Randomized, double-blind comparison of oral aprepitant alone compared with aprepitant and transdermal scopolamine for prevention of postoperative nausea and vomiting.

BACKGROUND: Aprepitant blocks the emetic effects of substance P. Scopolamine antagonizes muscarinic type 1 and histamine type 1 receptors. This study compares monotherapy and multimodal therapy by looking at complete response, nausea, vomiting, and rescue medication in patients at high risk for postoperative nausea and vomiting (PONV) treated with oral aprepitant with or without scopolamine. METHODS: We enrolled 120 patients in this randomized, double-blind trial. Inclusion criteria were: >18 yr old, ASA I-III, two or more Apfel four-point risk factors, undergoing an elective surgical procedure with a high risk of PONV expected to last at least 60 min. The primary outcome variable was complete response, that is, no emesis and no rescue therapy from 0 to 24 h. The outcomes measured included the incidences of nausea, vomiting, their composite, and the need for rescue medication. RESULTS: The aprepitant alone and aprepitant with scopolamine did not differ in complete responses (63% vs 57%, P=0.57) or net clinical benefit (26% vs 19%, P=0.38). The number who did not experience PONV and who used rescue medication did not differ. The incidence of PONV in the post-anaesthesia care unit did not differ nor did the use of rescue medications. CONCLUSIONS: This trial evaluating the effectiveness of aprepitant alone and in combination with scopolamine showed no difference between treatment groups. The primary objective, complete response, and secondary objectives, incidences of nausea, vomiting, their composite, and the need for rescue medication, all showed no statistical difference.

Detection of high levels of European bat lyssavirus type-1 viral RNA in the thyroid gland of experimentally-infected Eptesicus fuscus bats.

Two common bat lyssavirus species have been identified in many European countries: European bat lyssavirus type-1 and -2 (EBLV-1 and EBLV-2). Only limited knowledge on the susceptibility of the natural EBLV-hosts, insectivorous bats, to lyssavirus infection is available. Our study was undertaken to evaluate the susceptibility and pathology associated with an EBLV-1 infection in Eptesicus fuscus following different routes of virus inoculation including intracranial (n = 6), intramuscular (n = 14), oral (n = 7) and intranasal (n = 7). Blood and saliva samples were collected from all bats on a monthly basis. Four bats inoculated intracranially developed rabies with a mean of 11 days to death, whilst seven bats inoculated intramuscularly developed rabies, with an extended incubation period prior to death. We did not observe any mortality in the oral (p.o.) or intranasal (i.n.) groups and both groups had detectable levels of virus neutralizing antibodies (data not shown). Virus shedding was demonstrated in the saliva by virus isolation and the detection of viral RNA in ill bats, particularly immediately prior to the development of disease. In addition, the presence of virus and viral RNA was detected in the thyroid gland in bats challenged experimentally with EBLV-1, which exceeded that detected in all other extra-neural tissue. The significance of detecting EBLV-1 in the thyroid gland of rabid bats is not well understood. We speculate that the infection of the thyroid gland may cause subacute thyroiditis, a transient form of thyroiditis causing hyperthyroidism, resulting in changes in adrenocortical activity that could lead to hormonal dysfunction, thereby distinguishing the clinical presentation of rabies in the rabid host.

Experimental infection of serotine bats (Eptesicus serotinus) with European bat lyssavirus type 1a.

The serotine bat (Eptesicus serotinus) accounts for the vast majority of bat rabies cases in Europe and is considered the main reservoir for European bat lyssavirus type 1 (EBLV-1, genotype 5). However, so far the disease has not been investigated in its native host under experimental conditions. To assess viral virulence, dissemination and probable means of transmission, captive bats were infected experimentally with an EBLV-1a virus isolated from a naturally infected conspecific from Germany. Twenty-nine wild caught bats were divided into five groups and inoculated by intracranial (i.c.), intramuscular (i.m.) or subcutaneous (s.c.) injection or by intranasal (i.n.) inoculation to mimic the various potential routes of infection. One group of bats was maintained as uninfected controls. Mortality was highest in the i.c.-infected animals, followed by the s.c. and i.m. groups. Incubation periods varied from 7 to 26 days depending on the route of infection. Rabies did not develop in the i.n. group or in the negative-control group. None of the infected bats seroconverted. Viral antigen was detected in more than 50% of the taste buds of an i.c.-infected animal. Shedding of viable virus was measured by virus isolation in cell culture for one bat from the s.c. group at 13 and 14 days post-inoculation, i.e. 7 days before death. In conclusion, it is postulated that s.c. inoculation, in nature caused by bites, may be an efficient way of transmitting EBLV-1 among free-living serotine bats.

