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At least 451 records · Page 25Linked to original sources
PubMed2001

Rational development of prophylactic HIV vaccines based on structural and regulatory proteins.

The severity of the AIDS epidemic clearly emphasises the urgent need to expedite HIV vaccine candidates into clinical trials. Prophylactic HIV vaccine candidates have been evaluated in non-human primates. Based on specific proof of principle studies the first phase III clinical studies have recently begun in humans. However, a truly effective HIV vaccine is not yet at hand and many problems related to specific properties of the virus remain to be overcome. Previously proven empirical approaches have largely failed and now rational thinking based on an understanding of immunity to lentiviral infections is needed. This review addresses the scientific problems and complications facing the development of an HIV vaccine as well as the possible strategies currently available to overcome these problems. Recent attention has focussed on identifying the immune correlates and mechanisms of protection from either HIV infection or protection from disease progression. Based on these observations, the logic and rational behind the development of multiple component vaccine strategies are highlighted.

AIDS Vaccines↗
PubMed1999

Severe community-acquired pneumonia.

Severe CAP is a life-threatening condition defined by the presence of respiratory failure or symptoms of severe sepsis or septic shock. It accounts for approximately 10% of hospitalized patients with CAP. The majority of patients with severe pneumonia have underlying comorbid illnesses, with COPD, alcoholism, chronic heart disease, and diabetes mellitus being the most frequent. S. pneumoniae, Legionella spp, GNEB (especially K. pneumoniae), H. influenzae, S. aureus/spp, Mycoplasma pneumoniae, respiratory viruses (especially influenza viruses), and P. aeruginosa represent the most important causative organisms of severe CAP. Rapid initiation of appropriate antimicrobial treatment is crucial for a favorable outcome. Initial antimicrobial treatment should be based on an epidemiological (empiric) approach. Microbial investigation may be helpful in the individual case but is probably more useful to define local antimicrobial policies based on local epidemiologic and susceptibility patterns. Mortality rates range from 21% to 54%. The most important prognostic factors include general health state of the patient, appropriateness of initial antimicrobial treatment, and the existence of bacteremia, as well as factors reflecting severe respiratory failure, severe sepsis, septic hypotension or shock, and the extent of infiltrates in chest radiograph. Initial antimicrobial treatment should consist of a second (or third) generation cephalosporin and erythromycin. Modifications of this basic regimen should be considered in the presence of distinct comorbid conditions and risk factors for distinct pathogens. Promising new approaches of nonantimicrobial treatment, including noninvasive ventilation, treatment of hypoxemia, and immunomodulation, are under investigation.

Adult↗
PubMed2001

China's one-child policy: the economic choices and consequences faced by pregnant women.

This paper addresses the important issue of the effect of China's one-child policy on prenatal and obstetric care utilization. The paper provides the first detailed empirical approach to this question, exploiting a unique high quality household survey. China officially codified a set of rules and regulations in 1979 governing the approved size of Chinese families, commonly known as the one-child policy. The policy imposed economic and social costs on families failing to adhere to the family size limits. In particular, the policy raised the price of obstetric medical services for unapproved pregnancies in comparison to approved pregnancies and imposed fines on families with unapproved births. Using data from an eight-province longitudinal household survey (The China Health and Nutrition Survey), we investigate whether or not the one-child policy's financial penalties were associated with the avoidance of obstetric care by pregnant Chinese women with unapproved pregnancies. The one-child policy variables of particular interest were a dichotomous measure of the approval status of the pregnancy, a continuous measure of the fine imposed upon families with unapproved births, and a continuous measure of the prices of prenatal care and delivery services net of any subsidy available for approved births. The results partially confirm the hypotheses that the one-child policy's economic and social costs caused women to forego seeking modern obstetric care services. The fine was found to be a significant deterrent to the utilization of prenatal care. Additionally, the unapproved-status of a pregnancy was strongly negatively associated with "the use of obstetric care. However, higher prices were not consistently found to be a significant deterrent to the use of obstetric care.

Adolescent↗
PubMed2002

Sequential vs. parallel protein-folding mechanisms: experimental tests for complex folding reactions.

The recent emphasis on rough energy landscapes for protein folding reactions by theoreticians, and the many observations of complex folding kinetics by experimentalists provide a rationale for a brief literature survey of various empirical approaches for validating the underlying mechanisms. The determination of the folding mechanism is a key step in defining the energy surface on which the folding reactions occurs and in interpreting the effects of amino acid replacements on this reaction. Case studies that illustrate methods for differentiating between sequential and parallel channel folding mechanisms are presented. The ultimate goal of such efforts is to understand how the one-dimensional information contained in the amino acid sequence is rapidly and efficiently translated into three-dimensional structure.

