Knowledge, attitudes and practices of health care professionals towards adverse drug reaction reporting in public sector primary health care facilities in a South African district.

PURPOSE: Adverse drug reactions (ADRs) have an appreciable impact on patients' health. Little is known however about ADR reporting in ambulatory care environments especially in low- and middle-income countries. Consequently, our aim was to determine knowledge, attitudes and practices (KAP) among health care professionals (HCPs) towards ADR reporting in primary health care (PHC) facilities in South Africa. The findings will be used to direct future activities. METHODS: Descriptive, cross-sectional design using quantitative methodology among 8 public sector community health care centres and 40 PHC clinics in the Tshwane Health District, Gauteng Province. A self-administered questionnaire was distributed to 218 HCPs, including all key groups. RESULTS: A total of 200 responses were received (91.7%). Although an appropriate attitude towards ADR reporting existed, the actual frequency of ADR reporting was low (16.0%). Of the respondents, 60.5% did not know how to report, where to report or when to report an ADR and 51.5% said the level of their clinical knowledge made it difficult to decide whether or not an ADR had occurred. Over 97.5% stated they should be reporting ADRs with 89% feeling that ADR reporting is a professional obligation and over 70% that ADR reporting should be compulsory. When results were combined, the overall mean score in terms of positive or preferred practices for ADR reporting was 24.6% with pharmacists having the highest scores. CONCLUSION: Under-reporting of ADRs with gaps in KAP was evident. There is a serious and urgent need for education and training of HCPs on ADR reporting in South Africa.

'Believe in me and I will believe in myself', a rural Australian health service learns how to mangan dunguludja ngatan (build strong employment) for Aboriginal and Torres Strait Islander people: a qualitative study.

BACKGROUND: Australian Aboriginal people have higher rates of unemployment and poorer health than non-Aboriginal Australians. Historical segregation policies that spanned 60 years negatively impacted workforce inclusion. A Victorian regional health service recently developed an Aboriginal Employment Plan (AEP) targeted to reach 2% employment of Aboriginal people by 2020. This study aimed to identify strategies that will build strong Aboriginal employment. METHODOLOGY: A qualitative research protocol was designed. Purposive recruitment of people with a vested interest in the growth of Aboriginal employment at the health service participated in focus groups and individual interviews. RESULTS: Twenty-four people including local Elders, past and present Aboriginal employees, key community stakeholders and health service executives participated. Learnings from the past, the present and strategies for the future emerged from two important stories: (1) the story of a strong group of local Aboriginal people who successfully approached the matron of the hospital in the early 1960s for employment. (2) The story of the 'verandah babies'. DISCUSSION: The history of the health service in question demonstrated the power of the possible with a self-determined group of Aboriginal people, who, in the face of cultural inequity, achieved employment at the health service. The opportunity for healing and a new start was illustrated by the story of women who gave birth on the verandahs due to their exclusion from the main hospital. Today, the 'verandahs' have been replaced with a modern hospital decorated with Aboriginal art, expressing cultural safety and inclusion, presenting fertile ground for strengthening and sustaining Aboriginal employment. CONCLUSION: Eleven strategies have emerged from three themes; safety, equity and pathway, offering mainstream health services insight into how to mangan dunguludja ngatan (build strong employment). Cultural safety can be achieved through acknowledging the past and reconciling that through engaging, partnering and collaborating with the Aboriginal community. Visual representations of culture and participation in celebratory activities engender awareness and understanding. The development of local, flexible career development pathways for Aboriginal people facilitates a 'sense of belonging' to the health service and a dual 'sense of pride' within the community: whereby the Aboriginal person feels proud to represent their community and the community is proud to be represented. Cultural equity is facilitated through mutual learning and reciprocal understanding of difference.

Why Australia needs to define obesity as a chronic condition.