Analysis of vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) after oral rabies vaccination campaigns in Germany and Austria.

To eradicate rabies in foxes, almost 97 million oral rabies vaccine baits have been distributed in Germany and Austria since 1983 and 1986, respectively. Since 2007, no terrestrial cases have been reported in either country. The most widely used oral rabies vaccine viruses in these countries were SAD (Street Alabama Dufferin) strains, e.g. SAD B19 (53.2%) and SAD P5/88 (44.5%). In this paper, we describe six possible vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) detected during post-vaccination surveillance from 2001 to 2006, involving two different vaccines and different batches. Compared to prototypic vaccine strains, full-genome sequencing revealed between 1 and 5 single nucleotide alterations in the L gene in 5 of 6 SAD isolates, resulting in up to two amino acid substitutions. However, experimental infection of juvenile foxes showed that those mutations had no influence on pathogenicity. The cases described here, coming from geographically widely separated regions, do not represent a spatial cluster. More importantly, enhanced surveillance showed that the vaccine viruses involved did not become established in the red fox population. It seems that the number of reported vaccine virus-associated rabies cases is determined predominantly by the intensity of surveillance after the oral rabies vaccination campaign and not by the selection of strains.

Susceptibility of North American big brown bats (Eptesicus fuscus) to infection with European bat lyssavirus type 1.

The aim of this study was to determine the susceptibility of insectivorous bats (using the big brown bat as a model) to infection with European bat lyssavirus type 1a (EBLV-1a), to assess the dynamics of host immune responses and to evaluate the opportunity for horizontal viral transmission within colonies. Two isolates of EBLV-1a, originating from Slovakia (EBLV-1aSK) and Germany (EBLV-1aGE), were tested. Four different routes of inoculation were used with isolate EBLV-1aSK [10(4.8) mouse intracerebral median lethal dose (MICLD(50)) in 50 mul]: intramuscular (i.m.) in the deltoid area or masseter region, per os (p.o.) and intradermal (i.d.) scratches. Isolate EBLV-1aGE (10(3.2) and 10(2.2) MICLD(50) in 20 mul) was inoculated via the intranasal (i.n.), i.m. (low- and high-dose groups, into pectoral muscles); p.o. and intracerebral (i.c.) routes. None of the bats infected by the i.n., p.o. or i.d. route with either virus isolate developed disease during the experiments (91 or 120 days, respectively). Incubation periods were 9-12 days for i.c.-inoculated bats (66 % mortality), 12-33 days for bats inoculated i.m. with the higher dose (23-50 % mortality) and 21-58 days in bats inoculated i.m. with the lower dose of virus (57 % mortality). Virus or viral RNA in bat saliva was detected occasionally, as early as 37 days before death. All i.d.-inoculated and the majority of i.m.-inoculated bats seroconverted within 7-10 days of inoculation. These observations suggest that exposure of bats to varying doses of EBLV-1 from rabid conspecifics via natural (i.d.) routes could lead to an abortive infection and serve as a natural mode of immunization resulting in the presence of virus-neutralizing antibodies in free-ranging bats.

Rabies in red foxes (Vulpes vulpes) experimentally infected with European bat lyssavirus type 1.

The susceptibility of red foxes (Vulpes vulpes) to European bat lyssavirus type 1 (EBLV-1) infection was examined. Eight foxes were inoculated intramuscularly (i.m.) with 10(4.9) foci-forming units (FFU) (n = 4) and 10(5.1) FFU (n = 4) and observed for up to 90 days. All foxes showed manifestations of a neurologic disorder (e.g. seizures, myoclonus, agitation), starting as early as 5 days post-infection (p.i.). Subsequently, all animals showed improvement followed by one or more relapses. One fox was killed 3 days after it recovered, 26 days post-infection. Two other foxes were also killed 38 and 54 days post-infection after severe neurologic signs returned. All foxes developed a humoral immune response against EBLV-1 as determined in serum and brain tissues. However, no rabies virus antigen was detected in the brain, other tissues and secretions examined (e.g. salivary gland, saliva, tonsils, lungs) by using different standard diagnostic techniques [fluorescent antibody test, reverse transcription polymerase chain reaction (RT-PCR), rabies tissue culture inoculation test], with the exception of one fox in which EBLV-1 RNA was detected by RT-PCR in only the spinal cord. Brain tissues showed moderate to severe multifocal, mononuclear encephalomyelitis in the three foxes that were killed during the observation period, although no EBLV-1 virus was detectable in these tissues.

Susceptibility of ferrets (Mustela putorius furo) to experimentally induced rabies with European Bat Lyssaviruses (EBLV).

