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Incomplete entry of bacteriophage T7 DNA into F plasmid-containing Escherichia coli.

The penetration of bacteriophage T7 DNA into F plasmid-containing Escherichia coli cells was determined by measuring Dam methylation of the entering genome. T7 strains that cannot productively infect F-containing cells fail to completely translocate their DNA into the cell before the infection aborts. The entry of the first 44% of the genome occurs normally in an F-containing cell, but the entry of the remainder is aberrant. Bypassing the normal mode of entry of the T7 genome by transfecting naked DNA into competent cells fails to suppress F exclusion of phage development. However, overexpression of various nontoxic T7 1.2 alleles from a high-copy-number plasmid or expression of T3 1.2 from a T7 genome allows phage growth in the presence of F.

Bacteriophage T7↗

Efficacy of follow-up and contact tracing of women who test positive for genital tract chlamydia trachomatis prior to pregnancy termination.

We examined the efficacy of follow-up, contact tracing and the need for retreatment in women who were screen-positive for genital tract Chlamydia trachomatis prior to termination of pregnancy. Eighty-six of 1363 (6.3%) women screened positive. These women were significantly younger than those who screened negative (P < 0.0001). The genitourinary medicine (GUM) clinic was notified of 73 (84.9%) screen-positive women and 41 (47.7%) attended for follow-up. Contact tracing was undertaken in 38 (92.7%) women who attended and 29 (70.7%) women who attended required retreatment for Chlamydia. The median duration between pregnancy termination and GUM clinic attendance was significantly longer in women who required retreatment compared to those who did not require retreatment (P = 0.003). In conclusion, follow-up and contact-tracing of women who screen positive for genital tract C. trachomatis was incomplete. This may substantially compromise the cost-effectiveness of a screen-and-treat programme.

Abortion, Induced↗

Time trends of ectopic pregnancies.

Whether the increase of ectopic pregnancies could be explained by methodological problems or by changing age structure was examined in data from one hospital (Tampere, Finland) between 1972 and 1984. Numbers of ectopic pregnancies, births, and induced and spontaneous abortions were obtained by 5-year age-groups and county of residence from the hospital discharge register. Introduction of a more sensitive pregnancy test in 1979 was coincident with the most rapid increase in the role of ectopic pregnancies. Use of incomplete denominators and varying catchment areas and correction of changing age-distribution of pregnant women did not markedly influence the time trends. Our analysis suggests that the observed increase in ectopic pregnancies in this area was partly real and partly due to better diagnosis.

Age Factors↗

Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome.

Antiphospholipid antibody syndrome (APS) is associated with adverse pregnancy outcomes and maternal complications including thrombotic events and early pre-eclampsia. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents a unique form in the spectrum of pre-eclampsia. This report describes four patients with pregnancy-associated hepatic infarctions. All four had APS and HELLP syndrome, which was complete in one patient and incomplete in three patients, with elevated liver enzymes in all, and either thrombocytopenia or hemolysis in two. In the literature, we found descriptions of an additional 24 patients who had 26 pregnancies with concomitant hepatic infarction. Of the total 28 patients, anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC) were assessed in 16 patients, out of whom 15 were found to be positive. Hepatic infartction during pregnancy was associated almost always with APS, with HELLP (2/3 complete, 1/3 incomplete), and only in one-third of the pregnancies with pre-eclampsia (PE).

Abortion, Habitual↗

Randomized outpatient clinical trial of medical evacuation and surgical curettage in incomplete miscarriage.

OBJECTIVE: To compare the efficacy and safety of misoprostol in outpatient medical evacuation with surgical curettage in uncomplicated incomplete spontaneous miscarriage. METHODS: Eighty women with a history of vaginal bleeding, and passage of some products of the conceptus were randomized into two groups. Forty patients in Group 1 received 200 microg misoprostol q.i.d. after the application of 200 microg intravaginal misoprostol for 5 days; 40 patients in Group 2 had a surgical curettage performed. All of the patients were re-evaluated after 10 days. The success rates, mean number of days of bleeding, mean decreases in hemoglobin levels, the complications and the rates of patient dissatisfaction in the two groups were compared. RESULTS: The success rate in the misoprostol-administered group was 95% [corrected]. Although the mean number of days of bleeding was significantly higher in the misoprostol-administered group, the mean decreases in hemoglobin values in the two groups were not significantly different. The patient dissatisfaction rate was 2.5% in the misoprostol group, compared to 35% in the control group. The difference between the two groups was significant. CONCLUSIONS: The use of misoprostol in the outpatient treatment of uncomplicated incomplete spontaneous miscarriage is safe and effective and can be an alternative to surgical evacuation and expectant management.

