beta-Lactamases of increasing clinical importance.

Resistance to b-lactam-containing antimicrobial agents continues to increase, frequently due to the presence of b-lactamases in Gram-negative bacteria. Over the past twenty-five years broad-spectrum enzymes such as TEM- and SHV-variants and the metallo-b-lactamases have become more prolific. As a result of the ability of plasmids to continue to acquire additional resistance determinants, many of the b-lactamase-producing Gram-negative pathogens have become multi-drug resistant. In combination with decreased permeability, the organisms can become virtually untreatable with current therapies. The major groups of b-lactamases that pose the most serious therapeutic problems include the extended-spectrum b-lactamases, the plasmid-mediated cephalosporinases, the inhibitor-resistant TEM- or SHV-derived b-lactamases and the carbapenem-hydrolyzing b-lactamases. Those enzymes that can be transferred on mobile elements are the most serious of the newer b-lactamases, and include enzymes in each of the four groups outlined above.     

Harvey A. K. Whitney Lecture. Of perceived value.

Current issues in pharmacy are discussed and recommendations are made to help pharmacy demonstrate its value in health care. There is a need for pharmacy to actively demonstrate and communicate its value in health care. Educational requirements should reflect the values of the profession. In the debate over the entry-level Pharm.D. degree, the profession must not lose sight of the principal goal of elevating the basic competencies of all pharmacists. Graduate-level education will continue to be valuable, but the degrees and programs should be modified to meet current and future needs. Residency training will become increasingly essential. A well-defined corps of pharmacy technicians is needed. The profession should strive to meet the needs of society rather than confining itself to traditional practice definitions. This will involve increased interaction with patients. Also, pharmacy directors must become more creative in allocating existing resources and building arguments for expansion. When patients recognize the value of pharmacy services, they will seek out and demand those services. Pharmacists must get involved in deliberations regarding health-care reform. They have a responsibility to promote preventive medicine and healthy life-styles. They should actively promote the rational use of all medications. Although tremendous progress has been made in advancing the concept of pharmaceutical care, the profession still has work to do in communicating its value to the public.     

2007年1～10月我院病区医嘱审核情况分析

目的：归纳总结我院医嘱中不合理用药问题,希望能引起广大医务人员的重视。方法：整理归纳医嘱中的不合理用药问题,探讨临床药师在药物治疗中的作用。结果：我院临床药师发现整理药物治疗中存在不合理问题。结论：合理用药日益成为社会各界关注的焦点问题,临床药师的作用也日益彰显,在临床药物治疗中起着越来越积极的作用,成为合理用药中不可缺少的一份子。     

Haemolytic activity of maltopyranoside surfactants.

The haemolytic activity of a number of maltopyranoside surfactants was studied. The study included octyl, nonyl, decyl, dodecyl, tetradecyl, cyclohexyl-propyl, cyclohexyl-hexyl, and dimethyl-heptyl maltopyranoside. The in vitro haemolytic activity was determined by employing a static method in which surfactants are added to an erythrocyte suspension and the released haemoglobin is determined. It was found that alkyl maltopyranosides become more haemolytic the longer the alkyl chain. Branching or presence of cyclic groups clearly decreases haemolytic activity, but it also increases the critical micelle concentration. As a result, the cyclic or branched surfactants do not become better solubilizing excipients than the straight-chain surfactants. The most useful surfactant for pharmaceutical applications appears to be tetradecyl maltopyranoside, which is the least haemolytic surfactant relative to its critical micelle concentration.     

Chemometrics in pharmaceutical analysis.

Pharmaceutical analysis is undergoing a slow revolution as chemometric principles become increasingly incorporated. This paper reviews some of the more recent advances, with particular focus on spectrophotometry, chromatography and expert systems.     

美国、日本临床药学教育发展对我国的启示

目的：通过借鉴美国、日本临床药学人才培养模式,加快我国临床药学教育发展。方法：介绍美国、日本临床药学教育发展历程与取得成绩,分析我国临床药学教育发展中存在的问题．加快完善临床药学的学科设置和管理制度。结果：目前Pharm.D项目已成为美国药学院校的核心教育体系,日本也着手实施新的6年制药学教育．临床药学教育已成为国际药学教育的发展趋势。结论：我国应顺应时代发展要求．加快发展临床药学教育．促进药学学科发展。     

Programmed investigation bed.

A single programmed investigation bed has become a useful addition to a busy male medical ward. Patients had to wait only a short time before being admitted and their stay was shorter than it would have been before the bed was introduced. The use of the bed requires careful planning and the full co-operation of all medical and nursing staff.     

