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The efficacy of oral Mifepristone (RU 38,486) with a prostaglandin E1 analog vaginal pessary for the termination of early pregnancy: complications and patient acceptability.

Outpatient terminations were performed on 100 ultrasonographically confirmed pregnancies of less than or equal to 63 days with a single oral dose of RU 38,486 (600 mg) and a single vaginal pessary of 16,16-dimethyl-trans-delta 2-prostaglandin E1 (1 mg) 48 hours later. Abortion occurred in all patients; in 95 it was complete, in four it was incomplete, and one resulted in a missed abortion. In 88% the abortion occurred within 4 hours of prostaglandin treatment. A total of 25% of patients had nausea and 15% vomited after RU 38,486 treatment. After prostaglandin-treatment, 13% vomited, 10% had diarrhea, and 23% required administration of an opiate analgesic agent. No patient was transfused and there was no genital tract trauma; one case of suspected pelvic infection occurred. If the need for termination arose again, 88% would elect to use the method again, 9% would not. The combination of the antiprogestin RU 38,486 and a vaginal prostaglandin pessary appears to offer a safe, efficient, acceptable nonsurgical outpatient method of termination. Further studies on dosage and treatment protocols would be justified.

Abortifacient Agents↗

Immunohistochemical staining properties of PCNA, Ki-67, p53, beta-hCG and HPL in trophoblastic disease.

OBJECTIVE: In this study proliferating markers PCNA (proliferating cell nuclear antigen) Ki-67 and mutation of supressor gene p53 were investigated in gestational trophoblastic disease (GTL). These markers were tested by using immunostaining with beta subunits of human chorionic gonadotropin (hCG) and human placental lactogen (HPL). MATERIAL AND METHODS: Twenty curetting samples, 20 spontaneous abortions, 16 hydatidiform moles and two choriocarcinomas were studied and compared. Hydatidiform moles were subdivided into 10 complete and six partial moles by using flow cytometry analysis. All slides were stained with PCNA, Ki-67, p53, hCG, and HPL immunohistochemically. PCNA and Ki-67 stained slides were studied quantitatively to determine the PCNA and Ki-67 index. Other slides that were stained with p53, hCG, HPL were evaluated according to staining percentage and intensity. Staining properties of all groups were compared with each other. Variance analysis and the Mann Whitney U test were used for statistical analysis. Choriocarcinomas were not included in the statistical analysis. Ki-67 and the PCNA index in two choriocarcinoma cases found 81.4% and 41%, and 44% and 64%, respectively. One case was stained in 70% with (++) intensity by p53. While both were stained in 80% with (++) intensity by hCG, one was stained in 30% field (+) intensity by HPL. RESULTS: The four groups of complete and incomplete diagnosed hydatiform moles, spontaneous abortions and retention curettage were matched in pairs and evaluated according to the PCNA index. This index showed significant differences among the groups. The differences among the Ki-67 index, p53, hCG and HPL staining properties were not statistically significant. CONCLUSION: Our findings showed that PCNA is a significant and useful marker for trophoblastic diseases and can be used as a prognostic factor.

Adult↗

Cytokines and the protective host immune response to Chlamydia psittaci.

The immunobiology of enzootic abortion of ewes (EAE) is incompletely understood. The causative agent is Chlamydia psittaci, which infects many ruminant species and has zoonotic potential. The organism can survive in the ovine host for many months without causing clinical symptoms but does not generate a sterile immunity during this time. It has been postulated that the organism persists in the host entering at a latent phase, possibly mediated by host cytokine production. The effects of cytokines on chlamydial multiplication vary between host species, between different cell types within those species and also vary between chlamydial species and strains. The multiplication of the EAE strain of C. psittaci in ovine ST-6 cells can be restricted by interferon-gamma (IFN-gamma) but not with comparable concentrations of IFN-alpha. Altering the nutrient composition of the cultures by addition of tryptophan partially reverses the antichlamydial effects of the IFN-gamma. This offers a potential mechanism by which C. psittaci can persist in sheep. The implications of these observations for the pathogenesis of EAE are discussed.

