Diverging effects of diabetes mellitus in patients with peripheral artery disease and abdominal aortic aneurysm and the role of advanced glycation end-products: ARTERY study - protocol for a multicentre cross-sectional study.

INTRODUCTION: Diabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end-pRoducts in patients with peripheral arTery disEase and abdominal aoRtic aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD. METHODS AND ANALYSIS: This cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events. TRIAL REGISTRATION NUMBER: trialregister.nl NTR 5363.

Hazard perception of Dutch farmers and veterinarians related to dairy young stock rearing.

A group of 110 dairy farmers and 26 bovine veterinarians participated in a web-based questionnaire using the adaptive conjoint analysis technique to rank their perception regarding several hazards during 6 subsequent periods of the process of dairy young stock rearing. The method applied only involved selected respondents with a high consistency in their answering (correlation >30%). For the ranking, answers were first transformed into a utility score (US) for each hazard. The final ranking for each of the 6 periods was based on the US per hazard separately for farmers and veterinarians. Besides the ranking, the absolute values and the US itself were also compared between farmers and veterinarians to determine any statistically significant differences between the levels of the score despite the ranking. The overall conclusion is that, for almost every designated period, the ranking of the hazards differed between farmers and veterinarians. Only 1 period was observed (period IV, Pregnancy period until 4 weeks before calving) where veterinarians and farmers had the same top 3 ranking of the hazards, namely "Mastitis," "Abortion," and "Poor growth rate of the pregnant heifer." Major differences between farmers and veterinarians were seen during period II (feeding milk until weaning) for the hazard "Diarrhea in older calf," which was considered less important by farmers compared to veterinarians, and period number III (weaning until insemination) for "Over-condition," which, again, was seen as the most important hazard by veterinarians, but only ranked as number 5 by farmers. Besides the ranking, significant differences in absolute US values between veterinarians and farmers were seen in "Infection with Johne's disease" (14.5 vs. 7.8), "Diarrhea in newborn calf" (18.2 vs. 12.2), and "Insufficient feed intake" (16.2 vs. 8.4) in period I (colostrum until transition to milk replacer). Lameness represented the most important significant difference in absolute values in period III (weaning until insemination; 6.3 vs. 14.3), which was again significant in period V (4 wks before calving until calving; 7.4 vs. 12.1). The outcome of this study shows that hazard perception of veterinarians and farmers differs for most rearing periods (in ranking and absolute values). The outcome of this study can be used for 2 purposes: first, to improve communication between farmers and their consulting veterinarian about hazards and hazard perception in young stock rearing; and second, the US scores can be used to select top priority hazards which should at least be integrated into management advisory programs to improve dairy young stock rearing.

Shedding consistency of strongyle-type eggs in Dutch boarding horses.

Faeces of 484 horses were sampled twice with an interval of 6 weeks while anthelmintic therapy was halted. Faecal eggs counts revealed that 267 (55.2%) horses had consistently low numbers of eggs per gram faeces (EPG) (EPG < 100 or = 100), 155 (32.0%) horses had consistently high EPGs (EPG > 100). Horses with consistently high EPGs were more often mares with access to pasture, aged less than 6 or more than 23 years, that were dewormed at intervals longer than 6 months, and were treated for the last time more than 3 months before the start of the study. Horses with consistently low EPGs were more often male horses with no or limited access to pasture, that were dewormed at maximally 6-month intervals, and were aged between 6 and 23 years. The results are an indication that some horses have consistently low EPGs and perhaps could be used as non-treated animals in a selective anthelmintic treatment scheme aimed at the prevention of the development of anthelmintic resistance.

[Infections with endoparasites in dogs in Dutch animal shelters]. / Infecties met endoparasieten bij honden in Nederlandse dierenasielen.

Faecal samples from 224 dogs from 23 animal shelters in the Netherlands were examined for endoparasites. In total 20.5% of the faecal sample were positive for helminth and/or protozoa infections. Eggs of Toxocara canis were found in 8.5% of the faecal samples. Other endoparasites found were Toxascaris leonina (0.5%), Trichuris vulpis (4.9%), Uncinaria stenocephala (2.2%), Dipylidium caninum (1.3%), Taenia spp. (0.5%), Cystoïsospora canis (1.3%), and C. ohioensis (1.3%). Dogs younger than 1 year and stray dogs showed the highest prevalence of infection. T. vulpis was found more often in dogs from shelters with a high cleaning frequency.

[Infections with helminths and/or protozoa in cats in animal shelters in the Netherlands]. / Infecties met helminthen en/of protozoën bij katten in asielen in Nederland.

