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Portrait of the national veterinary service as a surveillance continuum.

National veterinary services emerged in response to the animal disease challenges of centuries past. Their often singular preoccupation with exogenous disease preclusion yielded, by the early 1900s, to parallel commitments to control a number of serious indigenous, zoonotic infections. Advances in clinical pathology and epidemiology opened the door in many countries to disease, if not agent, eradication initiatives by the latter part of that century. The attending interval witnessed the explosive growth of international trade and the emerging or re-emerging conditions that threaten to accompany it. Animal disease agents, their hosts and the environments within which they interact vary considerably from nation to nation. Depicted as a medieval metaphor, the exogenous cluster around the walls of the castle, awaiting entry upon the next uninspected, unsuspecting fomite or beast. Some of these threats reside comfortably within the structure's bedding and detritus, sapping the vitality of its residents until detected and exterminated. Others emerge from the least expected crevices, growing insidiously or explosively in tandem with changes wrought by humans or nature. In anticipation of, or in response to, these myriad challenges, national veterinary services mount surveillance campaigns. From the national survey that denies the presence of exogenous disease to the post-eradication assessment that confirms its demise, surveillance forms the sensory acumen of the service. From the passive assessments that detect the emerging to the active regimens that plot progress against the indigenous, they form a continuum that defines the very nature of the national veterinary service.

Animal Diseases↗

Role of the nitric oxide-cGMP pathway in the cardiovascular effects of anesthetic agents: a review.

Over the past 10 years, there has been an explosion of new information on the physiological and pathophysiological roles of nitric oxide (NO) within the cardiovascular system. With the increasing knowledge on the importance of NO in the regulation of cardiovascular function, possible involvement of the NO-cyclic guanosine-monmphosphate (cGMP) pathway in myocardial effects of anesthetics has attracted wide attention. This paper reviews the literature on the role of the nitric oxide-cGMP pathway in cardiovascular effects of volatile and intravenous anesthetics.

Anesthetics↗

Safety and security issues relating to low capacity storage of AN-based fertilizers.

Motivated by both the Toulouse explosion, and a series of recent unexpected handling and storage accidents in well-developed countries, the safety issues associated with the storage of fertilizer grades of ammonium nitrate (AN) are considered with a focus on low storage capacity premises. Such facilities are numerous and, in large agricultural countries, include thousands of end-users and hundreds of small distributors. The strong oxidative (sometimes explosive) properties of products containing significant amounts of AN have led to a long history of major accidents including mass explosions in large storage units and pre 1950s, to mass explosions in ships. A major breakthrough in safety was achieved in the 1950s, with the promotion - amongst other improvements - of better anti-caking agents. Although modern AN fertilizers complying with current standards are not considered as explosive material per se, the latent risk of accidental detonation under specific conditions remains a real issue, and from a scientific point of view, cannot be completely ruled out-as dramatically demonstrated by the Toulouse disaster in France. The new insight provided here is derived from: (1) a literature review on hazardous properties of AN and AN-based fertilizers; (2) a review of accidents focusing more particularly on the reporting of recent new cases involving relatively small quantities of previously 'thought safe' products; (3) an examination of both the relevant regulatory framework and the level of hazard control achieved; (4) appropriate discussions of the economical, technical and organizational factors that could lead to some underestimation of the risk compared to large scale storage facilities. In terms of research requirements, the complex potential scenario 'mass explosion following a fire' requires further attention, as does the role and properties of molten ammonium nitrate, which could be the precursor for such an event to occur. Beyond research needs, reinforced legislative control by the authorities and further promotion of safe storage practices must be encouraged by the industry for end-users particularly. Such users have inherently the highest potential for undesirable situations, due both to the nature of their activities and also a possible lack of awareness of the real danger.

Europe↗

Effect of pindolol administration on serum levels of thioridazine, haloperidol, phenytoin, and phenobarbital.

