Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation.

Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC).

A cross-sectional analysis of physical activity and obesity indicators in European participants of the EPIC-PANACEA study.

OBJECTIVES: Cross-sectional data suggest a strong association between low levels of physical activity and obesity. The EPIC-PANACEA (European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project was designed to investigate the associations between physical activity and body mass index (BMI) and waist circumference based on individual data collected across nine European countries. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 519 931 volunteers were recruited between 1992 and 2000, of whom 405 819 had data on main variables of interest. Height, body weight and waist circumference were measured using standardized procedures. Physical activity was assessed using a validated four-category index reflecting a self-reported usual activity during work and leisure time. The associations between physical activity and BMI and waist circumference were estimated using multilevel mixed effects linear regression models, adjusted for age, total energy intake, smoking status, alcohol consumption and educational level. RESULTS: A total of 125 629 men and 280 190 women with a mean age of 52.9 (s.d. 9.7) and 51.5 (s.d. 10.0) years, respectively were included. The mean BMI was 26.6 kg/m(2) (s.d. 3.6) in men and 25.0 kg/m(2) (s.d. 4.5) in women. Fifty percent of men and 30% of women were categorized as being active or moderately active. A one-category difference in the physical activity index was inversely associated with a difference of 0.18 kg/m(2) in the mean BMI (95% confidence interval, CI, 0.11, 0.24) and 1.04-cm (95% CI 0.82, 1.26) difference in waist circumference in men. The equivalent figures for women were 0.31 kg/m(2) (95% CI 0.23, 0.38) and 0.90 cm (95% CI 0.71, 1.08), respectively. CONCLUSIONS: Physical activity is inversely associated with both BMI and waist circumference across nine European countries. Although we cannot interpret the association causally, our results were observed in a large and diverse cohort independently from many potential confounders.

Evaluation of human recombinant tissue factor-activated thromboelastography in 49 dogs with neoplasia.

BACKGROUND: Abnormal routine coagulation assay results have been reported to be common in veterinary patients with neoplasia, but the overall hemostatic functional state, including hypercoagulability, has not been described. HYPOTHESIS: The overall hemostatic functional state, including hypercoagulability, can be assessed in dogs with neoplasia by tissue factor (TF)-activated thromboelastography (TEG). ANIMALS: Thirty-six dogs with malignant neoplasia and 13 dogs with benign neoplasia presented to the Small Animal Veterinary Teaching Hospital, The University of Copenhagen, Frederiksberg, Denmark. METHODS: Prospective study evaluating the overall hemostatic functional state in dogs with neoplasia by a newly validated TF-activated TEG assay and routine coagulation parameters activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, and D-dimer concentration. RESULTS: Hemostatic dysfunction was observed in 28/49 (57%) dogs with neoplasia. Twenty-four were dogs with malignant neoplasia, the majority of which 18/36 (50%) were hypercoagulable, whereas 6/36 (17%) were hypocoagulable. All hypocoagulable dogs had metastatic disease. The proportion of dogs with altered hemostasis was significantly different between dogs with malignant and benign neoplasia. CONCLUSIONS AND CLINICAL IMPORTANCE: TF-activated TEG detected hypercoagulable and hypocoagulable states in this population of dogs with neoplasia. The most common hemostatic abnormality in dogs with malignant neoplasia was hypercoagulability. These findings suggest that this novel hemostatic function test may be of value as a cage side method for the assessment of overall hemostatic function in dogs with cancer, including the detection of both hyper- and hypocoagulable states as well as mixed disorders.

Identification and expression of alternatively spliced aryl hydrocarbon nuclear translocator 2 (ARNT2) cDNAs from zebrafish with distinct functions.