To determine the prevalence of infections with helminths and protozoa in cats in animal shelters, faecal samples from 305 cats from 22 animal shelters in the Netherlands were examined, using a centrifugation-sedimentation-flotation-technique. The association between potential risk factors and the occurrence of an infection was also tested. Infections with helminths and/or protozoa were found in 160 samples (52.5%). Toxocara cati was found in 86 cats (28.2%), Cystoisospora felis in 59 cats (19.3%), Cystoïsospora rivolta in 43 cats (14.1%), Capillaria spp. in 34 cats (11.2%), Ancylostoma tubaeforma in 9 cats (3.0%), Taenia taeniaeformis in 9 cats (3.0%), Aelurostrongylus abstrusus in 8 cats (2.6%), Giardia intestinalis in 3 cats (1.0%), Dipylidium caninum in 2 cats (0.7%) and Toxoplasma gondii in 1 cat (0.3%). The highest prevalence was seen in kittens and stray cats. The main preventive factor against infection was a short stay in a shelter.

Resilience of second year grazing cattle to parasitic gastroenteritis following negligible to moderate exposure to gastrointestinal nematode infections in their first year.

The influence of gastrointestinal nematode infections on performance of four groups of female Holstein Friesian calves was monitored until the end of the second grazing season (SGS). In the first year three groups were grazed and one group (G4) was permanently housed. General and grazing management during the first grazing season (FGS) was arranged such that G1 acquired moderate infections, G2 low infections and G3 very low infections with gastrointestinal nematodes. These infections were monitored through faecal egg counts, differentiation of faecal larval cultures, pasture larval counts, serum pepsinogen values, ELISA with a recombinant Cooperia oncophora protein, weight gain, tracer worm counts and sentinel worm counts. In 1998 all four groups were grazed together as one herd from 23 April to 26 October and infections were monitored with the same techniques with the exception of sentinel calves. In the FGS weight gain was higher in G4 than in the other groups and higher in G3 (28. 6kg) than in G1. Weight gain of G2 was intermediate to G1 and G3 but did not significantly differ from either group. In the SGS weight gain in G4 was far less than in any other group and the mean weight at the end of the experiment was 41.9, 38.6 and 50.9kg lower than G3, G1 and G2, respectively. Though no significant differences were observed between G1, G2 and G3 at the end of the experiment it was obvious that the weight gain advantage of G3 over G1 at the end of the FGS had disappeared. Parasitological and serological findings in the SGS indicated that G3 and G4 had build up less immunity during the FGS compared to G1 and G2. The conclusion of the experiment is that resilience to parasitic gastroenteritis in the SGS depends on the level of exposure to nematodes in the FGS. However, problems with poor weight gain only will be expected when exposure is very low in the FGS and high in the SGS.

The effect of oxfendazole terminated infections with Haemonchus contortus on the development of immunity in sheep.

The relative contribution of third (L3), fourth (L4) or adult stages of Haemonchus contortus to the development of immunity was evaluated in three groups of sheep subjected to infections terminated by oxfendazole treatments at the L3, L4 or adult stage. A control group did not receive immunising infections. All the groups were challenged with 5000 L3, to evaluate the protection provided by the different protocols. All sheep were necropsied at the end of the experiment to count the abomasal worm burdens. A marked reduction in egg counts after challenge infection was only observed in sheep in which the infection was terminated in the adult stage (Group 4). A significant reduction in worm burden was also observed in Group 4. The immunising infections and/or the challenge infection resulted in moderately elevated IgG antibody levels against L3, L4 and adult somatic antigens in all the groups. In contrast, a strong IgG response against H. contortus excretory/secretory (ES) antigens was observed in the groups in which the immunising infection was terminated in the L4 and the adult stage. An elevated lymphocyte proliferation response against Haemonchus ES antigens was found only in the group that had their immunising infection terminated at the adult stage. The combined data suggest that exposure to and elicited immunological responses to ES antigens are important for the development of immunity against H. contortus.

Evaluation of the effect of ivermectin administered topically at zero and six weeks after turnout on gastrointestinal nematode infection in first-season grazing cattle.

A field study was conducted between May and October 1995 to examine the efficacy of 0.5 mg/kg ivermectin pour-on on parasitic gastroenteritis of set-stocked calves at turnout and 6 weeks later. A treated group of 10 calves was compared with a separately grazed group of 10 non-treated calves; 14 calves were used as tracer animals. Initial infection levels appeared to be very low in both groups and faecal egg counts, pasture larval counts, serum pepsinogen levels and optical density (OD) values of an ELISA with a specific recombinant antigen for Cooperia oncophora remained low for 4 months. Thereafter, a rapid build up of gastrointestinal nematode infections occurred in both groups.

