possible that Thr338 hydrogen bonds to Lys335, thus indirectly affecting anion permeability; (ii) the fragment (111)PDNKE could be an ion sensor; (iii) motifs in the two nucleotide-binding domains reflect differential ATP binding and hydrolysis; and (iv) an interaction in the R domain involving (765)RRQSVL and the C terminal end of the domain results in an inhibitory conformation. Major adaptations in fishes include variations in the postulated ion sensor (111)PDNKE, and the absence of a proline residue in the R domain with consequent higher chloride efflux.

Adenosine Triphosphate↗

Inhibitors of NADH-ubiquinone reductase: an overview.

This article provides an updated overview of the plethora of complex I inhibitors. The inhibitors are presented within the broad categories of natural and commercial compounds and their potency is related to that of rotenone, the classical inhibitor of complex I. Among commercial products, particular attention is dedicated to inhibitors of pharmacological or toxicological relevance. The compounds that inhibit the NADH-ubiquinone reductase activity of complex I are classified according to three fundamental types of action on the basis of available evidence and recent insights: type A are antagonists of the ubiquinone substrate, type B displace the ubisemiquinone intermediate, and type C are antagonists of the ubiquinol product.

Enzyme Inhibitors↗

Quantifying molecular partition into model systems of biomembranes: an emphasis on optical spectroscopic methods.

Optical spectroscopies have been intensively used to determine partition coefficients by a plethora of methodologies. The present review is intended to give detailed and useful information for the determination of partition coefficients and addresses several relevant aspects, namely: (i) definition and calculation of the partition coefficient between aqueous and lipidic phases; (ii) partition coefficients vs. "binding" formalisms; (iii) advantages of spectroscopic methodologies over separation techniques; (iv) formalisms for various experimental approaches based on UV-Vis absorption or fluorescence parameters (fluorescence intensity, lifetime, anisotropy and quenching); (v) experimental hints, artifacts and model limitations; and (vi) a brief survey of nonoptical techniques.

Cell Membrane↗

Clinically useful, research validated assessment of persons with alcohol problems.

Advances in treatment approaches available for persons with alcohol problems, particularly the advent of cognitive behavioral and motivational approaches, have made systematic assessment of these problems more important than ever for clinicians. There is a plethora of assessment instruments available, and it is a difficult task for clinicians to conceptualize, select and use these instruments in a coherent fashion. Particularly important in this task is the identification of research validated instruments that provide both clinically useful and psychometrically sound data. This paper presents a model of alcohol assessment and reviews selected research validated instruments that can be assembled into an assessment battery that provides useful data to guide treatment of alcohol problems while also addressing practical concerns encountered by clinicians in practice.

Adaptation, Psychological↗

Factors associated with dropout in a group cognitive behaviour therapy for mood disorders.

The high prevalence of premature attrition from psychotherapy is a phenomenon which has been well recognized in the psychological literature. The pressing concern that a number of clients may not be benefiting from treatment because they are dropping out has led to a plethora of research in the area of individual psychotherapy. No studies, however, have attempted to investigate the characteristics of dropout in group cognitive behaviour therapy for depression. To address this gap in research, the present study examined the factors associated with dropout in a group cognitive behaviour therapy for depression, using 131 Ss who went through the group therapy for 12 weeks. The results showed that sociodemographic measures (e.g. age) and measures of depressive symptoms (e.g. depression scores) did not discriminate dropouts from completers. An investigation of patterns of mood changes in the course of the therapy also failed to find significant differences between the dropouts and completers. However, weekly therapist rating of client participation revealed that dropouts participated significantly less than completers during the therapy sessions. The results are discussed in light of the findings of current literature and future research in premature attrition.

Adolescent↗

Species-specific differences in the usage of several caspase substrates.

The activation of caspases cleaving a plethora of specific substrates is pivotal for initiation as well as execution of apoptosis. The recognition motif for caspases is a tetrapeptide sequence containing an essential aspartic acid residue at the fourth position (often DXXD). Here, we report that the caspase cleavage sites of most identified substrates show a high degree of conservation between different species. However, we have identified differences in the cleavage sites of five substrates between murine and human proteins leading to either select processing in only one species or to different cleavage patterns. Finally, we provide evidence that murine c-Abl but not its human homolog serves as efficient substrate during apoptosis.

3T3 Cells↗

Biopanning of endotoxin-specific phage displayed peptides.

Systemic bacterial infections frequently lead to a plethora of symptoms termed "endotoxic shock" or "sepsis." Characterized by hypotension, coagulation abnormalities, and multiple organ failure, treatment of sepsis still remains mostly supportive. Of the various experimental therapeutic interventional strategies, neutralization of endotoxin by peptides or proteins is becoming popular recently. Hence, design of endotoxin binding peptides is gaining currency as their structural complexity and mode of recognition of endotoxin precludes mounting of resistance against them by the susceptible bacteria by genetic recombination, mutation, etc. Earlier work from our laboratory had shown that the amphiphilic cationic peptides are good ligands for endotoxin binding. In this study, we report the results of studies with the 12 selected lipid A binding phage displayed peptides by biopanning of a repertoire of a random pentadecapeptide library displayed on the filamentous M-13 phage. A comparison of the sequences revealed no consensus sequence between the 12 selected peptides suggesting that the lipid A binding motif is not sequence specific which is in accord with the sequence variation seen with the naturally occurring anti-microbial and/or endotoxin binding peptides. Thus, the flexibility of the peptides coupled with their plasticity in recognizing the lipid A moiety, explains their tight binding to endotoxin. At a structural level, asymmetric distribution of the charged polar residues on one face of the helix and non-polar residues on the opposite face appears to correlate with their activity.