Abortion, Veterinary↗

Induction of abortion in the second trimester of pregnancy by intramuscular 15-methyl prostaglandin F 2 alpha (Prostin 15M).

40 patients, pregnant clinically from 12 to 24 weeks in whom pregnancy termination for medical or medicosocial reasons was indicated, were given 250 micrograms Prostin 15M (15 methyl prostaglandin F 2 alpha, Upjohn) intramuscularly every three hours in total dose from 500 micrograms to 3000 micrograms. The Committee for Medical Ethics of the Committee for Medical and Social Security of SRS approved the study to be performed at the University Gynecological Hospital of Ljubljana using the drug and following the protocol of Upjohn (Tehnoservis). 36 patients (90%) aborted within 48 hours after the first injection (mean interval was 15.43 hours). In three out of 40 patients (7.5%) the abortion was complete, in 34 (85.0%) it was incomplete. In two patients, dilatation of cervical canal was complete, but the expected abortion did not take place. One patient aborted in 52 hours and 10 minutes. Only in a single case induction of abortion was completely unsuccessful. The drug is considered effective for induction of abortion in the second trimester of pregnancy.

Abortion, Induced↗

Bilaterality of idiopathic macular holes.

BACKGROUND: There has been wide variation in estimates of the incidence of bilateral idiopathic macular holes in the literature. This report of a large series of patients with macular holes provides further information regarding incidence of bilaterality, interval between onset in the first and the second eye, and visual outcome. METHODS: A retrospective chart review was done of 550 patients with idiopathic macular holes examined at the Bascom Palmer Eye Institute between 1968 and 1994. The incidence of bilaterality was estimated from 365 patients in whom the fellow eye was normal at the initial examination. The rate of onset in the fellow eye was evaluated by survival analysis. Mean follow-up was 31 months (median 17 months). RESULTS: Patients with incomplete macular holes (stage 1, aborted stage 1, lamellar) or full-thickness holes had a 19% incidence of bilaterality at 48 months follow-up. In the subset of 32 patients with full-thickness macular holes in the first eye, 13% developed full-thickness holes in the fellow eye within 48 months. The median interval between the onset in the first and in the second eye was 17.5 months. Visual acuity was excellent and stable in eyes with aborted stage 1 and lamellar holes. The visual acuity in the first eye with full-thickness macular hole decreased to 20/200 or worse in 79% of cases within 36 months' follow-up. CONCLUSION: The incidence of bilaterality and poor visual function in the majority of full-thickness idiopathic macular holes by 3 years' duration should be considered when advising patients and planning management.

Aged↗

Immunologic aspects of recurrent abortion and fetal death.

Although mechanisms that prevent rejection of the conceptus are incompletely understood, recent evidence suggests that maternal immunologic aberrations may cause repeated abortions. Autoimmune conditions associated with antiphospholipid antibodies sometimes produce vascular abnormalities in the decidua and placenta; successful pregnancies can be achieved in most of these women by treatment with corticosteroids and low-dose aspirin. Abnormal maternal immune responses to paternal or trophoblast alloantigens, with insufficient production of blocking antibodies or suppressor cells, have also been implicated. Immunization of these patients with paternal or third-party leukocytes has resulted in a number of live births. However, the mechanism of action, effectiveness, and safety of all treatment regimens remain controversial. Present recommendations for the evaluation of recurrent-abortion patients include diagnosis and appropriate treatment of traditional nonimmunologic and more recently recognized autoimmune factors. The remaining patients with no detectable cause for repetitive pregnancy loss are candidates for referral to research centers for further immunologic evaluation and experimental immunotherapy.

Abortion, Habitual↗

Abortion at Gondar College Hospital, Ethiopia.

