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[Progression of tumors: etiologic, morphologic and molecular-biological aspects].

Two aspects can be distinguished in multistage carcinogenesis: etiological one (every stage is induced by a specific for this stage agent) and morphobiological aspect (every stage is characterized by specific morphological, genetic and other properties). The schema of the multistage carcinogenesis is presented in which morphological stages (diffuse and focal hyperplasia, benign tumours, dysplasia, carcinoma in situ, various phases of malignant tumour progression) are placed against genetic alterations. L. Foulds concept of tumour progression is discussed with special emphasis on precancerous stages, possibilities of cancer development de novo, and independent progression of different tumour characters. The following types of carcinogenesis are listed on the basis of interrelationship between etiological and genetic factors: 1) carcinogenesis induced by genotoxic agents; a) one agent is acting at high dose and for a long time thus ensuring the activation of protooncogenes and all stages of tumour progression (initiation, promotion, various phases of malignant tumour); b) those acting during a very short time, however sufficient for developing the genetic program working automatically without further exposure to known carcinogens (irradiation in case of the atomic bomb explosion or effect of short-living alkylating agents): in this case there is no stage of promotion; 2) carcinogenesis by non-genotoxic carcinogens (their mode of action is still unclear, the only human example is carcinogenesis by hormones); 3) development of tumours in frane of the two (or three) stage carcinogenesis when every stage is provoked by its own etiological factor, no human examples are known as yet; 4) development of tumours due to the genetic mechanism making the organism highly susceptible to the minimal doses of carcinogens as is the case with skin cancer by ultraviolet light in patients with xeroderma pigmentosum, the genetic damage in itself has nothing to do with tumour formation; 5) genetic damage leading to the development of tumour without visible participation of any known carcinogens or promoters (gene Rb in retinoblastoma, gene Wt in Wilms tumour, etc.).

Animals↗

Inhaled anesthetics: an historical overview.

Inhalational agents have played a pivotal role in anesthesia history. The first publicly demonstrated anesthetic of the modern era, diethyl ether, was an inhalational anesthetic. The attributes of a good agent, ability to rapidly induce anesthesia, with limited side effects has led research efforts for over a hundred and fifty years. The explosion hazard was largely conquered with the development of the halogenated agents in the 1950s. Rapid emergence, with limited nausea and vomiting continue to drive discovery efforts, yet the 'modern' agents continue to improve upon those in the past. The future holds promise, but perhaps the most interesting contrast over time is the ability to rapidly introduce new agents into practice. From James Young Simpson's dinner table one evening to the operating suite the next day, modern agents take decades from first synthesis to clinical introduction.

Anesthesia↗

Liquid-phase study of ozone inactivation of Venezuelan equine encephalomyelitis virus.

Ozone, in a liquid-phase application, was evaluated as a residue-free viral inactivant that may be suitable for use in an arboviral research laboratory. Commonly used sterilizing agents may leave trace residues, be flammable or explosive, and require lengthy periods for gases or residues to dissipate after decontamination of equipment such as biological safety cabinets. Complete liquid-phase inactivation of Venezuelan equine encephalomyelitis virus was attained at 0.025 mg of ozone per liter within 45 min of exposure. The inactivation of 10(6.5) median cell culture infective doses (CCID50 of Venezuelan equine encephalomyelitis virus per milliliter represented a reduction of 99.99997% of the viral particles from the control levels of 10(7.25-7.5) CCID50/ml. A dose-response relationship was demonstrated. Analysis by polynomial regression of the logarithmic values for both ozone concentrations and percent reduction of viral titers had a highly significant r2 of 0.8 (F = 63.6; df = 1, 16). These results, together with those of Akey (J. Econ. Entomol. 75:387-392, 1982) on the use of ozone to kill a winged arboviral vector, indicate that ozone is a promising candidate as a sterilizing agent in some applications for biological safety cabinets and other equipment used in vector studies with arboviruses.

Animals↗

Biologicals: principles, techniques and mechanisms of action.

