Several “high throughput methods” have been introduced into research and routine laboratories during the past decade. Providing a new approach to the analysis of genomic alterations and RNA or protein expression patterns, these new techniques generate a plethora of new data in a relatively short time, and promise to deliver clues to the diagnosis and treatment of human cancer. Along with these revolutionary developments, new tools for the interpretation of these large sets of data became necessary and are now widely available. Tissue microarray (TMA) technology is one of these new tools. It is based on the idea of applying miniaturisation and a high throughput approach to the analysis of intact tissues. The potential and the scientific value of TMAs in modern research have been demonstrated in a logarithmically increasing number of studies. The spectrum for additional applications is widening rapidly, and comprises quality control in histotechnology, longterm tissue banking, and the continuing education of pathologists. This review covers the basic technical aspects of TMA production and discusses the current and potential future applications of TMA technology.
tissue microarray; high throughput techniques; quality control
This article surveys the beliefs concerning the supernatural characteristics and powers of sacred trees in Israel; it is based on a field study as well as a survey of the literature and includes 118 interviews with Muslims and Druze.
Both the Muslims and Druze in this study attribute supernatural dimensions to sacred trees which are directly related to ancient, deep-rooted pagan traditions. The Muslims attribute similar divine powers to sacred trees as they do to the graves of their saints; the graves and the trees are both considered to be the abode of the soul of a saint which is the source of their miraculous powers. Any violation of a sacred tree would be strictly punished while leaving the opportunity for atonement and forgiveness. The Druze, who believe in the transmigration of souls, have similar traditions concerning sacred trees but with a different religious background.
In polytheistic religions the sacred grove/forest is a centre of the community's official worship; any violation of the trees is regarded as a threat to the well being of the community. Punishments may thus be collective.
In the monotheistic world (including Christianity, Islam and Druze) the pagan worship of trees was converted into the worship/adoration of saints/prophets; it is not a part of the official religion but rather a personal act and the punishments are exerted only on the violating individual.
To a non-lawyer, references to law reports can appear confusing and complicated. This brief article attempts to explain how to decode such references and thus get to the reports. Those wishing to pursue the matter further are referred to more detailed explanations. This article deals primarily with English case law and is up to date as of December 1987.
Tree worship is very common worldwide. This field study surveys the ceremonies and customs related to sacred trees in present-day Israel; it includes the results of interviews with 98 informants in thirty-one Arab, Bedouin, and Druze villages in the Galilee.
The main results are:
1. Sacred trees were treated as another kind of sacred entity with all their metaphysical as well as physical manifestations.
2. There is not even one ceremony or custom that is peculiar only to a sacred tree and is not performed in other sacred places (such as a saint's grave or a mosque).
3. Few customs, such as: quarrel settling (= Sulkha), leaving objects to absorb the divine blessing and leaving objects for charity) seem to be characteristic of this region, only.
4. In modern times, sacred trees were never recorded, in Israel, as centres for official religious ceremonies including sacrifices, nor as places for the performing of rites of passage.
5. There is some variation among the different ethnic groups: Kissing trees and worshipping them is more common among the Druze although carrying out burials under the tree, leaving water and rain-making ceremonies under them have not been recorded in this group. Passing judgments under the tree is more typical of the Bedouin in which the sacred trees were commonly used as a public social centre.
Most of the customs surveyed here are known from other parts of the world. The differences between Muslims and Druze are related to the latter's belief in the transmigration of souls.
To determine whether or not there are any significant differences in the effects of wound dressings on bacterial bioburden.
A selection of non-occlusive, non-adhesive dressings was tested for their effect on bacterial bioburden. The dressings selected included two dressings with antimicrobial properties (one containing silver and one containing PHMB), a cotton-based dressing enclosed in a perforated sleeve of poly(ethylene terephthalate), a carboxymethyl cellulose-based dressing, a fibre-free alginate dressing, and a 12-ply 100% cotton gauze. Using the colony-drip flow reactor (DFR) model, a meticillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa biofilm was grown underneath a dressing sample. Biofilm growth was examined via plate counts, fluorescent microscopy and scanning electron microscopy.
The dressings containing antimicrobial agents had the greatest effect on bacterial load. In the MRSA experiments, both antimicrobial dressings produced lower bacteria counts than the other dressings (p≤0.001), while in the P. aeruginosa experiments, only the silver-containing sample had fewer bacteria (p≤0.0001). However, neither antimicrobial dressing was able to completely eradicate the bacteria when testing with either microorganism.