Abortifacient Agents, Nonsteroidal↗

Specific, nonproductive cleavage of packaged bacteriophage T7 DNA in vivo.

The morphogenesis of bacteriophage T7 includes assembly of a procapsid that subsequently both packages DNA and changes in structure. The DNA packaged by T7 is concatemeric and is cleaved to mature length during packaging. In the present study, packaged DNA obtained from T7-infected cells was analyzed after release from DNase-treated capsids. After fractionation by agarose gel electrophoresis, in-gel probing with oligonucleotides reveals that some of this DNA is shorter than mature T7 DNA; most of this short DNA has the T7 right end, but not the left end. Some of this short, packaged DNA is the product of left-to-right injection of DNA at the beginning of a T7 infection. However, subsequently produced short, packaged DNA has characteristics of a DNA that was produced during DNA packaging (incompletely packaged DNA or ipDNA). In contrast to results previously obtained in vitro, the profile of right-end-containing ipDNA is sometimes dominated by discrete bands. Some of the band-forming right-end-containing ipDNA appears with the kinetics of an abortive end product of packaging; cleavage in vivo appears to have arrested DNA packaging in this case. Other band-forming right-end-containing ipDNA appears with kinetics that have some characteristics expected of a precursor to the mature DNA; cleavage appears to have occurred after arrest of packaging in this case. The findings here of both left-to-right injection and right-to-left packaging is the most direct demonstration of polarity for these events in vivo.

Bacteriophage T7↗

The vanishing twin.

In general, it has not been recognized that many twin or multiple gestations are lost in utero early in pregnancy. Until the advent of ultrasound, the ability to document early human fetal loss in multiple gestation was difficult. However, recent reports of serial ultrasound examinations of pregnant women have documented the "disappearance" of at least one of two gestational rings. Furthermore, the number of twins observed at delivery was significantly less than the number of twin conceptions originally identified by ultrasound during the first trimester. These observations led to the concept of the "vanishing twin" [8,10,13,15,17,20,22,35,41]. In order to obtain reference and personal data on this subject, we reviewed the literature and corresponded with members of the International Society for Twin Studies and obstetricians affiliated with Northwestern University Medical School, Chicago, Illinois. The nine studies that have documented this phenomenon cite "disappearance" rates ranging from 0% to 78%, depending on patient population and timing of ultrasonography [8,10,13,15,17,20,22,35,41]. Several explanations are offered: physiological mechanisms of "disappearance" (resorption or formation of a blighted ovum or fetus papyraceus), artifactual error, incomplete scanning technique, and poor quality ultrasound equipment. The only complication thus far associated with "disappearance" of a fetus is slight vaginal bleeding.

Abortion, Spontaneous↗

Mechanism and control of interspecies recombination in Escherichia coli. I. Mismatch repair, methylation, recombination and replication functions.

A genetic analysis of interspecies recombination in Escherichia coli between the linear Hfr DNA from Salmonella typhimurium and the circular recipient chromosome reveals some fundamental aspects of recombination between related DNA sequences. The MutS and MutL mismatch binding proteins edit (prevent) homeologous recombination between these 16% diverged genomes by at least two distinct mechanisms. One is MutH independent and presumably acts by aborting the initiated recombination through the UvrD helicase activity. The RecBCD nuclease might contribute to this editing step, presumably by preventing reiterated initiations of recombination at a given locus. The other editing mechanism is MutH dependent, requires unmethylated GATC sequences, and probably corresponds to an incomplete long-patch mismatch repair process that does not depend on UvrD helicase activity. Insignificant effects of the Dam methylation of parental DNAs suggest that unmethylated GATC sequences involved in the MutH-dependent editing are newly synthesized in the course of recombination. This hypothetical, recombination-associated DNA synthesis involves PriA and RecF functions, which, therefore, determine the extent of MutH effect on interspecies recombination. Sequence divergence of recombining DNAs appears to limit the frequency, length, and stability of early heteroduplex intermediates, which can be stabilized, and the recombinants mature via the initiation of DNA replication.

