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C-reactive protein in pediatrics.

CRP levels have been found to be helpful in differential diagnosis and in following the clinical course and response to treatment of various disorders. Of particular interest is their value in the diagnosis of serious bacterial infections in neonates, such as meningitis, septicemia, and osteomyelitis. While no individual has been reported to be deficient in CRP, it is possible that abnormalities of CRP synthesis and function will be found. As increasing knowledge of the role of CRP accumulates, it is conceivable that CRP may acquire some therapeutic value. Increasing availability of rapid quantitative methods for CRP is likely to result in greater clinical usefulness.

Adolescent↗

Leukocyte Enzymes in birth defects- a review.

The utilization of peripheral leukocytes, mixed preparations or specific populations for the detection of homozygous and heterozygous states of inborn errors of metabolism via enzyme assay or detection of accumulated metabolites are reviewed. Additionally, present knowledge of metabolic activities in leukocyte populations and areas of potentially fruitful investigation are discussed.

Amino Acids↗

[Opiates and opioids in the treatment of tumor-related pain].

Although opiates have been used by mankind for millenia and were undoubtedly during a long time among the most active drugs available, many unsettled questions have remained about their optimal use. In recent years new knowledge about active metabolites has been accumulated. An overview of the effects and side effects of morphine and various other opioids and their applications in the treatment of tumor pain is presented.

Drug Tolerance↗

[Role of superoxide dismutase in the reduction of reperfusion injury of the ischemic myocardium. Lessons of the first experimental animal models].

Myocardial reperfusion is today the best alternative to save ischemic myocardium. However, reperfusion carries with him an aggressive potential that may mask its benefits. From a clinical point of view, it is necessary to create new complementary therapies to prevent such injury. One of such therapy in which a great deal of knowledge in experimental models has been accumulated is superoxide dismutase. In this work are presented some chemical, biological, and pharmacological characteristics of this enzyme. Several forms of reperfusion injury are discussed as well as the role of superoxide dismutase in their prevention. The experience gathered along the years is still small for prevention of cellular oedema, intramyocardial haemorrhage, and low/no-reflow. There is still some controversy about the role of superoxide dismutase in the reduction of myocardial necrosis. However, superoxide dismutase seems to be highly protective, as far as stunned myocardium and reperfusion arrhythmias are concerned.

Animals↗

Strategies for production of a potential candidate vaccine for cholera.

First attempt at cholera vaccination was made by Jaime Ferran in 1884. Since then, a variety of strategies and methods have been evolved to create a safe, efficacious vaccine against cholera. For the first few years emphasis was on the development of parenteral vaccines. However, as a result of accumulation of a tremendous amount of knowledge, not only on Vibrio cholerae-the causative agent, but also on its interaction with the host, emphasis has shifted towards the development of oral vaccines. Two such vaccines, one killed, a whole cell/B subunit combination vaccine and the other a live attenuated one, have shown promise. The combination vaccine in its present state of development confers only a transient protection in young children, while the live attenuated one produces adverse reaction. To combat these, various strategies are being evolved. In one attempt, a potential candidate vaccine strain has been constructed from a non-reactogenic clinical isolate of V. cholerae, which is devoid of all known major virulence genes and is also a good colonizer. In animal studies this construct has shown considerable promise. This review discusses the various strategies that have been employed so far in the quest for an ideal cholera vaccine.

Administration, Oral↗

Interference of sulphonylurea antidiabetica with mitochondrial bioenergetics under in vivo conditions.

Sulphonylurea antidiabetica effectively inhibits the basal hepatic glucose production. Since it has been firmly established that lipophylic sulphonylurea drugs exerted an uncoupling effect on mitochondrial oxidative phosphorylation, a relationship between the reduction of hepatic gluconeogenesis and the insufficient energy supply due to sulphonylureas could be supposed. In this study we have investigated the effects of glibenclamide and gliquidone on mitochondrial bioenergetics in liver after peroral treatments of normal rats with different doses. The treatment of rats with 5 mg/kg glibenclamide or gliquidone daily for 14 days elicited only a marginal inhibition on mitochondrial oxidation capacity and remained without any effect on mitochondrial ATPase activity. Only the supermaximal dose 50 mg/kg for 14 day produced a significant damage in the mitochondrial functions. The basal respiration increased with 60-80 per cent, whereas the ADP- or DNP-stimulated oxygen consumption significantly decreased independently from the respiratory substrates investigated. Similar alterations were found in the mitochondrial ATPase activity after treatment with these drugs. No essential differences have been observed in the actions between glibenclamide and gliquidone. However, the lowest dose applied in this study is many times higher than the usual therapeutic dose. Consequently, glibenclamide and gliquidone do not interact with mitochondrial bioenergetic processes under therapeutic conditions. On the other hand, in different liver and kidney damages we have no sufficient knowledge whether these drugs can be accumulated in these organs and therefore their elevated concentration may interfere with the mitochondrial energy metabolism.

