Thioredoxin peroxidases from Brugia malayi.

Parasite-derived antioxidant proteins have been implicated in playing an important role in protection against the oxygen radicals that are generated during aerobic metabolism and in defense against host immune cell attack. Here we report that filarial nematodes include the thioredoxin peroxidase/thiol-specific antioxidant (TPx/TSA) family of antioxidant proteins as part of their complex defense against radical-mediated damage. At the protein level, the TPx/TSA from Brugia malayi (Bm-TPx-1) was approximately 50% identical and approximately 60% similar to TPx/TSAs from mammals, amphibians and yeast. Bm-TPx-1 was also approximately 60% identical to putative TPx proteins from a related filarial nematode, Onchocerca volvulus, and from the free-living nematode Caenorhabditis elegans. That B. malayi may express multiple forms of molecules with TPx/TSA activity was indicated by the identification of a B. malayi gene encoding a second, distinct member of the TPx/TSA family (Bm-tpx-2). Bm-tpx-1 was found to be transcribed in all stages of the parasite present in the mammalian host and the 25 kDa translation product was present in all of the developmental stages studied. The results of immunohistochemical, immunofluorescent and immunoprecipitation studies showed Bm-TPx-1 to be localized in the cells of the hypodermis/lateral chord in adult parasites and not to be present at the surface or in excretory/secretory products. The distribution in the parasite suggests that Bm-TPx-1 may play its major role in countering radicals produced within cells. A recombinant form of Bm-TPx-1 was biologically active and capable of protecting DNA from oxygen radical-mediated damage. Thioredoxin peroxidases may prove to be a critical component in the parasite's defense against injury caused by oxygen radicals derived from endogenous and exogenous sources.

Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation.

The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 microgram/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED50 being 1.0 microgram/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46-60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning.

Methotrexate and misoprostol when surgical abortion fails.

OBJECTIVE: To describe the use of methotrexate and misoprostol to induce abortion in pregnancies up to 8 weeks when uterine or cervical anomalies make suction curettage difficult or impossible. METHODS: Four consecutive women, 8 weeks pregnant or less and with failed suction curettage, were given methotrexate 50 mg per square meter intramuscularly followed by a misoprostol 800-microgram suppository 72 hours later. A repeat dose of a misoprostol 800-microgram vaginal suppository was administered on day 4 if there was no bleeding, and an additional dose was given if the repeat beta-hCG titer had not decreased by at least 50%. Subjects were followed-up with serum or urine hCG assays. Complete abortion was defined by vaginal bleeding and a negative urine pregnancy test. Subjects completed a daily symptom log and a satisfaction questionnaire when the abortion was complete. RESULTS: The four women referred after failed suction curettage had the following anatomic problems: a uterus bicornis bicollis, a bicornuate uterus, uterine leiomyomas, and cervical stenosis resulting from previous laser surgery. All subjects had a complete abortion from methotrexate and misoprostol. Mild gastrointestinal side effects were reported by all four subjects: nausea (two subjects), vomiting (two), and diarrhea (two). The satisfaction questionnaire revealed that all subjects agreed with the statements that "Overall, the procedure went well" and "I would recommend this procedure over a surgical abortion." CONCLUSION: Methotrexate and misoprostol can induce an abortion when uterine or cervical anomalies make suction curettage difficult or impossible.

Muscle actin gene from Aedes aegypti (Diptera:Culicidae).

A recombinant phagemid containing a 1,240-bp insert encoding an actin was isolated from a yellow fever mosquito, Aedes aegypti (L.), complementary DNA library. This insert (pBS-Act35) contained an open reading frame of 822 bp whose deduced amino acid sequence exhibited > 95% homology with the carboxyl terminal 274 amino acids of Drosophila melanogaster Meigen and silkworm, Bombyx mori (L.), actin genes. Reverse transcriptase-polymerase chain reaction was used to clone and determine the sequence of the additional 306 nucleotides that comprise the 5' end of the gene. The coding nucleotide sequence of the whole gene (designated Aeact-1) exhibited between 81 and 89% homology with coding sequences of D. melanogaster and B. mori actin genes, and its deduced amino acid sequence exhibited > 95% homology with those genes. The highest similarity of Aeact-1 gene at the amino acid sequence level was with B. mori and D. melanogaster muscle actins. Southern blot analysis indicated that the Aedes genome contains at least 5 actin-related sequences.