Kinetics↗
PubMed2001

From translational research to improved local control and survival: the Gilbert Fletcher Award Lecture, Lugano, March 2000.

Recent clinical trials have shown us that it is possible to improve local control and survival by the concomitant use of radiotherapy and chemotherapy in a large variety of solid tumors, such as head and neck, lung, cervical, and anal cancer. The selection of drugs for this combined treatment, however, has been based on a rather empiric approach. Further research combining the clinical and laboratory expertise now offers the possibility of predicting and improving treatment efficacy for radiotherapy and systemic treatment, given alone or in combination. New methods, such as chromosome and gene expression profiling of individual tumors, are now becoming available with the comparative genomic hybridization assay and microchip DNA arrays. These assays will hopefully be of help in selecting patients for their optimal treatment regimen in the near future. Detailed knowledge of the mechanisms of action of these two treatment modalities will also lead to the development of new and more effective drugs, to be used concomitantly. It is the challenge of translational research to implement its opportunities into daily clinical practice. In analogy to the results obtained with concomitant radiotherapy and chemotherapy, this will lead to improved local control and survival rates in cancer patients.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Informed consent: legal, behavioral, and educational issues.

The doctrine of informed consent is examined from legal, behavioral, and educational perspectives. A brief legal history of the doctrine is presented along with a discussion of contemporary standards of disclosure and the emerging right of the patient to understand informed consent disclosures. Behavioral and educational issues include the relationship between disclosure and patient anxiety, patient recall of disclosures, readability of consent forms, and alternatives to the traditional doctor-patient disclosure model. A role for the patient-health educator in strategies to improve both the consenting and informing processes of the informed consent requirement is suggested.

Cognition↗
PubMed2003

Cyclic vomiting syndrome: a brain-gut disorder.

Despite the "black box" surrounding CVS, the authors' understanding of this clinical entity has advanced substantially in the last decade as a result of an international interdisciplinary clinical and research effort. Although CVS is now recognized as a unique clinical entity, patients still undergo innumerable hospitalizations and diagnostic tests. Although controlled therapeutic studies are lacking, reasonably effective empiric approaches have been developed by trial and error using anti-migraine, anti-emetic, and anti-epileptic regimens. The ongoing investigations of migraine mechanisms through NMR spectroscopy, mitochondrial DNA mutations and cellular energetics, corticotropin-releasing factor and gastric motility, and brainstem regulation of autonomic function may lead to breakthroughs in the understanding of and new therapies for CVS in the next decade.

Diagnosis, Differential↗
PubMed2002

[Treatment of non-painful symptoms in terminally ill children].

The care of children at the end of life is gradually improving. Nevertheless, more than half suffer from intractable symptoms before dying. Although pain has been the subject of clinical research, evidence-based data are almost completely lacking for other symptoms, highlighting the need for clinical research in palliative care. We review the available evidence on fatigue, anorexia, dyspnea, respiratory secretions, cough, constipation, mouth dryness, urinary obstruction, terminal convulsions and gasping. When evidence is lacking, we offer our empiric approach. Short duration benzodiazepines have become an important component of treatment that should remain simple, while providing the dying child the comfort needed to experience the highest quality relationships with those around him.

Anorexia↗
PubMed1991

A consideration of the factors which influence and control the viability and developmental potential of the preimplantation embryo.

The advent of the new reproductive technologies (including in vitro fertilization) has led to a revolution in the treatment of infertility. It has not yet led to a marked improvement in our understanding of the control of development and of viability of the early embryo. It is the poor viability of embryos, with consequent implantation failure, which is the major limiting factor to successful outcomes. While much of the research in this area has concentrated on strategies of ovulation induction, experimental models have shown that the major cause of reduced embryo viability is due to the actual process of fertilization in vitro and subsequent culture of the preembryo in synthetic culture medium. It is likely that this is due to the absence of critical nutrients or trophic factors of maternal origin and work with co-culture of embryos with somatic cells suggests improved viability can be achieved. Such co-culture is not an option for routine clinical use, however. It is essential therefore to understand by detailed study of the physiology of embryonic development their requirements for optimal development. The empirical approach of comparing different formulations of culture media is unlikely to be successful because of the vast range of parameters to be tested and the large number of pregnancies required to demonstrate a significant improvement in outcome. The strategy that is most likely to be successful in the future, therefore, is the use of appropriate experimental models, such as the developing rodent embryo, to understand the essential physiological changes in the embryo during its development, the control processes in place, and the effect of the embryo's environment on the processes. This will allow the rational design of culture media which can then be rigorously tested for improved outcome. An example of successful application of this approach is the discovery of embryo-derived platelet activating factor (PAF). The production of embryo-derived PAF was first described and validated in the rodent. In the same species it was shown to have an essential role in pregnancy and to act as an autocrine mediator of embryo viability. This fundamental observation in rodents was then confirmed in humans, and recent work has shown that supplementation of culture human embryo media with PAF results in a dramatic increase in their developmental and pregnancy potential. This example should be the first of many such improvements based on a more fundamental understanding of the embryo's developmental requirements.