Adenosine Triphosphatases↗

Intention to claim a Medicare rebate among women receiving private Victorian pregnancy termination services.

OBJECTIVES: To determine the proportion of women who have pregnancy terminations as private patients in Victoria who do not intend to claim a procedure fee rebate from Medicare, to compare characteristics of women who intend to submit a Medicare claim with those who do not and to compare the findings to the results from a similar study conducted in NSW in 1992. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional observational study over a 12-week period. Women having a pregnancy termination service in eight large Victorian private clinics were invited to complete a brief written questionnaire. OUTCOME MEASURE: The proportion of women who did not have a Medicare card or who had a Medicare card but did not intend to use it to claim from Medicare. RESULTS: Of the 1,329 women who responded, 13.1% either did not have a Medicare card or did not intend to use their card to claim a Medicare rebate. A further 20.7% of respondents were not sure about whether they would submit a claim. Women who intended to claim a Medicare rebate were different from women who did not according to age, language spoken at home, residency, citizenship and distance travelled to the service. These results are very similar to the findings from the 1992 NSW study. CONCLUSION: Between 13.1% and 33.8% of private Victorian pregnancy terminations were estimated to not be recorded at the Health Insurance Commission. Health Insurance Commission records of Medicare rebate claims for pregnancy terminations are an incomplete and somewhat biased record of the services that are provided and are likely to have been so for some time.

Abortion, Induced↗

Serum progesterone and endovaginal sonography by emergency physicians in the evaluation of ectopic pregnancy.

OBJECTIVE: To determine a discriminatory level for serum progesterone (SP) in pregnant patients with no definite intrauterine pregnancy (IUP) on endovaginal ultrasonography (US) in the differentiation of ectopic pregnancy from normal IUPs. METHODS: A prospective observational study in a convenience sample of women at risk for ectopic pregnancy was performed at an urban teaching hospital from May 1991 until May 1994. Women aged > or =18 years presenting to the ED with a positive pregnancy test in combination with pelvic or abdominal pain, vaginal bleeding, orthostasis, adnexal mass or tenderness, or any historical risk factor for ectopic pregnancy were eligible. Hypotensive or unstable patients were excluded. Endovaginal US was performed and patients with no definite IUP had a serum beta-hCG and SP measured. RESULTS: 314 patients were enrolled, with 14 excluded for lack of follow-up or incomplete SP data, yielding 300 patients. The initial endovaginal US diagnoses included 169 definite IUP, 31 abnormal IUP, 5 definite ectopic pregnancy, and 95 no definite IUP. 68/95 had SP measured, with values of 22.8 +/- 13.4 ng/mL (mean +/- SD) for IUP; 4.9 +/- 6.5 for spontaneous abortion, and 7.5 +/- 7.2 for ectopic pregnancy. The mean values were significantly different (2-tailed t-test) for ectopic pregnancy vs IUP and for spontaneous abortion vs IUP. An SP of > or =11 ng/mL (sensitivity 91%; specificity 84%) was post hoc the best cutoff value for suggesting an IUP when the endovaginal US was not definite for IUP. CONCLUSIONS: SP cannot reliably discriminate ectopic pregnancy vs spontaneous abortion in pregnant patients with no definite IUP on endovaginal US; however, a low SP (<11 ng/mL) in this sonographic category suggests an abnormal pregnancy.

Abortion, Spontaneous↗

Endometrial regeneration after voluntary abortion.