Mifepristone and misoprostol for early abortion when no gestational sac is present.

The study was conducted to determine whether the administration of mifepristone followed by vaginal misoprostol can induce an abortion in early pregnancy when no gestational sac is present on sonogram. This report presents a prospective, pilot study of 30 healthy adult women, pregnant and seeking an abortion, and with no gestational sac on sonogram. All women had a baseline serum chorionic gonadotropin (hCG) level measured prior to using mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 48 h later, and then returned up to 4 days later for a repeat sonogram and serum hCG level. Women with initial hCG levels > 2000 IU/L were evaluated for ectopic pregnancy. At the first follow-up visit, if the hCG decreased by >50%, the women were followed with home pregnancy (25 IU/L) tests weekly until negative. If the levels did not decrease by 50%, a second dose of misoprostol was given. Surgical intervention was indicated for persistent hCG levels or excessive bleeding. Of the 30 women enrolled, the mean number of days of amenorrhea was 40 (SD 9) days. Two women had surgical intervention for continuing pregnancy, 2 had ectopic pregnancies, and 1 was lost to follow-up. Complete medical abortions occurred in 25/30 (88%) women, but when recalculated, in 25/27 (93%) women who completed the protocol and who did not have an ectopic pregnancy. There was 1 adverse event in a woman with an ongoing pregnancy who then received methotrexate. She was hospitalized a day later with a complicated pelvic infection and likely methotrexate-induced pneumonitis. Twenty-three women had a decrease in hCG at first follow-up visit of >50%. All 27 women who completed the protocol found the overall regimen acceptable. Mifepristone followed at 48 h by vaginal misoprostol were effective and acceptable in inducing an abortion in very early pregnancy. There may be a higher incidence of failure in very early pregnancies. Documentation of a complete abortion by hCG level is necessary to ensure the pregnancy is neither ongoing nor ectopic.

Low-dose mifepristone 200 mg and vaginal misoprostol for abortion.

The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women > or = 18 years, up to 8 weeks pregnant, and wanting an abortion. The women received 200 mg mifepristone orally, self-administered 800 micrograms misoprostol vaginally at home 48 h later, and returned 1-4 days later for ultrasound evaluation. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, persistent products of conception 5 weeks later, or other serious medical conditions. Of the 933 subjects, 906 (97%) had complete medical abortions, 22 had surgical intervention, two were protocol failures, and three were lost to follow up. Of the 746 subjects who had no or minimal bleeding before misoprostol, 80% bled within 4 h and 98% within 24 h of using misoprostol. By day 7, 95% of women had a complete abortion. Side effects were aceptable in 85% of subjects, and 94% found the procedure acceptable. Low-dose mifepristone followed by vaginal misoprostol was highly effective as an abortifacient.

PIP: The effectiveness, side effects, and acceptability of 200 mg of mifepristone (one-third the standard dose) to induce medical abortion were investigated in a trial conducted at 7 centers in the US. 933 women with pregnancies up to 8 weeks' gestation were enrolled. They were given a 200-mg oral dose of mifepristone to be followed 48 hours later by home administration of 800 mcg of vaginal misoprostol and instructed to return 1-4 days later for ultrasound evaluation. 906 women (97%) experienced complete medical abortion, 22 required surgical abortion, 2 were protocol failures, and 3 were lost to follow-up. The most common indication for surgery was persistent or severe bleeding. Of the 746 women who had little or no bleeding before misoprostol administration, 593 (80%) bled within 4 hours and 731 (98%) within 24 hours of misoprostol. By day 7, 95% of women had experienced a complete abortion. The mean duration of bleeding was 17.4 days. 73% of subjects used an oral narcotic for pain. The most common mifepristone-related side effects were nausea and cramping; misoprostol-related side effects included cramping, fever, and chills. 74% found the pain related to the procedure acceptable and 85% rated its side effects as tolerable. Overall, 94% of subjects rated the medical abortion regimen as acceptable. These findings indicate that low-dose mifepristone is highly effective and acceptable as a self-administered abortifacient. The advantages of a lower dose of mifepristone include reduced manufacturing costs and less exposure to potential side effects.

Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days.

The aim of this study was to compare the effectiveness, side effects, and acceptability of one-third the standard dose of mifepristone, i.e., 200 mg, and vaginal misoprostol 800 microg to induce abortion in subjects < or =56 days pregnant with subjects 57-63 days pregnant. A prospective multicenter trial enrolled healthy women > or =18 years, < or =63 days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 microg vaginally, and returned 1-4 days later for ultrasound evaluation. A second dose of misoprostol was administered, if necessary. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, or persistent products of conception 5 weeks later. Of 1137 subjects, 829 were in the < or =56 days pregnant group and 308 in the 57-63 days pregnant group. In all, 34 subjects had surgical intervention and 16 were lost to follow-up. Complete medical abortions occurred in 97% of subjects < or =56 days pregnant and 96% in the 57-63 days pregnant group. In all, 88% of subjects in the < or =56 days pregnant and 92% in the 57-63 days pregnant group bled within 4 h of using vaginal misoprostol. Comparing subjects < or =56 days pregnant with 57-63 days pregnant, there was less diarrhea (20% vs 29%, p = 0.002) and vomiting (33% vs 44%, p = 0.001), although side effects were acceptable to 82% of subjects in both groups. One subject in the < or =56 day group required a transfusion for delayed excessive bleeding. Although bleeding (p = 0.01) and pain (p = 0.02) were less acceptable in the 57-63 day group, 91% of subjects in both groups reported that the overall procedure was acceptable. In summary, low-dose mifepristone 200 mg and home administration of vaginal misoprostol 800 microg at 48 h were highly effective and acceptable to women < or =63 days pregnant, thereby expanding the number of women who can access a medical abortion.

PIP: The aim of this study was to compare the effectiveness, side effects, and acceptability of one-third the standard dose of mifepristone, i.e. 200 mg, and vaginal misoprostol 800 mcg to induce abortion in subjects 56 or fewer days pregnant with subjects 57-63 days pregnant. A prospective multicenter trial enrolled healthy women aged 18 years or older, 63 or fewer days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 mcg vaginally, and returned 1-4 days later for ultrasound evaluation. A second dose of misoprostol was administered, if necessary. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, or persistent products of conception 5 weeks later. Of 1137 subjects, 829 were in the 56 days or fewer pregnant group and 308 in the 57-63 days pregnant group. In all, 34 subjects had surgical intervention and 16 were lost to follow-up. Complete medical abortions occurred in 97% of subjects 56 or fewer days pregnant and 96% in the 57-63 days pregnant group. In all, 88% of subjects in the 56 days or fewer pregnant and 92% in the 57-63 days pregnant group bled within 4 hours of using vaginal misoprostol. Comparing subjects 56 or fewer days pregnant with 57-63 days pregnant, there was less diarrhea (20% vs. 29%, p = 0.0002) and vomiting (33% vs. 44%, p = 0.001), although side effects were acceptable to 82% of subjects in both groups. 1 subject in the 56 or fewer days group required a transfusion for delayed excessive bleeding. Although bleeding (p = 0.01) and pain (p = 0.02) were less acceptable in the 57-63 days group. 91% of subjects in both groups reported that the overall procedure was acceptable. In summary, low-dose mifepristone 200 mg and home administration of vaginal misoprostol 800 mcg at 48 hours were highly effective and acceptable to women 63 or fewer days pregnant, thereby expanding the number of women who can access a medical abortion.