OBJECTIVE: To review the pattern and magnitude of abortion in order to establish baseline facts and data for future studies. DESIGN: A descriptive cross-sectional study. SETTING: Gondar College of Medical Sciences Hospital, Gondar, Ethiopia. RESULTS: Most of the subjects originated from the Gondar city and were married housewives, parous and relatively young. The abortion rate and ratio per 100 pregnancies and deliveries were 11.5 and 16.4, respectively. Only 13.4% of the patients admitted history of interference with the pregnancy. Previous history of abortion was obtained in 10.6% of the patients. The mean gestational ages for septic and non-septic cases were 14.6 and 15.2 weeks, respectively even though pregnancies less than 12 weeks from the last normal menstrual period accounted for 50.5%. The commonly diagnosed clinical type was incomplete, followed by inevitable and threatened abortion. The vast majority of the clinical conditions were non-septic (85.1 %) and spontaneous(85.6 %). The most common complications registered were anaemia, genital tract infection, shock of various causes and soft tissue injury. Four mothers died of abortion-related complications. The mean hospital stays for non-septic and septic abortion were three and five days, respectively. CONCLUSION: The study has attempted to address the issue of abortion in its general clinical pattern in relation to the various parameters. Being comprehensive, it also provides awareness and sensitivity on the magnitude of abortion and is assumed quite helpful for policy and decision makers.

Abortion, Septic↗

Incomplete pregnancies and ovarian cancer risk.

The role of spontaneous and voluntary abortions was assessed in a case-control study conducted in Milan, northern Italy on 953 cases of epithelial ovarian cancer (median age, 54) and 2500 control subjects (median age, 52) in hospital for acute diseases other than malignant, gynecological, or hormonal disorders. Overall the inverse relationship between total number of incomplete pregnancies and ovarian cancer risk was statistically significant, estimated relative risks (RRs) being, respectively, 0.9 (95% confidence interval (CI), 0.7-1.1) for one abortion and 0.8 (95% CI, 0.6-1.0) for two or more as compared to none. Furthermore, the protections afforded by spontaneous and voluntary abortions were well comparable (RRs 0.7 and 0.8 for > or = 2 spontaneous and voluntary abortions, respectively, versus none). While the protective effect of incomplete pregnancy was not explicable in terms of other characteristics of women nor significantly different across strata of reproductive factors or oral contraceptive use, it seemed more marked in women whose ovarian cancer occurred below age 50. Etiologically, these findings suggest that interrupted pregnancy per se and not predisposition to spontaneous abortion affects ovarian cancer risk.

Abortion, Induced↗

Response of pregnant mares to equine herpesvirus 1 (EHV1).

Twenty-one pregnant mares were inoculated with EHV1. Nineteen became infected as evidenced by clinical signs and/or viremia but only one mare aborted a virus-infected fetus. The viremias were leukocyte-associated and appeared to be non-productive, latent infections of these cells. Infectivity, detectable by cocultivation, persisted in the circulating leukocytes for as long as 9 days without resulting in abortion. The data suggest that it is extremely difficult to evaluate the efficacy of vaccines in preventing EHV1 (Rhinopneumonitis) abortion due to the paucity of non-exposed mares, lack of tests which measure residual protection, and an incomplete understanding of the pathogenic mechanisms involved in abortion due to this virus.

Abortion, Veterinary↗

Hysteroscopic findings after missed abortion.

OBJECTIVE: To identify the relation of missed abortions and intrauterine pathology. DESIGN: A postabortal hysteroscopy was performed 8 to 12 weeks after a dilatation and curettage (D&C) for missed abortion. SETTING: Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel. PATIENTS: Sixty patients after a D&C for a missed abortion. MAIN OUTCOME MEASURES: The hysteroscopic appearance of the uterine cavity. RESULTS: Intrauterine adhesions occurred in only 10 patients (16.7%) with most of them of the mild type. A previous missed abortion was recorded in 60% of these cases. Uterine anomaly was found in one quarter of the cases, mainly an incomplete uterine septum. CONCLUSION: We believe that missed abortion does not predispose for intrauterine adhesions to the extent that was previously believed. A partial uterine septum is a major factor predisposing for the occurrence of missed abortion. Hysteroscopy after a missed abortion is an easy and efficient means for both identifying such uterine anomaly and excluding intrauterine adhesions.

