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Sumatriptan in acute migraine: pharmacology and review of world experience.

The introduction of sumatriptan, a novel abortive antimigraine agent, has generated a significant amount of preclinical and clinical interest during the past few years. At the scientific level, sumatriptan is unique in terms of its selective pharmacological properties. The effects of sumatriptan in various experimental paradigms have led to new insights into the pathophysiology of migraine. At the clinical level, sumatriptan appears to be an effective abortive anti-migraine agent with minimal side effects. Its ability to decrease, rather than exacerbate, the nausea and vomiting of migraine appears to be an important advance in the treatment of migraine.

Acute Disease↗

Tolerance induction during ontogeny. III. Carrier recognition by the immature and adult immune system determines tolerogenicity of hapten-carrier conjugates.

Hapten-specific B-cell tolerance may be induced by nonimmunogenic hapten derivatives of carboxylmethylcellulose or methylcellulose (MC) in adult, neonatal, or irradiated fetal liver reconstituted mice. Such tolerance was shown to occur independent of T cells, and a receptor blockade has been ruled out as a causative mechanism. Oxidation and subsequent reduction of the vicinal hydroxyl groups of both carriers significantly reduces their tolerogenic potential in adult mice, yet their hapten derivatives remain nonimmunogenic. Such chemical modification of the carrier does not affect the molecular weight and not only does not reduce the binding avidity but increases it for either free antibody- or antigen-binding cells. We have examined the ability of the immature immune system to functionally discriminate between the nominal and the chemically modified hapten conjugate. Like adult mice, the immunologically immature animals were invariably capable of distinguishing between the tolerogenic and the nontolerogenic carrier. Mice treated during ontogenic development with 2,4-dinitrophenyl (DNP)-MC were found to be hapten specifically tolerant when challenged at 4 weeks of age with the TI-2 antigen DNP-Ficoll (F) but not when challenged with the polyclonal activator lipopolysaccharide (LPS) or the TI-1 antigen DNP-Brucella. Moreover, neonatal mice treated for 8 weeks with 2,4,6-trinitrophenyl-ovalbumin (TNP-OVA) were hapten specifically tolerant when challenged with TNP-OVA or the TI-1 antigen TNP-LPS but responded to a challenge with the TI-2 antigen TNP-F. These data suggest that B-cell tolerance in adult as well as in immunologically immature mice is not only carrier dependent but, in addition, that the carrier selects the B subpopulation to be rendered unresponsive. The most popular version of the clonal abortion hypothesis puts no constraints upon the nature of the antigen as long as the B cell is ontogenically "predisposed" toward being rendered unresponsive upon contact with a ligand of sufficiently high binding avidity. Our data are at variance with this prediction.

Age Factors↗

RNA polymerases react differently at d(ApG) and d(GpG) adducts in DNA modified by cis-diamminedichloroplatinum(II).

Two duplexes (20-mers) were constructed containing either a single cis-[Pt(NH3)2[d(GpG)]] or cis-[Pt(NH3)2[d(ApG)]] intrastrand cross-link, the major DNA adducts of the antitumor drug cis-diamminedichloroplatinum(II). These synthetic duplexes were multimerized and the resultant polymers used as templates in single-step addition reactions of condensation of a single nucleoside triphosphate substrate to a dinucleotide primer (abortive elongation reaction) catalyzed by prokaryotic or eukaryotic RNA polymerases. Primer-substrate combinations were selected so as to direct trinucleotide product formation within the platinated bases of the templates. Transcription experiments established that cis-DDP-DNA adducts formed at d(ApG) or d(GpG) sites are not an absolute block to formation of a single phosphodiester bond by either Escherichia coli RNA polymerase or wheat germ RNA polymerase II. Furthermore, the kinetic data indicate that single-step addition reactions are much more impeded at the platinated d(GpG) than at the platinated d(ApG) site and that the mechanisms of inhibition of RNA polymerase activity are different at the two platinated sites. In particular, binding affinity between E. coli RNA polymerase and the d(GpG)-containing platinated template is lowered, as the apparent Km of enzyme for the platinated polymer is increased by a factor of 4-5. In contrast, binding affinity between the RNA polymerase and the d(ApG)-containing template is not affected by modification of the d(ApG) site by cis-diamminedichloroplatinum(II). Similar experiments were carried out with synthetic templates containing the adducts at the d(GpG) sites, in which one of the two platinated dG residues is paired with a dT residue.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Effects of donitriptan on carotid haemodynamics and cardiac output distribution in anaesthetized pigs.

