Severe Pulmonary Fascioloidosis in a Wild Mouflon (Ovis Musimon) - a Case Report.

A wild male mouflon (Ovis musimon) was shot due to the observed weakness. Necropsy revealed consolidated lungs and traces of black pigment and fibrin on the liver. On the cut surface, a juvenile fl uke was found in the lungs, while traces of destroyed fl ukes' migratory channels were found in the liver. F. magna infection in both, wild and domestic ruminants, causes three types of species-specific host-parasite interactions; definitive, dead-end and aberrant. mouflon are classifi ed as aberrant hosts and here we report unsuccessful migration of a juvenile fl uke that led to a severe pneumonia.

Monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.

A meta-analysis of the prevalence of cardiac valvulopathy in hyperprolactinemic patients treated with Cabergoline.

CONTEXT: Cabergoline is first line treatment for most patients with lactotrope pituitary tumors and hyperprolactinemia. Its use at high-dose in Parkinson's disease has largely been abandoned, because of its association with the development of a characteristic restrictive cardiac valvulopathy. Whether similar valvular changes occur in patients receiving lower doses for treatment of hyperprolactinemia is unclear, although stringent regulatory recommendations for echocardiographic screening exist. OBJECTIVE: To conduct a meta-analysis exploring any link between the use of cabergoline for the treatment of hyperprolactinemia and clinically-significant cardiac valvulopathy. DATA SOURCES: Full-text papers published up to and including January 2017 were found via PubMed and selected according to strict inclusion criteria. STUDY SELECTION: All case-control studies were included where patients had received ≥6 months cabergoline treatment for hyperprolactinemia. Single case reports, previous meta-analyses, review papers and papers pertaining solely to Parkinson's disease were excluded. 13/76 originally selected studies met inclusion criteria. DATA EXTRACTION: A list of desired data were compiled and extracted from papers by independent observers. Each also independently graded for paper quality (bias) and met to reach consensus. DATA SYNTHESIS: More tricuspid regurgitation was observed (OR 3.74; 95% CI 1.79-7.8 p<0.001) in the cabergoline treated patients compared to controls. In no patient was tricuspid valve dysfunction diagnosed as a result of clinical symptoms. There was no significant increase in any other valvulopathy. CONCLUSIONS: Treatment with low dose cabergoline in hyperprolactinemia appears to be associated with an increased prevalence of tricuspid regurgitation. The clinical significance of this is unclear and requires further investigation. 51.

De novo HNF1 homeobox B mutation as a cause for chronic, treatment-resistant hypomagnesaemia.

29-year-old female presenting with an 8-year history of unexplained hypomagnesaemia, which was severe enough to warrant intermittent inpatient admission for intravenous magnesium. Urinary magnesium was inappropriately normal in the context of hypomagnesaemia indicating magnesium wasting. Ultrasound imaging demonstrated unilateral renal cysts and computed tomography of kidneys, ureters and bladder showed a bicornuate uterus. Referral to genetic services and subsequent testing revealed a de novo HNF1B deletion. LEARNING POINTS: HNF1B loss-of-function mutations are one of the most common monogenic causes of congenital anomalies of the kidney and urinary tract.Those with HNF1B mutations may have some of a constellation of features (renal and hepatic cysts, deranged liver function tests, maturity onset diabetes of the young type 5 (MODY5), bicornuate uterus, hyperparathyroidism, hyperuricaemic gout, but presenting features are highly heterogeneous amongst patients and no genotype/phenotype correlation exists. HNF1B mutations are inherited in an autosomal dominant pattern but up to 50% of cases are de novo.HNF1B mutations can be part of the Chr17q12 deletion syndrome, a contiguous gene deletion syndrome.Inorganic oral magnesium replacements are generally poorly tolerated with side effects of diarrhoea. Organic magnesium compounds, such as magnesium aspartate, are better absorbed oral replacement therapies.

A cross-sectional study of the prevalence of cardiac valvular abnormalities in hyperprolactinemic patients treated with ergot-derived dopamine agonists.

