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PubMedDate not supplied

[Challenges for developing a comparative analytical model for health services].

This paper presents different models that describe health determinants, services, and systems. It highlights the important model developed by Contandriopoulos, proposing a separation between the health status and health care circuits. The article is intended as a contribution to the field of comparative analysis with a new theoretical, methodological, and evaluative approach. Problems were identified in the development of a new model. Decentralization and access are introduced as categories, suggesting that they may take part in such new model.

Health Services↗

PubMedDate not supplied

Onset of antidepressant activity: reexamining the structure of depression and multiple actions of drugs.

The question of when antidepressant drugs (AD) initiate significant clinical actions in depressed patients is still unsettled. Findings from early studies on whether there is a lag in the onset of therapeutic actions were in disagreement. More recent results with the selective serotonin reuptake inhibitors (SSRIs) and other new ADs indicate that clinical actions occur within the first 2 weeks. In this paper, evidence from efficacy studies with the ADs is reviewed and the methodologic and conceptual obstacles to achieving definitive results about the onset issue are analyzed. Depression, formerly viewed as a homogenous disorder, is now seen as heterogenous and multifaceted in structure. Such major structural components as anxiety and disturbed psychomotor functioning can be as significant to the core of the disorder as depressed mood itself. Further, the ADs have been shown to act initially on different facets of the clinical disorder which then result in multiple clinical actions, e.g., an initial reduction in anxiety followed by stimulation of motor activity. Data from the NIMH Collaborative Study of the Psychobiology of Depression are used to illustrate: (1) the componential structure of severe depressive disorder; (2) the sequence of change in the major behavioral components of the disorder associated with the tricyclic drugs; (3) the consequent "multiple" onsets of clinical actions; and (4) measurement of the clinical significance and visibility of the early behavioral changes. Recent results describing new behavioral and methodological approaches, the use of early clinical changes to predict outcome, and strategies for designing sound studies of onset are discussed.

Affect↗

PubMed1999

Recognition of sorting signals by clathrin adaptors.

Sorting of membrane proteins is generally mediated by cytosolic coats, which create a scaffold to form coated buds and vesicles and to selectively concentrate cargo by interacting with cytosolic signals. The classical paradigm is the interaction between clathrin coats and associated adaptor proteins, which cluster receptors with characteristic tyrosine and dileucine motifs during endocytosis. Clathrin in association with different sets of adaptors is found in addition at the trans-Golgi network and endosomes. Sequences similar to internalization signals also direct lysosomal and basolateral sorting, which implicates related clathrinadaptor coats in the respective sorting pathways. This review concentrates on the recognition of sorting signals by clathrin-associated adaptor proteins, an area of significant recent progress due to new methodological and conceptual approaches.

Adaptor Protein Complex alpha Subunits↗

PubMed1993

Facilitation of adaptation and acute tolerance to stressful sensory input by doxepin and scopolamine plus amphetamine.

This work characterizes a new methodologic and pharmacologic approach to control terrestrial and space motion sickness (SMS). The experimental design allowed separate evaluation of drug action on susceptibility and adaptability, and used repeated measures to approximate the chronic stressful motion of microgravity. Daily exposure to cross-coupled angular acceleration for 5 consecutive days demonstrated that the efficacy of doxepin and scopolamine plus amphetamine in the prevention of autonomic system dysfunction was not only apparent on the first test day (P < .01), but was also evident in the substantially enhanced resistance developed over the 5-day test period (P < .01) as compared with placebo. This indicates that daily use of these medications does not diminish therapeutic efficacy (tolerance). The efficacy of doxepin was anticipated because it possesses pharmacologic properties similar to those of established anti-motion sickness drugs. Comparable efficacy after doxepin loading for 4 hours, 3 days, or 21 days suggests a mechanism distinct from its antidepressant effects, possibly related to its potent antihistaminergic actions. Use of doxepin has operational significance to the National Aeronautics and Space Administration, in comparison with current preparations of scopolamine plus amphetamine, because of doxepin's minimal impact on cognitive performance, and most importantly, its favorable pharmacokinetic profile, particularly its long half-life.

Adaptation, Physiological↗

PubMed1998

Kinetic analysis of the mitotic cycle of living vertebrate cells by atomic force microscopy.

The atomic force microscope (AFM) is becoming an important tool for qualitative and quantitative analyses of biological material. However, the difficulties involved in maintaining long-term, steady-state physiologic conditions and the problems associated with analyzing force curves generated from highly viscoelastic biological structures impede the use of the AFM for studies of kinetic processes in living vertebrate cells. In this report, we describe a simple method to track reproducibly kinetic changes in the localized stiffness of vertebrate cells. We tested our method on a study of vertebrate cells in mitosis and found a marked but transient decrease in stiffness occurs in the mitotic spindle region during anaphase. We propose that physical-chemical changes in the mitotic apparatus, most probably, changes in the state of polymerization of interzonal spindle fibers which also have been reported to undergo a marked reduction in birefringence during anaphase, are responsible for the observed decrease in stiffness. Our methodology affords a new approach to studying mitotic events and should be applicable to studies of a variety of viscoelastic properties of living cells.

