Initial assessment of the economic burden of major parasitic helminth infections to the ruminant livestock industry in Europe.

We report a European wide assessment of the economic burden of gastrointestinal nematodes, Fasciola hepatica (common liver fluke) and Dictyocaulus viviparus (bovine lungworm) infections to the ruminant livestock industry. The economic impact of these parasitic helminth infections was estimated by a deterministic spreadsheet model as a function of the proportion of the ruminant population exposed to grazing, the infection frequency and intensity, the effect of the infection on animal productivity and mortality and anthelmintic treatment costs. In addition, we estimated the costs of anthelmintic resistant nematode infections and collected information on public research budgets addressing helminth infections in ruminant livestock. The epidemiologic and economic input data were collected from international databases and via expert opinion of the Working Group members of the European Co-operation in Science and Technology (COST) action COMbatting Anthelmintic Resistance in ruminants (COMBAR). In order to reflect the effects of uncertainty in the input data, low and high cost estimates were obtained by varying uncertain input data arbitrarily in both directions by 20 %. The combined annual cost [low estimate-high estimate] of the three helminth infections in 18 participating countries was estimated at € 1.8 billion [€ 1.0-2.7 billion]. Eighty-one percent of this cost was due to lost production and 19 % was attributed to treatment costs. The cost of gastrointestinal nematode infections with resistance against macrocyclic lactones was estimated to be € 38 million [€ 11-87 million] annually. The annual estimated costs of helminth infections per sector were € 941 million [€ 488 - 1442 million] in dairy cattle, € 423 million [€ 205-663 million] in beef cattle, € 151million [€ 90-213 million] in dairy sheep, € 206 million [€ 132-248 million] in meat sheep and € 86 million [€ 67-107 million] in dairy goats. Important data gaps were present in all phases of the calculations which lead to large uncertainties around the estimates. Accessibility of more granular animal population datasets at EU level, deeper knowledge of the effects of infection on production, levels of infection and livestock grazing exposure across Europe would make the largest contribution to improved burden assessments. The known current public investment in research on helminth control was 0.15 % of the estimated annual costs for the considered parasitic diseases. Our data suggest that the costs of enzootic helminth infections which usually occur at high prevalence annually in ruminants, are similar or higher than reported costs of epizootic diseases. Our data can support decision making in research and policy to mitigate the negative impacts of helminth infections and anthelmintic resistance in Europe, and provide a baseline against which to measure future changes.

Welfare assessment in rabbits raised for meat and laboratory purposes in enclosures with two floor types: Perforated plastic with holes versus slats.

Due to welfare concerns and legal restrictions in certain countries, alternatives to wire net floors must be developed in rabbit husbandries. Also, there is a difference in regulations in Europe for laboratory rabbits vs. rabbits bred and kept for meat production. While there are regulations concerning floor design of enclosures for rabbits bred for meat production in many European countries, the European Directive 2010/63 lacks regulations for rabbits used for scientific purposes. This study compares two floors, which meet the Austrian legal requirements for growing rabbits intended for consumption as well as the requirements for laboratory rabbits. The dual use of rabbits bred for meat production and applicable for scientific purposes would avoid the problem of surplus animals of specialized producers for laboratory rabbits. A noryl floor with 12 mm circular holes was compared to a 10 mm slatted plastic floor. Parameters were soiling of cages and animals, parasitic burden, clinical health, and losses using objective scoring. Soiling of cages and animals and coccidial oocytes were significantly higher on the floors with circular holes. Obvious signs of disease showed a non-significant trend to be more frequent in the group with circular holes. This was linked with significantly higher losses. In conclusion, our study clearly shows that the floor with circular hole design cannot be endorsed, although it meets legal requirements. The slatted floor type can be cautiously recommended; however, to assure animal welfare in laboratory rabbits, legal authorities in Europe should take on the responsibility of regulating floor design in this sector.

A case of ocular infection with Onchocerca lupi in a dog from Germany.

Onchocerca lupi is an emerging zoonotic parasite infecting the ocular connective tissue of dogs, cats and humans. The only known case of canine ocular onchocerciasis in Germany was documented in 2002 in a shelter dog. However, the species of Onchocerca causing the infection could not be identified. Here, we report a case of the ocular infection with O. lupi in a dog, confirmed by PCR and sequencing of the cox1 gene. Further investigations are required to assess the risk factors for transmission and spread of the parasite in Germany.

Hormonal contraception and depression: a survey of the present state of knowledge.