We investigated the effects of donitriptan, which possesses a uniquely high affinity and efficacy at 5-HT1B/1D receptors, on carotid and systemic haemodynamics in anaes thetized pigs. Donitriptan (0.16-100 microg kg(-1), i.v.) dose-dependently decreased total carotid blood flow and vascular conductance (maximum response: -25 +/- 3%). This effect was entirely due to a selective reduction in the cephalic arteriovenous anastomotic fraction (maximum response: - 63 +/- 3%; ED50%: 92 +/- 31 nmol/kg); the nutrient vascular conductance increased. Donitriptan did not decrease vascular conductances in or blood flow to a number of organs, including the heart and kidneys; in fact, vascular conductances in the skin, brain and skeletal muscles increased. Cardiac output was slightly decreased by donitriptan, but this effect was confined to peripheral arteriovenous anastomoses. The haemodynamic effects of donitriptan were substantially reduced by the 5-HT1B/1D receptor antagonist GR127935. These results show that donitriptan selectively constricts arteriovenous anastomoses via 5-HT1B receptor activation. The drug should be able to abort migraine headaches and it is unlikely to compromize blood flow to vital organs.

Animals↗

Anatomic uterine defects.

Congenital or acquired uterine defects remain important considerations in the investigation of recurrent pregnancy loss. When repeated first or second trimester losses, preterm delivery, or abnormal fetal presentations are documented, the suspicion of a structural uterine abnormality should be high. The diagnosis of uterine defects is no longer elusive. The combination of radiologic imaging techniques, hysteroscopy, and laparoscopy enables an accurate diagnosis in nearly every case. The optimal treatment for uterine malformations is still a matter of considerable controversy. Therefore, when a uterine defect is diagnosed, tough clinical decisions must be made. When alternate causes of pregnancy loss are excluded, pregnancy potential will depend primarily on the specific type of uterine anomaly that is detected. It is important to recognize that not all uterine defects are amenable to therapy, but in carefully selected patients, reparative surgery may be rewarding.

Abortion, Habitual↗

Experience with first level ultrasound and echocardiography for a selected and an unselected population.

OBJECTIVE: To evaluate the difference in prevalence, distribution and prenatal detection rate of congenital heart disease (CHD) in both newborns and second trimester termination of pregnancy (TOP) in two separate time periods. PATIENTS AND METHODS: At the University Hospital of Bari, an observational study was performed, which included all cases of CHD in newborns and second trimester TOP during the periods 1998-99 and 1992-93. Prevalence, distribution and prenatal diagnosis in each group were evaluated, also selecting cases with and without known risk factors. RESULTS: Prevalence of CHD in livebirths and aborted fetuses did not change between the two periods and the same was observed for distribution of CHD spectrum. In the more recent period antenatal detection of CHD significantly increased only in TOP. Moreover, classifying all cases as low or high risk, detection rates were significantly increased in high risk cases while they were unchanged in the general population. CONCLUSION: Our data show that antenatal detection of CHD is ameliorated by concentrating expertise and good equipment on high risk cases, while it remains low in the general population.

Abortion, Induced↗

A report on six months experience of committee for the control of abortion.

During the first six months experience of a committee for the control of abortions, within the framework of Kupat Holim (Workers' Sick Fund of 'Histadrug' in Israel), 70 pregnant women sent by their physicians appeared before the committee for the interruption of their pregnancies. The reasons brought before the committee were of a medical, genetic, psychiatric or social nature. Discussed here are the socio-psychiatric cases, under the heading of the country of origin, age of the women, their cultural background and social situation of their families. Some conclusions are drawn in connection with the motivations which seem to have determined the positive or negative position of the committee and some possible implications are discussed concerning the legislation of the whole subject.