Biological agents for the treatment of IBD are the result of both the explosion of knowledge precipitated by the techniques of molecular biology, and by the ability to use these same techniques to produce agents. Thus, there has been a greatly facilitated translation of basic knowledge into clinical therapy. An astounding number of biologic agents are currently in development for the treatment of IBD and other immune-mediated conditions. These include native microbiologic preparations isolated for beneficial properties, recombinant cytokines and anticytokines, monoclonal antibodies, antisense oligonucleotides, and in the future, somatic gene therapy. This work seeks to describe the principles and techniques of biologic agent development, as well as prime sites of action targeted by these agents. Recent advances in the techniques of molecular biology have made possible unprecedented progress in the treatment of many conditions. The techniques of molecular biology have provided new methods of drug discovery and at the same time have elucidated new therapeutic targets. Most notable has been the progress made in the treatment of chronic inflammatory and immune mediated conditions, including inflammatory bowel disease. This paper is intended to highlight the methodological principles behind biologic agents, methods of discovery and production, and to highlight potential therapeutic targets for these new agents.

Antibodies, Monoclonal↗

Laparoscopy explosion hazards with nitrous oxide.

BACKGROUND: During laparoscopic surgery utilizing carbon dioxide as the insufflating agent, nitrous oxide will diffuse into the peritoneal cavity if it is used as part of the anesthetic. Bowel perforation and the subsequent release of volatile bowel gas could create a explosion hazard. METHODS: Two related studies were undertaken. The first quantified the transfer of nitrous oxide, over time, in 19 female patients undergoing laparoscopy. The second established the lower limits of flammability of a range of concentrations of methane and hydrogen diluted with nitrogen (simulated bowel gas) in a range of concentrations of nitrous oxide diluted with carbon dioxide (simulated peritoneal gas). RESULTS: The mean concentrations of N2O at 10, 20, and 30 min from the time of insufflation were 19.9 +/- 4.8%, 30.3 +/- 6.8%, and 36.1 +/- 6.9%, respectively. The maximum reported concentrations of methane and hydrogen in bowel gas are 56% and 69%, respectively. The concentration of nitrous oxide necessary to support combustion of 56% methane is approximately 47%. By contrast, the concentration of nitrous oxide needed to support combustion of 69% hydrogen is approximately 29%. CONCLUSIONS: The authors have shown that it is possible for nitrous oxide to reach concentrations in the peritoneal cavity that can support combustion of bowel gas.

Adult↗

Letter: Fire hazard.

Explore the source record for details and available documents.

Anti-Infective Agents, Local↗

Inflammable antiseptics and theatre fires.

This paper describes an investigation designed to find out if theatre fires could be started by the antiseptic painted on the patient's skin being ignited by cautery or diathermy. It was found that hot wire cautery or diathermy generated enough heat to ignite all alcohol-based antiseptics even if these contained as little as 20 per cent alcohol. They could also cause iodine to explode in the presence of nitrous oxide, and nobecutane to explode in the presence of nitrous oxide or increased oxygen. The likelihood of these combinations causing fires is discussed, and it is recommended that when diathermy or cautery is to be used near the surface of the body, either an aqueous-based antiseptic is used or if spirit solutions are required they are carefully dried off before proceeding.

Anti-Infective Agents, Local↗

DNA-based detection of onchocerca volvulus.

During the 1980s, the idea of using deoxyribonucleic acid probes for specific identification and diagnosis of infectious agents became very fashionable. There was therefore an explosion in the development of these tools and one particular group of organisms which received much attention was the parasitic nematodes. This review traces the development and use of such probes with the filarial nematode Onchocerca volvulus, with emphasis on their application to resolving certain 'problems' associated with this parasite, e.g. whether or not strains exist and difficulties in distinguishing the infective larval stage morphologically from related species.

Animals↗

Surrogate burns in deactivation furnace system.