CONTEXT: Concern exists in the literature that the long-term use of ergot-derived dopamine agonist drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking dopamine agonists as treatment for lactotrope pituitary tumors and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in a large group of patients who were receiving dopamine agonist therapy for hyperprolactinemia. Studies were performed in accordance with the British Society of Echocardiography minimum dataset for a standard adult transthoracic echocardiogram. Poisson regression was used to calculate relative risks according to quartiles of dopamine agonist cumulative dose using the lowest cumulative dose quartile as the reference group. SETTING: Twenty-eight centers of secondary/tertiary endocrine care across the United Kingdom participated in the study. RESULTS: Data from 747 patients (251 males; median age, 42 y; interquartile range [IQR], 34-52 y) were collected. A total of 601 patients had taken cabergoline alone; 36 had been treated with bromocriptine alone; and 110 had received both drugs at some stage. The median cumulative dose for cabergoline was 152 mg (IQR, 50-348 mg), and for bromocriptine it was 7815 mg (IQR, 1764-20 477 mg). A total of 28 cases of moderate valvular stenosis or regurgitation were observed in 24 (3.2%) patients. No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK cross-sectional study does not support a clinically concerning association between the use of dopamine agonists for the treatment of hyperprolactinemia and cardiac valvulopathy.

Establishing a multicentre clinical research network: lessons learned.

BACKGROUND: Within many health care disciplines, research networks have emerged to connect researchers who are physically separated, to facilitate sharing of expertise and resources, and to exchange valuable skills. A multicentre research network committed to studying difficult cancer pain problems was launched in 2004 as part of a Canadian initiative to increase palliative and end-of-life care research capacity. Funding was received for 5 years to support network activities. METHODS: Mid-way through the 5-year granting period, an external review panel provided a formal mid-grant evaluation. Concurrently, an internal evaluation of the network by survey of its members was conducted. Based on feedback from both evaluations and on a review of the literature, we identified several components believed to be relevant to the development of a successful clinical cancer research network. RESULTS: THESE COMMON ELEMENTS OF SUCCESSFUL CLINICAL CANCER RESEARCH NETWORKS WERE IDENTIFIED: shared vision, formal governance policies and terms of reference, infrastructure support, regular and effective communication, an accountability framework, a succession planning strategy to address membership change over time, multiple strategies to engage network members, regular review of goals and timelines, and a balance between structure and creativity. CONCLUSIONS: In establishing and conducting a multi-year, multicentre clinical cancer research network, network members were led to reflect on the factors that contributed most to the achievement of network goals. Several specific factors were identified that seemed to be highly relevant in promoting success. These observations are presented to foster further discussion on the successful design and operation of research networks.

Feasibility of administering zoledronic acid in palliative patients being cared for in the community: results of a pilot study.

Tumour-induced hypercalcemia (TIH) and pain from bone metastases are common complications of advanced malignancy and have a significant negative impact on quality of life. Many cancer patients in the advanced stages of their palliative illness prefer to avoid hospitalization and to receive their care in the community setting. This small open-label prospective pilot study explored the feasibility of administering zoledronic acid intravenously in the community setting (home and residential hospices). It enrolled a convenience sample of 12 patients with advanced cancer and TIH (n = 7), malignant bone pain (n = 3), or TIH and malignant bone pain (n = 2). The mean duration of infusion was 15 minutes (range: 14-30 minutes). The total nursing time required was 95 minutes, and the mean total cost, including nursing time, travel time, and drug costs was $708.97 per infusion. This cost was compared with costs for clodronate and pamidronate ($402.52 and $406.12 respectively). Calcium fell from a mean of 2.97 mmol/L on day 0 to 2.63 mmol/L on day 4 and to 2.54 mmol/L on day 10. Delirium resolved in 2 of 5 patients with TIH-associated delirium. Intravenous zoledronic acid administered in the community to palliative patients at the end of life is feasible and safe, and the short duration of infusion offers advantages to patients and nursing resources alike. The higher cost of zoledronic acid per infusion may be offset by the advantage of its short infusion time.

The malignant wound assessment tool: a validation study using a Delphi approach.