Animals↗

Leptin: physiology and pathophysiology.

The identification and sequencing of the ob gene and its product, leptin, in late 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. During this time, a considerable body of knowledge regarding leptin's actions has been accumulated and the field continues to expand rapidly. Currently there is particular interest in the interaction of leptin with other peripheral and neural mechanisms to regulate body weight, reproduction and immunological response. In this review, we attempt to place the current state of knowledge about leptin in the broader perspective of physiology, including its structural characteristics, receptors, binding proteins, signalling pathways, regulation of adipose tissue expression and production, secretion patterns, clearance mechanisms and functional effects. In addition, leptin's involvement in the pathophysiology of obesity, anorexia nervosa, diabetes mellitus, polycystic ovary syndrome, acquired immunodeficiency syndrome, cancer, nephropathy, thyroid disease, Cushing's syndrome and growth hormone deficiency will be reviewed.

Animals↗

Enhancing adherence to long-term medical therapy: a new approach to assessing and treating patients.

Poor adherence to medical therapy may cause as much as dollar 100 billion in unnecessary healthcare expenses each year. Nonadherence is a complicated and dynamic problem that involves patient, medication, and prescriber factors. The Case Management Adherence Guidelines (CMAG-1) are an evidence-based algorithm that introduces concepts and strategies for assessing medical knowledge and readiness to change (motivational interviewing). Once the assessment has been made, the guidelines can be used regularly to help patients become and remain adherent to their medication regimens. CMAG-1 and its tools, based on up-to-date information about adherence and ways to promote behavioral change, are designed to identify motivational and knowledge deficiencies that may block adherence. As information accumulates from centers that use it, CMAG-1 will be modified accordingly, with the goal of creating structured interaction with patients that will increase their knowledge and motivation to take medication appropriately.

Adolescent↗

Virulence factors of Helicobacter pylori: implications for vaccine development.

Helicobacter pylori is one of the most common infectious diseases in humans and causes gastritis, peptic ulcer disease and malignant tumours of the stomach. This review discusses how H. pylori can colonize the human stomach, an ecological niche that is protected against all other bacteria. Knowledge about the virulence factors of H. pylori has accumulated rapidly over the last decade. Together with the information contained in the complete H. pylori genome sequence, this knowledge is now being applied in the search for a vaccine against this global pathogen.

Animals↗

Metabolic model for cadmium in man.

A metabolic model for cadmium has been formulated in terms of a flow scheme for cadmium among eight body compartments. The mathematical description of the flow of cadmium between compartments consits of a number of differential equations, and the accumulation of cadmium may thus be calculated. Coeffcients for the flow of cadmium were estimated from empirical data both from animals and man. The modelling serves two main purposes: it provides a means of using present knowledge about metabolism in order to calculate expected accumulation in critical organs and other tissues and body fluids at certain intake levels and it makes it possible to define deficiencies in our present knowledge about metabolism. Data recently collected, partly as a result of considerations related to the model, have confirmed the assumptions of a very long biological half-time in other tissues and the small excretion of cadmium via bile.

Adult↗

Ammoniacal silver staining of lymph node cells. I. its potential value for the diagnosis of Hodgkin's disease.

Lymph node biopsy specimens from 76 cases of Hodgkin's disease, 23 non-Hodgkin's lymphomas and 19 reactive affections of lymph nodes were studied. Formalin-fixed and paraffin embedded tissues were stained with hematoxylin and eosin, and post-formalin ammoniacal silver staining was used after BLACK and ANSLEY. The presence of basic protein accumulation in the cytoplasm of both Sternberg and Hodgkin cells was confirmed. To our knowledge it is the first report concerning the presence of these accumulations in the cytoplasma of atypical reticulum cells in Hodgkin's disease and in 3 of 7 cases of reactive follicular hyperplasia, in foreign body giant cells and in some lymphoblasts from 5 cases of Hodgkin's disease. The possibility of using the ammoniacal silver staining for identifying Sternberg cells is discussed. Also, it is proposed that when Sternberg cells are absent, the ammoniacal silver staining pattern of Hodgkin cells in an appropriate histological setting may be very indicative of Hodgkin's disease.