Abortion, Missed↗

A beta subunit mutation disrupting the catalytic function of Escherichia coli RNA polymerase.

The substitution of the evolutionarily conserved Glu-813 for lysine in the beta subunit of RNA polymerase (RNAP) causes a partial loss of function in the assembled RNAP. In the presence of the four ribonucleoside triphosphates, the mutant RNAP displayed a decreased frequency of promoter clearance and diminished elongation rate. Both defects could be compensated by raising the ribonucleoside triphosphate concentration. In the abortive initiation reaction limited by the incomplete set of ribonucleoside triphosphates, the mutant RNAP generated aberrant patterns of products indicative of their enhanced loss from the RNAP-promoter complex. A model is proposed, attributing the multiple effect of the mutation to the malfunctioning of the RNAP active center.

Amino Acid Sequence↗

A mitochondrial DNA sequence is associated with abnormal pollen development in cytoplasmic male sterile bean plants.

Cytoplasmic male sterility (CMS) in common bean is associated with the presence of a 3-kb unique mitochondrial sequence designated pvs. The pvs sequence encodes at least two open reading frames (297 and 720 bp in length) with portions derived from the chloroplast genome. Fertility restoration by the nuclear restorer gene Fr results in the loss of this transcriptionally active unique region. We examined the effect of CMS (pvs present) and fertility restoration by Fr (pvs absent) on the pattern of pollen development in bean. In the CMS line, pollen aborted in the tetrad stage late in microgametogenesis. Microspores maintained cytoplasmic connections throughout pollen development, indicating aberrant or incomplete cytokinesis. Pollen-specific events associated with pollen abortion and fertility restoration imply that a gametophytic factor or event may be involved in CMS. In situ hybridization experiments suggested that significant reduction or complete loss of the mitochondrial sterility-associated sequence occurred in fertile pollen of F2 populations segregating for fertility. These observations support a model of fertility restoration by the loss of a mitochondrial DNA sequence prior to or during microsporogenesis/gametogenesis.

Amino Acid Sequence↗

Endomitotic megakaryocytes form a midzone in anaphase but have a deficiency in cleavage furrow formation.

Megakaryocyte differentiation is marked by development of progressive polyploidy and accumulation of large nuclear mass and cytoplasmic volume. During differentiation, megakaryocytes undergo repeated incomplete cell cycles in which mitosis is aborted in late anaphase with failure of cytokinesis, termed endomitosis. Recent studies have postulated that failure of Aurora-B kinase to localize to the spindle midzone is responsible for endomitosis in megakaryocytes. In diploid cells, the translocation of Aurora-B kinase is critical for positioning of the cleavage furrow, in part through its phosphorylation of the Rho family GTPase activating protein MgcRacGAP which in turn alters activity of RhoA. However, we have previously demonstrated that Aurora-B kinase localizes to centromeres and is functional in endomitotic megakaryocytes. Here, we show that endomitotic megakaryocytes form midzone structures that recruit Aurora-B kinase and its substrate MgcRacGAP. Although many cells with polyploid anaphases showed cortical localization of Aurora-B kinase, we did not observe accumulation of RhoA in furrows or formation of an actin ring. When mitotic exit was induced by inhibition of cdk1, diploid control cells formed furrows exhibiting cortical RhoA but megakaryocytes exited endomitosis without evidence of furrowing. Therefore, localization of Aurora-B kinase to the midzone is normal in endomitotic megakaryocytes but furrowing is abnormal. These data suggest that endomitotic MKs fail to complete cytokinesis due to aberrant regulation of furrowing at a step subsequent to the localization of Aurora-B kinase, possibly involving the activation or localization of RhoA. This work explores the mechanism of a normally occurring furrowing defect in a nonmalignant primary cell.