Malignant wounds, caused by the direct invasion of cancer into the skin, occur in cancer patients with primary skin tumours and as cutaneous metastasis in approximately 10% of patients with metastatic internal malignancies. Malignant wounds have a profound impact on patients, family members and health care providers. The assessment of the patient with malignant wounds can be complex and there is no widely accepted, consistent approach. Valid, descriptive survey research methods were used to develop the Malignant Wound Assessment Tool (MWAT). The authors developed two versions of the MWAT: a brief clinical version (MWAT-C) and a more detailed research version (MWAT-R). Domains include clinical wound features, physical effects and emotional and social impacts of the wound. The two tools underwent content and construct validity testing using a Delphi process. An international panel of professionals with clinical or research expertise related to malignant wounds was formed. Panelists participated in two rounds of review for each tool. Development and face validity testing of the MWAT-C and MWAT-R tools through the Delphi process have resulted in tools ready for clinical application and will support clinical and research activities to improve care for patients with this devastating condition.

First Report of Bacterial Soft Rot on Vanda Orchids Caused by Dickeya chrysanthemi (Erwinia chrysanthemi) in the United States.

Vanda orchids are epiphytes grown for their attractive flowers by commercial producers and hobbyists throughout Florida. In August 2007, five Vanda hybrids, with an economic value of $150 each, were found at a nursery in central Florida with leaves that were macerated, brown, and water soaked. According to the growers, the plants were normal the previous day but symptoms developed rapidly. The plants were immediately removed from the greenhouse to prevent potential disease spread. Bacteria were isolated according to the method of Schaad et al. (1). Isolated bacteria grew at 37°C, were gram negative, degraded pectate, and produced phosphatase. MIDI (Sherlock version TSBA 4.10; Microbial Identification 16 System, Newark, DE) (SIM 0.906) identified the bacteria as Erwinia chrysanthemi (Dickeya chrysanthemi Burkholder et al. 1953) Samson et al. 2005. PCR was performed on the 16S rRNA gene (GenBank Accession No. EU526397) with primers 27f (5'-GAGAGTTTGATCCTG GCTCAG-3') and 1495r (5'-TACGGCTACCTTGTTACGA-3') (2). Subsequent DNA sequencing and GenBank search showed the isolated strain is 99% identical to that of Dickeya chrysanthemi. Four leaves each of six Vanda hybrids were inoculated by injecting approximately 150 µl of a bacteria suspension at 1 × 108 CFU/ml into each leaf. One plant was inoculated with water in each of four leaves. Plants were enclosed in plastic bags and returned to the greenhouse under 50% shade at 29°C day and 17°C night temperatures. Within 24 h, soft rot symptoms appeared on inoculated leaves. The water control appeared normal. D. chrysanthemi was reisolated and identified with the above method, thus Koch's postulates were fulfilled. To our knowledge, this is the first report of a soft rot caused by D. chrysanthemi on Vanda hybrids. Because of the popularity and high value of Vanda orchids, proper identification of this rapidly progressing bacterial disease is of great importance for the commercial producer and homeowner alike. References: (1) N. W. Schaad et al. Erwinia soft rot group. Page 56 in: Laboratory Guide for Identification of Plant Pathogenic Bacteria. 3rd ed. N. W. Schaad et al., eds. American Phytopathological Society. St. Paul, MN, 2001. (2) W. G. Weisburg. J. Bacteriol. 173:697, 1991.

Pythium spp. Isolated from Bermudagrass During Overseed Transitions in Florida and Pathogenicity of Pythium irregulare on Poa trivialis.