In order to further establish zebrafish as a vertebrate model for studying the mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity it is necessary to characterize the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) signaling pathways in this species. In this study, three zfARNT2 cDNAs were isolated, expressed, and characterized and named zfARNT2b, zfARNT2c, and zfARNT2a. zfARNT2b, zfARNT2c, and zfARNT2a encode proteins with theoretical molecular weights of 81, 79, and 45 kDa, respectively. zfARNT2b and zfARNT2a proteins are identical over the first 403 amino acids but differ in their C-terminal domains as a result of alternative mRNA splicing. zfARNT2c is nearly identical to zfARNT2b, with the exception of an in frame 15 amino acid deletion adjacent to the basic region of zfARNT2c. Using quantitative RT-PCR methods the tissue distribution of each zfARNT2 isoform was determined. In COS-7 cells expressing zfARNT2b and zfAhR2, 10 nM TCDD causes a nine-fold induction of a dioxin responsive reporter gene. In COS-7 cells expressing zfARNT2a or zfARNT2c, TCDD does not induce reporter gene expression. In contrast, all three zfARNT2 proteins induce reporter gene activity under control of hypoxia responsive elements when cotransfected with the zebrafish endothelial specific PAS protein 1. DNA gel shift analysis suggests that the decreased function of zfARNT2a is due to inefficient binding of zfARNT2a/zfAhR2 complexes to dioxin responsive elements. These results also indicate that alternative mRNA splicing results in formation of ARNT proteins with distinct functional properties.

Allergy risk in an enzyme producing plant: a retrospective follow up study.

OBJECTIVE: To investigate the risk of enzyme sensitisation and clinical allergy in workers exposed to enzymes at Novo Nordisk A/S. METHODS: The study was a retrospective follow up study based on medical history and test data originally collected at routine screenings for enzyme allergy by the Occupational Health Service (OHS) of Novo Nordisk A/S during the period 1970-92. Workers were exposed to proteases, lipases, cellulases, and carboxyhydrases. Medical records of 3815 subjects were registered in the OHS database. According to criteria including possible enzyme exposure, allergy tests at the time of engagement, and participation in the allergy screening programme 1064 were selected for the present study. Outcomes were allergy symptoms, specific IgE test (radioallergosorbent test (RAST)) to enzymes, skin test reactions to common allergens and enzymes, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Potential risk factors were smoking habits, workplace, type of job, age, and sex. RESULTS: Sensitisation occurred to all types of enzymes handled in the plant, most often in production areas and laboratories; 8.8% developed clinical enzyme allergy during the first three years of employment. The risk declined during the period. The frequency of enzyme sensitisation, expressed as RAST values > 0.5 SU, was 36%, and the frequency of significant RAST values > or = 2 SU was 8%. Ranking diagnoses of enzyme allergy by severity, the frequency of asthma was 5.3%, rhinitis 3.0%, and urticaria 0.6%. Half of the cases occurred within the first 15 months of exposure. Smoking was an independent risk factor for clinical enzyme allergy (odds ratio (OR) = 2.3 (95% exact confidence interval (95% CI) 1.4 to 3.9), measurable RAST > or = 0.5 SU (OR = 1.5 (95% CI 1.1 to 2.1)), and RAST > or = 2 SU (OR = 4.5 (95% CI 2.2 to 8.4)). Atopic predisposition at the time of engagement was not a significant risk factor for enzyme allergy. This could be due to various selection mechanisms.

[Induced abortions in relation to the use of contraceptive agents]. / Provokerede aborter sat i relation til brugen af praeventive midler.

The aim of the study was to investigate the use of contraceptive methods among women referred to an induced abortion. The design was a prospective study of women seeking abortion, 854 were included consecutively. All were asked about the contraceptive methods used preceding their actual pregnancy. Was the contraceptive method used in a regular way, and what was the motive for her voluntary abortion? Of the 854 women, 831 chose to participate and answered the questions (97.3%). We found that 35% had used their contraceptive method in a regular way but became pregnant nevertheless. Another group of 33% had forgotten to use their contraceptives for a few days and became pregnant by accident. In the last group of 32% the women had not used any contraceptive methods. It is concluded that more information is necessary to get women and men to use contraceptive methods regularly with better precision and more seriousness.

Patellar taping: a radiographic examination of the medial glide technique.

The purpose of this study was to radiographically determine the effectiveness of the McConnell medial glide patellar taping technique. Twenty apparently healthy men, between ages 18 and 35, participated in this study. Subjects underwent a series of three radiographs in a modified Merchant view. First, a bilateral tangential view of the patellofemoral joints was taken to establish a baseline. Next, the same view was obtained with the experimental knees taped using the McConnell medial glide technique. Subjects then underwent a standardized exercise protocol to stress the tape and the accompanying knee structures. This was followed by a third view of the patellofemoral joints. Radiographs were measured using the Merchant congruence angle and analyzed statistically with dependent, mean difference tests. Results from this study indicate that the McConnell medial glide technique was effective in significantly moving the patella medially (P = 0.003), but that the tape was ineffective in maintaining this significance after exercise (P < 0.001). In 3 subjects (15%) of this sample, the tape was ineffective in moving the patella medially in any degree. One interesting finding was that exercise caused a statistically significant (P = 0.016) lateral shift from baseline in the control knees. This may suggest some clinical significance for patellar taping in preventing excessive lateral shift.

