Influence of border disease virus (BDV) on serological surveillance within the bovine virus diarrhea (BVD) eradication program in Switzerland.

BACKGROUND: In 2008, a program to eradicate bovine virus diarrhea (BVD) in cattle in Switzerland was initiated. After targeted elimination of persistently infected animals that represent the main virus reservoir, the absence of BVD is surveilled serologically since 2012. In view of steadily decreasing pestivirus seroprevalence in the cattle population, the susceptibility for (re-) infection by border disease (BD) virus mainly from small ruminants increases. Due to serological cross-reactivity of pestiviruses, serological surveillance of BVD by ELISA does not distinguish between BVD and BD virus as source of infection. RESULTS: In this work the cross-serum neutralisation test (SNT) procedure was adapted to the epidemiological situation in Switzerland by the use of three pestiviruses, i.e., strains representing the subgenotype BVDV-1a, BVDV-1h and BDSwiss-a, for adequate differentiation between BVDV and BDV. Thereby the BDV-seroprevalence in seropositive cattle in Switzerland was determined for the first time. Out of 1,555 seropositive blood samples taken from cattle in the frame of the surveillance program, a total of 104 samples (6.7%) reacted with significantly higher titers against BDV than BVDV. These samples originated from 65 farms and encompassed 15 different cantons with the highest BDV-seroprevalence found in Central Switzerland. On the base of epidemiological information collected by questionnaire in case- and control farms, common housing of cattle and sheep was identified as the most significant risk factor for BDV infection in cattle by logistic regression. CONCLUSION: This indicates that pestiviruses from sheep should be considered as a source of infection of domestic cattle and might well impede serological BVD surveillance.

The circadian variation of cardiovascular stress levels and reactivity: relationship to individual differences in morningness/eveningness.

Two studies assessed the circadian variation of cardiovascular responses to stress in healthy and coronary artery disease (CAD) populations. In within-subjects designs, stressors were administered to healthy male subjects and male CAD patients both in the morning and afternoon, and subjects were classified as either morning or evening types using the Morningness-Eveningness Questionnaire (Horne & Ostberg, 1976, International Journal of Chronobiology, 4, 97-110). No consistent circadian variation in blood pressure or heart rate responses was observed in the aggregate sample of either healthy subjects or CAD patients. However, there were significant interactions between circadian type and time of day. In both populations, morning subjects exhibited higher cardiovascular levels during the morning session, and evening subjects exhibited higher levels during the afternoon session. Analyses of cardiovascular reactivity revealed less consistent evidence for this interaction. Self-reports of stress revealed interactions between time of day and morningness/eveningness only in the CAD sample. In CAD patients, preliminary analysis of myocardial wall function, an index of myocardial ischemia, did not reveal a significant interaction between morningness/eveningness and time of day, perhaps due to small sample size. The presence of differing circadian patterns in stress response based on individual differences in morningness/eveningness is discussed in terms of its methodological implications for psychophysiological research and in terms of the role of stress as an acute trigger of CAD.

Lupus anticoagulant. Significance in habitual first-trimester abortion.

Therapy with steroids and aspirin has been reported to benefit pregnancies in patients with lupus anticoagulant (LA). In this study, habitual first-trimester aborters with LA using steroids and aspirin were compared to a control group of untreated habitual aborters without LA. In habitual aborters with LA, 12 of 24 (50%) pregnancies reached the second trimester as compared to 8 of 22 pregnancies (36%) in the control group. Since the treated group did no better than the control group, LA probably is not a cause of first-trimester abortion. However, once the second trimester is reached, a 50% incidence of growth retardation was found, and 42% of fetuses died in the second or third trimester in treated LA patients. Treatment with steroids and anti-platelet aggregating agents may be necessary despite the attendant risks to prevent those sequelae in the second and third trimesters. There was a 29% live birth rate in treated LA patients; the rate was 36% in control patients. However, this rate was produced only by early intervention, which was unnecessary in the control patients.

Automated physical activity monitoring: validation and comparison with physiological and self-report measures.