Abortion Applicants↗

[Mycoses in domestic animals].

In the present paper we will present a general view of the main mycoses affecting domestic animals. In the dog, we show the importance of the dermatophytoses, increased by its zoonosic character and the problem of the false negatives in the traditional microbiological culture. Under the general term of systemic mycoses we include a series of conditions considered usually as aspergillosis, bat with more and more fungal species implicated as possible etiological agents. In addition, fungi, especially yeasts, are being implicated in canine otitis; in our laboratory 86 % of canine chronic otitis involve a yeast etiology, alone or in collaboration with bacteria. In the cat, dermatophytes are more common than in the dog, and are the main source of infection in man, with the description of a high percentage of healthy carrier animals. Cryptococcosis is a severe disease, usually secondary to other process, especially feline immunodeficiency. In cows we refer to fungal abortion, with three main fungi implicated: Aspergillus, Candida and Zygomycetes. In some areas of our country the percentage of fungal abortion is around 10 %. A consequence of the multiple use of antibiotics in mastitis is selection of yeasts, especially those included in the genera Candida and Cryptococcus. Bovine dermatophytoses is an extensively disseminated disease in our country, with a commercial specific vaccine available. In small ruminants, Cryptococcus causes severe pneumonic processes that could be confused clinically with other conditions. An additional important question is the description of isolation of this fungus from tree leaves. In poultry, aspergillosis is a known and controlled disease, but with more importance in captive wild birds with an ecological value. In horses, we emphasize the lung infections by different fungi, specially Pneumocystis carinii, and arthritis by yeasts as consequence of wound contamination or surgery.

English Abstract↗

[Pregnancy and labor after insemination with frozen sperm from a donor].

A total of 168 out of 196 pregnancies that were obtained after A.I.D. have been followed up. Six cases were lost for follow-up (3%). The mean age was 30 years and 65% of the women had their ovulation induced. 130 nullipara were delivered. They were compared with a series of nullipara of the same age group and selected from 300 primiparous pregnancies who delivered in the department in the same year. The abortion rate was 12.5%. 79% of the pregnancies were normal in the 2nd and 3rd trimesters as compared with 83% in the control series. 94% delivered at term as compared with 97% in the control series. 21% of the women had Caesarean section as compared with 19.2% in the control series. The sex ratio was 1.08 as compared with 1.06 in the control series. There was no significant difference between the two series. It does seem, however, that the age factor is the most important factor of all in determining how frequent pathological conditions will be and the number of Caesareans that will have to be carried out. 14% were under 30 years of age as compared with 28.5% who were over 30 years of age, which is a significant difference. These results should be followed up in a larger series.

Abortion, Spontaneous↗

Screening for the lupus anticoagulant.

The lupus anticoagulant may be defined as an immunoglobulin (IgG, IgM or both) which interferes with one or more of the in vitro phospholipid-dependent tests of coagulation. For many years, lupus anticoagulants were regarded as a laboratory nuisance; consequently, reagents were often selected on the basis of insensitivity to lupus anticoagulants. Recently, lupus anticoagulants have been associated with a variety of clinical conditions including recurrent thromboembolic events (both arterial and venous), obstetrical complications including fetal death and spontaneous abortion, and a variety of hematologic and neurologic complications. As a result, many laboratories are now being asked to identify the presence of lupus anticoagulants in selected patient populations. In addition to assays for lupus anticoagulants, there are immunologic assays designed to detect phospholipid antibodies using solid phase systems (RIA or ELISA). A variety of screening tests have been designed to enhance sensitivity to lupus anticoagulants. Test systems with decreased amounts of phospholipid (phosphatidylserine) appear to be most sensitive to lupus anticoagulants. Of the various tests used, the activated partial thromboplastin time (APTT) appears to be most sensitive. The sensitivity of any screening test system is inversely proportional to the residual platelets in the patient sample. APTT reagents differ widely in their sensitivity to lupus anticoagulants. The dilute Russell viper venom time is also highly dependent on the choice and concentration of phospholipid with respect to its sensitivity. Once an abnormality of a screening test has been identified, it is necessary to prove the abnormal result is due to the presence of an inhibitor. This step in the diagnosis may utilize either mixing studies or plasma agarose gels. The final step in the diagnosis of lupus anticoagulants is the demonstration of phospholipid specificity of the inhibitor. Two approaches have been utilized: 1. test systems designed to enhance anticoagulant effect (phospholipid-depleted), and 2. test systems with increased or altered phospholipids which will bypass or neutralize the anticoagulant.

