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Clinical nurse specialist and nurse practitioner core curricula survey results.

The American Nurses' Association's Council of Clinical Nurse Specialists and Council of Primary Health Care Nurse Practitioners conducted a survey of all graduate nursing programs in the United States that prepare nurse practitioners and/or clinical nurse specialists. One hundred eight schools responded (73.5 percent), yielding data on 317 programs that could be further analyzed. For the 60 NP and 195 CNS programs analyzed, information was obtained on the following: required courses, number of hours of the required courses, students' clinical training settings and graduates' employment settings. Findings revealed marked similarity between the core curricula of NP and CNS graduate programs. The only significant differences found were that NP programs placed greater emphasis on pharmacology, primary care, physical assessment, health promotion, nutrition and history-taking in their curricula. In both the student clinical settings and graduate employment settings, NPs focused on primary care settings while CNSs focused on secondary or tertiary care settings. Based on the marked similarities between the core curricula of NP and CNS graduate programs, it is suggested that further investigations be conducted to determine whether objectives and/or teaching methods differ, and to further investigate the effects of practice setting on role development. Further, it is suggested that NPs and CNSs continue to interact through forums and conferences to continue the evolution and definition of graduate nursing education and advanced practice.

Curriculum↗

[Endoscopy or surgery in the treatment of obstructive jaundice].

The role of operative endoscopy as opposed to surgery in the treatment of obstructive jaundice is in continuous positive evolution due to the rapid technical progress made in the use of this method. Of a total of 93 patients treated over the course of 3 years, some received surgical treatment alone, others endoscopic treatment alone, and a third group received endoscopic therapy followed by surgery. Various parameters were taken into consideration for the three groups studied: the pathological cause of jaundice, age, sex, success of the method used, early and late complications, hospital deaths. Results were then compared.

Age Factors↗

Craniofacial surgery in children: concepts and questions.

Craniofacial surgery is an exciting new subspecialty of medicine. It is strictly a team project that will function well only in a tertiary medical center. Particular coordination is needed among the plastic surgeon, neurosurgeon, anesthesiologist, and pediatrician. This article considers many of the potential advantages and some of the disadvantages of performing craniofacial surgery on infants. It is difficult or impossible, based on current knowledge, to predict the ultimate limits of such new techniques. The history of surgical evolution, however, continues to demonstrate that what "at first observation" was thought to be impossible or undesirable often evolves, with more understanding, to be the desired course of action. It was entirely appropriate that the initial craniofacial surgical efforts be generally confined to adult-type patients, but the currently available technical refinements have developed such procedures to the point where they now have a definite place in infant surgery as well. Continued clinical investigative research will provide further information regarding the eventual benefits and perhaps will lead to surgical techniques in neonates that will actually prevent the development of certain predictable deformities.

Bone Diseases, Developmental↗

Population genetics of haemoglobin variants, thalassaemia and glucose-6-phosphate dehydrogenase deficiency, with particular reference to the malaria hypothesis.

The authors report data on the genetic distribution of thalassaemia and of glucose-6-phosphate dehydrogenase deficiency in the populations of certain Sardinian villages, many of which are not only of great antiquity but have maintained isolation for very long periods and therefore possess the following three requirements for suitability for investigation of the possible interrelationships among malaria, thalassaemia and G-6-PD deficiency: a reasonable degree of ethnic homogeneity, availability of reliable demographic data, and availability of malaria-free populations of adequate size and of ethnic background and genetic isolation similar to those of the malarial populations.Investigations including more than 6000 observations in 52 villages demonstrated a positive correlation between the incidences of thalassaemia and G-6-PD deficiency. It is suggested that the genotype that carries thalassaemia and/or the enzyme deficiency may have a high adaptive value in a malarial environment.It is concluded that there is a need further to investigate human genetic structure and the biological fitness of the principal genotype combinations in both existing environments and those that will result from continued cultural evolution.

Genetics, Population↗

[Cutaneous mastocytosis. Description of 4 cases].

The Authors describe four cases of cutaneous mastocytosis observed during paediatric age. They notice that the disease presents itself with a clinical polymorphous situation which sometimes exceeds the limits of the cutaneous gambit, until the illness reveals itself a systemic serious disease. Besides they point out uncertain etiopathogenesis, the utility of a correct diagnostic approach and the utility of a therapy which is continually in evolution.

Female↗

[Radiotherapy concomitant with cisplatin chemotherapy in the treatment of cancer of the cervix uteri].