Amino Acid Sequence↗

Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6.

Interleukin (IL)-6 is a multifunctional cytokine that can be induced by a plethora of chemical or physiological compounds, including the inflammatory cytokines tumor necrosis factor (TNF) and IL-1. The molecule TNF has a trimeric configuration and thus binds to membrane-bound, cellular receptors to initiate cell death mechanisms and signaling pathways leading to gene induction. Previously, we showed that induced clustering of the intracellular domains of the p55 TNF receptor, or of their respective 'death domains' only, is sufficient to activate the nuclear factor kappa B (NF-kappa B) and several mitogen-activated protein kinase (MAPK) pathways. NF-kappa B is the exclusive transcription factor for induction of the IL-6 gene in response to TNF and functions as the final trigger to activate a multiprotein complex, a so-called 'enhanceosome', at the level of the IL-6 promoter. Furthermore, the enhanceosome displays histone acetylation activity, which turned out to be essential for IL-6 gene activation via NF-kappa B. However, activation of NF-kappa B alone is not sufficient for IL-6 gene induction in response to TNF, as inhibition of the coactivated extracellular signal-regulated kinase and p38 MAPK pathways blocks TNF-mediated gene expression. Nevertheless, the transactivating NF-kappa B subunit p65 is not a direct target of MAPK phosphorylation. Thus, we postulated that other components of the enhanceosome complex are sensitive to MAPK cascades and found that MAPK activity is unequivocally linked to the histone acetylation capacity of the enhanceosome to stimulate gene expression in response to TNF. In contrast, glucocorticoid repression of TNF-driven IL-6 gene expression does not depend on abrogation of histone acetyltransferase activity, but originates from interference of the liganded glucocorticoid receptor with the contacts between NF-kappa B p65 and the promoter configuration around the TATA box.

Animals↗

Inflammatory signal transduction in Crohn's disease and novel therapeutic approaches.

Although signal transduction phenomena are well understood in vitro, their relevance for physiology and pathophysiology remains obscure. Recent years, however, have seen a plethora of attempts to link cell biochemistry and disease. At the Luxembourg conference it was attempted to link basal science to disease. In my presentation I focused on our research on stress activated kinases and other signalling elements in this respect in a variety of pro-inflammatory conditions. Knowledge of these pathways has now led to new therapeutic approaches, especially in Crohn's disease, which will be the subject of this commentary.

Anti-Inflammatory Agents↗

"Multivalent" saccharides: development of new approaches for inhibiting the effects of glycosphingolipid-binding pathogens.

A number of diseases are initiated by the adherence of viruses, bacteria, or bacterial toxins to cell surface carbohydrates, a number of which are components of glycosphingolipids (GSLs). Studies of the binding of lectins indicated that many adhered weakly to monomeric carbohydrate ligands. The seminal observation that lectins adhered more strongly to a ligand with multiple carbohydrate binding sites initiated a plethora of studies designed to identify effective "multivalent" carbohydrate ligands for pathogens expressing multiple carbohydrate-binding sites. In addition to more completely defining ligand specificity of the carbohydrate-binding pathogen, identification of "multivalent" carbohydrate ligands has led to studies of their efficacy as pathogen inhibitors. This commentary focuses on pathogens that recognize the carbohydrate portion of GSLs. Because many GSL-binding pathogens have been shown to bind "multivalent" saccharides, approaches for identifying and preparing them as well as methods for characterizing their effectiveness as ligands are reviewed. Also discussed are areas of promise that should be investigated and pitfalls that might be encountered in the development of "multivalent" saccharides as pharmacologic agents.

Animals↗

Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness.

BACKGROUND: A plethora of indirect findings suggests that mood disorders may be caused by or result in structural changes in the brain, namely decreased hippocampal cell proliferation. METHODS: To test for these hypotheses, we used a rat model of depression, learned helplessness. Moderate unpredictable and inescapable foot shocks induced learned helplessness only in a portion of the rats. Rats that showed helpless behavior were compared to those behaving normally after inescapable shock. Proliferating cells in the dentate gyrus were labeled with BrdU (bromodeoxyuridine). RESULTS: Helpless behavior appeared before the decrease of dentate gyrus cell proliferation was maximal. Cell proliferation was decreased to the same extent in animals that developed helplessness as those that were not helpless. Furthermore, immobilization stress, which reduced the rate of cell proliferation, did not induce learned helplessness. CONCLUSION: These results are in line with reports that the rate of dentate gyrus cell proliferation is acutely down-regulated by stress, but the development of helpless behavior does not correlate with this process. Further studies will have to clarify if during learned helpless behavior neurogenesis is impaired by altered differentiation or survival of cells.

Analysis of Variance↗