[Infections with Baylisascaris procyonis in humans and raccoons]. / Infecties met Baylisascaris procyonis bij de mens en de wasbeer.

Baylisascaris procyonis is an ascarid which parasitizes the small intestine of raccoons. The parasite is not very pathogenic in the raccoon because larvae do not migrate in this host. In other animals the larvae migrate through the body. They do not develop into adult worms in the intestine but rather become encysted in granulomas, showing a preference for the brain. In humans these larvae cause different larva migrans syndromes. Patients with neural larva migrans syndrome show severe brain symptoms and the disease is sometimes fatal. This article describes the life cycle of the worm and the incidence, symptoms, diagnosis, treatment, and prevention of larva migrans syndromes, paying special attention to the Dutch situation.

The effect of repeated moves to clean pasture on the build up of gastrointestinal nematode infections in calves.

The build up of gastrointestinal nematode infections was followed in two grazing experiments. Both experiments included four groups of six calves, a permanently housed non-infected control group and three groups which were grazed from May to October. One of these was moved to aftermath in the beginning of July, the second in the beginning of July and August and the third in the beginning of July, August and September. The build up of gastrointestinal nematode infections was followed by performing faecal egg counts, differentiation of faecal larval cultures, pasture larval counts, serum pepsinogen values, serum antibodies against Cooperia oncophora, weight gain and worm counts. In the second experiment four of the principal trial animals of each group were treated with oxfendazole and subsequently challenged with 100,000 larvae of Ostertagia ostertagi to examine development of immunity against O. ostertagi. The faecal egg counts and the worm counts of the sentinels necropsied in July indicated low initial infections in both experiments. Infection levels in experiment 1 remained low in each group until the beginning of September. However, during the last month, moderate to high infections were acquired by the groups which were moved once or twice. In contrast, low to moderate infections were maintained in the group moved three times. In the second experiment moderate C. oncophora burdens were already observed in the sentinels grazed until the beginning of August. Tracers grazing in August-September with the group moved once acquired high O. ostertagi and C. oncophora infections, whereas those grazed with both other groups acquired moderate infections. In October high infections with both species occurred in the groups moved once and twice, whereas low to moderate infections were observed in the group moved three times. The challenge infection demonstrated a reduction of establishment of O. ostertagi of approximately 70% in all three groups on pasture. The results demonstrate that moving calves at monthly intervals to clean pasture can be an effective method for the control of parasitic gastroenteritis. In addition, the data indicate that it is essential that the last move does not occur more than 1 month before the end of the grazing season.

The efficacy of Michel's dose and move system on gastrointestinal nematode infections in diary calves.

The efficacy of a move to aftermath in July combined with moxidectin or fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in calves was evaluated in three field experiments in the Netherlands. In all five treated groups high gastrointestinal nematode infections and PGE were prevented by a dose and move in July. Cooperia infections increased to moderate levels in two groups treated with moxidectin and one group treated with fenbendazole. In both other groups and also for Ostertagia in these three groups, low to extremely low infections were acquired. In the first experiment high primary infections, resulting in high faecal egg counts and a moderate increase of blood pepsinogen values occurred before the dose and move. Nevertheless, these primary infections were not high enough to result in PGE. In both other experiments primary infection levels were low and faecal egg counts increased to 100-650 eggs/g faeces at the end of the grazing season. The blood pepsinogen values of non-treated control groups demonstrated that it took more than a month after their move to aftermath before substantial reinfection occurred on the new pasture. In the first and the last experiment only, high Ostertagia and Cooperia infections developed in the control group at the end of the grazing season, though it did not result in clinical PGE. The experiments demonstrate all theoretical risks of the dose and move system: (1) PGE early in the grazing season as a result of high overwintered pasture infectivity. (2) PGE just before the move as a result of an early midsummer increase in pasture infectivity. (3) PGE around housing as a result of insufficient suppression of pasture infectivity late in the grazing season. (4) Underexposure to nematode infections due to a high suppression of nematode infections. Nevertheless, it can be concluded that under normal conditions the dose and move system remains to be a valuable and easily applicable system for the control of PGE.

Anthelmintic efficacy of oxibendazole against some important nematodes in dogs and cats.

The anthelmintic efficacy and safety of the oxibendazole component in a combination oxibendazole-niclosamide paste were investigated in dogs and cats and in litters of pups with naturally acquired nematode infections. A single dose of 15 mg oxibendazole/kg body weight given to 70 dogs and to 29 cats reduced faecal worm egg counts (EPG) by 97.6% for Toxocara canis, 95.7% for Trichuris vulpis, 94.6% for Ancylostoma caninum, and 100% for Toxascaris leonina. In cats, 96.7% efficacy was demonstrated against Toxocara cati. In a second trial, 119 pups in 22 litters were treated with the same dosage at 2, 4, and 6 weeks of age. After treatment on two consecutive days, 95% of the pups did not shed T. canis eggs, compared with 85% after only a single treatment. Side effects were rare and only recorded in young animals. A 2-day treatment schedule is recommended for unweaned pups.