Animals↗
PubMed2003

Self-consciousness, self-agency, and schizophrenia.

Empirical approaches on topics such as consciousness, self-awareness, or introspective perspective, need a conceptual framework so that the emerging, still unconnected findings can be integrated and put into perspective. We introduce a model of self-consciousness derived from phenomenology, philosophy, the cognitive, and neurosciences. We will then give an overview of research data on one particular aspect of our model, self-agency, trying to link findings from cognitive psychology and neuroscience. Finally, we will expand on pathological aspects of self-agency, and in particular on psychosis in schizophrenia. We show, that a deficient self-monitoring system underlies, in part, hallucinations and formal thought (language) disorder in schizophrenia. We argue, that self-consciousness is a valid construct and can be studied with the instruments of cognitive and neuroscience.

Awareness↗
PubMed1999

Statistical methods for the Ames Salmonella assay: a review.

The Ames Salmonella assay remains the most widely used in vitro genotoxicity assay. Several statistical methods have been proposed for its analysis [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Natl. Acad. Sci., 78 (1981) 3779-3783; L.E. Myers, N.H. Saxton, L.I. Southerland, T.J. Wolff, Regression analysis of Ames test data, Environ. Mol. Mutagen., 3 (1981) 575-586; A.G. Stead, V. Hasselblad, J.P. Creason, L. Claxton, Modelling the Ames test, Mutation Res., 85 (1981) 13-27; L. Bernstein, J. Kaldor, J. McCaan, M.C. Pike, An empirical approach to the statistical analysis of mutagenesis data from the Salmonella test, Mutation Res., 97 (1982) 267-281; N.E. Breslow, Extra-Poisson variation in log-linear models, Appl. Stat., 33 (1984) 38-44; J. Wahrendorf, G.A.T. Mahon, M. Schumacher, A nonparametric approach to the statistical analysis of mutagenicity data, Mutation Res., 147 (1985) 5-13; D.G. Simpson, B.H. Margolin, Recursive nonparametric testing for dose-response relationships subject to downturns at high doses, Biometrika, 73 (1986) 589-596; D.G. Simpson, B.H. Margolin, Nonparametric testing for dose-response curves subject to downturns: Asymptotic power considerations, Annals Stat., 18 (1990) 373-390.]. In this paper we review recent literature to see what statistical methods are in fact employed for the analysis of the Ames assay. We then note that these methods can be classified into a common category in the framework of Haynes and Eckardt's mutation induction kinetics model [R.H. Haynes, F. Eckardt, Mathematical analysis of mutation induction kinetics, in: F.J. de Serres, A. Hollaender (Eds. ), Chemical Mutagens, Principles and Methods for Their Detection, Vol. 6, Plenum, New York, 1980, pp. 271-307]. The value in knowing this is that most methods of analysis considered here will likely exhibit common statistical behavior. These analyses are computationally intensive, e.g., [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Nat. Acad. Sci., 78 (1981) 3779-3783], hence the ready availability of computer programs is essential if biologists are to use these methods. We briefly review two statistical software programs that are available in the public domain, and describe in detail a third program, Salm, [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Nat. Acad. Sci., 78 (1981) 3779-3783; B.H. Margolin, B.S. Kim, K. Risko, The Ames Salmonella/microsome assay: Issues of inference and validation, J. Amer. Stat. Assoc., 84 (1989) 651-661]. The Salm program is obtainable through the file transfer protocol (ftp) or using a WWW browser. Finally, we discuss two statistical consequences of naively applying the two-fold rule, a method of analysis employed by a number of researchers.

Dose-Response Relationship, Drug↗
PubMed1994

The population dynamics of parasitic helminth communities.