BACKGROUND: In Australia people with a diagnosed chronic condition can be managed on unique funded care plans that allow the recruitment of a multidisciplinary team to assist in setting treatment goals and adequate follow up. In contrast to the World Health Organisation, the North American and European Medical Associations, the Australian Medical Association does not recognise obesity as a chronic condition, therefore excluding a diagnosis of obesity from qualifying for a structured and funded treatment plan. BODY: The Australian guidelines for management of Obesity in adults in Primary Care are structured around a five step process -the '5As': Ask & Assess, Advise, Assist and Arrange'. This article aims to identify the key challenges and successes associated with the '5As' approach, to better understand the reasons for the gap between the high Australian prevalence of overweight and obesity and an actual diagnosis and treatment plan for managing obesity. It argues that until the Australian health system follows the international lead and defines obesity as a chronic condition, the capacity for Australian doctors to diagnose and initiate structured treatment plans will remain limited and ineffective. CONCLUSION: Australian General Practitioners are limited in their ability manage obesity, as the current treatment guidelines only recognise obesity as a risk factor rather than a chronic condition.

Assessment of the dimensionality of the Wijma delivery expectancy/experience questionnaire using factor analysis and Rasch analysis.

BACKGROUND: Fear of childbirth has negative consequences for a woman's physical and emotional wellbeing. The most commonly used measurement tool for childbirth fear is the Wijma Delivery Expectancy Questionnaire (WDEQ-A). Although originally conceptualized as unidimensional, subsequent investigations have suggested it is multidimensional. This study aimed to undertake a detailed psychometric assessment of the WDEQ-A; exploring the dimensionality and identifying possible subscales that may have clinical and research utility. METHODS: WDEQ-A was administered to a sample of 1410 Australian women in mid-pregnancy. The dimensionality of WDEQ-A was explored using exploratory (EFA) and confirmatory factor analysis (CFA), and Rasch analysis. RESULTS: EFA identified a four factor solution. CFA failed to support the unidimensional structure of the original WDEQ-A, but confirmed the four factor solution identified by EFA. Rasch analysis was used to refine the four subscales (Negative emotions: five items; Lack of positive emotions: five items; Social isolation: four items; Moment of birth: three items). Each WDEQ-A Revised subscale showed good fit to the Rasch model and adequate internal consistency reliability. The correlation between Negative emotions and Lack of positive emotions was strong, however Moment of birth and Social isolation showed much lower intercorrelations, suggesting they should not be added to create a total score. CONCLUSION: This study supports the findings of other investigations that suggest the WDEQ-A is multidimensional and should not be used in its original form. The WDEQ-A Revised may provide researchers with a more refined, psychometrically sound tool to explore the differential impact of aspects of childbirth fear.

Identifying women who are afraid of giving birth: A comparison of the fear of birth scale with the WDEQ-A in a large Australian cohort.

BACKGROUND: The WDEQ-A is the most widely used measure of childbirth fear in pregnant women; however there is increasing discussion in the literature that simpler, more culturally transferrable tools may offer a better solution to identifying fearful women in clinical practice. AIM: To compare the two item Fear of Birth Scale (FOBS) with the 33 item WDEQ-A in a large cohort of Australian pregnant women. METHOD: Self-report questionnaires during second trimester including Wijma Delivery Expectancy Questionnaire (WDEQ-A) and Fear of Birth Scale (FOBS). Correlation of FOBS and WDEQ-A was tested using Spearman's correlation coefficients. Receiver operating characteristic (ROC) curve assessed the sensitivity and specificity of possible cut-points on the FOBS against WDEQ-A cut-point of ≥85. Sensitivity, specificity, positive and negative predictive values were determined. Fearful and non-fearful women as classified by both instruments were compared for differences in demographic, psycho-social and obstetric characteristics. RESULTS: 1410 women participated. The correlation between the instruments was strong (Spearman's Rho = 0.66, p < 0.001). The area under the ROC was 0.89 indicating high sensitivity with a FOBS cut-point of 54. Sensitivity was 89%, specificity 79% and Youden index 0.68. Positive predictive value was 85% and negative predictive value 79%. Both instruments identified high fear as significantly associated with first time mothers, previous emergency caesarean and women with self-reported anxiety and/or depression. Additionally FOBS identified a significant association between fearful women and preference for caesarean. CONCLUSION: This study supports the use of the FOBS in clinical practice to identify childbirth fear in pregnant women.