Blood Coagulation Factors↗

A pregnancy following PGD for X-linked dominant [correction of X-linked autosomal dominant] incontinentia pigmenti (Bloch-Sulzberger syndrome): case report.

Incontinentia Pigmenti (Bloch-Sulzberger syndrome) is a rare multisystem, ectodermal disorder associated with dermatological, dental and ocular features, and in <10% of cases, severe neurological deficit. Pedigree review suggests X-linked dominance with lethality in affected males. Presentation in female carriers is variable. Following genetic counselling, a mildly affected female carrier diagnosed in infancy with a de novo mutation was referred for preimplantation sexing, unusually selecting for male gender, with an acceptance of either normality or early miscarriage in an affected male. Following standard in-vitro fertilization and embryo biopsy, fluorescence in situ hybridization (FISH) unambiguously identified two male and two female embryos. A single 8-cell, grade 4 male embryo was replaced. A positive pregnancy test was reported 2 weeks after embryo transfer, although ultrasonography failed to demonstrate a viable pregnancy. Post abortive fetal tissue karyotyping diagnosed a male fetus with trisomy 16. This is an unusual report of preimplantation genetic diagnosis (PGD) being used for selection of males in an X-linked autosomal dominant disorder and demonstrates the value of PGD where amniocentesis or chorion villus sampling followed by abortion is not acceptable to the patient. This case also demonstrates the importance of follow-up prenatal diagnosis.

Adult↗

[Doppler flow measurements of the uterine artery. A prognostic factor for success in treatment by IVF?].

117 patients treated for infertility with IVF-ET were included in a prospective study to evaluate the prognostic value of Doppler-flow measurements in the uterine artery on the day of oocyte retrieval. The PI was calculated after transabdominal pulsed Duplex-Doppler-flow measurement in the uterine artery, which was localised in the B-scan or using a colour Doppler. The success of the IVF procedure could be predicted statistically significant for both--pregnant or not--(p = 0.0316) and--ongoing pregnancy or first trimester abortion--(p = 0.0079) by better uterine flow. At the same time the diameter of the endometrium was measured. There is only a statistical trend for better results in cases with larger endometrial diameter comparing pregnant and non-pregnant patients (p = 0.0708). The results suggest that the uterine flow measurements might be helpful in selecting cycles for successful embryo transfer.

Abortion, Spontaneous↗

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs.

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

Acute Disease↗

Abortion training in family practice residency programs.

BACKGROUND: Despite a relatively fixed demand for services, access to abortion services has become increasingly limited, in part due to fewer training opportunities for OB-GYN residents. The recommended core educational guidelines for family practice residents include voluntary interruption of pregnancy up to 10 weeks gestation, but the availability of and interest in such training have not been reported. METHODS: A survey questionnaire assessing availability of abortion training, percentage of residents participating, program demographics, and resident interest in training was sent to all US family practice residency program directors and randomly selected third-year residents during the 1993-1994 academic year: A total of 301 of 399 (75%) program directors and 253 of 399 (63%) third-year residents completed the questionnaire. RESULTS: Twelve percent of programs nationwide offered abortion training during 1993-1994. Western programs were more likely to offer training (18 of 50 or 36%) than Northeastern (7 of 55 or 12%), Midwestern (6 of 98 or 6%), or Southern programs (4 of 98 or 4%). When available, 45% of trainees chose to participate. Training was primarily in suction curettage up to 12 weeks gestational age. The median duration of training was 4 weeks. Training was provided in both freestanding clinics and hospitals. Religious hospitals were less likely to offer training. CONCLUSIONS: About one of eight family practice residency programs nationwide offer training in abortion. When offered, nearly half of family practice residents choose to participate in this training. Interested family practice residents could be trained to fill an increasing need for physicians willing and able to perform first-trimester abortions.