Anaphase↗

PubMed1982

Volatile alkanes produced by erythrocytes: an assay for in vitro studies on lipid peroxidation.

Lipid peroxidation in erythrocytes is currently studied by measuring the formation of malonyldialdehyde (MDA). A new and simple methodological approach to the measurement of the extend of lipid peroxidation is described here. Erythrocytes from freshly drawn human blood were washed and suspended in isoosmotic phosphate-buffered saline and incubated with sodium azide to inhibit the catalase. Oxidation of red cell lipids was induced by the addition of hydrogen peroxide. MDA formation was measured by the 2-thiobarbituric acid (TBA) reaction. After the same procedure of incubation the production of volatile alkanes (pentane, ethane, ethylene, n-butane, and propane) was estimated by gas chromatography. The total amount of pentane formation from red cells after 120 min of incubation with hydrogen peroxide was much higher than of the other alkanes. This assay provides a useful model to elucidate the role of lipid peroxidation of erythrocytes and is a simple method to study changes in their membrane lipid in diseases and red cell aging.

Alkanes↗

PubMed2006

Lessons from large population studies on timing and tempo of puberty (secular trends and relation to body size): the European trend.

Ever since the publication of the first textbook on human growth by Johann Augustin Stoeller in 1729, temporal changes (or secular trends) in growth and pubertal maturation have been observed throughout the world. Data covering the longest time span are often reported from European populations. For example, in Norway and Denmark the age at menarche has fallen rapidly since the 19th century, by up to 12 months per decade. These changes have broadly paralleled increases in adult height in most European countries over the last century, with rates of around 10-30mm per decade. These secular trends are influenced by background ethnic, geographical and socio-economic factors, and clearly nutritional changes have an important role as reflected by positive correlations between age at puberty onset or age at menarche and childhood body size. Changes in height, pubertal maturation, and childhood body size have all also been related to rate of weight gain in infancy, and there is growing evidence to suggest that this early postnatal period may represent an early window of susceptibility to long-term 'programming' of various outcomes in humans. There is debate as to whether the secular trends in pubertal maturation are continuing or have reached their limit. Even where temporal changes are overall clearly significant, they are most marked in the more nutritionally deprived sub-groups. Whether over-nutrition and increasing childhood obesity will continue to lead earlier puberty is uncertain. The confirmation of an estimated advance in the age at menarche of 6-12 months per 100 years will require a long-term perspective on behalf of current investigators, and new consideration of methodological approaches in an age of increasing recognition of children's rights for privacy.

Adolescent↗

PubMed2004

RNA interference in neuroscience.

One of the most exciting findings in recent years has been the discovery of RNA interference (RNAi). RNAi is an important system that allows sequence-specific gene silencing through targeted degradation of mRNA by cognate double-stranded RNA (dsRNA). RNAi plays a role in endogenous cellular processes, such as developmental control and heterochromatin formation, and serves as an antiviral defense mechanism. Recent findings suggest that RNAi and related pathways are involved in protecting the genome against instabilities caused by transposons and repetitive sequences. Several rapidly developing RNAi methodologies provide a new approach for elucidation of gene functions. RNAi technology is also currently being evaluated as a potentially useful method to develop highly specific dsRNA-based gene-silencing therapeutics. In this paper, we review the use of RNAi in neuroscience research and as a possible therapeutic tool for treatment of neurological diseases.

Animals↗

PubMed2000

Identification of novel genes in late-onset Alzheimer's disease.

Four genes affecting Alzheimer's Disease (AD)(AP, PS1, PS2, and APOE) have been identified and a fifth potential gene localized to chromosome 12. Collectively, these genes explain at most half of the genetic effect in AD. Understanding the genetics of AD is critical to developing new treatments. The quest to find the remaining AD genes led us to undertake a large genomic screen using over 466 families (730 affected sibpairs) in late-onset AD. In conjunction with this increase in power, we initiated several novel approaches to identify potential AD-related genes. This included stratification of the data into an autopsy-confirmed subset of 199 AD families. Each of these targeted analyses resulted in the identification of novel regions containing potential AD genetic risk factors. Our most significant finding was on chromosome 9 in the autopsy-confirmed subset where we obtained an MLS of 4.31. These approaches, together with new methodologies such as conditional linkage analysis, generalized family-based association tests (PDT), and a new generation of genetic markers (SNPs), opens the door for additional AD gene discovery. Such strategies are necessary if we are to understand the subtle and complex threads that, woven together, create the intricate tapestry of AD.