The results presented herein illustrate that bacteria can grow unchallenged within the dressing environment and that an antimicrobial dressing can limit this bacterial growth.
antimicrobial dressings; biofilms; plate counts; fluorescent microscopy; scanning electron microscopy
Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.
functional magnetic resonance imaging; sacred values; utility; deontologic; rules
We discuss the role of comparators in H. pylori treatment trials and why design of an anti-H. pylori therapeutic trial for an infectious disease is fundamentally different from that of common gastrointestinal diseases (eg, the absence of a placebo response, the expectation that cure rates in excess of 95% are routinely possible, and the ability to understand why treatment fails). No comparator is absolutely required other than to 100% success; comparison trials should be limited to comparisons between therapies that reliably achieve 90% or greater success (i.e., good therapies). Comparisons to known low success regimens (i.e., bad therapies) are unethical as is withholding information from the subject regarding current effectiveness of a regimen even if that information would reduce the likelihood that the subject would volunteer. We also discuss how it is possible to predict the outcome of a published but locally untried new regimen. The reason for different outcomes of typical gastrointestinal therapies is shrouded in mystery. In contrast, treatment success for H. pylori should be predictable and treatment failures explainable. For too long expectations and analyses of H. pylori therapy has been confused with what is appropriate for gastrointestinal disease such as constipation or irritable bowel syndrome rather than for infectious diseases such as pneumonia.
The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease.
In the past 10 years, molecular biology has found major applications in pathology, particularly in oncology. This has been a field of enormous expansion, where pure science has found a place in clinical practice and is now of everyday use in any academic unit. This demystified review will discuss the techniques used in molecular pathology and then provide examples of how these can be used in oncology.
molecular pathology; oncology; polymerase chain reaction; fluorescent in situ hybridisation; Southern blotting; microarray analysis
“Research” means different things to different people. “Organized curiosity” has been proposed as a suitable description for family-practice research. Studies involving patients in community practices are becoming recognized as a unique type of research that contributes new understanding to matters relating to primary care. Such research, however, requires an infrastructure that makes a study as unobtrusive as possible in participating practices. One approach is the development of a primary care research unit (PCRU): a central co-ordinating communications office which can provide the human and technical resources needed to assist each community office with protocol and data-collection steps. The author of this article describes the functional components of a PCRU in five groupings: namely, technical, human, communication and support systems, a network of community physicians, and facilities. Finally, several important principles about funding primary care research are suggested.
family practice; research; primary care research unit
The process of applying to the National Institutes of Health (NIH) for grant funding can be daunting. The objective of this article is to help investigators successfully navigate the NIH grant application process. We focus on the practical aspects of this process, which are commonly learned through trial and error. Our target audience is generalist faculty and fellows who are applying for NIH funding to support their career development or a clinical research project.
clinical research; academic medicine; NIH; funding; grants
The basic physiology of leucocyte emigration from the intravascular space into the tissues is now known to be dependent on a class of cell surface molecules that have come to be known as adhesion molecules. Many cell–cell interactions are dependent on adhesion and signal transduction via the various adhesion molecules, particularly the integrins. The study of the functions of these molecules has been enhanced by the development of blocking and activating monoclonal antibodies, knockout mice, and by the rare “experiments of nature” in the human population, in whom there is absence or dysfunction of one of the adhesion molecules. This review describes these leucocyte adhesion defects and discusses how they have provided important insights into the function of these molecules.
leucocyte adhesion defect; Glanzmann's thrombasthenia; integrins
The Escherichia coli protein SufI (FtsP) has recently been proposed to be a component of the cell division apparatus. The SufI protein is also in widespread experimental use as a model substrate in studies of the Tat (twin arginine translocation) protein transport system. We have used SufI-GFP (green fluorescent protein) fusions to show that SufI localizes to the septal ring in the dividing cell. We have also determined the structure of SufI by X-ray crystallography to a resolution of 1.9 Å. SufI is structurally related to the multicopper oxidase superfamily but lacks metal cofactors. The structure of SufI suggests it serves a scaffolding rather than an enzymatic role in the septal ring and reveals regions of the protein likely to be involved in the protein–protein interactions required to assemble SufI at the septal ring.
