[Security: a shared concern]. / Sécurité: l'affaire de tous.

During a stay abroad, travelers are exposed to dangers and threats. This is nothing new, and most of the risks (e.g. traffic accidents) remain the same for many years. Large territories have nonetheless become inaccessible due to political instability, national or international conflicts, terrorist threat, or kidnapping risk. It is thus necessary to consider the problematic of security, whether at the time of preparation or at the destination. Beyond the usual pre-departure health counseling, the primary care physician may have a role to accompany the traveller in the management of his or her security. The aim should be to make travelers conscious of hazards and direct him or her towards available resources for planning, decision making support, and implementation of risk mitigation measures.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2012.

197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats.

En 2012, on a enregistré 197 annonces de réactions après application de médicaments vétérinaires autorisés par Swissmedic (2011: 167). La répartition de ces annonces, tant en ce qui concerne les espèces que les classes de médicaments, est inchangée par rapport aux années précédentes: on a annoncé le plus souvent des réactions à des produits antiparasitaires (37.6 %), antiinfectieux (15.7 %) ou antiinflammatoires (11.7 %) chez les petits animaux (94 annonces concernaient des chiens, 53 des chats) suivis par les bovins (29 annonces). En outre 45 cas annoncés par le Centre suisse d'information toxicologique de Zürich dans le cadre de ses activités de conseil ont été étudiés. Une réaction paradoxale d'agressivité sous l'effet possible de l'acépromazine et un protocole modifié pour le traitement des intoxications à la perméthrine chez le chat sont présentés. Pour ce qui est de la vaccinovigilance effectuée par l'IVI, on a enregistré 95 annonces de réactions après l'application de divers vaccins, principalement chez des chiens et des chats.

[Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2011]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2011.

167 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2011 (2010: 160). Species and drug classes remain comparable with previous years: most of the reactions occurred following the use of antiparasitic products (39 %), antiinfectives (20 %) or non-steroidal antiinflammatory drugs (11 %) in companion animals (85 dogs and 27 cats) followed by cattle/calves (37). We received 15 cases of adverse reactions following reconverted use, 8 of them in treated cats. Additionally the Swiss Toxicological Information Centre in Zürich processed 84 enquiries and transmitted them to Swissmedic. One case of a successful new therapy to treat ivermectin poisoning in a pony is presented. Finally, the vaccinovigilance program received 60 declarations following the application of various vaccines, mainly to dogs or cats.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2010]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2010.

In 2010, we observed again an increase in the number of declarations reported to the vigilance system for veterinary medicinal products up to a total of 160. The species and drug classes reported remained the same as in previous years: the majority of adverse drug reactions (ADRs) concerned either dogs or cats and the most frequently involved drugs were either antiparasitic products or antiinfectives. Adverse reactions following reconversions and 8 cases of suspected allergic reactions following the use of amoxicillin-clavulanic acid combinations in dogs were reported. Additional enquiries were processed by the Swiss Toxicological Information Centre and transmitted to Swiss medic. 11 of these reported accidental ingestions of flavoured tablets in overdose by dogs and some cats. The vaccino vigilance program received 179 declarations following immunization against blue tongue disease as well as 82 declarations following the application of other vaccines. The vigilance system increases the chance to identify rare reactions or interactions and thereby contributes to the security of veterinary medicinal products.

Health and security risks of humanitarian aid workers during field missions: Experience of the International Red Cross.