Age of Onset↗

PubMed1999

Manometric study of hiatal hernia and its correlation with esophageal peristalsis.

The pathogenesis of gastroesophageal reflux disease (GERD) is considered multifactorial, but alterations of the esophagogastric junction (EGJ) and hiatal hernia play a prominent role. The correlations between hiatal hernia and the other pathogenetic factors are as yet unclear, and they need to be investigated by a methodological approach based on new anatomic and functional criteria. Our aim was to study, by stationary manometry, the relationships between small reducible hiatal hernia, identified by endoscopy, and esophageal peristalsis, in patients with and without GERD. According to the absence or presence of esophagitis (E), and the absence or presence of hiatal hernia (H), 58 subjects were divided into four groups: controls 10; H 14; E 10; and HE 24. Stationary manometry was performed by the rapid pull-through (RPT) technique, with catheter water perfused, to study the lower esophageal high pressure zone [lower esophageal sphincter (LES) and diaphragmatic crura] and the parameters of esophageal peristalsis. In patients with hiatal hernia, the various combinations of peak and/or deflection of manometric line pressure identified five EGJ profiles, only one of which reveals (by one-peak profile due to superimposed LES and diaphragmatic crura) the reducibility of the hernia. The frequency of the five profiles was calculated in the HE and H groups: a two-peak profile was significantly more prevalent in these patients, although less so in the group with esophagitis. In E patients the distal amplitude and the distal propagation of esophageal waves were significantly lower than in the other three groups (P < 0.05 vs controls and group HE; P < 0.01 vs group H). Furthermore, the distal amplitude was significantly higher in the group H than in the HE (P < 0.01). Our results show a better definition of hiatal hernia morphology, via the RPT technique, disclosing five pressure profiles. In addition, a significant link was found between small reducible hiatal hernia without GERD and wave amplitude of the distal esophagus. The amplification of peristaltic clearing may be considered the initial protective process against acid reflux; the breakdown of this mechanism may trigger the pathological sequence of GERD.

Adult↗

PubMed2002

Vascular proteomics and subtractive antibody expression cloning.

The cloning of genes expressing proteins that are differentially expressed in the organ microvasculature has the potential to address a variety of problems ranging from the analysis of disease pathogenesis to drug targeting for particular tissues. This study describes a methodology designed to analyze differential protein expression in the brain microvasculature. The method can be applied to other organs and is particularly suited to the cloning of cDNAs encoding membrane proteins. The technology merges a tissue-specific polyclonal antiserum with a cDNA library expression cloning system. The tissue-specific antiserum is subtracted with protein extracts from control tissues to remove those antibodies that recognize common antigenic proteins. Then, the depleted antiserum is used to expression clone tissue-specific proteins from a cDNA library expressed in mammalian cells. The methodology was evaluated with a rabbit polyclonal antiserum prepared against purified bovine brain capillaries. The antiserum was absorbed with acetone powders of liver and kidney and then used to screen a bovine brain capillary cDNA library in COS cells. The initial clone detected with this expression methodology was the Lutheran membrane glycoprotein, which is specifically expressed at the brain microvasculature compared with liver and kidney tissues. This subtractive expression cloning methodology provides a new approach to "vascular proteomics" and to the detection of proteins specifically expressed at the microvasculature, including membrane proteins.

Amino Acid Sequence↗

PubMed2003

Salivary metal levels of orthodontic patients: a novel methodological and analytical approach.

The purpose of this study was to qualitatively and quantitatively assess the nickel, chromium, and ferrous levels in a population of 17 orthodontic patients undergoing treatment, compared with seven untreated individuals, employing a novel methodological approach and a new analytical technique. Salivary samples obtained from patients before and after rinsing with double distilled water were processed for Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) for simultaneous estimation of the concentration of the metallic elements. No statistically significant difference was detected between control and patient groups with respect to salivary metal content, regardless of element. The range of salivary metal levels found did not exceed those of daily intake through food and air. The lack of a continuous monitoring scheme for salivary metal concentrations in real time may impose substantial obstacles to defining the release rate of metals in vivo. The results of this study emphasize the necessity of incorporating the dimension of time in assessing the release potential of orthodontic alloys.

Adolescent↗

PubMed2006

Phenon cluster analysis as a method to investigate epidemiological relatedness between sources of Campylobacter jejuni.