Tat, twin arginine translocation; GFP, green fluorescent protein; T1, mononuclear type I; LB0N, LB without 10g NaCl per liter; NCS, non-crystallographic symmetry; SufI; FtsP; Tat; cupredoxin; X-ray crystallography
Biological dressings like collagen are impermeable to bacteria, and create the most physiological interface between the wound surface and the environment. Collagen dressings have other advantages over conventional dressings in terms of ease of application and being natural, non-immunogenic, non-pyrogenic, hypo-allergenic, and pain-free. This study aims to compare the efficacy of collagen dressing in treating burn and chronic wounds with that of conventional dressing materials.
Materials and Methods:
The records of 120 patients with chronic wounds of varied aetiologies and with mean age 43.7 years were collected and analyzed. The patients had been treated either with collagen or other conventional dressing materials including silver sulfadiazine, nadifloxacin, povidone iodine, or honey (traditional dressing material). Patients with co-morbidities that could grossly affect the wound healing like uncontrolled diabetes mellitus, chronic liver or renal disease, or major nutritional deprivation were not included. For the purpose of comparison the patients were divided into two groups; ‘Collagen group’ and ‘Conventional group’, each having 60 patients. For assessment the wound characteristics (size, edge, floor, slough, granulation tissue, and wound swab or pus culture sensitivity results) were recorded. With start of treatment, appearance of granulation tissue, completeness of healing, need for skin grafting, and patients’ satisfaction was noted for each patient in both groups.
With two weeks of treatment, 60% of the ‘collagen group’ wounds and only 42% of the ‘conventional group’ wounds were sterile (P=0.03). Healthy granulation tissue appeared earlier over collagen-dressed wounds than over conventionally treated wounds (P=0.03). After eight weeks, 52 (87%) of ‘collagen group’ wounds and 48 (80%) of ‘conventional group’ wounds were >75% healed (P=0.21). Eight patients in the ‘collagen group’ and 12 in the ‘conventional group’ needed partial split-skin grafting (P=0.04). Collagen-treated patients enjoyed early and more subjective mobility.
No significant better results in terms of completeness of healing of burn and chronic wounds between collagen dressing and conventional dressing were found. Collagen dressing, however, may avoid the need of skin grafting, and provides additional advantage of patients’ compliance and comfort.
Burns; chronic wounds; collagen dressing
In the first half of the third century B.C, two Greeks, Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, became the first and last ancient scientists to perform systematic dissections of human cadavers. In all probability, they also conducted vivisections of condemned criminals. Their anatomical and physiological discoveries were extraordinary. The uniqueness of these events presents an intriguing historical puzzle. Animals had been dissected by Aristotle in the preceding century (and partly dissected by other Greeks in earlier centuries), and, later, Galen (second century A.D.) and others again systematically dissected numerous animals. But no ancient scientists ever seem to have resumed systematic human dissection. This paper explores, first, the cultural factors--including traditional Greek attitudes to the corpse and to the skin, also as manifested in Greek sacred laws--that may have prevented systematic human dissection during almost all of Greek antiquity, from the Pre-Socratic philosopher-scientists of the sixth and fifth centuries B.C. to distinguished Greek physicians of the later Roman Empire. Second, the exceptional constellation of cultural, political, and social circumstances in early Alexandria that might have emboldened Herophilus to overcome the pressures of cultural traditions and to initiate systematic human dissection, is analyzed. Finally, the paper explores possible reasons for the mysteriously abrupt disappearance of systematic human dissection from Greek science after the death of Erasistratus and Herophilus.
Acidified cupric acetate soaks were tested for eradication of Xanthomonas campestris from naturally infected crucifer seeds. The pathogen was eradicated from seeds by soaking in 0.5% cupric acetate dissolved in 0.005 N acetic acid for 20 min at 35, 40, 45, and 50°C but not 25°C. Moreover, normal bacterial flora of crucifer seeds and the seed-borne Phoma lingam and Alternaria spp. were reduced by 95, 92, and 81%, respectively, after the cupric acetate treatment at 40°C. The seed germination percentage was generally reduced, but the amount of reduction depended upon the treatment temperature and plant cultivar. At 50°C, less than 50% of the seed of all 12 cultivars tested germinated, whereas at 40°C more than 50% of the seeds of most cultivars germinated. Treating seeds in cupric acetate at 40°C should prove useful for eradicating X. campestris from seeds of breeding lines and stock seed used for hybrid seed production. Furthermore, a significant reduction in total bacterial flora and seed-borne fungi suggests the usefulness of the treatment for other microorganisms associated with other seeds or foodstuffs.