BACKGROUND: Humanitarian disaster environments put relief workers at risk, both physically and mentally. Research looking at the growing humanitarian workforce's health and working conditions is lacking. METHODS: A questionnaire was presented to ICRC (International Committee of the Red Cross) workers during debriefing between 2016 and 2018. Participants were queried about their experience abroad including security incidents (the primary objective), health, and malaria prevention. Descriptive statistics and multivariate logistic regressions were used for data analysis. RESULTS: Security incidents were reported by 12% (95/796) of expatriates, mainly armed threats and attacks (83%, 79/95). Accidents or injuries occurred for 7.5% (60/796), of which 42% (25/60) were due to sporting activities and 22% (13/60) to road accidents. Many engaged in risky behaviours (15%, 119/795), such as driving too fast or inebriated (37%, 44/119) and/or engaging in unsafe sex, (unfamiliar partner, no condom) (71%; 84/119). Compliance to malaria prophylaxis was low 43% (113/263). Over 40% (324/795) found the mission more stressful than expected. Almost a third (28%, 219/796) reported worsened health on their return. CONCLUSIONS: Humanitarian aid workers display a worsening of their health when on mission due to violence, accidents and risky behaviours. To preserve their staff's wellbeing, humanitarian organizations should pay attention to medical history, pre-travel training specific to assignment, and continuous medical and psychological support.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2009.

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.

[Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2008]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2008.

With 106 reports of suspected adverse reactions to veterinary medicinal products (VMPs) there was a slight decrease in the year 2008 compared to 2007. However, the distribution according to species and drug classes remained grossly the same: dogs were involved in 45 % of the cases followed in frequency by cats (26 %) and cows or calves (21 %). Most often the reports described reactions following the use of either an antiparasitic drug (46 %) or an antibiotic (22 %). One particular case of off-label use and serious skin reactions are presented. For the vaccinovigilance a total of 310 reports were received, with 250 of them related to adverse events following vaccination against blue tongue disease. In most cases, aborts and elevated cell count in the milk were reported. A detailed evaluation of these cases is presented. Finally, 305 enquiries were received by the Swiss Toxicological Information Center in Zürich (concerning mostly dogs or cats). Most of the cases concerned either preparations for the nervous system or anti-inflammatory drugs (human medicinal products) or antiparasitics (VMPs).

[Vigilance for veterinary medicinal products: declarations of suspected adverse reactions in the year 2007]. / Vigilance der Tierarzneimittel: Gemeldete unerwünschte Wirkungen im Jahr 2007.

163 reports of suspected adverse reactions were received in the year 2007: 111 for veterinary medicinal (VMPs) and 52 for immunologic products. Half of the reported reactions for VMPs concerned either an antiparasitic drug (26%) or an antibiotic (24%). Reconversions (use in another target species or for another indication as registered) made the third most frequently mentioned group with 11 reports. For immunologicals, half of the declarations were related to an adverse reaction in dogs, the most frequently reported reaction in companion animals being allergies. Moreover, 272 enquiries were received by the Swiss Toxicological Information Center in Zürich. Most of these were related to dogs (73%) and the number of enquiries regarding VMPs correlated positively with the most frequently used therapeutic classes like antiparasitics (47%) and anti-inflammatory drugs (23%). The complexity of proscessing reports regarding the detection of residues in milk after prescribed withdrawal times is discussed in detail. In conclusion, the year 2007 is seen as a consolidation of the established system with a tendency towards increase in the number of complex cases.

Sudden death in sport and riding horses during and immediately after exercise: A case series.

