Toll-like receptors: how they work and what they do.

The Toll-like receptors are the primary sensors of the innate immune system. This assignment of function was predicated on positional cloning, and was the result of long and painstaking inquiry into the mechanism of responses to bacterial endotoxin, the abundant lipopolysaccharide component of the outer membrane of Gram-negative bacteria. The sequence of events that led to the discovery of Toll-like receptor function carries an important lesson that should guide further analysis of the innate immune system.     

gamma/delta and other unconventional T lymphocytes: what do they see and what do they do?

T lymphocytes recognize specific ligands by clonally distributed T-cell receptors (TCR). In humans and most animals, the vast majority of T cells express a TCR composed of an alpha chain and a beta chain, whereas a minor T-cell population is characterized by the TCR gamma/delta. Almost all of our knowledge about T cells stems from alpha/beta T cells and only now are we beginning to understand gamma/delta T cells. In contrast to conventional alpha/beta T cells, which are specific for antigenic peptides presented by gene products of the major histocompatibility complex, gamma/delta T cells directly recognize proteins and even nonproteinacious phospholigands. These findings reveal that gamma/delta T cells and alpha/beta T cells recognize antigen in a fundamentally different way and hence mitigate the dogma of exclusive peptide-major histocompatibility complex recognition by T cells. A role for gamma/delta T cells in antimicrobial immunity has been firmly established. Although some gamma/delta T cells perform effector functions, regulation of the professional and the nonprofessional immune system seems to be of at least equal importance. The prominent residence of gamma/delta T cells in epithelial tissues and the rapid mobilization of gamma/delta T cells in response to infection are consistent with such regulatory activities under physiological and pathologic conditions. Thus, although gamma/delta T cells are a minor fraction of all T cells, they are not just uninfluential kin of alpha/beta T cells but have their unique raison d'être.     

Antipsychotic use in the elderly: What doctors say they do,and what they do

Objective: To review psychiatrists’ attitudes and actual practice on the use of typical and atypical antipsychotics in the elderly. Methods: Audit data were collected from 18‐old‐age psychiatry units across Australia. The attitudes of old age psychiatrists and their perceptions of the efficacy, tolerability and clinical usefulness of antipsychotics were examined. Results: The medications used for 321 patients were audited, and the attitudes of the 57 prescribing doctors were assessed. All available atypicals were prescribed and reported as more efficacious and clinically useful than typicals. Adverse events perceived by doctors as an obstacle to prescribing were more frequent than reported adverse event rates in product information. All diagnostic groups improved. Off‐label use comprised almost 22% in this sample. Conclusions: Adverse events are impediments to prescribing, more so with typical than atypical antipsychotics. All available atypicals were used and appeared effective in this elderly population.     

Indexes for the evaluation of scientific publications: what they are and what they are used for]

Today, medicine lives the paradigm of Evidence-Based Medicine, which integrates the most recent discoveries of Research in day-to-day Clinical Practice. Simultaneously, there is an exponential growth in biomedical scientific knowledge, and, with it, of the number of scientific papers and biomedical journals. Currently, the assessment of the quality of biomedical scientific information is based on the peer review method, which also has different types of bias. In this setting, quantitative indexes are increasingly being used to assess it. Three of these indexes are the quotation rate, the impact factor and the Immediacy Index that, despite their objectivity, have several limitations. The impact factor, which is a valid tool to estimate the quality of a scientific journal, is not suited to evaluate single articles, scientists or research groups. In these cases, the best methodology is quotation analysis. No method, however, can replace the individual reading and study of the contents of the scientific work. Of the new potentialities of biomedical information, the possibility of discussing scientific articles before their publication is particularly promising. With this purpose, the netprints servers, which are new sites on the Internet, were created. Other sites where we can have access to databases with summaries of guidelines have also been created in an attempt to reduce the gap between research and clinical practice.     

What are killer cells and what do they do?

Cytotoxic effector function of the immune system is mediated predominantly by killer cells and with the exception of complement-mediated lysis all forms of immune-directed cell death are attributable to these cells. The heterogeneous collection of cells with cytotoxic properties ranges from the phylogenetically primitive granulocyte and natural killer (NK) cell lineages to the more complex and versatile macrophage and antigen-specific cytotoxic T lymphocyte. Most killer cells are capable of the dual functions of cytotoxicity and immunoregulation. Granulocytes, macrophages and NK cells constitute an effective 'first line' cellular defence against invasive microbial pathogens and emerging malignancies. Through direct cytotoxicity or by the secretion of cytokines, NK cells also prevent overproliferation of precursor cell populations, thereby exerting a more discriminating control over antigen-specific T and B cell responses. The ultimate refinement of the killer cell is the cytotoxic T cell which is directed by an antigen receptor comparable in specificity and diversity to the immunoglobulin molecule. The mechanisms underlying the initial interaction between killer cell and target and the subsequent lytic event are imperfectly understood. Although many cytokines with lytic properties have been identified and in some cases cloned, their relative importance and intricate interactions with other components of the immune system are still largely unknown. In addition to the prevention of infection and malignancy, killer cells of all lineages are important in the pathogenesis of human disease. Of particular interest is the role of macrophages, NK cells and cytotoxic T cells in autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analyses of cost effectiveness in the management of essential hypertension: What they can and what they do not teach us

There are approximately 50 million hypertensive individuals in the United States, and their treatment is often life-long. Most are asymptomatic, so the goal of treatment is to prevent complications, which often occur decades after the condition is detected. Although the management of hypertension is potentially very costly, it is now clear that antihyperten-sive therapy can substantially reduce cardiovascular mortality and morbidity. This constellation of an asymptomatic process with a very high prevalence capable of producing severe and potentially costly complications is precisely the circumstance under which cost effectiveness of therapy becomes an important consideration. Several such analyses have been performed, examining the question of which patients should be treated, what procedures should be used in their evaluation, and which therapeutic agents should be used. These studies highlight important issues, but also illustrate the potential pitfalls and fallacies of such analyses, particularly when outcome data are unavailable or inadequate. This article reviews the literature concerning cost-effectiveness analyses in the management of hypertension and discusses the value of this approach.     