Cancer of the cervix presents an increasing incidence and mortality in advanced stages. Failure of treatment consists in local recurrence, continuation of evolution or in distant metastasis. One of the strategies of improving the treatment response is the association of radiosensitization chemotherapy with irradiation. The aim of this paper is the study of the effect of cisplatin administration simultaneously with radiotherapy of primary cancer of the cervix and recurrences. This association has proved to be favourable as regards immediate and short period local control with an acceptable digestive and hematologic tolerance (gr. I-II).

Adult↗

Clonal diversity of Ig and T-cell-receptor gene rearrangements identifies a subset of childhood B-precursor acute lymphoblastic leukemia with increased risk of relapse.

Current prognostic indicators such as age, sex, and white blood cell count (WBC) fail to identify all children with more aggressive forms of B-precursor acute lymphoblastic leukemia (ALL), and a proportion of patients without poor prognostic indicators still relapse. Results obtained from an analysis of 65 pediatic B-precursor ALL patients indicated that subclone formation leading to clonal diversity, as detected by Ig and T-cell receptor (TCR) gene rearrangements, may represent a very useful prognostic indicator, independent of age, sex, and WBC. Disease-free survival was significantly shorter in those patients showing clonal diversity at presentation. Furthermore, clonal diversity was detected not only in the majority of high-risk patients who relapsed but was also associated with a high probability of relapse in standard-risk patients. Sixty-five percent (13/20) of standard-risk patients who also showed clonal diversity subsequently relapsed, whereas the percentage of relapses among standard-risk patients without clonal diversity was much lower at 19% (7/36). Continued clonal evolution during disease progression is an important feature of aggressive B-precursor ALL. All 5 patients with clonal diversity who were followed up in our study showed a change in the pattern of clonality between presentation and relapse. This implies an important role for clonal diversity as a mechanism of disease progression through the process of clonal variation and clonal selection.

Adolescent↗

Evolving roles of life and health sciences librarians for the twenty-first century.

The twenty-first century will provide exciting challenges for life and health sciences librarians that will force us to redefine our position in the world of information. This rapidly changing environment influences the profession in a variety of ways including whom we serve and through what service, how and where we practice librarianship, and even the very composition of the profession itself. We must look at the changes in society and make the appropriate reciprocal changes in how we educate future librarians, how we market the profession, and how we develop the profession as a whole. We, as life and health sciences librarians, need to meet these challenges head on in order to continue the evolution of the profession well into the twenty-first century.

Curriculum↗

Stepwise molecular evolution of bacterial photosynthetic energy conversion.

The concept of continuity in molecular evolution implies a stepwise formation of metabolic systems and processes. In this manner, chemical and biological evolution have given rise, step by step, to such complicated systems as the photosynthetic apparatus and thus, such elaborate processes as photosynthesis in the living cell. Among currently living organisms, the bacteria contain a much less complex photosynthetic system than the algae and higher plants, which uniquely are capable fo splitting H2O. But also the bacterial system is a very highly evolved and sophisticated, membrane-bound apparatus for the transformation of light energy to other biologically useful energy forms. The study of its molecular evolution is here undertaken by the method of attempting to break down the system into its main components and functions in order to elucidate how they had originated and evolved, and how, by divergent and convergent evolutionary steps, the stage was set for the arrival of bacterial photophosphorylation.

Adenosine Triphosphatases↗

Directed enzyme evolution.

Laboratory evolutionists continue to generate better enzymes for industrial and research applications. Exciting developments include new biocatalysts for enantioselective carbon-carbon bond formation and fatty acid production in plants. Creative contributions to the repertoire of evolutionary methods will ensure further growth in applications and expand the scope and complexity of biological design problems that can be addressed. Researchers are also starting to elucidate mechanisms of enzyme adaptation and natural evolution by testing evolutionary scenarios in the laboratory.

Bacterial Proteins↗

A molecular description of the evolution of resistance.