The deactivation furnace system at the Deseret Chemical Depot in Utah is designed for processing explosive components from munitions containing nerve and mustard agents. The system was installed during the period of 1989 through 1993. The Utah Division of Solid and Hazardous Waste (UDSHW) required that trial burns be conducted using surrogate chemicals prior to introducing chemical agents into the system. The selected surrogate chemicals were monochlorobenzene and hexachloroethane based on the criteria established by the UDSHW. Three surrogate runs were conducted in October, 1995. The gaseous emissions and liquid and solid effluents were sampled and analyzed using approved EPA methods. The trial burns demonstrated the desirable destruction and removal efficiency for the selected surrogate chemicals. The pollution abatement system demonstrated the desired scrubbing efficiency for acid gases generated during incineration of chlorinated surrogate chemicals. The particulate removal efficiency during the trial burns was also considerably higher than required by regulations. After comprehensive review of the performance of the deactivation furnace system during the surrogate trial burns, UDSHW approved introduction of GB nerve agent into the system to prepare it for agent trial burns.

Air Pollutants↗

Disposable electrochemical sensor for determination of nitroaromatic compounds by a single-run approach.

Environmental and security applications have generated major demands for effective field-deployable tools for detecting nitroaromatic compounds, such as chloramphenicol (an antibiotic), parathion (an organophosphate nerve agent), and TNT (2,4,6-trinitrotoluene, an explosive) in a fast, simple, sensitive, reliable, and cost-effective manner. We report here a single-run approach for such a purpose. The reduction potential of different nitroaromatic compounds was found to systematically shift with the substituent group at an electrochemically preanodized screen-printed carbon electrode. The preanodization treatment makes the peak sharp and hence provides a precise way to identify the substituent effect on nitroaromatic compounds. By using potential shifts as analytical characteristics of nitroaromatic compounds, a suitable internal standard can be chosen based on the criteria of well-separated peak potential and rarely found in the real sample of interest. Simply by measuring the ratio of peak currents between analytes of interest and internal standard, the analysis can be done in a single-run measurement. Both the matrix effect and the variation of electrode during the preparation process can be canceled out in this approach and thus allows for a high-precision analysis. Just by placing a 20-microL drop on a single-use amperometric sensor strip incorporating a three-electrode configuration is enough for rapid and sensitive detection of nitroaromatic compounds by square-wave voltammetry. For example, the linear detection range can be up to 100 microM with a detection limit of 0.42 microM (S/N = 3) in the detection of chloramphenicol. This approach was successfully demonstrated in real sample analysis to verify the applicability of the method. The promising performances open new possibilities for rapid determination of nitroaromatic compounds in environmental and biological samples.

Calibration↗

New radiation techniques in gynecological cancer.

Radiation therapy has been a major therapeutic modality for eradicating malignant tumors over the past century. In fact, it was not long after the discovery of radium that the first woman with cervical cancer underwent intracavitary brachytherapy. Progress in the way that this cytotoxic agent is manipulated and delivered has seen an explosive growth over the past two decades with technological developments in physics, computing capabilities, and imaging. Although radiation oncologists are educated in and familiar with the wealth of new revolutionary techniques, it is not easy for other key members of the team to keep up with the rapid progress and its significance. However, to fully exploit these enormous gains and to communicate effectively, medical and gynecological oncologists are expected to be aware of state-of-the-art radiation oncology. Here, we elucidate and illustrate contemporary techniques in radiation oncology, with particular attention paid to the external beam radiotherapy used for adjuvant and primary definitive management of malignancies of the female pelvis.

Brachytherapy↗

Recent advances in the study of the taxonomy, pathogenicity, and infectious syndromes associated with the genus Aeromonas.

Over the past decade, the emergence of Aeromonas species as bona fide human pathogens and their probable role as etiologic agents of bacterial gastroenteritis have resulted in an explosion of scientific interest in the genus. Major accomplishments occurring in this field during that interval include a more refined taxonomy, identification of new cell-associated factors (surface layers, pili), and the molecular analysis of selected extracellular gene products that may play a critical role in pathogenesis (hemolysins, enterotoxins). This review provides an updated overview of recent systematic, clinical, and pathophysiologic advances and defines key areas of medical and scientific interest in which major questions remain unanswered.