[Facial mask--effective protection against blood spattering]. / Ansigtsvisir--en effektiv beskyttelse mod blodstaenk.

The protective effect of a see-through face visor was evaluated in four different types of operation. In a clinical trial, the visor was used 150 times by eight different surgeons, and the number of blood spatters, type of operation and blood loss was registered. There was no correlation between the size of the blood loss and the number of blood spatters. At caesarean section, a median of four blood spatters per operation was found on the visor. At the other three types of operation (hysterectomy, operation for vaginal prolapse and episiotomy) the median was one blood spatter per operation. The area surrounding the eye constituted three percent of the visor's area. We thus found the risk of getting a blood spatter in the area of the eye at caesarean section to be four percent (95% confidence limits 0.1-20.4). In conclusion, we found the face visor offered good protection against blood spatters.

Normal karyotype in cultured chorionic villus cells, but mosaicism in amniotic and fetal cells.

A case with a normal male karyotype in cultured chorionic villus cells, but 46,XY/45,X/46,X,i(Yq) mosaicism in amniotic and fetal tissue is reported. The fetus was a phenotypic male. Pathological examination revealed discrete features, which might indicate a syndrome, and histological examination showed large, bright cells in the tubules of the testes. Possible explanations for discordance between the karyotype of embryonic and extraembryonic tissue are discussed.

[Postmenopausal estrogen therapy. Recent aspects of parenteral administration of 17-beta estradiol]. / Postmenopausal østrogenbehandling. Nyere aspekter ved parenteral administration af 17 beta-østradiol.

Oral treatment with micronized 17-beta-oestradiol or oestradiol valerate in daily doses of 2 mg postmenopausally resulta in plasma concentrations of free oestrone which are more than double the concentrations in fertile women and plasma oestradiol concentrations which only comprize 20-25% of the oestrone concentrations. On oral treatment, the metabolism in the liver is influenced and this results in increased synthesis of a series of plasma proteins in the liver and changes in lipid and lipoprotein pattern with a fall in serum cholesterol and low density lipoprotein cholesterol and increase in high density lipoprotein cholesterol. Parenteral administration of 17-beta-oestradiol results in plasma concentrations of oestradiol corresponding to those in fertile women. Parenteral administration may take the form of: 20-100 mg oestradiol "pills" implanted subcutaneously, percutaneous administration of 0.05-0.1 mg oestradiol-containing capsules stuck to the skin every 24 hours, 3 mg daily or every second day in a water-alcohol gel, vaginally in cream, suppositories of impregnated vaginal synthetic material (Silastic) rings in daily doses of 0.5-0.25 mg. Percutaneous administration in gel from and partially with vaginal administration in cream or suppositories result in not inconsiderable diurnal variation and inter-individual variation in the plasma oestradiol concentrations obtained. In all of the cases, a relationship is found between the oestradiol and oestrone concentrations which are greater than or equal to one. Implantation treatment is associated with a considerable risk of overtreatment on account of increasing plasma oestradiol concentrations on repeated implantations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Progesterone and gestagen treatment. Pharmacologic and clinical aspects]. / Progesteron- og gestagenbehandling. Farmakologiske og kliniske aspekter.

A review is presented of progestogens which assume a central position in future replacement therapy. The types and dosages of progestogens are of considerable significance for the effects and side effects. Attention is, therefore drawn to the plasma concentration and the minimal effective doses in the following two clinical treatments. Oestrogen primed endometrium is correctly transformed after treatment for 12 days with the following daily dosages: Dydrogesterone = 20 mg, medroxyprogesterone = 10 mg, norethisterone/norethisterone acetate = 0.7 mg, desogestrel = 150 micrograms or levonorgestrel approximately 100 micrograms. Inhibition of ovulation and contraception are obtained by means of the following daily doses: Medroxyprogesterone = 10 mg, norethisterone/norethisterone acetate = 350 micrograms, levonorgestrel = 50 micrograms, desogestrel = 60 micrograms, gestodene = 40 micrograms or norgestimate 250 micrograms.