A survey of Toxocara infections in cat breeding colonies in The Netherlands.

Faecal samples from 225 adults cats and 112 kittens and dust and soil samples from 25 catteries in the Netherlands were examined for Toxocara eggs. The results of this survey showed a low nematode infection rate in the investigated Dutch catteries since only four adult cats (2%) from two catteries (8%) were found to shed Toxocara cati eggs. No other helminth eggs were seen in the faecal samples. Nematode eggs were not present in the environmental dust and soil samples from houses and kennels; only Dipylidium caninum eggs were found in only two samples of household dust.

Nematode infections in dog breeding kennels in The Netherlands, with special reference to Toxocara.

Faecal samples from 286 adult dogs and 159 pups and dust and soil samples from 32 dog breeding kennels in the Netherlands were examined for nematode eggs. Dogs that shed nematode eggs were found in 41% of the kennels. The kennel prevalence of nematode infection of adult dogs was 33%. The kennel prevalence for infection of adult dogs and pups with nematode species was 21% and 48% for Toxocara canis, respectively, 29% and 0% for Trichuris vulpis, and 20% and 0% for Toxascaris leonina. Kennels with more than two litters per year and with regular import of new animals had a significantly higher prevalence of T. canis (p < 0.01 and p < 0.05 respectively). T. vulpis infections in adult dogs occurred significantly more often in kennels that used deworming products other than benzimidazoles (p < 0.05). Embryonated T. canis ova were recovered from 20% of the house and kennel dust samples and from 50% of the soil samples. This survey shows that the nematode infection rate in dog breeding kennels is high. Better deworming strategies should be used to improve the health status of the dogs and to reduce the risk of zoonotic infection in humans.

The reappearance of strongyle eggs in the faeces of horses after treatment with moxidectin.

The reappearance of strongyle eggs in the faeces of horses treated with moxidectin (0.4 mg/kg of body weight) was compared with that in the faeces of horses treated with ivermectin (0.2 mg/kg of body weight). The study was performed from December 1995 till June 1996. Horses were infected naturally in the preceding grazing period. Two groups of 24 horses each were treated with moxidectin and ivermectin respectively at week 0. No side effects were seen after treatment. Horses were housed from week -1 till week 17. From week 17 onwards the horses were on pasture. Faecal samples were taken from each horse at week -1, week 0 and weekly from week 3 to week 25. The ivermectin treated horses had to be retreated in week 17 to prevent pasture contamination. For this reason this group was withdrawn from the trial in week 17. Individual faecal egg counts and group faecal cultures and larval differentiation were performed. In the ivermectin treated group strongly eggs were seen for the first time after treatment in week 8. A steady rise in the mean number of eggs per gram faeces (EPG) was seen from week 8 till week 15. After week 15 a plateau was reached. In the moxidectin treated group mean egg counts remained very low throughout the study. A plateau was reached in week 19, with egg counts varying from 10 to 30 EPG between week 19 and week 25. The difference between the egg output after moxidectin- and ivermectin treatments can be explained by a higher efficacy of moxidectin against mucosal stages or by a longer residual effect of moxidectin than ivermectin.

Controlled dose confirmation study of a 2% moxidectin equine gel against equine internal parasites in The Netherlands.

The efficacy of a 2% moxidectin equine gel at a dosage rate of 0.4 mg kg-1 was evaluated in a controlled trial at Utrecht University. Twelve yearling castrated male Shetland ponies grazed a pasture of 2 ha from May 1994 until housing in November. Six ponies were treated with moxidectin, whereas the others served as non-treated controls. Necropsy was carried out 35 days after treatment. Greater than 99% efficacy of moxidectin was observed on faecal egg output. No effect of moxidectin was observed on mucosal inhibited early cyathostome L3 (EL3) or on the total numbers of mucosal developing stages. However, a 89.6% reduction was observed on large mucosal fourth stage larvae (L4). Moxidectin treatment probably triggered resumption of development of EL3. Moxidectin appeared to be highly effective (95-100%) on lumenal L4 cyathostomes, adult strongylids, Strongylus vulgaris larvae from the arteries, S. edentatus larvae from the abdominal wall and Trichostrongylus axei. Moxidectin had relatively poor efficacy against Gasterophilus intestinalis and had no effect on Anoplocephala perfoliata. No side-effects of moxidectin treatment were observed.