Grandparents and adult grandchildren: what do they do for one another?

This article reports findings from a study in which the functional exchange of services, emotional (expressive) and tangible (instrumental) between grandparents and adult grandchildren were examined. The reciprocal (equivalent) and nonreciprocal (excessive giving or receiving) exchange of services was measured by the frequency of exchange and perception of potential support between the dyad. Noninstitutionalized Jewish grandparents (118, 65+ years of age) with at least one adult grandchild (18+ years of age) were randomly selected from an apartment house in Miami Beach. The results showed that the majority of grandparent-adult grandchild relationships are not reciprocal in either expressive or instrumental support. Grandparents' perception of reciprocity is that they receive more than they give. Social-work knowledge of functional exchange between this dyad may strengthen the social-support network of the elderly.     

慢性乙型肝炎治疗的难点与热点

目前,对抗HBV治疗是慢性乙型肝炎治疗的最重要治疗手段已毋庸置疑,抗病毒治疗的概念、理念也已为广大临床所接受.经过10余年的慢性乙型肝炎治疗实践,对慢性乙型肝炎抗病毒治疗的适应证,药物选择和疗效的判断等均有了较为明确的认识.尽管对慢性乙型肝炎治疗的目标、适应证、方法、策略在各国指南中均已有清楚描述,但随着治疗人群增加和治疗时间延长,在临床实践中又出现新的难点和热点问题.     

Chronic low back pain in older adults: What physicians know, what they think they know, and what they should be taught

Chronic low back pain (CLBP) is a common and debilitating problem in older adults. Little exists in the literature about primary care physicians' (PCPs') knowledge of and confidence in managing this problem. A self-administered survey was mailed to PCPs in western Pennsylvania to measure knowledge of the evaluation and treatment of common contributors to CLBP in older adults, confidence in diagnosing these contributors through physical examination, and the association between confidence levels and knowledge. The survey combined items with an ordinal scale on which PCPs ranked their confidence in detecting various contributors to CLBP (e.g., fibromyalgia) using physical examination and patient vignettes followed by multiple choice questions designed to assess knowledge. One hundred fifty-three of 634 surveys were returned (24.1%). Overall, the majority of PCPs did not feel "very confident" in their ability to diagnose any of the contributors of CLBP listed (most items <40%). PCPs felt most confident in detecting scoliosis and least confident detecting myofascial pain of the piriformis muscle. There was a wide range in the number of respondents answering all questions related to a particular topic correctly (3.9% for sacroiliac joint syndrome to 70.4% for hip osteoarthritis). There was no relationship between knowledge scores and confidence ratings (P > .05 for all comparisons). The results point to a need for more PCP education about CLBP in older adults. It also suggests that accurate needs assessment should not rely on physician confidence ratings alone.     

Mice lacking the thyrotropin-releasing hormone gene: what do they tell us?

Thyrotropin-releasing hormone (TRH) is localized in the brain hypothalamus and stimulates the secretion and synthesis of pituitary thyrotropin (TSH). Although TRH deficiency caused by artificial hypothalamic destructions has been reported to result in significant decreases in TSH secretion in rodents, clinical observations from the patients with possible TRH deficiency did not entirely agree with these animal results. Because of its ubiquitous distribution throughout the brain and in the peripheral tissues, TRH has been suggested to possess a wide variety of functions in these regions. However, the neurobehavioral and peripheral actions of TRH still remains to be established. It has been, therefore, anticipated that detailed analysis of TRH-knockout mice might provide insight into the physiological significance of endogenous TRH. The present review focuses on the phenotypic findings of mice deficient in TRH.     

Contrast media safety: what do we know and how do we know it?

Use of an intravenous injection of a water-soluble iodine compound (sodium iodide) for visualizing the urinary tract was first described by Osborne in 1923. However, sodium iodide was accompanied by a high incidence of side effects and the image quality was not good. As newer, improved contrast agents were introduced, a number of investigators reported on the incidence of death and side effects incurred by their use. In 1975, the first large-scale, multicenter, prospective study on the incidence of fatal and nonfatal reactions was reported by Shehadi. In this series, the overall incidence of adverse reactions was 5.65%, of which 3.77% were mild, 1.77% were moderate, 0.02% were severe, and 0.0007% were fatal. Shehadi also noted that a history of allergy doubled the risk of adverse reaction and a history of a previous adverse reaction to contrast material trebled the risk; also, the risk of a reaction to an intraarterial injection was half that of the risk associated with an intravenous injection. With the introduction of low osmolar nonionic agents, other large-scale studies were performed because these agents appeared to cause significantly fewer adverse reactions. However, they were from 10 to 15 times more expensive than their predecessors. In 1987, Lasser reported on the increased safety of ionic agents when patients were pretreated with steroids. Palmer in Australia and Katayama in Japan collected 120,000 and 335,000 patients, respectively, and compared the incidence of adverse reactions of the ionic versus the nonionic agents. Wolf recently reported a study that included a direct comparison of ionic agents with pretreatment with steroids versus nonionic agents.(ABSTRACT TRUNCATED AT 250 WORDS)