Methotrexate and misoprostol for early abortion.

OBJECTIVES: This study examined the effectiveness of an abortion by methotrexate and misoprostol, including side effects, subjects' satisfaction, and optimal treatment strategies. METHODS: The study evaluated a prospective ongoing trial of women with an 8-week gestation or less wanting an abortion. Subjects received intramuscular methotrexate (50 mg per m2 of body surface area) on day 1. Subjects self-administered misoprostol 800 micrograms orally or as a vaginal suppository or vaginal tablets either on day 3 to 4 or day 5 to 7. Repeat misoprostol 800 micrograms doses were used vaginally if there was no significant bleeding and the gestation was less than 12 weeks. Subjects with continuing pregnancies had a surgical abortion. Subjects completed a daily symptom log and a satisfaction questionnaire. A successful medical abortion was defined by vaginal bleeding without surgical intervention and either a negative urine pregnancy test or a negative transvaginal ultrasound. RESULTS: Of the 282 subjects, 274 (97%) had a medical abortion. Eight (3%) subjects required surgical intervention--four for continued pregnancies and four for excessive bleeding. One hundred and sixty-two (57%) subjects required only one dose of misoprostol and started bleeding, on average, 6.2 hours later. One hundred and twelve subjects (40%) required an average of 2.5 misoprostol doses and started bleeding, on average, 12.4 days after initial methotrexate injection. Misoprostol was more effective vaginally than orally. Gastrointestinal side effects were common, mild, and brief. Eighty-eight percent of the subjects agreed that the procedure went well. Subjects monitored with ultrasound completed the study sooner than those followed by beta-hCG levels. CONCLUSION: Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks' gestation. The procedure is a promising alternative to surgical abortion.

Methotrexate. A single agent for early abortion.

OBJECTIVE: To determine whether methotrexate as a single agent for induced abortion in pregnancies up to 5 weeks is as effective, has fewer side effects and is as acceptable to subjects as the combination of methotrexate and misoprostol. STUDY DESIGN: Women with no greater than a 5-week gestation were compared with a historical control group of consecutive women presenting for a medical abortion matched for gestational age. Subjects received intramuscular methotrexate on day 1. The study group received no misoprostol until day 21, when it was offered if the abortion had not yet occurred. The control group self-administered one or more doses of misoprostol within the first week after methotrexate. A complete abortion was defined by either negative transvaginal ultrasound or negative urine pregnancy test. All subjects completed a daily symptom log and satisfaction questionnaire. The analysis consisted of a comparison of the study group and control group for completion and timing of the abortion, symptoms and subject satisfaction. RESULTS: There were 40 study subjects and 53 controls. All subjects had a medical abortion without surgery. Ten (25%) of the 40 study subjects reached study day 21 without bleeding: 4 used misoprostol and 6 chose to wait for the abortion to occur spontaneously. One of the 10 subjects had persistent embryonic cardiac activity at 21 days and aborted after misoprostol. The mean number of days to bleeding was 15.5 days (SD 7.8 days) for the study group as compared with 8.1 days (SD 11.3) (P = .0003) for the control group. There was no significant difference in the number of days of bleeding, gastrointestinal side effects or reported subject satisfaction. CONCLUSION: While methotrexate as a single agent was effective in inducing abortion in early pregnancy, 15% of the study subjects finally used misoprostol, the abortion took significantly longer, and side effects were not less common as compared with those in subjects who received the combination of methotrexate and misoprostol.

Information on a shoestring: a practical database at an adolescent pregnancy program.

Adolescent pregnancy programs provide services to a socially high risk population with complex and continuing needs. Data describing the characteristics of the patient population is useful for directing program efforts, examining program outcomes, and documenting the need for additional services. The Rochester Adolescent Maternity Program has developed a simple, inexpensive data collection system in which demographic, social and reproductive information is routinely collected on all program patients. Such a system could be of use to other adolescent maternity programs.