Twenty-six male patients with intermittent explosive disorder secondary to organic brain disease were studied. Each had been treated with long-term administration of thioridazine, haloperidol, phenytoin, and/or phenobarbital, either singly or in combination. The effect of adding increasing doses of pindolol--a beta-adrenergic blocking agent previously demonstrated to be effective in the treatment of intermittent explosive disorder--on serum levels of each long-term medication was determined. Moderate, dose-related increases in serum levels of thioridazine and two of its metabolites were found when pindolol was added. Conversely, higher-than-expected serum pindolol levels occurred in patients receiving thioridazine. No serum level increases were found for haloperidol, phenytoin, or phenobarbital when pindolol was added to each of these drugs individually, but serum phenytoin levels did rise in two patients receiving all three drugs simultaneously when pindolol was added. Three treatment failures with pindolol occurred in association with low serum pindolol levels.

Adult↗

Idiopathic inflammatory myopathy: management and prognosis.

We are entering an exciting era in our understanding and management of the connective tissue diseases and, in particular, inflammatory myopathy. There is an established array of immunosuppressive regimens available to clinicians; rehabilitative and physical therapeutic interventions are evolving to provide many nonpharmacologic options to complement current therapy. Our ability to quantify [table: see text] the disease burden, using newly developed tools to distinguish myositis disease activity from disease damage, will allow us to measure with greater sensitivity the effects of treatment interventions. These measures, together with the development of international consensus regarding the standardization of many clinical trial design parameters, will enhance our capacity to conduct well-designed, prospective, multicenter studies of established and newly developed therapies. The explosion of immunopathogenetic information, in conjunction with novel biologic agents (Table 4), will afford investigators a treatment menu with multiple therapeutic options. The continuing challenge for the practitioner is the development of a logical, well-studied, multifaceted, and multidisciplinary holistic approach that optimizes the risk: benefit ratio for each individual patient and uses a rational combination of immunomodulatory agents in conjunction with ancillary measures.

Biological Products↗

The immune system and gynaecological cancer.

There have been major advances in our understanding of the cellular and humoral immune mechanisms involved in antitumour activities. The characterization of soluble mediators of the immune response and their synthesis as recombinant proteins has led to an explosion of research activity concerning their role as antitumour agents and also as contributors to the pathogenesis of cancer. It is evident that cytokine production is not restricted to cells of the immune system, and that cytokines are involved in a variety of cell regulatory processes ranging from embryonic development to tissue differentiation. Their production by immune cells may enable interactions between the immune system and other homeostatic systems of the body. The therapeutic role of some cytokines such as the interferons and IL-2 in the routine management of gynaecological cancers needs to be investigated further because of their promise as antitumour agents. The study of cytokine production and cytokine receptor expression by cancers is potentially of great therapeutic value. Identification of cytokines that contribute to tumour progression may paradoxically lead to the treatment of cancers by agents that antagonize their biological effects and to rationalization of future trials of cytokine therapy.

Cytokines↗

Current status and future potential of transdermal drug delivery.

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of the most important of these innovations, offering a number of advantages over the oral route. In this article, we discuss the already significant impact this field has made on the administration of various pharmaceuticals; explore limitations of the current technology; and discuss methods under exploration for overcoming these limitations and the challenges ahead.

Acoustic Stimulation↗

Issues, goals, and guidelines in selecting first-line drug therapy for hypertension.

Modern antihypertensive therapy is enriched by an explosion in drug development that makes available increasingly specific agents whose effects have advanced our understanding of pressor mechanisms. This and other research into hypertensive mechanisms has defined the clinical, pharmacological, and endocrinologic heterogeneity of human hypertension. The sum of these developments is a greatly enhanced ability to identify curable and definable causes of hypertension and to pathophysiologically stratify the remaining cases of essential hypertension. Modern treatment can be much more specific than before. When long-term drug therapy is indicated, the regimen is more likely to achieve a primary goal for each patient, that is, the fewest possible drugs in the smallest amount and in lowest frequency. Two clinically quantifiable mechanisms for long-term arteriolar vasoconstriction can be identified within the spectrum of human hypertension. The first, renin-mediated vasoconstriction, is directly related to the plasma renin level. The second, sodium-volume-related vasoconstriction, is marked by a reciprocally subnormal renin level and involves abnormal sodium retention and calcium transport. A baseline renin-sodium profile can identify the pressure of one of these two forms of vasoconstriction and therefore is the key for the diagnosis of the two curable disorders that fully express one of the two pressor mechanisms--renovascular hypertension and primary aldosteronism. Renovascular hypertension, more common than once thought, is often cured by angioplasty. It is important to diagnose these curable forms before beginning long-term drug therapy. The renin-sodium profile, used in conjunction with serum potassium and creatinine measurements, is valuable not only in screening patients for curable forms, but also for stratifying the remainder according to the pathophysiological vasoconstrictor mechanism that underlies the hypertension. Converting enzyme inhibitors or beta-blockers are, by themselves, often effective in correcting the hypertension of high- or medium-renin patients, whereas calcium antagonists, diuretic agents, or alpha-blockers alone are most effective against the low-renin form of vasoconstriction. In the large midzone of renin values, if monotherapy fails, a rational basis for combined antirenin-antisodium volume therapies can be developed.