Statewide dissemination of a rural, non-chain restaurant intervention: adoption, implementation and maintenance.

The obesity epidemic calls for greater dissemination of nutrition-related programs, yet there remain few studies of the dissemination process. This study, guided by elements of the RE-AIM model, describes the statewide dissemination of a simple, point-of-purchase restaurant intervention. Conducted in rural counties of the Midwest, United States, the study targeted randomly selected, non-chain, family-style restaurants. Owners were recruited through mail, then telephone follow-up. Data were collected through telephone at baseline, and 3, 6, 12 and 18 months post-adoption. Using mixed methods, measures captured the program adoption rate, characteristics of adopters and non-adopters, program implementation and maintenance issues, and owner and customer satisfaction. Analyses involved descriptive statistics and summaries of qualitative data. The program adoption rate was 28%. Adopters were similar to responding non-adopters demographically, but varied in attitudes. The majority of restaurants maintained the program for at least 12 months. Adopters and their customers expressed satisfaction with the program. With some adjustments, the RE-AIM model was helpful in guiding evaluation of this process. Results provide implications for future dissemination of this and other programs with regard to research procedures and potential barriers that may be encountered. Research on alternative strategies for widespread dissemination of such programs is needed in this and other settings.

Rural Victorian Telestroke project.

BACKGROUND: Intravenous thrombolysis improves functional outcomes in acute ischaemic stroke. However, many rural stroke patients are denied thrombolysis because of a rural neurologist shortage. 'Telestroke' facilitates thrombolysis by providing remote access to neurologists via videoconferencing systems. AIMS: To develop a safe and feasible Telestroke system in a rural Victorian hospital that facilitates delivery of intravenous thrombolysis to acute ischaemic stroke patients. METHODS: A pilot videoconferencing Telestroke system was set up between Royal Melbourne Hospital and Northeast Health Wangaratta. Acute stroke patients presenting within 4.5 h of symptom onset without intracranial haemorrhage were eligible for Telestroke. However, eligible patients were excluded from Telestroke if they had haemorrhagic risk factors. Data were collected from intervention (October 2009-September 2010) and control group (October 2008-September 2009) by medical file audit. Primary outcome measure was percentage of patients thrombolysed. Secondary outcome measures included incidence of symptomatic intracerebral haemorrhage and door-to-computed tomography time. RESULTS: One hundred and forty-five acute stroke patients presented in control year and 130 patients in intervention year. Fifty-four patients in intervention and 36 patients in control group were eligible for thrombolysis. In intervention group, 24 patients had Telestroke activated and 8 patients underwent thrombolysis. There was no thrombolysis in the control group. There were neither symptomatic intracerebral haemorrhages nor deaths attributable to thrombolysis. Median door-to-computed tomography time did not significantly differ between eligible patients in control and intervention groups. CONCLUSION: Telestroke has the potential to bridge the gap of rural-metropolitan inequality in acute stroke care. Our Telestroke system successfully introduced safe thrombolysis and early specialist review of acute stroke patients in rural Victoria.

Transmammary transmission of Strongyloides stercoralis in dogs.