Biopsy↗

[The initial and continuing education of hospital nursing personnel: alternating practical work with education].

Who, as a trainer, has never heard this irritating leitmotiv on the lips of those who work in the area? Therefore, each of them is convinced that the other is wrong or does not do what he should. Beyond the anecdote, the problem of the difficult conjunction between school and the real world is posed. Two places and two logics: the first one is concerned with learning, the second one considers production as its daily objective. But the words of our imaginary interlocutor also remind us of the confrontation between two fields: theory and practice and their apparently irrecondilable nature. Two disconnected worlds in which the students come and go with the frequent impression that they live two lives. There is a lot of professional literature on the subject of the "hands on" theory of education. The pedagogical device to which we refer enables the trainee to eventually make a link between what he learns at school and what he does during his training period. Once this has been asserted, it seems to us that the problem still remains unresolved. How can you create links between theory and practice? Which skills are required for the trainers? Which training device is necessary? The hypothesis of the paper we are presenting is that the question of work is at the centre of the problematics of "hands on" education. Work appears as the interface between the world of school and the one of field work. This assertion means that the practive produces knowledge just as research does and we must therefore accept that the practitioners carry on their work thanks to the accumulation, the construction and the transmission of this practical knowledge. Assuming that the question of work serves as a link between theory and practive means reconciling the vision of the teacher and the one of the practitioner. It implies that the trainer must make the effort of going on the field to observe, to understand and formalize what this knowledge coming from the daily experience is made of. This know-how is the result of the mobilization of the intelligence of the operators who are faced all the time with the hazards of real life. In the following work, we intend to put a pedagogical practice to the test of reality, according to the above mentioned hypothesis, to test its effectivity, to sort out the possibilities of change it enables it imposes and to mark its limits. Our wish is not to make the absolute proof of the validity of a point of view. We know by experience that the reality often escapes its observer and that trying to get in contact with it to possibly change it, means that you must be faced with it through action, and you must admit that success will not always be the result of your attempts.

Clinical Competence↗

Accumulation of triacylglycerol in cultured rat hepatocytes is increased by ethanol and by insulin and dexamethasone.

Isolated hepatocytes from female rats were cultured in HI-WO/BA medium for 6 days. To the medium was added oleate, ethanol, dexamethasone and insulin. With oleate To alone, triacylglycerol accumulated; ethanol augmented the accumulation by 90%. To the best of our knowledge, this is the first demonstration that ethanol in vitro increases the content of triacylglycerol in liver cells. Further addition of dexamethasone or insulin did not alter the accumulation of triacylglycerol, indicating that these hormones did not play permissive roles for the effect of ethanol in the present system. Dexamethasone and insulin, in the absence of ethanol, increased the accumulation of triacylglycerol by 30% and 50% respectively. The concentration of glycerol 3-phosphate was increased in the presence of ethanol; however, with time the concentration of glycerol 3-phosphate declined almost to control values, while the accumulation of triacylglycerol continued linearly; this suggests that the effect of ethanol was not mediated via fluctuations in the concentration of glycerol 3-phosphate. These results are discussed in relation to earlier investigations in vivo and in vitro.

Animals↗

[The proposed classification of epilepsies and epileptic syndromes (1989) and its clinical significance].

The development of a rational approach and prognostication of epilepsy is based on a special profile of seizure events or the suggested diagnosis of a specific disorder. Although classifications based on neurobiological knowledge would be highly desirable, the present state of inadequate information makes such task difficult. Current classification schemes are, therefore, based on clinical signs and symptoms which are readily identifiable. The significant progress of epileptology has brought us to the stage where one can delineate a number of epileptic syndromes, provide a precise definition, and orient individual syndromes. With further accumulation of both clinical experience and new knowledge in neurosciences, the proposed classification will develop to more appropriate schemes.

Epilepsy↗

Role of leukotriene B4 in the pathogenesis of hepatic ischemia-reperfusion injury in the rat.