Antihypertensive Agents↗

Pharmacological treatment of traumatic brain injury: a review of agents in development.

Successful treatment strategies for patients with traumatic brain injury (TBI) remain elusive despite standardised clinical treatment guidelines, improved understanding of mechanisms of cellular response to trauma, and a decade of clinical trials aimed at identifying therapeutic agents targeted at mediators of secondary injury. The information explosion relative to mechanisms of secondary injury has identified several potential targets for intervention. Depending on the type of injury to the brain and the intensity and the success of resuscitation, necrosis, apoptosis, inflammatory and excitotoxic cellular damage can be seen. These same processes may continue postinjury, depending on the adequacy of clinical care. Each of these mechanisms of cellular damage can initiate a cascade of events mediated by endogenous signals that lead to secondary neurological injury. Several factors contributed to the failure of earlier clinical trials. Now that these have been recognised, a positive impact on future drug development in TBI has been realised. Both the US and Europe have organised brain injury consortiums where experts in the treatment of TBI provide insight into study design, implementation, conduct and oversight in conjunction with the pharmaceutical industry. Consequently, future clinical trials of new investigational treatments have greater potential for identifying therapies of merit in specific populations of patients with TBI. Pharmacological strategies under investigation are targeting sites involved in the secondary cascade that contribute to overall poor outcome following the primary injury. These treatments include ion channel antagonists including calcium channel antagonists, growth factors, antioxidants, stem cells, apoptosis inhibitors, and inhibitors of other signal modulators. In conclusion, the complexity of TBI pathology and the mechanisms contributing to secondary injury present unique therapeutic challenges. Appropriate research targets for intervention continue to be investigated, however, the likelihood of improving outcomes with a single approach is extremely small. There is a need for collaborative efforts to investigate the optimal time for drug administration and the logical sequence or combination of treatments that will ultimately lead to improved neurological outcomes in this population.

Animals↗

Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha.

The growing knowledge of the tight connection between apoptosis and cancer has lead to an explosion of research revolving around apoptotic induction with chemotherapeutic agents and small molecule inhibitors. The chemotherapeutic agent paclitaxel (Taxol) activates mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase and, combined with MEK inhibition, synergistically enhances apoptosis. Here we implement a proteomic approach using two-dimensional gels coupled with mass spectrometry to identify proteins altered with this coordinated combination treatment. We found that the combined treatment of paclitaxel and MEK inhibitor uniquely altered the proteins RS/DJ-1 (RNA-binding regulatory subunit/DJ-1 PARK7) and RhoGDIalpha (Rho GDP-dissociation inhibitor alpha). Functional proteomic analysis by exogenous expression or short interfering RNA targeting confirmed a role in survival and apoptosis for these proteins. Analysis of primary lung tumors with matched adjacent normal tissue confirmed RS/DJ-1 overexpression in non-small cell lung carcinoma. This study shows the power of proteomic profiling coupled with functional analysis for the discovery of novel molecular targets and potential cancer cell-specific biomarkers.

Antineoplastic Combined Chemotherapy Protocols↗

[Silicosis and bronchial cancer (author's transl)].