Objectives: This study was designed to investigate the effect on skin temperature of different methods of use of a hydrogel dressing.
Methods: Twelve volunteers had temperature measured under a hydrogel dressing with different combinations of air movement and bandaging.
Results: A large drop in skin temperature was only achieved when the dressing was left exposed with air movement over the surface of the dressing.
Conclusions: A temperature that gives effective analgesia is not reached if the dressing is used in accordance with the manufacturer's instructions (covered with an insulating layer). This explains the authors' observation that paramedics and patients often leave these dressings uncovered.
The function of SufI, a well-studied substrate of the TatABC translocase in Escherichia coli, is not known. It was earlier implicated in cell division, based on the finding that multiple copies of sufI suppressed the phenotypes of cells with mutations in ftsI (ftsI23), which encodes a divisomal transpeptidase. Recently, sufI was identified as both a multicopy suppressor gene and a synthetic lethal mutant of ftsEX, which codes for a division-specific putative ABC transporter. In this study, we show that sufI is essential for the viability of E. coli cells subjected to various forms of stress, including oxidative stress and DNA damage. The sufI mutant also exhibits sulA-independent filamentation, indicating a role in cell division. The phenotypes of the sufI mutant are suppressed by factors that stabilize FtsZ ring assembly, such as increased expression of cell division proteins FtsQAZ or FtsN or the presence of the gain-of-function ftsA* (FtsA R286W) mutation, suggesting that SufI is a divisomal protein required during stress conditions. In support of this, multicopy sufI suppressed the divisional defects of mutants carrying the ftsA12, ftsQ1, or ftsK44 allele but not those of mutants carrying ftsZ84. Most of the division-defective mutants, in particular those carrying a ΔftsEX or ftsI23 allele, exhibited sensitivity to oxidative stress or DNA damage, and this sensitivity was also abolished by multiple copies of SufI. All of these data suggest that SufI is a division component involved in protecting or stabilizing the divisomal assembly under conditions of stress. Since sufI fulfils the requirements to be designated an fts gene, we propose that it be renamed ftsP.
There have been many misconceptions in the past about various disorders of the gastrointestinal tract. Many ‘sacred cows’ in this field have been eliminated during the past few years thanks to objective statistical evaluations. This article outlines some of the misconceptions with particular reference to diet and gastric function. Reference is also made to diseases of the gut which alter immunity.
There have been different ethical approaches to the issues in the history of philosophy. Two American philosophers Beachump and Childress formulated some ethical principles namely 'respect to autonomy', 'justice', 'beneficence' and 'non-maleficence'. These 'Four Principles' were presented by the authors as universal and applicable to any culture and society. Mawlana, a great figure in Sufi tradition, had written many books which not only guide people how to worship God to be close to Him, but also advise people how to lead a good life to enrich their personality, as well as to create a harmonious society and a peaceful world.
In this study we examined the major works of Mawlana to find out which of these 'Four Principles of Bioethics' exist in Mawlana's ethical understanding.
We have found in our study that all these principles exist in Mawlana's writings and philosophy in one form or another.
We have concluded that, further to Beachump and Childress' claim that these principles are universal and applicable to any culture and society, these principles have always existed in different moral traditions in different ways, of which Mawlana's teaching might be presented as a good example.
The twin-arginine translocation (Tat) pathway in Escherichia coli transports fully folded and assembled proteins across the energy-transducing periplasmic membrane. In chloroplasts, Tat transport requires energy input only from the proton motive force. To elucidate the mechanism and energetics of bacterial Tat protein transport, we developed an efficient in vitro transport assay using TatABC-enriched inverted membrane vesicles and the physiological precursor pre-SufI. We report transport efficiencies of 60–80% for nanomolar pre-SufI concentrations. Dissipation of the pH gradient does not reduce pre-SufI transport efficiency. Instead, pre-SufI transport requires at least two electrical potential (Δψ)–dependent steps that differ in both the duration and minimum magnitude of the required Δψ. The data are consistent with a model in which a substantial Δψ of short duration is required for an early transport step, and in which a small Δψ of long duration is necessary to drive a later transport step.
Objectives: This paper provides the most complete accounting of the National Library of Medicine's (NLM's) Native outreach since 1995, when there were only a few scattered projects.