Pythium spp. were isolated from nonoverseeded bermudagrass and from bermudagrass overseeded with cool-season turfgrass species from October 2000 to July 2001 from two sites in Florida. Pythium spp. were isolated from nonoverseeded and overseeded, and fumigated and nonfumigated, bermudagrass plots from October 2001 to July 2002 from one of the two sites. The vast majority of isolates of Pythium spp. were obtained from the bermudagrass, rather than the cool-season turfgrass species (Poa trivialis or Lolium perenne) used as overseed. In the first year at the Ft. Lauderdale site, Pythium graminicola dominated (91% of isolates obtained). In the first year at the Gainesville site, P. graminicola (56% of isolates) and P. irregulare (36%) dominated; however, after fumigation and replanting, P. graminicola comprised only 11% of all isolates. P. irregulare comprised 30% of all isolates, but was found only in nonfumigated plots. A different species, P. ultimum var. ultimum, not isolated in the first year, was recovered (34% of isolates) from the replanted field in February and March. In preemergence pathogenicity tests, three of four isolates of P. irregulare were moderately to highly pathogenic on Poa trivialis, but not on L. perenne, and isolates of Pythium graminicola and P. ultimum var. ultimum were not pathogenic on either turfgrass species. Pathogenic Pythium spp. may survive from season to season on bermudagrass and, under favorable conditions, may cause damping-off or blight on the overseeded cool-season turfgrass.

First Report of Gaeumannomyces graminis var. graminis on Seashore Paspalum in the United States.

Gaeumannomyces graminis var. graminis is an ectotrophic, root-infecting fungus found on some warm-season turfgrass species (1). A sample of seashore paspalum (Paspalum vaginatum) exhibiting rotted roots and stolons was taken from dying patches of turf in a home lawn in Hernando County, FL, and submitted to the Florida Extension Plant Disease Clinic, Gainesville, in October 2001. The lawn had been established within the previous year. Strongly lobed hyphopodia typical of G. graminis var. graminis (3,4) were present on diseased roots and stolons, and no other fungal plant pathogens were detected in the sample. Diseased roots and stolons with lobed hyphopodia were surface-sterilized and placed on one-quarter-strength potato dextrose agar (PDA) amended with rifampicin and streptomycin. One isolate produced structures characteristic of G. graminis var. graminis (3,4), including dark, strongly lobed hyphopodia, and perithecia and ascospores in PDA after incubation. The isolate (PDC 2965) was grown on a sterile ryegrass seed substrate at 25°C for 4 weeks to produce inoculum (2). The isolate was used to inoculate pots of 'Sea Isle 1' seashore paspalum grown in sterile soil from sprigs. An inoculum layer, 1 to 2 cm deep, was placed 2 to 4 cm below each sprig and covered with an overlay of sterile soil prior to sprigging (2). Following 4 weeks of plant growth in a greenhouse, dark, necrotic lesions appeared on leaf bases. Very dark lesions developed on roots, and brown runner hyphae and strongly lobed hyphopodia were observed on root and shoot tissues. Selected pieces of symptomatic root and shoot tissue were surface-sterilized and placed on PDA. One week later, dark mycelia and deeply lobed hyphopodia were observed growing from roots and shoots on the PDA. After 1 month, black, flask-shaped perithecia, 156 to 234 µm in body width, developed in cultures. Hyaline, filiform, septate ascospores ranged from 75 to 100 µm (mean = 89 µm; n = 250) long and were approximately 2.5 µm wide. Hyphopodia, perithecia, and ascospores were characteristic of G. graminis var. graminis (3,4). To our knowledge, this is the first report of take-all root rot disease due to G. graminis var. graminis on seashore paspalum in the United States. References: (1) L. E. Datnoff et al. Plant Dis. 81:1127, 1997. (2) M. L. Elliott. Plant Dis. 79:699, 1995. (3) M. L. Elliott and P. J. Landschoot. Plant Dis. 75:238, 1991. (4) P. J. Landschoot. Taxonomy and biology of ectotrophic root-infecting fungi associated with patch diseases of turfgrasses. Pages 41-71 in: Turfgrass Patch Diseases. B. B. Clarke and A. B. Gould, eds. American Phytopathological Society, St. Paul, MN, 1997.

Families for children: international strategies to build in-country capacity in the Philippines, Thailand, Romania, and India.