BACKGROUND: Sudden death affects the health of horses, the safety of riders and the public perception of animal welfare during equestrian events. OBJECTIVES: To describe the signalment, clinical history, sudden death episode, rider injuries and causes of sudden death during exercise or closely thereafter in sport and pleasure riding horses. STUDY DESIGN: Retrospective case series based on an online questionnaire. METHODS: An online questionnaire was distributed to the veterinary and equestrian community. Connections of animals reported in the press to have died suddenly were sent the survey. Responses were analysed to obtain information. RESULTS: Fifty-seven cases met inclusion criteria with enough information to be analysed. The most common discipline was eventing (n = 23, 40.4%), and the most common breed involved was Thoroughbred (n = 23, 40.4%). Forty-one (71.9%) horses collapsed during exercise, and 16 (28.1%) shortly thereafter. Twenty-four (42.1%) horses died during or near the time of competition and 33 (57.9%) during or near the time of training or a pleasure ride. In 16 (28.1%) horses, the cause of death was known or strongly suspected based on a post-mortem result, and a cardiovascular origin was reported in 13 of these 16 cases. Riders were injured in 13 (22.8%) cases, and injuries to their extremities were the most frequent. MAIN LIMITATIONS: There is potential for misdiagnosis and recall and selection bias, and in the absence of data on the total number of horses engaged in equestrian sports and riding, prevalence cannot be calculated. CONCLUSIONS: Sudden death occurred in many types of equestrian sports and in riding horses. Death outside competition was more common suggesting that registries based on reports from official veterinarians underestimate the magnitude of this problem. Rider injuries were not uncommon when ridden horses collapsed and died. A definitive diagnosis for the cause of death was not commonly achieved and cardiovascular origin was the most common where a diagnosis was proposed by survey respondents.

[Reported adverse reactions due to veterinary drugs in 2006]. / Gemeldete unerwünschte Wirkungen von Tierarzneimitteln im Jahr 2006.

We received 190 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2006: 118 declarations for veterinary drugs and 72 declarations following the application of immunolgical medicinal products. Most of the 118 declarations relate to the use of antiparasitic drugs (48%) and every second declaration to drug use in dogs. Other drug classes concerned were, in decreasing order, antiinfectives (20%) and drugs used off-label (12%; other target species or other indication). For the vaccines, most of the reactions occurred in dogs (62%) followed by horses (11%) and cattle (10%). The most frequently reported reactions concerned the use of a vaccine against piroplasmosis. Another 349 requests for information were processed by the Swiss Toxicological Information center. We also present a case of a serious adverse reaction in form of a Stevens-Johnson syndrome in a cat as well as a case of ketamine abuse. We note the growing interest of practicing veterinarians with pleasure and are currently working on further adaptations to the system.

[Reported adverse reactions of veterinary drugs and vaccines in 2005]. / Gemeldete unerwünschte Wirkungen von Tierarzneimitteln im Jahr 2005.

We received 105 reports of suspected adverse events (SARs) following the use of veterinary drugs for the year 2005. This corresponds to a 35% increase compared to 2004. Practicing veterinarians sent most of these declarations. 73% of these concerned drugs used on companion animals. Antiparasitic drugs approved for topical use were the most frequently represented group with 48%, followed by drugs used to treat gastrointestinal disorders (11%) and drugs used off-label (14%; other target species or other indication). For the first time 2 declarations concerning the application of permethrin containing spot-on preparations used by mistake on cats were received. An overview of 20 declarations about adverse reactions following application of different vaccines is also presented with emphasis on the problem of fibrosarcoma in cats. We are pleased by the growing interest shown by practicing veterinarians for the vigilance system and hope to further develop this collaboration in the future.

[Swiss veterinary drug compendium as a tool for reconversions]. / Das Tierarzneimittelkompendium als Umwidmungshilfe.

The new Swiss ordinance on veterinary drugs poses a new challenge to the veterinarians, specially those working with farm animals. A complete overview about the registered veterinary drugs and immunobiologicals is absolutely necessary to cope with these new tasks: the internet version of the Swiss Veterinary Drug Compendium is a versatile tool to satisfy this needs (http://www.tierarzneimittel.ch). Due to the frequent updates and powerful search possibilities, this database is a reliable and comprehensive information system regarding Swiss veterinary drugs. We will demonstrate how this system can be used as a valuable help in the case of reconversions of drugs (e.g. use of small animal drugs in farm animals).

Chemical quantification of unscheduled DNA synthesis in cultured hepatocytes as an assay for the rapid screening of potential chemical carcinogens.