1. At world level, silicosis does not predispose to bronchial cancer. But from region to region, the relationship silicosis-cancer varies and depends on factors other than silica. 2. It has not been proved that silica is cancerigen in laboratory animal. 3. Subjects exposed to silica can also be exposed in other circumstances to known carcerigen agents (ionizing radiations, iron oxides, arsenic, exhaust gases of explosion engins). In Switzerland, it is possible that miners in galeries could breath low concentrations of radon and benzopyrene. But it is very difficult to know to what extent these potential risks are involved. 4. Bronchial carcinoma in silicotic patients does not own any characteristics. It is quite similar to that found in the remainder of the population. On the other hand, its diagnosis and treatment are more difficult because of the presence of silicosis. 5. The fortuitous association of silicosis and bronchial cancer is due to overlapping of the profiles of both diseases. The increasing life span of the silicotic patient and the high frequency of bronchial cancer explain why this association is not more exceptional.

Animals↗

Classifying threats with a 14-MeV neutron interrogation system.

SeaPODDS (Sea Portable Drug Detection System) is a non-intrusive tool for detecting concealed threats in hidden compartments of maritime vessels. This system consists of an electronic neutron generator, a gamma-ray detector, a data acquisition computer, and a laptop computer user-interface. Although initially developed to detect narcotics, recent algorithm developments have shown that the system is capable of correctly classifying a threat into one of four distinct categories: narcotic, explosive, chemical weapon, or radiological dispersion device (RDD). Detection of narcotics, explosives, and chemical weapons is based on gamma-ray signatures unique to the chemical elements. Elements are identified by their characteristic prompt gamma-rays induced by fast and thermal neutrons. Detection of RDD is accomplished by detecting gamma-rays emitted by common radioisotopes and nuclear reactor fission products. The algorithm phenomenology for classifying threats into the proper categories is presented here.

Algorithms↗

A field test for the detection of peroxide-based explosives.

A rapid and simple field test for the detection of triacetone-triperoxide (TATP) and hexamethylenetriperoxidediamine (HMTD), two explosives which find significant illegal use, has been developed. Unknown samples are first treated with a catalase solution to remove hydrogen peroxide traces, in order to provide selectivity towards peroxide-based bleaching agents which are contained in commercial laundry detergents. Subsequently, the peroxide-based explosives are decomposed via UV irradiation, thus yielding hydrogen peroxide, which is determined by the horseradish peroxidase (POD) catalysed formation of the green radical cation of 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonate (ABTS). The limits of detection for this method are 8 x 10(-6) mol dm(-3) for TATP and 8 x 10(-7) mol dm(-3) for HMTD, respectively. As an option, p-hydroxyphenylacetic acid (pHPAA) may be used as peroxidase substrate, resulting in lower limits of detection (8 x 10(-7) mol dm(-3) for TATP and HMTD). The complete method uses a mobile setup to be applied under field conditions.

Explosions↗

The pharmacologic treatment of conduct disorders and rage outbursts.

Although this article focuses on psychopharmacology, pharmacotherapy is only part of a comprehensive treatment program. Treatment should be individualized to the patient's condition and level of intellectual functioning (e.g., conduct disorder, mental retardation). Clinicians should be acquainted with the Food and Drug Administration's regulations and the Physician's Desk Reference's guidelines. Psychoactive agents should be prescribed judiciously under careful clinical and laboratory monitoring, especially when given on a long-term basis. Knowledge of potential short- and long-term side effects is imperative to minimize impairment (cognitive, sedation) and to maximize achievement of adaptive behaviors. Aggressiveness is a low-frequency behavior and therefore difficult to assess. Aggressiveness with an explosive affective component and rage seems to be more responsive to pharmacotherapy than aggressiveness alone. Children who present with covert conduct disorder symptoms, such as stealing and lying, might not be as responsive to psychoactive agents as the conduct disorder with explosive characteristics. The neuroleptics are considered the standard drugs for the treatment of aggression but sedation and concern over tardive dyskinesia have led investigators to explore and study other classes of drugs. Lithium carbonate has been studied in short-term clinical trials and has been shown to be an effective alternative to the neuroleptics. Carbamazepine and propranolol seem to be promising agents but require further critical assessment in children and adolescents. Stimulants should be considered the first choice of treatment in coexisting conduct disorder and ADHD or in milder forms of aggression. In conclusion, there is a need for systematic investigation of the effectiveness and safety of psychoactive agents in children and adolescents with aggressiveness, explosiveness, and rage outbursts. There is some supportive evidence that some patients with these target symptoms are good responders to certain drugs. Future research should compare pharmacotherapy to psychosocial treatment and the combination of both.