Aeromonas↗

Medication use in the breastfeeding mother.

Historically, the risks associated with drugs in breast milk were not a major clinical concern. The small percentage of infants who were breastfed and the low use of drugs in postpartum women stimulated little interest in studying medication use in the breastfeeding mother. However, explosive growth in the number of new pharmacologic agents, concerns over environmental contaminants, and a significant increase in breastfeeding, dramatically altered the interest in this clinical issue. Providers of health care to women and children often are asked to advise breastfeeding women on the choice and risks of a particular medication. However, medical professionals too often simply discourage breastfeeding when this situation arises. This short review examines factors that determine whether a drug that enters breast milk poses a risk to the breastfeeding infant. A series of questions and practical decisions are presented that should enable nurses and other health care providers to more effectively address the issue of medication use in a breastfeeding woman.

Adult↗

Cancer chemotherapy in historical perspective.

Effective systemic cancer therapy has evolved during the past 50 years. Prior to that time a variety of treatments were attempted, many of which seemed to have had their origins in sorcery rather than science. The 1950s and 1960s produced an explosion of knowledge and many of the chemotherapeutic agents in use today were synthesized during that time frame. Currently we are exploring a variety of new therapeutic approaches to cancer, and the future promises to be increasingly productive.

Antineoplastic Agents↗

Green primary explosives: 5-nitrotetrazolato-N2-ferrate hierarchies.

The sensitive explosives used in initiating devices like primers and detonators are called primary explosives. Successful detonations of secondary explosives are accomplished by suitable sources of initiation energy that is transmitted directly from the primaries or through secondary explosive boosters. Reliable initiating mechanisms are available in numerous forms of primers and detonators depending upon the nature of the secondary explosives. The technology of initiation devices used for military and civilian purposes continues to expand owing to variations in initiating method, chemical composition, quantity, sensitivity, explosive performance, and other necessary built-in mechanisms. Although the most widely used primaries contain toxic lead azide and lead styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are also used. Novel environmentally friendly primary explosives are expanded here to include cat[Fe(II)(NT)(3)(H(2)O)(3)], cat(2)[Fe(II)(NT)(4)(H(2)O)(2)], cat(3)[Fe(II)(NT)(5)(H(2)O)], and cat(4)[Fe(II)(NT)(6)] with cat = cation and NT(-) = 5-nitrotetrazolato-N(2). With available alkaline, alkaline earth, and organic cations as partners, four series of 5-nitrotetrazolato-N(2)-ferrate hierarchies have been prepared that provide a plethora of green primaries with diverse initiating sensitivity and explosive performance. They hold great promise for replacing not only toxic lead primaries but also thermally unstable primaries and poisonous agents. Strategies are also described for the systematic preparation of coordination complex green primaries based on appropriate selection of ligands, metals, and synthetic procedures. These strategies allow for maximum versatility in initiating sensitivity and explosive performance while retaining properties required for green primaries.

Cations↗

Biodegradation of explosives by transgenic plants expressing pentaerythritol tetranitrate reductase.

Plants offer many advantages over bacteria as agents for bioremediation; however, they typically lack the degradative capabilities of specially selected bacterial strains. Transgenic plants expressing microbial degradative enzymes could combine the advantages of both systems. To investigate this possibility in the context of bioremediation of explosive residues, we generated transgenic tobacco plants expressing pentaerythritol tetranitrate reductase, an enzyme derived from an explosive-degrading bacterium that enables degradation of nitrate ester and nitroaromatic explosives. Seeds from transgenic plants were able to germinate and grow in the presence of 1 mM glycerol trinitrate (GTN) or 0.05 mM trinitrotoluene, at concentrations that inhibited germination and growth of wild-type seeds. Transgenic seedlings grown in liquid medium with 1 mM GTN showed more rapid and complete denitration of GTN than wild-type seedlings. This example suggests that transgenic plants expressing microbial degradative genes may provide a generally applicable strategy for bioremediation of organic pollutants in soil.

Biodegradation, Environmental↗