AIMS: To develop a method for assessing the relative epidemiological significance of possible infection sources for human campylobacteriosis. METHODS AND RESULTS: Using fluorescent amplified fragment length polymorphism (AFLP), 243 apparently epidemiologically unrelated Campylobacter jejuni isolates were genotyped (77 human, 46 cattle, 49 pet and 71 poultry isolates). In total 136 different phena were identified, of which 48 were clusters grouping at least two isolates. Isolates from different sources were frequently clustered together, underlining the high degree of source mixing and the lack of host specificity of C. jejuni. The phena were classified into different phenon types according to the sources of the isolates they contained. The occurrence of these phenon types was analysed using an area-proportional Euler diagram to describe epidemiological relatedness among C. jejuni isolates. Group separation statistics revealed that 43% of analysed human isolates expressed maximum similarity to other human isolates, 9% to cattle isolates, 21% to pet isolates and 27% to poultry isolates; these results were in accordance with the pattern observed in the phenon cluster analysis. CONCLUSIONS: Based on the grouping of strains into molecular similarity clusters, ecological patterns between sources can be investigated. SIGNIFICANCE AND IMPACT OF THE STUDY: This approach is a new methodological contribution to establish the relative epidemiological significance of concurrent infection sources.

Animals↗

PubMed2006

Mentoring: a framework for developing health disparities researchers.

Health disparities have been conceptualized as being the result of a confluence of factors: environmental, social, biological, economic, and cultural to name a few. Given the increasingly deleterious impact of health disparities on the lives of all Americans, new research methodological research approaches are needed to adequately understand and address the component parts of health disparities. To effectively address health disparities, an increased focus is needed on implementing transdisciplinary approaches to health disparities research. One approach is to focus on mentoring young investigators and students. This article discusses the centrality of mentoring in developing young health disparities researchers. An overview of health disparities research and researchers, and a summary of the different aspects of mentoring are provided. In addition, a case study of the implementation of a transdisciplinary mentoring framework at a higher education institution is presented.

Career Mobility↗

PubMedDate not supplied

[Integrative processes in modern epidemiology].

The integration of achievements in population ecology and the molecular genetics of pathogenic microorganisms into nowadays epidemiology of infectious diseases and the formation of its corresponding trends are discussed. The decisive role of highly complicated key problems of general epidemiology, such as the regularities of the autochthonous existence of pathogenic bacteria in the environment, the mechanisms of the pathogenicity regulation of infective agents and the formation of their epidemic variants, the mechanisms of the prolonged reservation of pathogenic bacteria at interepidemic (interepizootic) periods, the mechanisms of transformation of active (vegetative) and dormant forms in bacterial populations at different stages of epidemic and epizootic cycles, is demonstrated. The detection and analysis of such processes, and especially their latent mechanisms, become possible with the use of new concepts and methodological approaches, highly productive for the progress of epidemiology.

Adaptation, Physiological↗

PubMed2003

How computer technologies might be used to foster professional development: a case report of www.perfusionkorea.org.

Advances in the Internet and communication technologies have enabled many perfusion-related websites to provide detailed and reliable information to perfusionists. However, these websites are also faced with various member needs that require updating for fast, flexible responses. Despite the rapid increase in the number of these websites, little is known about the structure, performance, and effective utilization methods of such websites. This case report examines the www.perfusionkorea.org, a virtual organization that works across space and time with links strengthened by webs of communication technologies. In addition, website maintenance and resource management tasks, which are important factors for long-term survival, are discussed using the log analyzer and internet protocol tracing programs. Finally, using www.perfusionkorea.org, as a prototype of virtual organization activities, what we can expect to see more commonly in the near future, is discussed. Although we used a tremendous amount of multimedia techniques to attract members, we found that the significance of the perfusionists' website would come from active participation of members rather than a new, complicated technology or eye-catching graphics. This case report shows the synergistic effects that Korea's application of the Internet to the field of perfusion. It also suggests that new methodological strategies and approaches can be developed and tested to provide perfusionists with a direction for tomorrow's health care system.

Education, Continuing↗

PubMed2004

[Osteoarticular tuberculosis in children: data extrapolation of a specialized clinic to the situation in the Russian Federation].

Analyzing the activities of the Surgery Department for Osteoarticular Tuberculosis (OAT), Saint Petersburg Research Institute of Phthisiopulmonology, in children in 1990-2002 suggests that there is no system for comprehensive registration of OAT and in most cases its treatment is performed without taking into account the current surgical requirements. New organizational, methodological, therapeutic approaches recommended to ascertain the true OAT situation in children and to improve the results of its diagnosis and treatment, are presented.

Adolescent↗

PubMed2005

[Proteomics and its role in medicine].

Proteomics is a new methodological and conceptual approach to the study of live systems, which aims to map the whole proteom - the protein complement of genome. It aspires to describe quantitatively and qualitatively all proteins present at the given moment in the cell, tissue or the organism. The principal tools of proteomics are separation techniques based on electrophoresis and chromatography, which are used to fractionate complex protein mixtures and namely the mass spectrometry used for the identification of individual proteins. Proteomics represents very young and rapid developing specialization, which has already proved its valuable potential for the study of various physiological and pathlogical molecular mechanisms and for the direct use in the diagnostics of serious diseases.

Chromatography↗