Adverse perinatal outcomes: is physician specialty a risk factor?

An investigation was conducted in a community hospital to determine whether physician specialty (obstetrics vs family medicine) is a risk factor for adverse perinatal outcomes. Over a three-year period, there were 6,856 deliveries, of which 713 (10.4 percent) were attended by family physicians. Overall, there were 301 (4.4 percent) cases with adverse outcomes, of which 32 (10.6 percent) were attended by family physicians. The charts of a weighted random sample of 117 cases with adverse outcomes and 468 controls were reviewed to determine potential risk factors, including prenatal risk status, race, insurance, and specialty of the attending physician. The risk ratio for family physician as attending was 0.99 (95 percent confidence interval, 0.69 to 1.42) after multivariate adjustment for the other risk factors. Only high prenatal risk status was found to be an independent predictor (risk ratio 1.75, 95 percent confidence interval, 1.23 to 2.49). A chart review of a random sample of 146 patients (73 each of family physicians and obstetricians) revealed no difference in the proportion of high-risk patients in each specialty. It is concluded that in the setting studied, specialty is not a risk factor for adverse perinatal outcomes, and that this finding is not confounded by the patient's prenatal risk status.

Culdocentesis.

Culdocentesis is a procedure to obtain free fluid from the cul de sac of women. Physicians who provide comprehensive or gynecologic care to women should be capable of this procedure. The main indications are suspected ectopic pregnancy and suspected acute salpingitis or pelvic inflammatory disease. Although the procedure is not difficult or dangerous, many fine points of technique improve the outcome. Results are usually clear-cut and provide immediate and critical information for the management of the patient.

Vaginal misoprostol administered at home after mifepristone (RU486) for abortion.

BACKGROUND: There have been no US studies published on the effectiveness, safety, time to bleeding, and acceptability of misoprostol administered by vagina at home and repeated, if needed, after mifepristone was administered for abortion in women up to 8 weeks pregnant. METHODS: A prospective trial was conducted with women up to 8 weeks pregnant wanting an abortion. After receiving mifepristone 600 mg orally, subjects self-administered vaginal misoprostol 800 micrograms at home 2 days later. Subjects returned within 7 days, and if the gestational sac was still present on ultrasound, a repeat dose of misoprostol was administered in the office. Subjects completed a daily symptom log and a questionnaire on the acceptability of the procedures. RESULTS: Of the 166 subjects, 163 (98%) had a complete medical abortion. Three subjects presented with persistent bleeding and an incomplete abortion from 27 to 35 days after taking mifepristone and required surgical intervention. Vaginal spotting or bleeding occurred in 104 (62%) subjects before taking misoprostol, and 18 (11%) did not use misoprostol. Bleeding occurred on average 3.5 hours (SD, 3.2) after taking misoprostol. Six (4%) subjects required a second dose of misoprostol. Gastrointestinal side effects were common, mild, and brief. One hundred fifty-nine (96%) subjects agreed that the procedure went well, and 146 (90%) agreed that home administration of misoprostol was acceptable. CONCLUSIONS: Two days after taking mifepristone, misoprostol administered by vagina was found to be safe, highly effective, and acceptable to women. Since only 6 subjects needed a second dose of misoprostol, conclusions about repeat doses are not possible. This procedure is a promising alternative to surgical abortion.

Second-trimester spontaneous abortion, the IUD, and infection.

Nineteen cases of spontaneous second-trimester abortion associated with the intrauterine device (IUD) are reviewed and compared to 30 cases of spontaneous second-trimester abortion not associated with the IUD. Fifteen of the IUD's were Dalkon shields and four were Lippes loops. 16 of the 19 IUD-associated abortions began either with prolonged rupture of membranes or signs and symptoms of infection. Infection occurred in 18 or 19 of the cases (95%) but only 30% of the comparison group. Eleven major complications occurred in eight patients in the IUD group but only 8 complications occurred among 7 patients in the comparison group. It is suggested that when the IUD remains in utero during pregnancy, it may be a causal factor in second-trimester spontaneous abortion, and that intrauterine infection is the distinguishing characteristic of such cases. Mechanisms are suggested by which the IUD might cause infected abortion.