Technical modifications of the quantitative determination of unscheduled DNA synthesis in cultured hepatocytes are described which allow for the rapid identification of potentially carcinogenic chemicals on a large-scale screening basis. The test is based on the biochemical quantification of [methyl-3H]thymidine incorporation into DNA in the presence of hydroxyurea following isolation of nuclei from hepatocytes treated with the agent under study. This procedure ("nuclei procedure") eliminates most of the background radioactivity which otherwise obscures the stimulation of DNA repair synthesis by agents that induce a relatively weak response. By combining the nuclei procedure with a double-labeling technique, test results can be obtained within a few hr after exposure of hepatocytes to the test agents. A test series involving 41 agents confirmed the reliability of the nuclei procedure for the assay of DNA repair synthesis. In addition, chemicals which had yielded conflicting results previously in the autoradiographic hepatocyte DNA repair test, such as 4-acetylaminofluorene, or which had passed unrecognized in previous in vitro tests, such as the potent liver carcinogen methapyrilene hydrochloride, scored clearly positive in our test protocol.

[Suspected adverse drug reactions in 2004]. / Meldungen zu unerwünschten Wirkungen von Tierarzneimitteln im Jahr 2004.

We received 62 reports of suspected adverse events (SARs) for the year 2004. Their number and repartition according to affected animals and active substances were comparable with the previous year. The distributors or manufacturers submitted most of the declarations, but the proportion submitted by practicing veterinarians is slowly growing. 72% of the declarations dealt with adverse reactions in small animals (cats and dogs), followed by cattle and horses. Antiparasitics, anti-inflammatory drugs and immunologicals were the most frequently mentioned therapeutic classes, which are listed here according to the international ATCvet classification. A report from abroad about a fatality following injection of an antibiotic preparation for cattle prompted Swissmedic to review the security of this medication also sold on the Swiss market. It was decided to modify the package insert to warn about the danger of inadvertent self-injection in humans, to reduce the risk of similar accidents in Switzerland. We hope that the pharmacovigilance system will enjoy an increasing awareness by the practicing veterinarians.

Interactions of poly(ADP-ribose) with nuclear proteins.

The molecular mechanisms whereby poly(ADP-ribosyl)ation primes chromatin proteins for an active role in DNA excision repair are not understood. The prevalent view is that the covalent linkage of ADP-ribose polymers is essential for the modification of target protein function. By contrast, we have focused on the possibility that ADP-ribose polymers interact non-covalently with nuclear proteins and thereby modulate their function. The results show that ADP-ribose polymers engage in highly specific and strong non-covalent interactions with a small number of nuclear proteins, predominantly histones, and among these only with specific polypeptide domains. The binding affinities were largely determined by two factors, ie the polymer sizes and the presence of branches. This provides an explanation for the target specificity of the histone shuttle mechanism that was previously reported by our laboratory. Interestingly, the polymer molecules being most effective in protein targeting in vitro, are strictly regulated in mammalian cells during DNA repair in vivo.

The effect of dopamine on hepatic-splanchnic blood flow after open heart surgery.

Dopamine (3,4 dihydroxyphenylethylamine) increases cardiac output and in particular the renal blood flow at the expense of other regional vascular beds not yet defined. Since the results of dopamine-induced changes in splanchnic perfusion are inconsistent, the effect of 6 mcg/kg/min dopamine was studied in 9 patients early after open heart surgery. Estimated hepatic blood flow (EHBF) was calculated from the concentration-time slopes of Indocyanine Green (ICG, Cardiogreen) in arterial and hepatic venous blood following single intravenous injection. Blood volume was measured using 51Cr tagged red cells. Cardiac output was determined according to the Fick method. 6 mcg/kg/min dopamine caused a mean EHBF-increase of 82%, from 492 +/- 64 to 824 +/- 80 ml/min/m2 (P less than 0.001). Related to the corresponding increase in cardiac index (CI) from 2.6 +/- 0.2 to 3.8 +/- 0.3 1/min/m2 (P less than 0.001), the EHBF/CI-ratio changed from 18.5 to 21.7% (P less than 0.025). The arterial-hepatic venous oxygen difference was reduced from 7.40 +/- 0.53 to 4.91 +/- 0.60 Vol% (P less than 0.001). It was concluded that splanchnic perfusion does not contribute to the preferential increase of renal blood flow under dopamine under the above mentioned conditions. Dopamine had the most beneficial effect on EHBF in two cases where the latter was severely reduced.