Physical activity can be assessed via self-report, via physiological measures such as heart rate and oxygen uptake, or via automated monitor. An electronic accelerometer-based physical activity device (Actigraph) has been reported as an improvement over other activity measurement techniques in terms of utility and accuracy. Four studies provide systematic validation and reliability testing for this device and comparisons with other techniques for assessing daily activities. In the first study, the sensitivity of the Actigraph was determined for differentiating physical activities (walking, running, stair climbing, knee bends) versus sedentary activities (reading, typing, playing video games, and performing a mental arithmetic task). Fifteen healthy adults wore the Actigraph on their wrist during activities; oxygen uptake and heart rate were simultaneously recorded. Results revealed that the Actigraph significantly differentiated between the physical activities (p < .0001) and the sedentary activities (p < .0001). Actigraph counts also correlated significantly with oxygen uptake (r = .73) and heart rate (r = .71) during physical activities (r = .46) and sedentary activities (r = .35), respectively. Test-retest reliability was very high for 12 activities (r = .98). The high level of activity differentiation and strong relationship to oxygen uptake and heart rate suggest the usefulness of this device for behavioral and biomedical studies. However, these studies also indicate that the wrist may not always be the most adequate placement for indexing rate and intensity of daily activities and that further studies are needed to determine the optimal site of monitor attachment. Advantages and disadvantages of self-report, physiological, and automated measures of activity are discussed.

Congenital malformations after immunotherapy for habitual abortion: is there an increase?

The risk of congenital malformations as assessed in infants born to women who underwent immunotherapy for habitual abortion. One hundred and eighty women were immunized with paternal mononuclear cells and 85 were not. Of 135 pregnancies in immunized patients, 27 (20%) were miscarriages, and 4 of the remaining 108 had congenital malformations. Two (encephalocele and common AV canal) were diagnosed in the 20th and 21st week of gestation. A case of esophageal atresia and Fallot's tetralogy were diagnosed at birth. Of 65 pregnancies in the non-immunized group 38 (58.5%) were miscarriages, and of the remaining 27, 1 case of Down's syndrome occurred. In a subgroup of 7 habitually aborting couples with parental balanced chromosomal anomalies, the balanced translocation was transferred to the infant in 1 case. No other congenital anomalies were found in either group. Consequently, these anomalies are probably not the result of abnormal pregnancies retained as a result of immunization.

Aging of endometrium and oocytes: observations on conception and abortion rates in an egg donation model.

OBJECTIVE: To assess the comparative contribution of endometrial and oocytic aging to the decline in fertility with age. DESIGN: Retrospective analysis of conception and abortion rates in an egg donation program, with respect to donor and recipient ages. PATIENTS: All oocyte recipients had ovarian failure. Donors were women undergoing in vitro fertilization who contributed up to a third of retrieved oocytes. INTERVENTIONS: None. RESULTS: Thirty pregnancies (28 intrauterine) were recorded in 169 reception cycles originating from 91 donation cycles. Women who conceived were younger than those who did not (median age 31 versus 37; P less than 0.046), with no difference in age of donors. There was a significant difference in spontaneous abortion rate by age of donor rather than by age of recipient. Donors to successful pregnancies were younger than donors to aborted pregnancies (median age 27.5 versus 33; P less than 0.0211), but the 11 women with aborted pregnancies did not differ in age from the 17 women with successful pregnancies. CONCLUSIONS: In women, endometrial function as expressed by conception rate in the recipients declines with age, whereas it is oocyte age that primarily influences risk of abortion.

A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats.

In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q-T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q-T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes.

Cardiovascular reactivity and mental stress-induced myocardial ischemia in patients with coronary artery disease.

This report evaluates the relationships of hemodynamic reactivity and determinants of myocardial oxygen demand to myocardial ischemia during mental stress in coronary artery disease patients. Thirty-nine patients and 12 controls were studied by radionuclide ventriculography during three mental tasks (arithmetic, Stroop task, and simulated public speaking). Patients were subdivided into three groups based on the severity of ischemic wall motion responses to the mental stressors. Results revealed that systolic blood pressure (SBP) levels during the mental tasks and SBP reactivity (increases) to stress were highest for the severely ischemic group, lowest for controls, with the mild-moderate ischemic and nonischemic patients in between. Severely ischemic patients started out with lower double product (heart rate x SBP) levels, and reached higher levels during the Stroop and speech tasks. There were no reliable group effects for diastolic blood pressure, heart rate, or left ventricular end-diastolic volumes. Among severely ischemic patients, the most potent task in eliciting ischemia (the speech) was associated with higher cardiovascular levels and elicited greater heart rate, double product, and ventricular volume responses. The present data indicate a relationship between cardiovascular levels and reactivity and the magnitude of ischemia induced by mental stress.

