Non-medical use of loperamide in the UK and the USA.

BACKGROUND: Loperamide is a mu-opioid receptor agonist that is available as an over-the-counter anti-motility agent in the US and UK; recommended maximum doses of 12-16 mg/day. Anecdotal reports of non-medical use (NMU) have increased over the past decade with supra-therapeutic doses (70-800 mg/day) associated with cardiotoxicity. Little data exists on the prevalence of loperamide NMU. AIM: The aim of this study was to determine the prevalence of loperamide NMU in the UK and US and to describe characteristics of non-medical loperamide users. DESIGN: The Researched, Abuse, Diversion and Addiction Related Surveillance (RADARS® ) Survey of Nonmedical Use of Prescription Drugs (NMURx) was utilized to study NMU of loperamide among the adult population in the UK and US in 2017. The RADARS® NMURx is anonymous and self-administered online. METHODS: A total of 40,029 completed surveys were included (10,019 from the UK and 30,010 from the US). Respondents were asked questions about medical and NMU of loperamide, frequency of and reasons for NMU, route of use problematic drug use markers, and demographics. RESULTS: Prevalence of lifetime loperamide use (95% CI) and lifetime NMU of loperamide were: UK 28.5% (27.67-29.4), and 0.66% (0.5-0.8), respectively; US 33.7% (33.1-34.2), and 5.19% (4.9-5.5), respectively. Problematic drug use markers were elevated in those who reported NMU of loperamide in both the UK and US, however high-risk use was more prevalent in the UK than in the US. CONCLUSION: NMU of loperamide is common. In the current international environment of opioid addiction involving both therapeutic and illicit opioids, awareness of the NMU of loperamide is important.

Adoptive transfer of vaccine-induced resistance to Leishmania donovani.

BALB/c mice were immunized with three subcutaneous injections combining killed parasites and glucan, or were untreated. Spleen cells were transferred to syngeneic recipients. Mice which received 5 X 10(8) spleen cells from vaccinated donors demonstrated significant protection against Leishmania donovani challenge as compared to untreated mice receiving immune sera, or mice which received untreated spleen cells.

Leishmania donovani: immunization against infection as a function of parasite growth phase.

C57BL/6 mice were immunized against Leishmania donovani infection with a subcutaneous vaccination protocol. Groups received 3 injections at 4-day intervals combining glucan and killed promastigotes harvested from either logarithmic or stationary phase cultures. Controls were immunized with glucan alone, stationary or log phase promastigotes alone, or were untreated. All groups were challenged intravenously with stationary phase promastigotes at day 45 post-immunization. Results revealed that animals immunized with the glucan-killed parasite vaccine, utilizing promastigotes derived from either log (GPL) or stationary phase cultures (GPS), demonstrated significant resistance against infection as compared to controls or untreated mice. Additionally, the reduction in hepatic amastigote proliferation in mice immunized with GPS was significantly greater than in mice immunized with GPL.

The effect of BCG-vaccine upon experimental visceral leishmaniasis in hamsters.

Stimulation with Bacillus Calmette-Guerin (BCG) vaccine has been reported to enhance resistance of mice against Leishmania donovani infection. Such infection is usually lethal in hamsters, thus providing a more stringent animal model to assess the effect of BCG upon visceral leishmaniasis. Animals receive two IP injections (2-8 X 10(7) BCG) pre or post IC challenge with 4 X 10(6) amastigotes. Controls received BCG alone (with no infection) or were untreated (NT). Pretreated animals exhibited significantly fewer (P less than 0.05) hepatic or splenic amastigotes than NT animals at days 7, 14, and 28 post challenge, but most BCG treated hamsters died earlier than NT. Post treated hamsters showed no significant reduction in parasite burdens, or in median time to death as compared to NT group. Hamsters which received BCG but were not infected appeared healthy during the study. The reason for increased susceptibility of BCG-treated hamsters to disease is not clear, but observed pathologic complications of L. donovani infected hamsters appear to be exacerbated by BCG stimulation.

Resistance against Leishmania donovani induced with an aluminum hydroxide vaccine.

Mice immunized with a subcutaneous protocol combining killed parasites and aluminum hydroxide gel exhibited significant resistance against subsequent challenge with Leishmania donovani promastigotes. Protection was greatest using 25 mg of aluminum hydroxide per injection. Resistance elicited by this killed parasite and aluminum hydroxide protocol was as effective on day 14 as that provided by immunization with a glucan and killed parasite preparation, and more effective in hepatic amastigote reduction at day 28. The effectiveness of aluminum hydroxide as an adjuvant appears to result, at least in part, from its ability to activate macrophages, thus aiding in the elimination of this intracellular parasite.

Effect of hydroxyethyl starch (HES) in reducing parasite load in experimental visceral leishmaniasis.

Leishmania donovani primarily infects phagocytic cells of the reticuloendothelial system. Hydroxyethyl starch (HES) has been shown to concentrate transiently in these organs. The effect of HES administration was assessed upon infection and also upon vaccination against this parasite. Animals received HES intraperitoneally thrice weekly, either alone (HES) or with a subcutaneous immunization protocol utilizing aluminum hydroxide and killed parasites (ALP-HES). Controls were untreated (NT) or received only the vaccination protocol (ALP). Results showed that animals treated with HES alone exhibited significantly fewer parasites as compared to untreated animals (p less than 0.001). The ALP animals also were protected against infection but demonstrated greater parasite burdens than HES animals. Immunized animals which also received HES demonstrated infection levels similar to those treated with HES alone, thus negating any synergistic effect. The reason for increased protection against L. donovani infection in animals treated with HES is not clear, but it may result from a transient increase in host resistance.