Vertical transmission of larvae is a major pathway in the life cycle of several species of Strongyloides, but evidence for it occurring in humans or dogs with Strongyloides stercoralis is absent. In an effort to determine if vertical transmission could occur with S. stercoralis, each of 3 female dogs was infected with filariform larvae at a different stage of the reproductive cycle, i.e., preconception, gestation, or postpartum. Results showed that none of 6 pups born to a female infected before conception or any of 6 pups born to another female infected during gestation harbored any stage of S. stercoralis when necropsied at parturition. Conversely, all 5 pups that nursed from the female infected immediately postpartum became infected with adult S. stercoralis in their small intestines (range, 56-129 adult worms). Significantly, live filariform larvae of S. stercoralis were observed on 2 different occasions from milk samples taken from the lactating female. Because arrested development of larvae is not known in S. stercoralis, there is no reservoir of larvae in the parenteral tissues of females to queue for passage to the pups and, thus, it is not surprising that only timely infections, perhaps very late in gestation and during lactation, can be successful. These data support previous work in dogs with S. stercoralis, which concluded that vertical transmission through prenatal pathways does not occur, but they are the first from the dog to indicate that vertical transmission of this parasite through transmammary routes is possible. Whether transmammary transmission of S. stercoralis occurs in humans remains unknown but given its immense pathological potential, it should not be overlooked.

Validating a framework for participatory ergonomics (the PEF).

Participatory ergonomics is reported in an increasing number of case studies, but there is little evidence of emerging supportive theory and relatively little generic advice or guidance. The paper describes an effort to provide clarity and organization to the field of participatory ergonomics. A framework has been developed to define a range of different participatory ergonomics initiatives, establishing a number of levels at which to operate. This participatory ergonomics framework (the PEF) was validated through retrospective description of seven independently conducted case studies and through peer evaluation. The exercise suggests that the PEF can be used as a first basis to produce practical guidance on participatory ergonomics programmes.

Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration.

OBJECTIVES: To investigate the role of 2 specific alleles of the Stargardt disease gene (ABCA4) in the pathogenesis of age-related macular degeneration (AMD). Secondary objectives were to investigate differences in frequency of the G1961E allele in selected ethnic groups as well as to examine the segregation of both G1961E and D2177N alleles in 5 multiplex families with AMD. METHODS: Five hundred forty-four patients with AMD and 689 controls were ascertained from 3 continents. Blood samples from 62 normal individuals of Somalian ancestry were also obtained. Participants were screened for the presence of these ABCA4 alleles with a combination of restriction digestion and single-strand conformation polymorphism analysis of polymerase chain reaction amplification products. Detected alleles were confirmed by DNA sequencing. The number of subjects exhibiting the G1961E or D2177N variants were compared between AMD and control groups using a 2-tailed Fisher exact test. RESULTS: There was no significant difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant difference (P< .001) in the frequency of the G1961E alleles between normal individuals of Somali ancestry (11.3%) and normal individuals from other populations (0.4%). There was no evidence of cosegregation of these alleles and the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4 alleles were slightly more frequent in patients with AMD with choroidal neovascularization (2.7%) than those without this complication (2.5%). CONCLUSIONS: Somali ancestry is more than 100 times more strongly associated with presence of the G1961E allele than the AMD phenotype. This study did not find any statistically significant evidence for involvement of the G1961E or D2177N alleles of the ABCA4 gene in AMD. CLINICAL RELEVANCE: The ABCA4 gene is definitively involved in the pathogenesis of Stargardt disease and some cases of photoreceptor degeneration. However, it does not seem to be involved in a statistically significant fraction of AMD cases.

Systemic efficacy of nodulisporic acid against fleas on dogs.

Nodulisporic acid A (NSA) is a novel natural product from a new structural class that was shown previously to have insecticidal activity against blowfly larvae. To determine if there was useful systemic efficacy against fleas (Ctenocephalides felis). NSA was evaluated in an artificial membrane flea feeding device and in dogs. In the artificial membrane flea feeding device, adult C. felis were allowed to feed on bovine blood containing various concentrations of NSA through a Parafilm membrane. NSA killed the fleas with a 50% lethal concentration of 0.68 microg/ml and was approximately 10-fold more potent than the systemic insecticide ivermectin. In the initial probe dog test, a single beagle was challenged with 100 C. felis before oral dosing with 15 mg/kg of NSA. Flea counts conducted at 72 hr postdosing showed an 88% reduction relative to control. Re-challenge of the same dog at 5 days postdosing showed 50% reduction of fleas at day 7, demonstrating some residual flea activity. In a confirmatory study, 8 dogs were challenged with 100 fleas just before oral dosing with 15 mg/kg of NSA (4 dogs) or vehicle (4 dogs). There was 99% reduction of fleas at 48 hr postdosing in the NSA-treated dogs relative to control. Additional challenges with 100 fleas were performed on these 8 dogs at 48-hr intervals to determine the duration of efficacy, and there was 97, 51, and 0% reduction of fleas relative to control on days 4, 6, and 8, respectively. No adverse effects were observed in the dogs in these studies. These data show that NSA has potent oral activity in the dog for the control of fleas, while lacking overt mammalian toxicity.

