Managing miscarriage.
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Biomedical subjects
Publications and source records attributed to L Regan.
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Some of the new developments that are improving our understanding of the mechanisms underlying recurrent early pregnancy failure are reviewed. Etiologies such as genetic causes, structural causes, chronic maternal disorders, drugs, environmental pollutants, endocrine causes, and immunologic causes are discussed, along with strategies for management.
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Several noteworthy papers have been published in the past year in which the creation of interesting novel proteins, either by de novo design or the redesign of existing proteins, has been reported. Highlights include the successful design of proteins for binding specific ligands.
The incidence and natural history of serum anti-paternal cytotoxic antibody (APCA) in normal pregnancy and spontaneous abortion was investigated prospectively in 306 women (64 primigravidae and 242 multigravidae), in order to establish whether serum APCA is a useful screening test in the diagnosis, treatment and prognosis for patients with recurrent pregnancy loss. Pre-pregnancy, serial pregnancy and post delivery serum samples were tested against partner's lymphocytes, using a microdroplet lymphocytotoxicity assay. The incidence of serum APCA in the 256 pregnancies successfully completed was 32%, compared with 10% amongst the 50 pregnancies ending in spontaneous abortion. The lower incidence of positive APCA tests in unsuccessful pregnancies was explained by our finding that positive APCA tests are related to the gestational age of the pregnancy and are rarely demonstrable before 28 weeks gestation. Since APCA usually disappears between pregnancies, its usefulness as a diagnostic test for immunotherapy against recurrent abortion should be questioned.
The ultimate goal of protein engineering is to create novel proteins which will adopt predetermined structures, bind specified ligands, and catalyze new reactions. Here we describe the successful introduction of metal-binding activity into a model four helix bundle protein. The designed binding site is tetrahedral and is formed by two Cys and two His ligands on adjacent helices. We have introduced this site into the protein and characterized the binding activity. Using 65Zn(II), we have shown that the protein binds Zn(II), that the sulfhydryls are essential for binding, and that binding occurs to the protein monomer. The designed protein binds metals with high affinity: we estimate the dissociation constants as 2.5 X 10(-8) M for Zn(II) and 1.6 X 10(-5) M for Co(II). The characteristic absorption spectrum of the Co(II)-substituted protein fully supports the model of a tetrahedral binding site comprised of two Cys and two His ligands. Circular dichroism studies indicate that no significant changes in secondary structure occur between the metal-bound and metal-free forms of the protein. However, the metal-bound form is substantially stabilized toward denaturation by GuHCl compared to the metal-free form.
The relation between prepregnancy follicular-phase serum luteinising hormone (LH) concentrations and outcome of pregnancy was investigated prospectively in 193 women with regular spontaneous menstrual cycles. The group included 26 nulliparous and 167 multiparous women with various obstetric histories. Of the 147 women with LH concentrations of less than 10 IU/l (normal LH group) 130 (88%) conceived, whereas only 31 (67%) of the 46 women with LH values of 10 IU/l or more (high LH group) did so. In the high LH group, 20 (65%) of the pregnancies ended in miscarriage, whereas only 15 (12%) of pregnancies in the normal LH group did so. The adverse effect of a high prepregnancy LH concentration on fertility and outcome of pregnancy was seen in primigravidae, women with previously successful pregnancies, and women with a history of recurrent miscarriage. These data indicate an important role for hypersecretion of LH before conception in miscarriage. This finding offers the possibility of a simple predictive test for women before pregnancy, and could also be used to identify patients with an endocrine abnormality that can be remedied.
Microbiological investigations and clinical follow-up were performed on 516 patients undergoing first-trimester termination of pregnancy, over a 2-year period. Chlamydia trachomatis was isolated by pre-operative microbiological screening in 6.7% of patients, gonococcus in 0.4% and Trichomonas vaginalis in 2%. Candida spp and Gardnerella vaginalis were isolated from 16% and 28% of the women, respectively. Patients who had positive cervical chlamydial isolation were significantly younger (less than 22 years) than those who did not. Doctor's clinical diagnosis of genital tract infection was found to be associated with a positive screening result but not with the likelihood of postabortal pelvic infection. Among the 175 patients followed up in the outpatient clinic, 4 of the 15 patients with a positive result for N. gonorrhoeae, C. trachomatis and/or T. vaginalis developed postoperative pelvic infection, which is significantly more than the group who did not harbour any of these three organisms (9/114).
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