A common feature to most models of ischemia-reperfusion injury is the accumulation of polymorphonuclear leukocytes (PMNs) into the post-ischemic tissue during the reperfusion period. Interventions that lead to decreased PMN infiltration protect against tissue injury and therefore a knowledge of the chemotactic mediators leading to PMN accumulation is essential to understanding the pathogenesis of the injury and to the development of successful therapeutic strategies. Leukotriene B4 (LTB4), a metabolite formed via the 5-lipoxygenase pathway from arachidonic acid, is one of the most potent chemotactic mediators known. We have investigated the formation of LTB4 in a well characterized model of hepatic ischemia-reperfusion injury in the rat and made use of a specific leukotriene biosynthesis inhibitor, L663,536, to determine the importance of LTB4 in the pathogenesis of the injury. LTB4 concentrations were measured with a specific and sensitive gas chromatographic-mass spectrometric method previously developed in our laboratory. In liver tissue LTB4 levels were below the detection limit of 20 pg/g before 45 min ischemia and did not increase during the first 6 h of reperfusion. However, at 15 h and 24 h reperfusion LTB4 concentrations had increased to levels 50-fold those in control liver (867 +/- 267 pg/g). The increase of plasma alanine aminotransferase (ALT) activities indicated two phases of injury, an initial phase during the first few hours of reperfusion, and a second more severe injury phase between 6 h and 24 h reperfusion. PMNs accumulated in tissue throughout the reflow period reaching 700 +/- 49 per 50 high power fields (HPF) at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Therapeutic use of low molecular weight heparins: the knowledge to date as applied to therapy.

Indeed, the accumulating evidence indicates that certain LMWH administered subcutaneously may replace classic intravenous heparin therapy. Certain of these subcutaneously administered LMWH do not require monitoring. The simplified care offered by LMWH therapy presents the possibility of transferring care from in-hospital to out of hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMWH therapy will likely prove to be highly cost-effective. It is uncertain at present whether the findings associated with an individual LMWH preparation can be extrapolated to a different LMWH. For this reason, the findings of clinical trials apply only to the particular LMWH evaluated and cannot be generalized to the LMWH at large.

Animals↗

Stringent control in the archaeal genus Sulfolobus.

Six Archaea belonging to the phylum Euryarchaeota were previously analyzed with respect to stringent control. Only one of the strains studied was shown to possess Bacteria-like stringent control over stable RNA accumulation; ppGpp and pppGpp production was totally lacking in all Archaea analyzed. To broaden our knowledge of stringent control in the Archaea, we examined here the accumulation of stable RNA and the production of ppGpp and pppGpp under amino acid starvation in three species of the genus Sulfolobus belonging to the Crenarchaeota, an archaeal phylum distant from the Euryarchaeota. In these species the accumulation of sRNA was arrested when aminoacylation of tRNA was inhibited by pseudomonic acid. Furthermore, stringent control of stable RNA accumulation was relaxed by some protein synthesis inhibitors that do not interfere with aminoacylation of tRNA, a feature typical of bacterial stringent control. Neither ppGpp nor pppGpp could be detected during growth or under amino acid starvation, and the intracellular GTP levels did not decrease in the course of the stringent response. These results show that: (1) stringency is widespread in wild-type thermoacidophilic archaea; (2) in the crenarchaeal species analyzed here SC depends on the deaminoacylation of tRNA; (3) in the strains analyzed ppGpp is not produced during normal growth nor during the stringent reaction; it is therefore not an effector either of SC over sRNA synthesis or of growth control. (p)ppGpp appears to be completely absent from the Archaea and thus constitutes an additional feature that distinguishes the Bacteria from the Archaea.

Guanine Nucleotides↗

The role of the citric acid cycle in fungal organic acid fermentations.

Filamentous fungi are well known for their potential to accumulate organic acids in the medium when supplied with large amounts of sugar. Commercial applications of this are the production of citric and itaconic acids. The present review attempts to present the current state of knowledge on the biochemical basis of organic acid accumulation by filamentous fungi (citric, itaconic, fumaric and oxalic acids), particularly with respect to the role of citric acid cycle reactions. The explanations offered are based on recent advances in understanding the compartmentation of the fungal cell, and regulation of some key enzymes. The general conclusion is that fungi accumulate organic acids by mechanisms which avoid the channeling of substrates into the citric acid cycle under conditions of strongly active glycolysis.

Carboxylic Acids↗