A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis.

BACKGROUND: Before the September 1996 approval of 1% penciclovir cream for the treatment of herpes labialis, no other prescription topical therapy was approved for the treatment of this recurrent viral disease affecting approximately 20% of the adult population of the United States. Local anesthetics, such as tetracaine, have been used in over-the-counter topical products, but are only labeled for the relief of pain and itching associated with cold sores and fever blisters. OBJECTIVE: The purpose of this study was to determine whether a topical preparation of a tetracaine cream is safe and effective in the treatment of recurrent herpes labialis in immunocompetent patients. METHODS: A double-blind, placebo-controlled study was conducted to assess the relative effectiveness and safety of 1.8% tetracaine equivalent in a cream base versus placebo in the treatment of herpes labialis in immunocompetent adults. In this study, patients applied medication up to 6 times daily until the lesions healed (scab loss), but for no more than 12 days. The patients were monitored on the day of enrollment, once during the course of treatment, and at a final visit after the lesions had healed. Patients assessed themselves the day of scab formation and the day the scab fell off. They also graded, on a daily basis, their perception of relief from itching and pain and the overall benefit. RESULTS: The results from 72 patients (35 = placebo; 37 = active) showed that scab formation occurred in a mean of 2.4 +/- 0.27 days for the placebo group and 2. 3 +/- 0.26 days for the active group. Healing time (scab loss) occurred in a mean 7.2 +/- 0.36 days for the placebo group and in 5. 1 +/- 0.35 days in the active group. The difference observed for healing time between the placebo and the active tetracaine cream was statistically significant (P =.0002). This represents an approximately 30% reduction in the healing time for the active group compared with the placebo group. In addition, the study patients ranked the benefit of their treatment on a daily basis and graded the overall benefit of the therapy at their final visit. The ranking was on a 1 to 10 index scale (1 = no benefit at all; 10 = very effective treatment). At the final visit there was a statistically significant difference in the benefit index for active preparation versus placebo for this subjective evaluation (placebo index, 5.9 +/- 0.6; active index, 7.3 +/- 0.48 [P =.0359]). The subjects also evaluated relief from itching and pain on a daily basis. Relief from itching was significantly greater in the active group than in the placebo group on days 2 and 3 after initiation of the treatment. Pain was not found to be severe in either the placebo or active treatment groups. At day 2 of treatment and beyond, pain scores never were greater than 3.2 +/- 0.28 for active on a scale in which 1.0 represented "no pain at all" and 10 represented "most severe pain imaginable." Although mean values for pain were always less for the active therapy, lesional pain scores never reached statistically significant lower values for active compared with placebo. CONCLUSION: Our findings indicate that a 1.8% topical tetracaine cream, when applied frequently, significantly reduces the healing time of recurrent herpes labialis lesions. Additionally, it is perceived by the study subjects to reduce itching of the lesions and to have a beneficial overall effect.

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

OBJECTIVE: To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. PATIENTS: Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. METHODS: Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. RESULTS: Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. CONCLUSIONS: A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. CLINICAL RELEVANCE: The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

Safety pictograms: are they getting the message across?