Actins↗

Megagametophyte abnormalities of near-isogenic female partial-sterile soybean mutants ( Glycine max; Leguminosae).

Megagametogenesis of soybean, Glycine max (L.) Merr., cultivars Clark and Clark k2, and F1 hybrid of Clark (female parent) crossed with Clark k2 (male parent) were studied using stereo light microscopy and confocal scanning laser microscopy. Reproductive development in Clark and Clark k2 plants was compared to F1 hybrid plants. In mature pods, 6.4% of the ovules of Clark, 8.1% of the ovules of Clark k2, and 41.4% of the ovules of F1 hybrid plants were aborted. This female partial sterility was due to incomplete megagametophyte development: undeveloped polar nuclei-or developed but not in a position for fertilization; increased megagametophyte wall thickness; abnormal shape and/or premature degeneration of synergids and intact synergids throughout the life of the ovule; egg cell not well-developed or absent; and megagametophyte remaining uninucleate. Each of these abnormalities contributed to either lack of double fertilization or early megagametophyte abortion.

Fertility↗

Abortion and breast cancer risk in seven countries.

Epidemiologic studies have been inconsistent in suggesting an association between abortion and breast cancer risk. Whether the protection provided by a full-term pregnancy also results from a short-term pregnancy or whether a prematurely terminated pregnancy could increase the risk of breast cancer is unclear. Data from a large, international collaborative study were used to evaluate the association between abortions, whether spontaneous or induced, and breast cancer risk. The data from seven countries included 3,958 breast cancer cases and 11,538 hospital controls with information on abortion history obtained through interviews. Compared with nulliparous women with no abortion (baseline), the odds ratios (OR) and 95 percent confidence intervals (CI) were: for nulliparous women with a history of prior abortion, 0.86 (CI = 0.68-1.08); for parous women with no history of abortion, 0.63 (CI = 0.57-0.69); for parous women with abortion before first birth, 0.82 (CI = 0.69-0.97); and, for parous women with abortion only after first birth, 0.70 (CI = 0.63-0.79). When restricting analysis to parous women, those with a history of abortion exhibited an elevated OR suggesting a 29 percent risk increase if the incomplete pregnancy occurred before first birth (CI = 1.16-1.36) and an 11 percent risk increase for abortion only after first birth (CI = 1.02-1.20) compared with women without such history. The associations observed were stronger among the youngest women. These results do not support a large overall association between abortion and breast cancer risk.

Abortion, Induced↗

Survival with trisomy 18--data from Switzerland.

We collected records of 352 cases of trisomy 18 karyotyped between 1964 and May 2003 from the two major cytogenetic laboratories in Northeastern Switzerland. For more detailed information about the cases we contacted the referring physicians and/or the families of the patients. In this way we collected data about survival and malformations of 161 live births, 136 induced abortions and 29 stillborns or spontaneous abortions. In 26 cases of trisomy 18, only incomplete records were available. We observed that each year more cases of trisomy 18 were cytogenetically diagnosed in the two laboratories. Before 1984 almost no prenatal diagnoses were made; however, after this date the number of prenatal diagnoses increased and in the last 10 years, accounted for 75% of all cases. A decrease in the number of postnatally diagnosed cases was also observed over the same period of time. One third of the live-born children with trisomy 18 died during the first day of life. After 1 week, 1 month and 1 year of life the survival rates were 40, 22 and 6%, respectively. The median survival was 4 days, and only 1% of the children survived until their 10th birthday. Females were more likely to survive long term. In 63 cases autopsy reports were available for review. In 97% of these cases three or more malformations were found: 67% had VSD, 32% had horseshoe kidneys, 21% had esophageal atresia, 14% had omphalocele, 14% had facial clefts, and 11% had diaphragmatic hernias. In more than 50% genital hypoplasia was also described. We further analyzed survival of live-borns in relation to the length of gestation and to VSD and esophageal atresia.

Abnormalities, Multiple↗