Pregnancy potential of human oocytes--the effect of cryopreservation.

BACKGROUND: In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? METHODS: The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. RESULTS: Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). CONCLUSIONS: The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation.

Transvaginal sonographic measurement of fetal kidneys in the first trimester of pregnancy.

Fetal renal size late in the first trimester of pregnancy was evaluated by transvaginal ultrasonography in 50 patients not at risk for congenital kidney disease and whose pregnancies resulted in a normal outcome. Both kidneys were reliably identified in all patients scanned at 12 weeks, 13 weeks, and 14 weeks, menstrual age. Kidney diameter measurements obtained in this study are presented for reference in evaluating patients in late first trimester whose fetuses are at risk for kidney abnormalities.

Glucose tolerance in pregnant women following treatment for sterility.

The incidence of glucose intolerance in 76 patients with polycystic ovary disease (PCOD) who became pregnant after treatment for ovulation was compared with that in 95 healthy women, matched with respect to age and diabetic background, who conceived without intervention. The incidence of abnormal glucose tolerance test results in the treated group was twice that in the normal group (19.7% vs. 9.5%; P less than .03). Moreover, within the treated group abnormal test results occurred more frequently in patients who became pregnant following induction of ovulation with human menopausal gonadotropin (29%) than in those who conceived as a result of other treatment modalities (12%).

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Development of human embryos in the presence of a copper intrauterine device.

This study was designed to examine the teratogenic potential of copper releasing intrauterine contraceptive devices on the developing embryo. The tissues and organs of 11 whole embryos between 7 and 12 weeks of gestation were histologically examined for copper absorption after exposure to a copper intrauterine device in utero. The findings were not significantly different when compared with a control group of 7 embryos. No malformation or copper aggregates were observed in the various organs and placentas. The observations in this small sample would suggest that the copper-releasing intrauterine device has no deleterious effects on fetal development. The question remains whether malformations reported in some cases are associated with copper deposits in the tissues or with free copper ions in the fetal circulation. The implications are discussed.

PIP: The study was designed to examine the teratogenic potential of copper releasing intrauterine contraceptive devices IUD's on the developing embryo. the pregnancy rate with copper-bearing IUD's in situ has been reported as less than 5% per annum. 18 healthy fertile women aged 20-40 were studied. 11 conceived while using a copper-bearing IUD (Nova-T in 5 and Multiload in 6 cases); 7 women served as controls who conceived spontaneously with no previous history of using an IUD. Between 7 and 12 weeks of gestation an artificial abortion was induced in all 18 women. All 18 embryos were removed in toto, without injury. After fixation in neutral formalin the embedding process was carried out in paraffin and sectioning was performed, enabling examination of the brains, eyes, inner ear, heart and lungs, liver, pancreas, mesonephron, kidneys gonads vertebrae and limbs. All sections were stained for copper in accordance with Uzman's procedure. 2 mice were injected with a copper solution to verify the accuracy of the staining method. Maternal blood samples were taken on the day of the abortion and examined for plasma levels of copper and ceruloplasmin. The procedure of Dawson et al. was applied to determine the copper level and Richterich's for assessment of ceruloplasmin. The plasma levels of the copper and ceruloplasmin were within normal range, with no significant difference between the study and control groups (163.4+-41.4 va 137.8+- 37.0% mcg copper and 70.4+-14.9. vs 69+-19.9% mg ceruloplasmin). No organic malformations were found in either groups and the embryonic tissue was free of copper deposits. There was no structural impairment and no trace of copper deposits in the placentae when examined histologically however, traces of copper were found in the organs of mice. These results do not prove unequivocally that embryos exposed to copper contamination because of in site IUD are free of terato-genic risk, since the size of the study sample was small.

Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial.

Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3-12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.

Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures.

Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.

Programmed oocyte retrieval: clinical and biological effects of oral contraceptives administered before in vitro fertilization.

We have prospectively compared two regimens of suppression of the hypothalamic-pituitary-ovarian axis by oral contraceptives (OCs) for 15 or 30 days and two ovarian stimulation protocols. The latent phase, which represents a period of ovarian insensitivity, was prolonged and directly correlated to the duration of suppression. Thirty days' suppression, compared with 15 days', resulted in the cancellation of more cycles and a lower fertilization and pregnancy percentage. No significant increase in either serum progesterone or luteinizing hormone was noted in suppressed cycles. It is concluded that if programming is desired, OCs should be used for the shortest period possible. The variation in the length of the follicular phase indicates that there is a different 'fixed' day for retrieval for each suppression-stimulation protocol and this day should be established prospectively.