The discovery of addiction. Changing conceptions of habitual drunkenness in America.

The modern conception of alcoholism as a progressive, addictive disease dates from the late 18th century. By the mid-1800s it had become an integral part of American Temperance thought, as did the belief that total abstinence offered the only remedy for intemperance.     

Drug trafficking stories: Everyday forms of Narco-folklore on the U.S.–Mexico border

The United States government's so-called “War on Drugs” is predicated on the idea that drug consumption and drug trafficking are unequivocally harmful and dangerous activities that the country's population will fear and reject. Yet, ethnographic findings from the U.S.–Mexico border indicate that drug trafficking has become such a common activity that it has generated its own sub-cultural style, including music and folklore. To date, anthropological studies of border drug-trafficking culture have mainly focused on narcocorridos, a genre of Mexican folk/pop music that celebrates and chronicles the drug trade and the lives of high-level traffickers. These studies provide valuable insights into the inner workings of drug organizations and the cultural context from which they emerge. However, most workers in the drug trade are not the wealthy superheroes or villains portrayed in narcocorridos. They are common people whose primary motivation for engaging in drug trafficking is economic survival. Drawing on a rich folklore about drug-trafficking that has become pervasive in the El Paso/Ciudad Juárez border region, this ethnographic study shows how drug commerce has become a “normal,” expectable part of everyday life. The quotidian folklore surrounding drug trafficking indicates the degree to which the drug trade affects border residents on multiple levels. The desensitizing of the population to drug trafficking, as illustrated by everyday drug folklore, and its very mundaneness in the border region, are a direct challenge to the idea that the government is winning the “Drug War.”     

Fluorescent imaging in living systems.

The use of fluorescent imaging techniques in the study of living biological systems has become an important experimental tool in modern biology. Over recent years novel imaging technologies have been developed and older techniques refined. New fluorescent probes continue to become available and the ways in which they are used is increasingly creative. Commonly used imaging methods such as confocal and multiphoton microscopy, when combined with techniques such as fluorescence resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM), can provide powerful strategies with which to study molecular events in intact cells.     

Epidemiological context of signalling.

Epidemiology has become the conscience and soul of signal detection and interpretation from assuring insights into the strengths and limitations of the data source to articulating the disease natural history and its relationship to other diseases, outcomes and treatments. The epidemiologist has struggled to bring several issues into focus including the analysis and interpretation of surveillance data, the integration of signalling and causality criteria, the statistical issues of multiple comparisons and multiple looks at the data, whether one significant disproportion is a signal or whether it should persist over time before it is 'declared'. However, epidemiology, like signalling, has its proper place with its own strengths and limitations. This paper will attempt to bring everyone up to speed on the role of epidemiology in the context of signalling and how signalling fits into the broader context of epidemiology, how perceptions and biases may affect our application of these methods and why context and communication have become so important in this field.     

Addiction and withdrawal--current views.

The final common pathway of addiction (the dopamine hypothesis of reward) has recently been evolving, with the mesocorticolimbic dopaminergic system now seen as key to natural rewards and drug-seeking behaviour, though perhaps having less of a role in the maintenance of such behaviour. The perception of a common pathway has meant that treatments for one drug of addiction have 'crossed-over' and become possible treatments for other addictive drugs.     

Melanocortin receptors: perspectives for novel drugs.

The cloning of five different subtypes of melanocortin receptor subtypes have recently opened up new possibilities for the development of drugs. The physiological roles of the five melanocortin receptors have started to become understood, and compounds with selective actions on some of the five subtypes have become available. Presently, most clinically promising application for drugs active on melanocortin receptors are for control of feeding homeostasis and body weight and for treatment of inflammatory diseases. I review here the cloning, localisation, function and structure of the melanocortin receptors, in relation to the possibilities to develop selective drugs for these receptors.     

Enzyme-activated targeting of liposomes.

It has become increasingly evident that tissues utilize specific localization of enzymes to perform certain tasks, often associated with various types of tissue remodeling. The ubiquitous presence of such enzymes, along with their specific localizations, provides an ideal opportunity to elicit specific delivery via an enzyme-triggered mechanism. A survey of some of the recent progress in enzyme-activated targeting of delivery systems, with a focus on a few liposomal systems, is presented.     

Lysosomotropic agents. 1. Synthesis and cytotoxic action of lysosomotropic detergents.