This paper describes a mathematical model which allows us to compare the data collected from short-term cross-sectional surveys with the population dynamics of host and parasite populations over longer periods of time. The model extends an earlier framework for two parasite species in one host, to one for an arbitrary number of parasite species. We show that the conditions necessary for the coexistence of two parasite species extend to expressions for the coexistence of three or more parasite species. Furthermore, the model suggests that those species which form the 'core' of the parasite community are those whose high fecundity and transmission efficiency permit them to colonize hosts readily. In contrast, those species which are classified as 'satellite' species of the community are either species with low fecundity, or low transmission efficiencies. This work confirms earlier studies that suggest that increasing degrees of aggregation are crucial in allowing several species of parasites to coexist in the same species of hosts. The properties of the model are compared with patterns observed in data collected for helminth parasites of Anolis lizards, wood mice and eels. This combined theoretical and empirical approach confirms the importance of the life history strategies of the parasite in determining the abundance of each species in the community. It suggests that studies of parasite community structure have to pay more attention to the strategies pursued by each individual species before interactions between species are considered.

Animals↗
PubMed1994

Synthetic peptides and purified antigens as vaccines.

Molecular biology and, in particular, knowledge of the immune response at the molecular level provide the research community with the opportunity to design vaccines that will elicit the appropriate responses for many diseases. The critical issue is to identify the immune response that correlates with protection. It is remarkable how well the empirical approach has worked; it is essential, therefore, not to ignore the lessons to be learned from these successes. It is particularly essential that each disease and the immune response that affords protection be studied individually so that the appropriate responses can be induced.

Antigens↗
PubMed2002

Bringing the patient back in. Guidelines, practice variations, and the social context of medical practice.

We challenge assumptions that have guided much research and policy aimed at understanding and reducing medical practice variation. Paramount is the focus on doctors as the cause of variation to the neglect of other possible influences. Some research literature suggests that patients, families, and the community context of practice may also influence treatment decisions. Failure to question present assumptions, despite weak evidence in support of them, may account for inability to explain persistent practice variation, develop appropriate implementable guidelines, or anticipate the effect on treatment decisions of greater patient involvement. In this paper, we discuss the weak response to the NIH Consensus Conference on early stage breast cancer because it may have reflected these problems. We urge a more complex and more empirical approach in explaining treatment choice and guidelines sensitive to the potential for value differences.

Attitude to Health↗
PubMed2005

Florida Cognitive Activities Scale: initial development and validation.

We used a rational-empirical approach in the construction and validation of a cognitive activity scale for use with elderly populations. The scale development effort produced a 25-item scale with a reasonably high level of internal consistency in a sample of 200 elderly individuals. Scale scores were positively correlated with years of education and measures of various domains of cognitive ability. In a separate cross-validation sample, a similar pattern of reliability and validity coefficients was obtained. The full scale score was found to contribute significantly to the prediction of cognitive ability after controlling for the effects of age, education, and gender. Two subscales (Higher Cognitive Abilities and Frequent Cognitive Abilities) and a measure of self-reported maintenance of cognitive activity were also developed. In a separate study, the maintenance score was found to differ significantly between the validation sample and a sample of individuals with a history of neurological disorder, with a moderate effect size (d approximately = .7). Further cross-validation studies in minority groups and groups of varying socioeconomic status will be critical in establishing the research and clinical value of the scale and subscales.

Aged↗
PubMed1998

Gas chromatography.

This review of the fundamental developments in gas chromatography (GC) includes articles published from 1996 and 1997 and an occasional citation prior to 1996. The literature was reviewed principally using CA Selects for Gas Chromatography from Chemical Abstracts Service, and some significant articles from late 1997 may be missing from the review. In addition, the online SciSearch Database (Institute for Scientific Information) capability was used to abstract review articles or books. As with the prior recent reviews, emphasis has been given to the identification and discussion of selected developments, rather than a presentation of a comprehensive literature search, now available widely through computer-based resources. During the last two years, several themes emerged from a review of the literature. Multidimensional gas chromatography has undergone transformation encompassing a broad range of activity, including attempts to establish methods using chromatographic principles rather than a totally empirical approach. Another trend noted was a comparatively large effort in chromatographic theory through modeling efforts; these presumably became resurgent with inexpensive and powerful computing tools. Finally, an impressive level of activity was noted through the themes highlighted in this review, and this was particularly true with detectors and field instruments.

Chemistry Techniques, Analytical↗