Histone shuttle driven by the automodification cycle of poly(ADP-ribose)polymerase.

In mammalian cells, the incision step of DNA excision repair triggers a dramatic metabolic response in chromatin. The reaction starts with the binding of a zinc-finger protein, i.e. poly(ADP-ribose)polymerase to DNA nicks, activation of four resident catalytic activities leading to poly(ADP-ribose) synthesis, conversion of the polymerase into a protein modified with up to 28 variably sized ADP-ribose polymers, and rapid degradation of polymerase-bound polymers by poly(ADP-ribose)glycohydrolase. This automodification cycle catalyzes a transient and reversible dissociation of histones from DNA. Shuttling of histones on the DNA allows selected other proteins, such as DNA helicase A and topoisomerase I, to gain access to DNA. Histone shuttling in vitro mimics nucleosomal unfolding/refolding in vivo that accompanies the postincisional steps of DNA excision repair. Suppression of the automodification cycle in mammalian cells prevents nucleosomal unfolding and nucleotide excision repair.

Poly ADP-ribosylation in two L5178Y murine lymphoma sublines differentially sensitive to DNA-damaging agents.

PURPOSE: To characterize the response to X-irradiation of the poly ADP-ribosylation system in two closely related murine lymphoma sublines, L5178Y-R (LY-R) and L5178Y-S (LY-S), with differential sensitivity to various DNA damaging agents (UV-C and ionizing radiation, hydrogen peroxide). MATERIALS AND METHODS: LY cells were X-irradiated (2 Gy). NAD+ was determined in cell extracts by high-pressure liquid chromatography. ADP-ribose polymers were purified and analysed by densitometry after polyacrylamide gel electrophoresis. Nuclear matrix proteins were separated by SDS-polyacrylamide gel electrophoresis and processed for ADP-ribose polymer blots to estimate their ability to bind poly(ADP-ribose). RESULTS: In the radiosensitive LY-S cells, the constitutive levels of ADP-ribose polymers were twofold higher than in radioresistant LY-R cells, but unresponsive to a challenge with 2 Gy X-rays. The concentrations of NAD+ - the substrate for poly(ADP-ribose) synthesis - were identical in the two cell lines. X-rays (2 Gy) depleted NAD+ only in LY-S cells. These cells also produced shorter poly(ADP-ribose) molecules as compared with LY-R cells. Nuclear matrix preparations of LY-S cells exhibited lower poly(ADP-ribose)-binding capacity than those of LY-R cells. CONCLUSION: The results demonstrate disturbances in the poly ADP-ribosylation response of the radiosensitive LY-S cells and reduced poly(ADP-ribose)-binding affinity of the nuclear matrix of these cells.

Poly(ADP-ribose) catabolism in mammalian cells exposed to DNA-damaging agents.

DNA damage inflicted by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine, or by UV254nm, stimulated the catabolism of protein-bound poly(ADP-ribose) in the chromatin of cultured hepatocytes. The stimulation was highest at the largest doses of DNA-damaging treatment. As a consequence, the half-life of ADP-ribosyl polymers may drop to less than 41 s. This rapid turnover contrasts with the slow catabolism of a constitutive fraction of polymers exhibiting a half-life of 7.7 h. Our data suggest that post-incisional stimulation of poly(ADP-ribose) biosynthesis in DNA-excision repair is coupled with an adaptation of poly(ADP-ribose) catabolism in mammalian cells.