This study set out to investigate the role of pictograms in conveying consumer safety information. The experimental work was carried out in two parts. The first part investigated UK comprehension levels of 13 product related pictograms. A new method of judging levels of comprehension of the pictograms was developed. In general the pictograms surveyed were found to be poorly understood, particularly those which were abstract in nature. The second part of the research investigated the effect of different warning styles on noticeability and intended compliance. This was tested using the new European Standard pictogram developed to convey the small parts warning on toys. The effect on parents' intended purchase decisions of different pictograms and or text messages was investigated. Results indicated that parents' decisions on toy suitability were influenced by the perceived hazardousness of the product rather than warnings, regardless of their design. The paper discusses the advantages and limitations of pictograms as a method for conveying consumer information and makes recommendations for their effective use.

Cytochalasin-induced actin disruption of polarized enterocytes can augment internalization of bacteria.

Cytochalasin-induced actin disruption has often been associated with decreased bacterial internalization by cultured epithelial cells, although polarized enterocytes have not been systematically studied. In assays using confluent polarized HT-29 enterocytes, cytochalasin D appeared to increase internalization of wild-type Salmonella typhimurium, Proteus mirabilis, and Escherichia coli. HeLa and HEp-2 epithelial cells, as well as HT-29 and Caco-2 enterocytes, were used to clarify this unexpected observation. Resulting data showed that cytochalasin D was associated with increased internalization of S. typhimurium and P. mirabilis by both HT-29 and Caco-2 enterocytes and with increased internalization of E. coli by HT-29 enterocytes; with either HeLa or HEp-2 cells, cytochalasin was associated with no change or a decrease in internalization of these same bacterial strains. Cytochalasin caused decreased internalization of Listeria monocytogenes by HT-29, Caco-2, HeLa, and HEp-2 cells, indicating that cytochalasin did not consistently augment bacterial internalization by polarized enterocytes. Fluorescein-labeled phalloidin confirmed marked disruption of filamentous actin in cytochalasin-treated HT-29, Caco-2, HeLa, and HEp-2 cells. Cytochalasin had no noticeable effect on epithelial viability but caused distorted apical microvilli, cell rounding, and separation of adjacent enterocytes in confluent cultures (with a corresponding decrease in transepithelial electrical resistance). Scanning electron microscopy showed that cytochalasin-induced enhanced bacterial internalization was associated with preferential bacterial adherence on the exposed enterocyte lateral surface. Colchicine, used to disrupt microtubules, had no noticeable effect on bacterial internalization by HT-29 or Caco-2 enterocytes. These data indicated that for HT-29 and Caco-2 enterocytes, cytochalasin-induced disruption of filamentous actin might augment internalization of some bacterial species by a mechanism that appeared to involve exposure of the enterocyte lateral surface.

Eprinomectin: a novel avermectin for use as a topical endectocide for cattle.

Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel avermectin selected for development as a topical endectocide for all cattle, including lactating dairy cows. Herein, we show its anthelmintic, insecticidal and miticidal activity. To determine its anthelmintic capabilities, eprinomectin was tested topically on Jersey calves at 0.08, 0.2, or 0.5 mg kg-1 in a probe formulation against experimental infections of adult Haemonchus placei, ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Dictyocaulus viviparus. Eprinomectin removed > or = 99% and > or = 98% of the adult stage of every species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The lowest dosage (0.08 mg kg-1) produced maximal or near maximal efficacy against most of the adult endoparasites with the exception of T. colubriformis (87%) and C. oncophora (88%). In a separate test, eprinomectin was evaluated topically against the immature stages of species at the same dosages. Results showed > or = 99% and > or = 98% removal of the immature stages of each species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The 0.08 mg kg-1 dosage maintained > or = 97% efficacy against 6 species with reduced activity against H. placei (42%) and N. helvetianus (66%). For ectoparasites, eprinomectin was tested topically at 0.16, 0.24, 0.32 or 0.5 mg kg-1 on mixed breed cattle naturally infested with the sucking louse, Linognathus vituli. Complete elimination of lice at all dosages was observed by day 14. Topical delivery of eprinomectin at 0.16, 0.24, 0.32 or 0.5 mg kg-1 to Holstein calves experimentally challenged with horn fly, Haematobia irritans, produced 100% efficacy to challenge by week 2 post-treatment in all dosages groups and 94% and 99% efficacy to challenge at the 0.32 and 0.5 mg kg-1 dosage groups, respectively, at week 4. Topical delivery of eprinomectin at 0.16, 0.24 or 0.5 mg kg-1 to Deutsches Fleckvieh cattle infested with mange mites, Chorioptes bovis, produced > or = 95% control at all dosages levels by day 14 post-treatment and was maintained at or near this efficacious level for the 6-week duration of the trial. No adverse reaction was observed in any animal in any of these tests. In summary, these experimental data indicate that eprinomectin is an excellent broad-spectrum endectocide for cattle and is suitable for topical delivery.