Method: The descriptive overview is based on a review of project reports, inventories, and databases and input from the NLM Specialized Information Services Division, National Network Office of the Library Operations Division, National Network of Libraries of Medicine, and Office of Health Information Programs Development of the Office of the NLM Director. The overview focuses on NLM-supported or sponsored outreach initiatives involving Native peoples: American Indians, Alaska Natives, and Native Hawaiians.
Results: The review of NLM's relevant activities resulted in a portfolio of projects that clustered naturally into the following areas: major multisite projects: Tribal Connections and related, Native American Information Internship Project: Sacred Root, tribal college outreach and tribal librarianship projects, collaboration with inter-tribal and national organizations, participation in Native American Powwows, Native American Listening Circle Project, Native American Health Information, and other Native American outreach projects.
Implications: NLM's Native American Outreach reached programmatic status as of late 2004. The companion paper identifies several areas of possible new or enhanced Native outreach activities. Both papers highlight the importance of solid reporting and evaluation to optimize project results and programmatic balance and priorities.
Objectives: This paper examines the cost effectiveness of the compulsory bicycle helmet wearing law (HWL) introduced in New Zealand on 1 January 1994. The societal perspective of costs is used for the purchase of helmets and the value of injuries averted. This is augmented with healthcare costs averted from reduced head injuries.
Methods: Three age groups were examined: cyclists aged 5–12 years, 13–18 years, and ≥19 years. The number of head and non-head injuries averted were obtained from epidemiological studies. Estimates of the numbers of cyclists and the costs of helmets are used to derive the total spending on new bicycle helmets. Healthcare costs were obtained from national hospitalisation database, and the value of injuries averted was obtained directly from a willingness-to-pay survey undertaken by the Land Transport Safety Authority. Cost effectiveness ratios, benefit:cost ratios, and the value of net benefits were estimated.
Results: The net benefit (benefit:cost ratios) of the HWL for the 5–12, 13–18, and ≥19 year age groups was $0.3m (2.6), -$0.2m (0.8), and -$1.5m (0.7) (in NZ $, 2000 prices; NZ $1.00 = US $0.47 = UK £0.31 approx). These results were most sensitive to the cost and life of helmets, helmet wearing rates before the HWL, and the effectiveness of helmets in preventing head injuries.
Conclusions: The HWL was cost saving in the youngest age group but large costs from the law were imposed on adult (≥19 years) cyclists.
The evolution of surgical dressings is traced from 1600 b.c. to a.d. 1944.
The availability of an increasing variety of man-made fibres and films from 1944 onwards has stimulated work on wound dressings, and some of the more important contributions, both clinical and experimental, are discussed. The functions of a wound dressing and the properties which the ideal wound dressing should possess are given. The necessity for both histological and clinical evaluation of wound dressings in animals and in man is stressed.
Wound dressings are the most commonly used therapeutic agents, but there is no means whereby their performance can be assessed. An attempt should be made either nationally or internationally to establish a standard method of assessing the performance of wound dressings. For this it is necessary to have an internationally agreed standard dressing which could be used as a reference or control dressing in all animal and human work. The only animal with skin morphologically similar to that of man is the domestic pig. Three types of wounds could be used: (1) partial-thickness wounds; (2) full-thickness excisions; and (3) third-degree burns.
The development of standard techniques for the assessment of the efficiency of wound dressings would be of considerable benefit to the research worker, the medical profession, the patient, and the surgical dressings industry.
Torso burns following debridement and skin grafting usually require fairly complex dressings. The dressing consists of an interface layer, an absorbent layer and a retaining layer. Although numerous inner dressings are now available from multiple manufacturers, Gamgee dressing (pad of cotton and gauze) is often used as an outer absorbent dressing. Dressing the torso is usually a challenge, and the purpose of this paper is to present a custom-made over-dressing for torso burns, which reflects the current practice at our centre.
Materials and Methods:
A U-shape cut is made at one end of the Gamgee to design the shoulder straps. This custom-made dressing is held in place by a custom-designed netted vest.
This custom-made over-dressing for the torso was found to be comfortable for patients, easily made from locally available materials, easy to apply, absorbent and not restrictive of movement. The shoulder straps prevent sliding of the Gamgee, and in a nonrestrictive way. The netted vest provides the required compression to keep the Gamgee in firm contact with the inner layers of the dressing without compromising respiration.
In this report, we present our practice of a custom-made dressing that is very efficient and economical. We hope that this information will be of practical use to other centres managing burns.
Burns; Gamgee dressing; outer dressing; torso