Calgranulin C has filariacidal and filariastatic activity.

The calgranulins are a family of calcium- and zinc-binding proteins produced by neutrophils, monocytes, and other cells. Calgranulins are released during inflammatory responses and have antimicrobial activity. Recently, one of the calgranulins, human calgranulin C (CaGC), has been implicated as an important component of the host responses that limit the parasite burden during filarial nematode infections. The goal of this work was to test the hypothesis that human CaGC has biologic activity against filarial parasites. Brugia malayi microfilariae and adults were exposed in vitro to 0.75 to 100 nM recombinant human CaGC. Recombinant CaGC affected adult and larval parasites in a dose-dependent fashion. Microfilariae were more sensitive to the action of CaGC than were adult parasites. At high levels, CaGC was both macrofilariacidal and microfilariacidal. At lower levels, the percentage of parasites killed was dependent on the level of CaGC in the culture system. The larvae not killed had limited motility. The filariastatic effect of low-level CaGC was reversed when the CaGC was removed from the culture system. Immunohistochemical analysis demonstrated that human CaGC accumulated in the cells of the hypodermis-lateral chord of adult and larval parasites. The antifilarial activity of CaGC was not due to the sequestration of zinc. Thus, the cellular and molecular mechanisms that result in the production and release of CaGC in humans may play a key role in the regulation of filarial parasite numbers.

Combined methotrexate and misoprostol for early induced abortion.

OBJECTIVE: To determine the effectiveness and side effects of and subject satisfaction with an induced abortion by administration of methotrexate and intravaginal misoprostol. SUBJECTS AND DESIGN: Prospective trial of 100 consecutive pregnant women aged 18 years or older at 8 weeks' gestation or less and wanting an abortion. INTERVENTIONS: Intramuscular administration of 50 mg of methotrexate per square meter of body surface area on day 1 and a misoprostol 800-micrograms vaginal suppository on day 3. Administration of misoprostol was repeated the following day if no bleeding occurred after the first dose. PROTOCOL: After pregnancy dating by clinical criteria, subjects were followed up with serum beta-human chorionic gonadotropin (beta-hCG) determinations on days 1, 7, and 14 and a high-sensitivity urine hCG test every 2 weeks until the value was less than 10 IU/L. Subjects completed a daily symptom log and satisfaction questionnaire on day 14. MAIN OUTCOME MEASURES: Complete abortion as defined by vaginal bleeding and a beta-hCG value of less than 10 IU/L without surgical intervention, complications and side effects, and patient satisfaction. RESULTS: Ninety-seven subjects had a complete abortion and one subject had vaginal bleeding and a 94% decrease of her beta-hCG value on day 7 but was subsequently unavailable for follow-up. Two subjects required surgical procedures: one with a continued pregnancy and one for excessive bleeding. No failures or complications occurred in early gestations prior to 45 days from the last menstrual period. Seventy-three percent responded to misoprostol treatment with bleeding within 12 hours and had a mean decrease of 90% in their beta-hCG value on day 7. Twenty-seven percent had no immediate bleeding response to misoprostol administration, began bleeding on day 10 (SD, 8 days), and had a mean decrease of 10% in their beta-hCG value on day 7. Seventy percent reported nausea; 46%, diarrhea; and 23%, vomiting. Ninety-three percent agreed that the procedure was acceptable and 95% would recommend the procedure. CONCLUSIONS: Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks. Home administration of a compounded misoprostol vaginal suppository was successful. Although gastrointestinal tract side effects were common, women found the procedure and its side effects acceptable.

Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial.