Abortion, Induced↗

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.

Abdomen↗

Interaction between adenosine deaminase and ABO system polymorphisms: effects on intrauterine survival and reproduction.

Adenosine deaminase (ADA) phenotype and ABO blood groups have been determined in 572 consecutive newborn infants, in 770 schoolchildren, in 139 women delivering a liveborn infant, and in 87 women with habitual abortion. ABO-incompatible newborn infants showed a higher proportion of ADA2 carriers as compared to compatible newborns. The incidence of clinically relevant neonatal jaundice among incompatible infants carrying ADA2 was lower as compared to compatible infants carrying this gene. In newborn infants, schoolchildren, and women with habitual abortion the proportion of A, B, and AB among ADA2 carriers was higher as compared to ADA1/ADA1 individuals. In fertile women, on the contrary, the proportion of A, B, and AB among ADA2 carriers was lower as compared to ADA1/ADA1 women. This suggests that non-O ADA2 carrier genotypes may lose in the reproductive stage the selective advantage accumulated during the early stages of development.

ABO Blood-Group System↗

Immunization as therapy for recurrent spontaneous abortion: a review and meta-analysis.

OBJECTIVE: To determine the efficacy of immunotherapy as treatment for recurrent spontaneous abortion (three or more consecutive abortions without an intervening pregnancy of more than 20 weeks' gestation) using meta-analysis. DATA SOURCES: The search began with MEDLINE and was supplemented by reference lists from original research, review articles, and textbooks. We also corresponded with investigators and consulted experts in the field of infertility. METHODS OF STUDY SELECTION: We identified four randomized controlled trials and 19 case-series reports that examined the use of immunotherapy for recurrent spontaneous abortion. DATA EXTRACTION AND SYNTHESIS: A meta-analysis performed on four randomized controlled trials of leukocyte immunotherapy or trophoblast membrane infusion revealed a fixed-effects model odds ratio of 1.3 (95% confidence interval [CI] 0.77-2.3) and a random-effects model odds ratio of 1.3 (95% CI 0.44-3.8). CONCLUSION: The quality of evidence regarding this treatment is class I (best), and the strength of recommendation is D (fair evidence against its use). Unless its efficacy can be established through other randomized controlled trials, this treatment should be abandoned.

Abortion, Habitual↗

Increased risk of abortion after genetic amniocentesis in twin pregnancies.

Forty-seven twin pregnancies among 3676 patients who had a genetic amniocentesis between 1973 and 1979, are reported. The detection rate of twins at the time of amniocentesis was 62 per cent. Five (17 per cent) of the 29 women with detected twin pregnancy aborted spontaneously, these are compared with 1 (6 per cent) of 18 women with undetected twin pregnancies and with 3 (3 per cent) of 93 singleton pregnancies, selected as controls as they had amniocentesis performed immediately before and after each of the twin mothers. Two of 9 (22 per cent) twin pregnancies, who had at least two punctures in at least one sac aborted, while 3 of 20 twin pregnancies with one puncture in each sac aborted (15 per cent). One of 18 (6 per cent) twin pregnancies, where only one sac was punctured, because the twin pregnancies were undetected, aborted. Amniocentesis of both sacs in twin pregnancies seems associated with an increased risk of spontaneous abortion. The indications for amniocentesis in twin pregnancies should be critically evaluated.

Abortion, Spontaneous↗