Twenty ferrets (Mustela putorius furo) were inoculated by intramuscular (i.m.) injection with European Bat Lyssaviruses (EBLV) type-1 and 2 using 10(4.0) foci-forming units (FFU) EBLV-2 (n = 6), 10(4.0) FFU EBLV-1 (n = 7) and 10(6.0) FFU EBLV-1 (n = 7). Furthermore, 15 mice received 10(2.5) FFU EBLV-2 (n = 5), 10(2.5) FFU EBLV-1 (n = 5) and 10(4.5) FFU EBLV-1 (n = 5) by i.m. inoculation. All ferrets and mice receiving the higher dose of EBLV-1 succumbed to infection. In contrast, only three of seven ferrets and two of five mice inoculated experimentally with the lower EBLV-1 dose died. By comparison, all of the EBLV-2 infected ferrets and four of five mice survived infection. All 20 infected ferrets seroconverted. Using sensitive molecular tools, the virus was detected in different tissues, but it could not be found in any saliva samples taken during the 84-day observation period.

Safety studies of the oral rabies vaccine SAD B19 in striped skunk (Mephitis mephitis).

Safety of the modified live rabies virus vaccine, SAD B19, was studied in striped skunks (Mephitis mephitis). Seven skunks received 10(7.9) foci formatting units by direct oral administration. In four cages, a vaccinated animal was placed with a control animal, the other three vaccinated skunks were housed individually. Saliva and nasal swabs were collected 1, 2, 4, 24, 48, and 72 hr post-vaccination. From all vaccinated and control animals (n = 11) blood samples were collected 0, 28, 56, 84, and 296 days post-vaccination. Three of seven vaccinated skunks seroconverted. None of the control animals had detectable levels of rabies virus neutralizing antibodies. Also no vaccine virus was isolated from the nasal and saliva swabs collected from any animal. Thus, SAD B19 was innocuous for skunks in our study after direct oral administration at field concentration.

Comparative immunogenicity and efficacy studies with oral rabies virus vaccine SAD P5/88 in raccoon dogs and red foxes.

A comparative study of immunogenicity and efficacy of the oral rabies virus vaccine SAD P5/88 in raccoon dogs and foxes was conducted. The raccoon dogs received 10(6.9) (n = 6), 10(6.3) (n = 6) or 10(5.7) FFU SAD P5/88 (n = 5) by direct oral application, and subsequently all animals seroconverted. The foxes received 10(7.2) (n = 4), 10(6.2) (n = 4), 10(5.2) (n = 4) and 10(4.2) FFU SAD P5/88 (n = 5) by the same route. On days 106 and 196 post vaccination 10 raccoon dogs and 16 foxes were challenged with a relevant street virus, respectively. All 10 raccoon dogs vaccinated with 10(6.3) (n = 5) or 10(5.7) FFU SAD P5/88 (n = 5) survived the challenge, whereas all control animals (n = 5) died of rabies. Two foxes vaccinated with 10(4.2) FFU and one fox vaccinated with 10(5.2) FFU died of rabies on day 7, 17 and 12 post infection, respectively. Also all control foxes succumbed to rabies. Our findings demonstrate that SAD P5/88 is not only an effective vaccine for oral vaccination of foxes but also for that of raccoon dogs.

Single-vehicle data of highway traffic: a statistical analysis.

In the present paper, single-vehicle data of highway traffic are analyzed in great detail. By using the single-vehicle data directly, empirical time headway distributions and speed-distance relations can be established. Both quantities yield relevant information about the microscopic states. Several fundamental diagrams are also presented, which are based on time-averaged quantities and compared with earlier empirical investigations. In the remaining part, time-series analyses of the averaged as well as the single-vehicle data are carried out. The results will be used in order to propose objective criteria for an identification of the different traffic states, e.g., synchronized traffic.

[Problems relating to low temperature preservation of ram semen. 1. Effects of various cryoprotective agents on sperm]. / Probleme der Tieftemperaturkonservierung von Schafbockspermien. 1. Mitteilung: Der Einfluss verschiedener Kryoprotektiva auf die Spermien.

Studies into the action of several cryoprotective agents in sodium-citrate-yolk diluent on ram semen provided preliminary information regarding both concentration applicable in deep-freeze preservation and toxicity of the agents involved. Included in the tests were glycerin, dimethylsulphoxide, ethylene glycol, propylene glycol, polyethylene glycol, polyvinylpyrrolidome, and dimethylacetamide. The effect of adding cryoprotective-containing diluent at 5 degrees C was more favourable, in its impact on ram sperma, than that observed, when diluent was added at 30 degrees C.