Avermectins and milbemycins against Fasciola hepatica: in vivo drug efficacy and in vitro receptor binding.

Few studies have examined activity against trematodes for the avermectin/milbemycin class of anthelmintics. To gain insight into this, 12 different members of the avermectin/milbemycin mode of action class were tested against juvenile Fasciola hepatica in a mouse model. The compounds chosen were Avermectin A1, Avermectin A2, Avermectin B1, Avermectin B2, Ivermectin, Ivermectin monosaccharide, Ivermectin aglycone, 13-deoxy ivermectin aglycone, Moxidectin, 13-O-methoxyethoxymethyl ivermectin aglycone, 4"-deoxy-4"-epi-methylamino avermectin B1, and 4"-deoxy-4"-epi-acetylamino avermectin B1 5-oxime. Each of these compounds was administered orally to 4 mice at 2.0 mg kg-1. These mice had been administered 3 metacercariae of F. hepatica 14 days prior to treatment and all mice were necropsied 4 days after treatment. At necropsy, none of the individual avermectin or milbemycin-treated groups showed any significant activity (P > 0.05) against juvenile F. hepatica relative to a vehicle-treated control. In a receptor binding study, adult F. hepatica that had been obtained from sheep were homogenized, their membranes incubated in the presence of 3H-ivermectin, and then measured for high affinity binding sites. The same was done with the free-living nematode, Caenorhabditis elegans. While the C. elegans membranes displayed high affinity 3H-ivermectin binding sites over the range of ivermectin concentrations tested (5-100 nM), no significant 3H-ivermectin binding sites were detected in the F. hepatica membranes. Based on these data, it seems unlikely that any avermectin or milbemycin will show activity against F. hepatica, and certainly makes one pessimistic about possible activity of this mode of action class against trematodes in general.

Seven patients with respiratory infections due to Corynebacterium pseudodiphtheriticum.

Seven cases of lower respiratory tract infection due to Corynebacterium pseudodiphtheriticum are described. Lower respiratory tract infections with C. pseudodiphtheriticum in immunocompetent patients are usually associated with pre-existing chronic pulmonary disease, and are sometimes associated with endotracheal intubation. Antimicrobial susceptibility testing of these isolates showed uniform sensitivity to penicillin and variable results to erythromycin.

Antiviral activity of a sulphated polysaccharide from the red seaweed Nothogenia fastigiata.

The antiviral activity of polysaccharide fractions obtained from water extracts of the red seaweed Nothogenia fastigiata was investigated. Fraction F6, corresponding to a sulphated xylomannan, was found to inhibit efficiently the replication of herpes simplex virus type 1 (HSV-1). Furthermore, F6 selectively inhibited the replication of several other enveloped viruses including herpes simplex virus type 2, human cytomegalovirus (HCMV), respiratory syncytial virus, influenza A and B virus, Junin and Tacaribe virus and simian immunodeficiency virus. F6 was only weakly active against human immunodeficiency virus type 1 and 2. The mode of action of F6 against HSV-1 and HCMV could be ascribed to an inhibitory effect on virus adsorption.