PURPOSE: Depressive symptoms often occur among women of reproductive age. In this article we perform an analysis of existing studies to examine a possible correlation between depression and the use of hormone-based contraceptives. METHODS: The computerized databases MEDLINE/PubMed were searched for studies examining the relation between depressive disorders and hormonal contraception of the years 1976-2010. RESULTS: Data on this topic are limited. At least two confounding variables influence the analysis of the available data and make it difficult to draw firm conclusions: the inconsistent use of the term "depression" and the large number of combined contraceptives which vary in their composition. The association between the use of oral contraceptives and depression is not clear. We found that depression is not a common side effect of hormone-based contraceptives. CONCLUSION: Individual, patient-based decisions with consideration of the individual history and predispositions are recommended when starting oral contraceptives. If depressive symptoms or mood changes occur, decisions regarding discontinuation or medication change need to be made on an individual basis.

Hormone replacement therapy and endometrial cancer.

Postmenopausal hormone replacement therapy (HRT) using unopposed estrogens significantly increases endometrial cancer risk and should not be used in non-hysterectomized women. Even low-potency estrogens (oral estriol) or low-dose unopposed estrogens significantly enhance the risk to develop endometrial cancer. This risk is markedly reduced, when in addition to estrogens, progestins are administered for at least 10 days (better 14 days) per month. In some studies, a normalization of endometrial cancer risk to that of women receiving no HRT was only found when a continuous combined estrogen/progestin replacement was used. The use of progestins for less than 10 days per month and long-cycle regimens, where a progestin is added only every 3 months cannot be recommended. For women needing HRT, estrogen dose should be selected as low as possible and reassessment of the need of HRT should be performed annually.

Oocyte-sperm interaction in the course of IVF: a scanning electron microscopy analysis.

Interaction between the spermatozoon and the zona pellucida during the first steps of fertilization was analysed on approximately 500 polyploid and unfertilized IVF oocytes by scanning electron microscopy (SEM). Oocytes demonstrate high inter- and intra-individual variations in size and morphology which do not correlate either with the maturity of the oocytes or with the age of the women. During gamete interaction, corona radiata cells are widely dispersed around the zona but are still in contact with it through cytoplasmic filaments. Channels between granulosa cells guide spermatozoa towards the zona. In the course of fertilization, different types of attachment of the spermatozoon to the oocyte occur. Most commonly, a flat, tangential attachment of the sperm head to the surface of the zona appears, which is then followed by intrusion into the zona in precisely this horizontal position. However, vertical binding with penetration by the tip of the head first also occurs. In oocytes where large, cluster-like numbers of bound spermatozoa are visible, vertical binding and penetration is the most usual position. In the process of gamete interaction, both spermatozoa and zona pellucida are actively involved. Spermatozoa, including their tails, which are attached to the zona, are overgrown by filaments of zona material. These filaments of the zona are made of granules, which are the basic components of zona material. After the removal of the zona pellucida by laser, the oolemma becomes visible. It is covered by microvilli of highly variable numbers. Between these microvilli, cortical granules are evident, and appear even before sperm penetration.

[Hormonal therapy and chemotherapy of endometrial cancer]. / Hormon- und Chemotherapie beim Endometriumkarzinom.

Endometrial cancer is usually diagnosed at an early stage where surgery alone is the adequate therapy. Chemotherapy and hormonal treatment are therefore almost exclusively performed in palliative situations. Hormonal treatment with progestogens (medroxyprogesterone acetate and megestrol acetate) should be the therapy of choice primarily as these drugs are very well tolerated. Tamoxifen and GnRH analogs are further options but are seldom used. The response rates to hormonal treatment are relatively low (max. 25 %) with short remissions in most cases. - So far neither hormonal treatment nor cytotoxic chemotherapy has been shown to have substantial benefits in the adjuvant setting. In some selected high risk cases (serous papillary carcinomas, extra uterine manifestation) adjuvant chemotherapy may be an option following surgery, before or after radiotherapy. Age, general condition and morbidity of the patients need to be considered as limiting factors for chemotherapy. Crucial for the prognosis of all endometrial cancer patients however, is the stage adapted surgery. - Cytotoxic chemotherapy has failed to bring a break through in the therapy of advanced endometrial cancer. Cisplatin plus doxorubicin is the standard combination to date, with anthracyclines being the more important component. In a mono-therapy setting, doxorubicin and epirubicin are well tolerated and convenient in their efficacy. For recurrent and metastatic disease, docetaxel is being evaluated for efficacy and side effects in a multicenter phase II trial.