BACKGROUND: In vitro evolution has been used to obtain nucleic acid molecules with interesting functional properties. The evolution process usually is carried out in a stepwise manner, involving successive rounds of selection, amplification and mutation. Recently, a continuous in vitro evolution system was devised for RNAs that catalyze the ligation of oligonucleotide substrates, allowing the evolution of catalytic function to be studied in real time. RESULTS: Continuous in vitro evolution of an RNA ligase ribozyme was carried out in the presence of a DNA enzyme that was capable of cleaving, and thereby inactivating, the ribozyme. The DNA concentration was increased steadily over 33.5 hours of evolution, reaching a final concentration that would have been sufficient to inactivate the starting population in one second. The evolved population of ribozymes developed resistance to the DNA enzyme, reducing their vulnerability to cleavage by 2000-fold but retaining their own catalytic function. Based on sequencing and kinetic analysis of the ribozymes, two mechanisms are proposed for this resistance. One involves three nucleotide substitutions, together with two compensatory mutations, that alter the site at which the DNA enzyme binds the ribozyme. The other involves enhancement of the ribozyme's ability to bind its own substrate in a way that protects it from cleavage by the DNA enzyme. CONCLUSIONS: The ability to direct the evolution of an enzyme's biochemical properties in response to the behavior of another macromolecule provides insight into the evolution of resistance and may be useful in developing enzymes with novel or enhanced function.

Base Sequence↗

Rhythmicity in ethylene production in cotton seedlings.

Cotyledons of cotton (Gossypium hirsutum L.) seedlings grown under a photoperiod of 12 hour darkness and 12 hour light showed daily oscillations in ethylene evolution. The rate of ethylene evolution began to increase toward the end of the dark period and reached a maximum rate during the first third of the light period, then it declined and remained low until shortly before the end of the dark period. The oscillations in ethylene evolution occurred in young, mature, and old cotyledons (7 to 21 day old). These oscillations in ethylene evolution seemed to be endogenously controlled since they continued even when the photoperiod was inverted. Moreover, in continuous light the oscillations in ethylene evolution persisted, but with shorter intervals between the maximal points of ethylene evolution. In continuous darkness the oscillations in ethylene evolution disappeared. The conversion of [3,4-(14)C]methionine into [(14)C] ethylene followed the oscillations in ethylene evolution in the regular as well as the inverted photoperiod. On the other hand, the conversion of applied 1-aminocyclopropane-1-carboxylic acid into ethylene did not follow the oscillations in ethylene evolution, but was affected directly by the light conditions. Always, light decreased and darkness increased the conversion of applied 1-aminocyclopropane-1-carboxylic acid into ethylene. It is concluded that in the biosynthetic pathway of ethylene the conversion of 1-aminocyclopropane-1-carboxylic acid into ethylene is directly affected by light while an earlier step is controlled by an endogenous rhythm.

Journal Article↗

Intraepithelial and postinvasive neoplasia as a stochastic continuum of clonal evolution, and its relationship to mechanisms of chemopreventive drug action.

The progression of intraepithelial and postinvasive neoplasia depends on the occurrence of clonal evolution, defined as the continuous development of mutations and selective clonal expansions in the neoplastic cell population. The two continuously repeating events of clonal evolution, mutation and clonal expansion, occur at unpredictable times and locations. Therefore the neoplastic process is best characterized as a stochastic, i.e., probabilistic, continuum. The rate of intraepithelial neoplastic progression is continuously driven by the dosage level of exposure to mutagens and mitogens. For example, in chronic smokers the length of time before development of lung cancer depends on the number of cigarettes smoked per day. A commonly held misconception is that human carcinogenesis develops after an initial short period of mutation followed by a long period of stimulated proliferation (the multistage model). This incorrect idea derives from the sequential nature of the consecutive two- or three-step operational protocols imposed on experimental animal models by the experimenter. In reality, human carcinogenesis develops as the result of simultaneous and continuous exposure to mutagens and mitogens over the entire period of tumor development. A recent example is the finding that the intraepithelial neoplasia of colorectal adenomas continuously progresses through serial waves of mutation and clonal expansion. The rational design of chemopreventive agents should be based on blocking the two parameters which continuously drive neoplasia: mutagenesis and mitogenesis. In addition to blocking exposure, chemopreventive agents may act at many points during activation and DNA adduction of mutagens, or during stimulation of the proliferation signal pathway by mitogens. Based on the chemopreventive strategy of blocking mutagenesis and mitogenesis, chemopreventive agents are classed as either antimutagenic or antimitogenic. A third class, the antioxidants, are both antimutagenic and antimitogenic, and operate by the common mechanism of breaking free radical chain reactions initiated by reactive oxygen species. In the program of the Chemoprevention Investigational Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, preclinical development of antimutagens, antimitogens, and antioxidants is well under way, and some of these agents are highlighted here.

Antioxidants↗

Modelling viral evolution in vitro using exo- Klenow polymerase: continuous selection of strand displacement amplified DNA that binds an oligodeoxynucleotide to form a triple-helix.