Holt International Children's Services was founded in the 1950s to facilitate the adoption of Amerasian children in the aftermath of the Korean War. Today, its vision has expanded to encompass international policies, programs, and practices that will help establish nurturing, lifelong relationships for children. Working together with child welfare professionals and advocates, non-governmental organizations, and governments, Holt has helped to develop in-country, self-sustaining family resources for thousands of children. Efforts in the Philippines, Thailand, India, and Romania are highlighted.

Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain.

Oligodendrocyte precursor development in the embryonic spinal cord is thought to be regulated by the secreted signal, Sonic hedgehog (Shh). Such precursors can be identified by the expression of Olig genes, encoding basic helix-loop-helix factors, in the spinal cord and brain. However, the signaling pathways that govern oligodendrocyte precursor (OLP) development in the rostral central nervous system are poorly understood. Here, we show that Shh is required for oligodendrocyte development in the mouse forebrain and spinal cord, and that Shh proteins are both necessary and sufficient for OLP production in cortical neuroepithelial cultures. Moreover, adenovirus-mediated Olig1 ectopic expression can promote OLP formation independent of Shh activity. Our results demonstrate essential functions for Shh during early phases of oligodendrocyte development in the mammalian central nervous system. They further suggest that a key role of Shh signaling is activation of Olig genes.

Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube.

BACKGROUND: Organizing signals such as Sonic hedgehog are thought to specify neuronal subtype identity by regulating the expression of homeodomain proteins in progenitors of the embryonic neural tube. One of these, Nkx2.2, is necessary and sufficient for the development of V3 interneurons. RESULTS: We report that Olig genes, encoding basic helix-loop-helix (bHLH) proteins, are expressed in a subset of Nkx2.2 progenitors before the establishment of interneurons and oligodendroglial precursors. Gain-of-function analysis in transgenic mouse embryos indicates that Olig genes specifically inhibit the establishment of Sim1-expressing V3 interneurons. Moreover, coexpression of Olig2 with Nkx2.2 in the chick neural tube generated cells expressing Sox10, a marker of oligodendroglial precursors. Colocalization of Olig and Nkx2.2 proteins at the dorsal extent of the Nkx2.2 expression domain is consistent with regulatory interactions that define the potential of progenitor cells in the border region. CONCLUSIONS: Interactions between homeodomain and Olig bHLH proteins evidently regulate neural cell fate acquisition and diversification in the ventral neural tube. In particular, interactions between Olig and Nkx2.2 proteins inhibit V3 interneuron development and promote the formation of alternate cell types, including those expressing Sox10.

Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon.

In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern. We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions. They first appear within a region of anterior hypothalamic neuroepithelium that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex. Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HH) signalling is obligatory for oligodendrogenesis in the ventral telencephalon. Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex. Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures. Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain.

Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors.

The most common primary tumors of the human brain are thought to be of glial cell origin. However, glial cell neoplasms cannot be fully classified by cellular morphology or with conventional markers for astrocytes, oligodendrocytes, or their progenitors. Recent insights into central nervous system tumorigenesis suggest that novel molecular markers might be found among factors that have roles in glial development. Oligodendrocyte lineage genes (Olig1/2) encode basic helix-loop-helix transcription factors. In the rodent central nervous system, they are expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial progenitor. Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data provide evidence that neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. They further suggest the diagnostic potential of OLIG markers to augment identification of oligodendroglial tumors.

Oligodendrocyte development in the spinal cord and telencephalon: common themes and new perspectives.

There are clear parallels between oligodendrocyte development in the spinal cord and forebrain. However, there is new evidence that in both of these regions oligodendrocyte lineage development may be more complex than we earlier thought. This stems from the recent identification of three new transcription factor genes, Olig1, Olig2 and Sox10, that are expressed from the early stages of oligodendrocyte lineage development. In this article, we highlight the common themes underlying specification and early development of oligodendrocytes in the spinal cord and telencephalon. Then, we discuss recent studies of Sox10 and the Olig genes and their implications for oligodendrocyte specification. We conclude that although the mechanisms of oligodendrogenesis appear to be fundamentally similar at different rostro-caudal levels of the neuraxis, there are still many unanswered questions about the details of oligodendrocyte specification.