Androblastoma of the ovary: clinical, diagnostic and histopathologic features.

Androblastomas of Sertoli-Leydig cell tumors of the ovaries are classified into the group of sex cord stromal tumors and represent an extremely rare form of tumor (0.2% of all ovarian tumors) in women. Their malignant potential is lower than that of epithelial ovarian cancer. They cause signs of virilization, although these are not obligatory. In many cases secondary amenorrhea is the only symptom of the disease. This leads to an intensive search for the source of the disorder. Frequently only the elevated production of androgens gives a preoperative clue to the tumor type. The recommendation to include the measurement of androgen levels in the routine diagnosis of secondary amenorrhea must therefore be endorsed. The tumors are usually sonographically identifiable; in differential diagnosis, hyperandrogenemia of other origins (e.g., Cushing's disease, adrenal hyperplasia, pituitary adenoma, other causes of ovarian and adrenal androgen hypersecretion, intersexuality, medically induced androgenization) have to be ruled out. In view of the good prognosis, the therapy of choice consists simply in adnexectomy of the affected side. With regular measurement of serum androgen levels an effective control of the course of the disorder is possible. A conclusive pathological diagnosis is difficult as heterologous tumors and mixed tumors exist and, furthermore, other tumor types are capable of imitating Sertoli-Leydig cell tumors.

LH pulses and the corpus luteum: the luteal phase deficiency LPD).

The proper function of the GnRH pulse generator in the hypothalamus is essential for normal ovarian function, hence also for proper function of the corpus luteum. During the luteal phase LH pulses stimulate progesterone release, which is essential for normal endometrial transformation. Approximately one-half of all luteal phase deficiencies (LPD) are due to improper function of the GnRH pulse generator. Obviously, following ovulation the increased serum progesterone levels oversuppress the GnRH pulse generator, resulting in too few LH pulses and therefore improper luteal function. Also, latent hyperprolactinemia may lead to an LPD which can be effectively treated with plant extracts containing dopaminergic (prolactin-suppressing) compounds. Our increasing knowledge of auto- and paracrine mechanisms between nonsteroidogenic and steroidogenic cells now allow subclassification of LPDs of ovarian origin. The so-called small luteal cells are LH-responsive. If they develop improperly the regularly occurring LH pulses are unable to stimulate progesterone secretion from the small luteal cells, which results in what we call the small luteal cell defect. In addition, there is also evidence that the large luteal cells may function improperly. Hence, basal progesterone release is too low while LH-stimulated progesterone release from the small luteal cells appears to be intact. This subclassification of luteal phase deficiency results in the suggestion of different treatments. In cases where the corpus luteum is LH-responsive, such as the hypothalamic corpus luteum insufficiency and the large luteal cell defect, HCG treatment or pulsatile treatment with GnRH is advisable. In the case of LH/hCG-unresponsive small luteal cell defect a progesterone substitution is suggested.

Pseudo dicentric chromosome (5;21): a rare example of maternal germline mosaicism.

Karyotyping of a malformed male newborn revealed the unbalanced karyotype of 46,XY, psudic(5;21)(q12;p13), +5 resulting in trisomy for the short arm of chromosome 5 and partial trisomy for 5q. Both parents had normal karyotypes in their peripheral blood lymphocytes. A second pregnancy ended in a miscarriage at 16 weeks gestation, sonographically 12 weeks. Karyotyping of chorionic villi from the abortus revealed the same unbalanced karyotype that had been identified in the first child. Fluorescence in-situ hybridization analysis confirmed a trisomy 5p. Microsatellite marker analysis ruled out illegitimacy and proved the maternal origin of the trisomic section of chromosome 5. Extended chromosome analysis of 60 metaphase cells from maternal skin fibroblasts and 40 metaphase cells from lymphocytes did not reveal mosaicism for psudic(5;21). These findings suggest the presence of a maternal germline mosaicism.

Homozygous factor V Leiden mutation in a woman with multiple adverse pregnancy outcomes.

We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy.

Features of Antley-Bixler syndrome in an infant born to a mother with pregnancy luteoma.