Evolution comprises cycles of amplification, mutagenesis and selection. To study evolutionary phenomena, isothermal strand displacement amplification (SDA) of double-stranded DNA as an in vitro model for rolling-circle replication of viruses has been coupled to a positive selection procedure. First, two subsequent amplification reactions utilizing exo- Klenow polymerase were performed under direct observation using the fluorescent dye thiazole orange. Under the chosen conditions, the mutation rate was 1.5 x 10(-3) and 0.4 x 10(-3) for base substitutions and deletions, respectively. Then, a 16mer oligodeoxynucleotide with an acridine moiety coupled to its 5' end was used to select for double strands that retained their ability to form a triple-helix with the oligodeoxynucleotide. Conditions for triple-helix formation were chosen such that only 10 to 40% of the SDA products were allowed to bind the third strand. Non-denaturing polyacrylamide gel electrophoresis was used to separate triple-helices from unmodified double strands, and only triplex strands were used to initiate a new round of error-prone amplification and selection. Nine such rounds with about 270 molecular generations were performed. The final mutant spectrum was characterized and compared with those of amplification reactions without additional selection pressure. While without selection pressure base substitutions and deletions throughout the initial wild-type rapidly produce a diverse mutant distribution, the consensus after nine selection rounds clearly shows two mutational hotspot positions. Using gel shift assays and a newly developed non-radioactive DNase I footprinting technique, it could be shown that both the initial wild-type and the final consensus do not differ significantly in their triplex formation ability. As opposed to this, they do show different amplification efficiencies. The final consensus sequence is amplified with the highest rate in the exponential reaction phase, while the most abundant clone, which is characterized by two additional point deletions, is the sequence with the highest amplification rate in the linear growth phase.

Base Sequence↗

What does a molecule want? The myth of the self-replicating molecule (comments on the "selfish-gene" paradigm).

The non-equilibrium statistical mechanical autocatalytic theory, underlying the "selfish-gene" paradigm, is shown to be at several points insufficient and contradictory for the description of observed facts of biological systems. We analyze at some length these deficiencies as (1) statistical versus individual non-linear self-constraints, (2) the continuous versus discrete cause-effect evolutional transition, and (3) the nature of the emerging aim-directed biological systems. Concerning the latter, it is shown that it can only be described with reference to the origin of the genetic code, which cannot be accounted for by the continuous evolution of non-equilibrium statistical mechanical systems. We point out that these deficiencies might be covered by alternative (quantum) theoretical considerations. The theory of evolution according to which may have lead to aim-directedness in the primordeal times in a more consistent way, concerning both phenotype and genotype. The specific physical model adopted is an affine Hilbert spaces scheme, with a naturally emerging internal dynamics of measurement, monitored internally by (time-inversion) symmetry restoration. In this context, the physical relation of internal molecular symbolism (semiosis) and internal quantum mechanics is discussed.

Catalytic Domain↗

A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer: evolution of a regimen. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD).

The addition of leucovorin (LV) to 5-fluorouracil (5-FU) in advanced colorectal cancer has shown improved tumour response rates in many trials, but the optimal LV/5-FU regimen has yet to be determined. Seven studies carried out over the last 12 years to evaluate the safety and efficacy of various LV/5-FU regimens are reviewed. The initial bimonthly high-dose LV/5-FU regimen consisted of high-dose LV as a 2-h infusion followed by 5-FU as an intravenous (i.v.) bolus plus a 22-h continuous infusion (CI), repeated for two consecutive days every 2 weeks. A randomised comparison of this bimonthly high-dose LV/5-FU regimen and the NCCTG-Mayo Clinic regimen (LV [20 mg/m2/day] followed by 5-FU bolus [425 mg/m2/day] daily x 5, every 4 weeks) showed that the bimonthly high-dose LV/5-FU regimen was superior to the NCCTG-Mayo Clinic regimen in response rate and progression-free survival, but showed no difference in overall survival. In addition, toxicity was less with the bimonthly high-dose LV/5-FU regimen. These promising results led to a phase II trial of a simplified bimonthly high-dose LV/5-FU regimen consisting of LV (500 mg/m2/day) and a 48-h CI of 5-FU (1.5-2 g/m2/day) which has been administered alone or in combination. In summary, GERCOD-sponsored studies have further demonstrated that high doses of both LV and 5-FU given as a CI can improve response rates still more with acceptable toxicity. Further studies are focused on the effectiveness of combination with oxaliplatin or CPT-11 in metastatic disease and the use of high-dose LV/5-FU regimens for colorectal cancer in the adjuvant setting.

Antidotes↗