PIP: 2 oral contraceptive time courses for ovarian suppression and 2 ovarian stimulation protocols were compared to a control stimulation protocol, for oocyte retrieval before in vitro fertilization. 77 women with normal ovulatory cycles and infertility caused by tubal disease were grouped into 5 groups. 2 groups received Neogynon (50 mcg ethinyl estradiol and 35 mg levonorgestrel) for 15 days, 2 groups received Neogynon for 30 days, 2 groups were stimulated by clomiphene citrate 100 mg/day for 5 days and 2 ampules/day of human menopausal gonadotropin (hMG) from Cycle Day 8,2 groups were stimulated by 2 ampules/day of hMG and 2 ampules of pure FSH + hMG on Days 5 and 6. Control received clomiphene citrate 100 mg/day from Day 5 of the natural cycle and hMG 2 ampules/day from Day 8. hCG was given when serum estradiol levels rose above 400 pg/ml and 2 16-mm follicles were seen on ultrasound. Those treated with OC for 30 days had a prolonged latent phase of estradiol increase, lower baseline LH, fewer recovered and fertilized oocytes, more cancellations, and a lower pregnancy rate, 5.8%, compared to 33% in controls, and 34.7% in women suppressed for 15 days. It was concluded that 15 days of suppression by oral contraceptives was effective and produced acceptable pregnancy rates. The cancellation rate, normally due to premature LH surges, was not decreased by suppressing these patients with oral contraceptives, probably because the ovary was less sensitive to stimulation.

Cyclosporin-induced embryotoxicity in mice.

Pregnant ICR mice were injected daily with 30 mg cyclosporin (CS)/kg body weight on days 6-8 or 10-12 of gestation. In parallel, control mice were administered saline injections on the same gestational days. The mice were sacrificed on days 12, 15, 17 or 19 of gestation. The number of resorption sites counted, the embryos and placentae were carefully separated, weighed and examined macro- and microscopically, along with various other maternal organs. It was found that 30 mg CS/kg body weight, when administered to pregnant ICR mice in 3 successive injections, did not raise the maternal mortality rate. Histological examination of maternal organs revealed pathological alterations in the thymus, liver, kidney and spleen; most changes had disappeared by 1 week following the last injection. CS reduced the number of viable embryos and increased the number of embryos resorbed. Microscopic examination of the embryos showed that organogenesis was not affected by the drug. However, CS, in the administered dose, had a clear embryotoxic effect.

Fetal demise associated with lupus anticoagulant: clinical features and results of treatment.

There are many reports in the literature associating lupus anticoagulant with fetal death. Successful pregnancies have been reported following suppression of the antibody by prednisone and the addition of antiaggregants and possibly anticoagulants. This report describes our experience treating such patients and the outcome of subsequent pregnancies. The results are less successful than the figures in the literature, 13 live births out of 27 pregnancies in 19 patients. This may be due to lupus anticoagulant being diagnosed as the cause for a wide variety of clinical presentations including habitual first trimester abortion, mid trimester fetal death, intrauterine growth retardation and placental dysfunction in the third trimester. Our experience shows that steroids and antiaggregants have a definite place in cases of second and third trimester fetal death and in cases of clinical systemic lupus erythematosus. However, lupus anticoagulant is one of a spectrum of autoantibodies whose pathophysiology has not been fully elucidated. It is questionable whether this regimen of treatment has a place in patients with no previous fetal loss or in cases of primary habitual abortion.

Fetal intracranial anatomy in the first trimester of pregnancy: transvaginal ultrasonographic evaluation.

The normal values and ranges of fetal intracranial structures were studied by high resolution transvaginal ultrasonic scan at 12, 13 and at 14 weeks' gestation. The data including measurements of crown rump length (CRL), bi-parietal diameter (BPD), head circumference (HC), hemispheric width (HW), lateral ventricle width (LVW), LVW/HW ratio, thalamus and cerebellum may be useful in determining deviations from the normal and also in expanding the range of prenatal diagnoses of fetal structural abnormalities in early pregnancy.