UNLABELLED: We report a female newborn with characteristic signs of Antley-Bixler syndrome (ABS) such as midface hypoplasia, radiohumeral synostosis and multiple joint contractures. The newborn also presented ambiguous genitalia, stage Prader V, and congenital adrenal hyperplasia. The mother experienced midterm virilization due to a pregnancy luteoma. Her elevated androgen levels and virilization symptoms normalized post partum without treatment. The newborn had elevated serum testosterone and 17-OH-progesterone levels which remained elevated because of a 21-hydroxylase deficiency. The child's treatment in order of priority was: hydrocortisone substitution, craniofacial/skeletal anomaly management and surgical correction of the external genitalia. Mutations in the genes for fibroblast growth factor (FGF) 8 and receptors FGFR1, FGFR2, and FGFR3 were not detected. CONCLUSION: A newborn girl with manifestations of the Antley-Bixler syndrome showed severe virilization probably caused by the association of a mild 21-hydroxylase deficiency and maternal hyperandrogenism due to a pregnancy luteoma. Abnormalities of androgen metabolism may be responsible for virilization reported in other cases of the Antley-Bixler syndrome.

Hormonal interactions in endometrial cancer.

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.

X-Y sperm selection: fact or fiction?

Selecting the gender of offspring has given rise to various and sometimes amusing stories. But regardless of which prefertilisation technique is used to influence the sex ratio of offspring it must fulfill certain criteria. First of all it must achieve a complete separation of the X and Y bearing sperm in sufficient quantities. Secondly sperm must be viable after separation and capable of fertilising. Sex preselection methods can be divided into two general groups which either separate spermatozoa on the basis of subtle physical or kinetic features or those which rely on distinctive nuclear characteristics unique either to X or Y chromosome bearing sperm. These, in turn, can be divided into in vivo methods designed to produce optimal conditions for fertilisation by either the X or Y bearing sperm, or in vitro sperm separation methods designed to separate X or Y bearing sperm. According to all published data, the different separation techniques have been shown not to be very effective. Only sex selection of spermatozoa by chromatin differences (cell sorting by flow cytometry) has demonstrated a significant enrichment of the X bearing sperm.

Regulation of steroid production and its function within the corpus luteum.

During the second half of the luteal phase, the human corpus luteum becomes responsive to regular luteinizing hormone (LH) pulses. These LH pulses stimulate progesterone secretion tonically, and during this tonic stimulation, additional LH-independent progesterone pulses occur, which are particularly pronounced in women with human chorionic gonadotropin-stimulated luteal function. No progesterone pulses are seen in women suffering from corpus luteum deficiency due to absent LH pulses. The corpus luteum thus has a progesterone pulse generator turned on by gonadotropins but functioning for several hours without further gonadotropic support. This pulse generator appears to be regulated by intraluteal auto-/paracrine mechanisms, which we have investigated in a porcine model using molecular, cellular, and in vivo tools. Luteal oxytocin and progesterone release occurs in tightly coupled pulses. In vivo, oxytocin and prostaglandin F2 alpha(PGF2 alpha) stimulate estradiol and progesterone release and estradiol itself further stimulates progesterone release. Analysis of the different luteal cell compartments (large luteal cells, small luteal cells, fibroblasts) suggests an intraluteal circuit that involves paracrine effects of estradiol, oxytocin, and PGF2 alpha. At the time of luteolysis, the luteotropic effects of estradiol are inhibited by tumor necrosis factor derived from invading macrophages and the intraluteal circuit is thereby disrupted, leading to luteolysis.

Relevance of genetic counselling in couples prior to intracytoplasmic sperm injection.

Since the first reports of successful pregnancies after treatment with intracytoplasmic sperm injection (ICSI) in humans numerous attempts have been made to assess the genetic risks of this highly invasive technique. During the study period (February 1995-November 96), 142 couples were referred to our genetic counselling unit prior to ICSI. In three couples, genetic counselling revealed a high recurrence risk for a monogenic disease (myotonic dystrophy, hereditary ataxia and polycystic kidney disease). In nine out of 128 men (7%) an abnormal karyotype was identified, including three Robertsonian translocations, two reciprocal translocations, three sex chromosome aberrations and one case with centric fission of chromosome no. 7. A total of 14 men refused chromosomal analysis. Only one of the 122 women examined had an abnormal karyotype (47, XXX). Five out of six men with congenital bilateral absence of the vas deferens (CBAVD) had at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Three had mutations in both CFTR alleles, including one case in which the second mutation was the 5T allele. One patient with CBAVD and a single Delta F508 CFTR mutation also had left renal agenesis. In conclusion, we strongly recommend that genetic counselling, chromosomal analysis and, in the case of CBAVD, screening for CFTR mutations should be offered to all couples with a diagnosis of male or idiopathic infertility.