CONTEXT: The conventional timing of misoprostol administration after mifepristone for medical abortion is 2 days, but more flexible intervals, which may make the regimen more convenient, have not been studied. OBJECTIVE: To determine whether vaginal misoprostol administered 1, 2, or 3 days after mifepristone influences safety or effectiveness for abortion at up to 56 days' gestation. DESIGN: Prospective, randomized, open-label trial conducted from March 1998 to June 1999. SETTING: Sixteen US primary care and referral abortion facilities. PATIENTS: A total of 2295 healthy patients aged 18 years or older who were 56 or fewer days pregnant. Forty (1.7%) were lost to follow-up. INTERVENTIONS: Patients received 200 mg of oral mifepristone and were randomly assigned to self-administer 800 microg of vaginal misoprostol at home 1 (n = 745), 2 (n = 778), or 3 (n = 772) days later. Women returned to the clinic up to 8 days after mifepristone for ultrasonographic evaluation. A second dose of misoprostol was administered if the abortion was not complete. Patients with continuing pregnancy, excessive bleeding, or retained pregnancy tissue 5 weeks later received an aspiration curettage. MAIN OUTCOME MEASURES: Effectiveness of the procedure (ie, a complete medical abortion without surgical intervention), adverse effects, acceptability of the procedure based on patient questionnaires, reasons for surgical intervention, and adverse outcomes, compared among the study groups. RESULTS: Of the 2255 women completing follow-up, complete medical abortion rates were 98% (95% confidence interval [CI], 97%-99%) among those using misoprostol after 1 day, 98% (95% CI, 97%-99%) for those using misoprostol after 2 days, and 96% (95% CI, 95%-97%) among those using misoprostol after 3 days. Fifty-five subjects aborted before taking misoprostol, 9 had early surgery, and 103 did not take misoprostol on their assigned day. No blood transfusions were required. Cramping and nausea were the most common adverse effects reported, with similar percentages of patients in all 3 groups reporting such effects. Thirteen unexpected or serious adverse events occurred: 6 in those using misoprostol after 1 day; 4 in those using it after 2 days; and 3 in those using it after 3 days. Nearly all women (>90%) found the procedure to be acceptable. CONCLUSIONS: Our results suggest that vaginal misoprostol, 800 microg, can be used from 1 to 3 days after mifepristone, 200 mg, for early medical abortion, and need not be administered strictly 48 hours after mifepristone. JAMA. 2000;284:1948-1953.

Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor.

Filarial nematode parasites establish long-term chronic infections in the context of an antiparasite immunity that is strongly biased toward a Th2 response. The mechanisms that lead to this Th2 bias toward filarial antigens are not clear, but one possibility is that the parasites produce molecules that have the capacity to proactively modify their immunological environment. Here we report that filarial parasites of humans secrete a homologue of the human proinflammatory cytokine macrophage migration inhibitory factor (MIF) that has the capability of modifying the activity of human monocytes/macrophages. A cDNA clone isolated from a Brugia malayi infective-stage larva expression library encoded a 12.5-kDa protein product (Bm-MIF) with 42% identity to human and murine MIF. MIF homologues were also found to be expressed in the related filarial species Wuchereria bancrofti and Onchocerca volvulus. Bm-mif was transcribed by adult and larval parasites, and the protein product was found in somatic extracts and in the parasite's excretory-secretory products. Immunohistocytochemistry revealed that Bm-MIF was localized to cells of the hypodermis/lateral chord, the uterine wall, and larvae developing in utero. Unexpectedly, the activities of recombinant Bm-MIF and human MIF on human monocytes/macrophages were found to be similar. When placed with monocytes/macrophages in a cell migration assay, Bm-MIF inhibited random migration. When placed away from cells, Bm-MIF induced an increase in monocyte/macrophage migration that was specifically inhibited by neutralizing anti-Bm-MIF antibodies. Bm-MIF is the first demonstration that helminth parasites produce cytokine homologues that have the potential to modify host immune responses to promote parasite survival.