Amines whose pK values lie between about 5 and 9 are lysosomotropic because lysosomes are acidic intracellular compartments. If such amines bear long hydrophobic chains, they become detergents upon protonation inside the lysosomes, rupturing the lysosomal membrane and killing the cell. Six types of lysosomotropic amines have been prepared that all behave in the expected manner. They are cytotoxic to all lysosome-bearing cells but not red blood cells, which lack lysosomes. Their mode of action, the effect of alkyl chain length on activity, and the fact that their cytotoxic action appears only above a threshhold intracellular concentration support the belief that they behave as lysosomotropic detergents. Among the potential applications is cancer chemotherapy.     

Potential tumor- or organ-imaging agents. 26. Polyiodinated 2-substituted triacylglycerols as hepatographic agents

A series of omega-(3-amino-2,4,6-triiodophenyl)alkanoic acids and the corresponding 1,3-dipalmitoylglycerol 2-[omega-(3-amino-2,4,6-triiodophenyl)alkanoates] were synthesized, radioiodinated with iodine-125, and evaluated for their ability to selectively localize in the liver for potential use as hepatographic imaging agents. Acid analogues 1d and 1e afforded relatively high levels of radioactivity in the liver (45 and 49% injected dose) 5 min after intravenous administration to rats. These acids displayed a marked propensity to become bound to plasma albumin. In contrast, triacylglycerol analogues 10a and 10c did not become immediately associated with plasma albumin but instead rapidly became associated with plasma lipoproteins and showed a different tissue distribution profile than free acids 1a and 1c. Although long-chain triacylglycerol analogues 10d and 10e exhibited some capacity to accumulate in the liver at 5 and 30 min, respectively, analysis of the plasma revealed significant in vivo ester hydrolysis. It would thus appear that liver radioactivity following administration of 10d and 10e was due to uptake of the free acid and not the intact triacylglycerol. Triacylglycerol analogues 10a and 10c, on the other hand, were taken up intact and showed liver accumulations of 25 and 35% of the administered dose at 30 min.     

Drug-induced sclerosing peritonitis.

The records and case reports of 20 patients presenting with practolol induced sclerosing peritonitis have been reviewed revealing striking similarities: symptoms and signs of bowel obstruction or the presence of a vague abdominal mass in a patient who is currently taking or has previously taken practolol should alert one to the possibility of sclerosing peritonitis as the cause. Skin or eye reactions attributed to practolol provide further strong support for the diagnosis. Although practolol has now been discontinued in New Zealand its effects may become manifest months or years later.     

Severe hypernatraemia in adults.

In a prospective study of abnormalities of plasma sodium concentration carried out over one year 20 patients were identified who had a concentration exceeding 154 mmol(mEq)/1. Of these, eight patients had diabetes mellitus, eight had primary intracranial disorder, and four had become dehydrated. Five of the eight diabetics presented with hyperosmolar, non-ketotic precoma, and in all eight hypernatraemia developed despite treatment with hypotonic (0.45%) saline. There was a good correlation (r = -0.93) between the rates of change of plasma sodium and blood glucose concentrations, and thus a rise in plasma sodium concentration appeared to be a consequence of the treatment. In the early phase of treatment urinary sodium loss was extremely low despite a brisk diuresis, the infused sodium then predisposing the patients to hypernatraemia. All of the eight patients with intracranial disorders showed evidence of abnormal production of the antidiuretic hormone, six having frank diabetes insipidus. Severe hypernatraemia in this group was associated with a high mortality, fluid balance being difficult to maintain. Two of the four patients who had become dehydrated had had a recent gastrointestinal haemorrhage. In these patients infusion of 0.9% saline contributed to the hypernatraemia since urinary sodium loss was low. Severe hypernatraemia in adults is uncommon, but in established cases plasma and urinary biochemical indices should be measured frequently. Monitoring of the central venous pressure is usually necessary, and patients are best managed in an intensive care unit.     

Societal aspects of genetically modified foods.

This paper aims to examine some of the reasons behind public controversy associated with the introduction of genetically modified foods in Europe the 1990s. The historical background to the controversy is provided to give context. The issue of public acceptance of genetically modified foods, and indeed the emerging biosciences more generally, is considered in the context of risk perceptions and attitudes, public trust in regulatory institutions, scientists, and industry, and the need to develop communication strategies that explicitly include public concerns rather than exclude them. Increased public participation has been promoted as a way of increasing trust in institutional practices associated with the biosciences, although questions still arise as to how to best utilise the outputs of such exercises in policy development. This issue will become more of a priority as decision-making systems become more transparent and open to public scrutiny. The results are discussed in the context of risk assessment and risk management, and recommendations for future research are made. In particular, it is recommended that new methods are developed in order to integrate public values more efficaciously into risk analysis processes, specifically with respect to the biosciences and to technology implementation in general.