[Anxiety as an indication for referral for amniocentesis. Follow-up of the course of pregnancy]. / AEngstelse som indikation for henvisning til fostervandsprøve. Opfølgning af graviditetsforløbet.

A prospective epidemiological investigation was undertaken concerning 2,276 pregnant women referred for amniocentesis during a period of seven years. After exclusion of all of the pregnant women over the age of 35 years and some subgroups, the material consisted of 799 pregnant women under the age of 35 years who were uneasy about the result of pregnancy. These were subdivided and assessed: group A = 329 women with indications for amniocentesis according to the circulars issued by the Danish Ministry of Health and group B = 470 healthy anxious women who desired amniocentesis but without indications. Following genetic counselling, 256 women (B1) still desired amniocentesis while 214 women (B2) now rejected amniocentesis. The courses of the pregnancies in groups A, B1 and B2 were followed-up and assessed. No significant differences were observed between the courses of the pregnancies in group B1 and B2. The tendency demonstrated by this investigation was that anxiety probably did not bear any relation to the outcome of the pregnancy.

[Absorption of norethisterone acetate from tablets with normal and coarse particle size]. / Absorption af noretisteronacetat fra tabletter med normal og grov partikelstørrelse.

A clinical randomized double-blind trial with cross-over is presented. The object was to assess the absorption of 1 mg norethisterone acetate from tablets with particles of normal and coarse size. The hypothesis was that the coarse particles would result in retarded absorption. In this trial, eight healthy postmenopausal women with an average age of 72 years participated. The participants received the tablets in the morning with intervals of a week and the plasma concentration (C) was measured throughout 24 hours. The two absorption profiles showed significant differences after 30 minutes (p less than 0.05) with the following values: Tablets with normal particles resulted in C = 31.1 nmol/l while the analogous result with the coarse particles was C = 17.0 nmol/l. It is concluded that the coarse particles resulted in lower plasma concentrations initially.

Incidence of spontaneous abortion after amniocentesis: influence of placental localization and past obstetric and gynecologic history.

The influence of the localization of the placenta and some technical problems associated with the performance of amniocentesis (AC) on the incidence of spontaneous abortion (SA) after AC was evaluated in a prospective study comprising all women (2276) referred for AC at the University Hospital in Odense during a 7-year period. Women with predisposing factors for SA were excluded from this analysis, which comprised 1545 women. Of these, 1289 women had an AC and 256 were judged not to need an AC after ultrasonographic examination. The localization of the placenta per se had no influence on the incidence of SA. However, if the placenta was covering the whole anterior wall so that perforation of the placenta could not be avoided, or if more than one insertion was necessary, or there was macroscopic blood contamination in the amniotic fluid, the risk of SA was increased by a factor 4 to 5. The influence of previous obstetric or gynecologic complications on the incidence of SA was also examined. In this analysis the data from women with first trimester hemorrhage in the present pregnancy were included and the study population therefore consisted of 1594 women. Of these, 1318 had an AC, and 276 had ultrasound scanning only. Patients with one or more previous pregnancies with fetal loss had a significantly greater risk of SA after AC than patients with no previous pregnancies or successfully completed pregnancies. Two subgroups with special problems, namely, women with previous complaint of infertility of at least 2 years' duration and women with first trimester bleeding, also had an increased risk of SA.(ABSTRACT TRUNCATED AT 250 WORDS)

[Births, abortions and extrauterine pregnancies in the community of Funen during 1974-1986]. / Fødsler, aborter og ekstrauterine graviditeter i Fyns Amt i perioden 1974-1986.

A retrospective investigation was undertaken of all the births and abortions during the period 1974-1986 in the County of Funen. The material comprised 66,020 births, 23,179 induced abortions, 9,270 spontaneous abortions and 1,344 ectopic pregnancies. The distributions of the various types of pregnancy were assessed for the entire period and correlated with the age of the women. Comparison of the circumstances in 1974 and 1986 revealed significant changes (p less than 0.05) for pregnant women greater than or equal to 35 years with the following values: the number of births increased 20%, the number of spontaneous abortions increased 56%, the number of ectopic pregnancies increased 240% and the number of induced abortions fell 31%. These numerical values are probably representative for all Denmark.