Animals↗

Norwalk virus gastroenteritis aboard a cruise ship: an outbreak on five consecutive cruises.

An explosive outbreak of gastroenteritis caused by a parvovirus-like (PVL) agent (Norwalk agent) affected 521 (64%) cruise ship passengers in 1977. The illness was characterized as mild-to-moderate and lasted one to two days. Principal symptoms experienced by ill passengers were nausea, vomiting, and diarrhea; fever was reported for approximately 25% of the patients. The outbreak was compatible with a common-source exposure, but no such exposure was identified. On the next four cruises, passengers experienced a similar gastrointestinal illness, but the outbreaks were less explosive, affected fewer persons, and symptoms appeared milder, on each subsequent cruise. No common source was identified, and person-to-person transmission may have occurred. The etiology of these outbreaks would have remained unknown were it not for the recent development of a specific radioimmunoassay (RIA) for the serologic identification of Norwalk virus and the measurement of antibody titers to the virus. A fourfold or greater rise in serum antibody titers to Norwalk antigen in serum from seven of eight ill passengers and the identification of Norwalk antigen in stool specimens from two ill passengers on the first cruise demonstrated that Norwalk virus caused this outbreak. The symptoms experienced by passengers on the four subsequent cruises suggest that a Norwalk agent probably also caused these outbreaks. In addition, a stool specimen from an ill passenger on cruise 3 contained Norwalk antigen.

Disease Outbreaks↗

Recovery of Rhodococcus biosurfactants using methyl tertiary-butyl ether extraction.

In the present study, we proposed methyl tertiary-butyl ether (MTBE) as a solvent for extraction of biosurfactants from Rhodococcus bacterial cultures. After comparison with other well known solvent systems used for biosurfactant extraction, it was found that MTBE was able to extract crude surfactant material with high product recovery (10 g/l), efficiency (critical micelle concentration (CMC), 130-170 mg/l) and good functional surfactant characteristics (surface and interfacial tensions, 29 and 0.9 mN/m, respectively). The isolated surfactant complex contained 10% polar lipids, mostly glycolipids possessing maximal surface activity. Ultrasonic treatment of the extraction mixture increased the proportion of polar lipids in crude extract, resulting in increasing surfactant efficiency. Due to certain characteristics of MTBE, such as relatively low toxicity, biodegradability, ease of downstream recovery, low flammability and explosion safety, the use of this solvent as an extraction agent in industrial scale biosurfactant production is feasible.

Glycolipids↗

"One people, one blood": public health, political violence, and HIV in an Ethiopian-Israeli setting.

Between 1984 and 1996, public health authorities in Israel maintained a secret policy of discarding blood donations made by Ethiopian-Israeli citizens and immigrants. Officials later attempted to justify this policy on the grounds that immigrants from Ethiopia were subject to high rates of infectious disease (especially HIV). In 1996, this led to an explosive and violent confrontation between Ethiopian-Israeli protestors and agents of the state, including police and public health authorities. This essay explores the cultural and political context of that confrontation, including the discourse of political violence which it occasioned. The conflict between Ethiopian-Israelis and the state was located within a wider set of political contexts, including the Israeli-Palestinian conflict, which was linked to it through a shared trope of "spilled blood" common to both. Cultural analyses which ignore this dynamic political context are in danger of seriously misrepresenting the meaning of the "Blood Affair" to its participants. At the same time, this essay also engages a critical analysis of the public health policies which led to the crisis. Public health and nationalist discourse reinforced one another at the expense of Ethiopian immigrants in general, and so-called "Feres Mura" Ethiopians in particular.

Adult↗