Antithymocyte serum suppression of immunity in mice immunized to Leishmania donovani.

Mice immunized with a glucan-killed parasite vaccine exhibited enhanced resistance to Leishmania donovani infection as evidenced by decreased hepatic parasite burdens when compared to unvaccinated controls. This resistance was not seen in mice immunized with killed parasites alone. Glucan vaccination resulted in increased resistance at day 6, but this effect was no longer present by day 20 of the experiment. Treatment of vaccinated and control mice with antithymocyte sera abrogated protection against infection, whether such resistance was vaccine induced or the result of acquired immunity.

Trichomonas vaginalis: preliminary characterization of a sperm motility inhibiting factor.

This study determined the effects of Trichomonas vaginalis trophozoites, subcellular fractions, and medium from axenic T. vaginalis cultures on human sperm motility and viability. Spent medium (pH 7.0) caused complete cessation of sperm motility after 15 minutes incubation. Trophozoite soluble fraction or formalin-killed trophozoites caused a 50 percent reduction in sperm motility, compared to 25 percent reduction caused by the trophozoite particulate fraction or the sterile medium and three percent by saline (control). Spent medium from T. vaginalis cultures reaching stationary growth phase produced the greatest reduction in sperm motility, suggesting that potency was related to time in culture and trophozoites per ml. The T. vaginalis spermicidal activity was heat-stable, trypsin-sensitive, and had a molecular weight of 12-15,000 by gel filtration. This proteinaceous substance was present in and secreted by T. vaginalis trophozoites during normal growth in axenic culture. Since this T. vaginalis byproduct rapidly killed sperm in vitro, its effects in humans may contribute to infertility in infected couples.

An oligonucleotide probe that distinguishes isolates of low virulence from the more pathogenic strains of Newcastle disease virus.

A synthesized oligonucleotide, termed cleavage probe (NDV-CL), has been designed to complement the cleavage-activation site of the fusion gene of the Texas GB isolate of Newcastle disease virus (NDV). This oligonucleotide probe, 21 bases in length, bound with RNA from velogenic strains of NDV tested in a slot-blot hybridization assay. The probe also recognized RNA from the mesogenic strains used in this assay, although no signal was observed with RNA isolated from lentogenic NDVs or with that from other common avian viruses used as controls. This probe did not recognize RNA from isolates of other paramyxovirus serotypes (PMV-2 or PMV-3) included in this study. The ability of this probe to distinguish lentogenic NDVs, which cause little or no clinical disease, from those strains that may produce severe morbidity and/or mortality suggests a potential use for the probe in a molecular diagnostic assay.

A novel oligonucleotide probe for the detection of Newcastle disease virus.

An approach that possesses high specificity and broad applicability was used to obtain a DNA probe with potential diagnostic value. By utilizing synthesized oligonucleotide DNA, termed NDV probe, all 14 strains of NDV tested under high-stringency conditions were recognized in a slot-blot hybridization assay. The sequence of the NDV probe was generated from a highly conserved region of the NDV genome. No hybridization was observed with RNA isolated from other avian viruses, including avian influenza, infectious bursal disease, and infectious bronchitis. The specificity inherent in using an oligonucleotide probe offers advantages over probes obtained from cloned DNA fragments.

Quality assurance in weighing.

Weighing is the most used step in any analytical procedure, and the balance is the one essential piece of laboratory equipment in all analyses. Yet weighing is a common source of error in final analytical results and can be difficult to detect. Analysts may become complacent and expect all weighings to be accurate. Our laboratory experienced a problem in weighing and found that the principal error was due to drift. The ensuing investigation into the cause led to a procedure for reducing drift, which, in turn, ensured accurate weighings that have improved quality assurance in our total operations.

Bartonella spp infection as a possible cause of uveitis in a cat.

A 6-year-old castrated mixed-breed cat was evaluated because of unilateral anterior uveitis. The cat was seronegative for antibodies to Toxoplasma gondii, coronaviruses, and feline immunodeficiency virus, and antigens for FeLV p27 and Cryptococcus neoformans. Antibodies to Bartonella spp were detected in serum and aqueous humor. The antibody coefficient (C value) for IgG antibodies to Bartonella spp in the aqueous humor was 4.42; values > 1 suggest ocular production of antibodies and supports a diagnosis of ocular infection. Topical administration of prednisolone and oral administration of prednisone failed to induce a response; however, the uveitis resolved rapidly after the cat was given doxycycline orally. Clinical or laboratory evidence of immunodeficiency in this cat was not detected. Detection of a serum IgG antibody titer to Bartonella spp and ocular production of IgG antibodies to Bartonella spp, exclusion of other causes of uveitis, and response to doxycycline suggests that the cat may have had bartonellosis resulting in uveal tract inflammation.

Procedure for calibrating the Technicon Colorimeter I.

We describe a rapid method for calibrating the Technicon AutoAnalyzer colorimeter I. Test solutions of bromphenol blue are recommended for the calibration, in preference to solutions of potassium dichromate, based on considerations of the instrument's working range and of the stray light characteristics of the associated filters.