Endometrial biopsies were obtained on postabortal days 1 to 36 in 42 women without contraception, in 28 women using oral contraceptives, and in 12 women with intrauterine devices. Tissue samples were examined for day-to-day sequential changes, specifically: a)regenerative, repair, proliferative and secretory activity, b)involution of pregnancy changes, c)inflammation. In the absence of contraception, the endometrium promptly regenerated. The earliest evidence of ovulation was on day 9. One-third of the women ovulated before the first period. Incomplete placental and decidual involution was seen in 45% of patients, but its frequency progressively decreased toward the end of observation. Inflammation seen in 26% was limited to the retained decidua and was, therefore, thought to be a reactive rather than an infectious phenomenon. In women taking oral contraceptives, initial regeneration was also prompt. "On pill" changes resembled the nonpostabortal picture except for a few cases of cystic glandular dilation, or Arias-Stella-like phenomena. Retained decidua and inflammation were more frequent (75% and 68%) than in the noncontraceptive group, and the diminishing trend was not observed. In the intrauterine device group, inflammation was more frequent (83%) than in the other two groups and was not limited to the decidua.

Abortion, Induced↗

The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma.

BACKGROUND: In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. METHODS: Lymphadenectomy was called 'complete' when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and 'not-complete' when this was the case in 1-4 stations. RESULTS: A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3-6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR= 3.2 (95% ci: 1.3-7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. CONCLUSIONS: From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect on prognosis in case of positive nodes. The policy of aborting the procedure when lymph node metastases are found in frozen section should be questioned.

Carcinoma↗

Role of abortive retroviral infection of neurons in spongiform CNS degeneration.

Retroviruses are involved in several human neurological diseases with varying pathological features. Whether these diseases are due to a direct effect of the virus on nervous system cells is unknown. To gain insight into the pathogenesis of one retroviral neurological disease, we are studying the murine neurotropic retrovirus, Cas-Br-E, which causes lower motor neuron disease associated with spongiform degenerative changes in brain and spinal cord. Central nervous system (CNS) injury seems to be due to direct viral action, but the precise target cells of the virus are uncertain. After blood-borne virus enters the CNS it is found in capillary endothelial cells. No microscopic evidence for virus within glia or neurons has been found in some studies, whereas virus or incomplete particles have been observed in CNS cells in other studies. Here we identify the neuron as a major target for Cas-Br-E in the CNS, suggesting that this disease may be a direct result of viral infection of neurons. We also show that envelope protein (Env, encoded by the env gene), a major determinant of neurovirulence, cannot be detected in neurons but is present in non-neuronal cells, although spliced env messenger RNA is synthesized in CNS tissue. This suggests that a post-transcriptional step in Cas-Br-E Env protein synthesis is impaired and that the neurological disease may be a consequence of abortive replication of virus in neurons. This may explain the failure to find neuronal infection in other neurological diseases by conventional methods of virus detection.

Animals↗

The selective estrogen receptor modulator, raloxifene: segment II studies in rats and rabbits.

Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by Eli Lilly and Company primarily as a therapeutic agent for postmenopausal osteoporosis. Two Segment II studies were conducted that examined maternal reproductive parameters and fetal outcome following gestational exposure to raloxifene. Pregnant CD rats (25/group) and New Zealand white rabbits (20/group) were dosed once daily by oral gavage with 0, 0.1, 1, or 10 mg/kg on Gestation Days (GD) 6 through 17 and 7 through 19, respectively. Maternal body weight and food consumption were monitored throughout pregnancy. Caesarean sections were performed on GD 20 and GD 28 for rats and rabbits, respectively, to evaluate fetal viability, weight, and morphology. In rats, maternal body weight, body weight gain, and food consumption were reduced in all raloxifene treatment groups. Fetal viability was depressed in the 10-mg/kg group and was often associated with signs of hemorrhaging from the vagina. Fetal growth retardation was indicated in the 1- and/or 10-mg/kg groups by increased incidences of fetal runts and the developmental deviations, wavy ribs and kidney cavitation. There was no evidence of treatment-related malformations in rat fetuses. In rabbits, depressions in body weight gain and food consumption occurred in the 10-mg/kg group, and a single abortion occurred in the 1-mg/kg group. Fetal viability and weights were not affected in any of the raloxifene treatment groups. The overall proportions of fetuses with malformations, deviations, or variations were not affected by treatment with raloxifene; however, one fetus each from the 0.1-, 1-, and 10-mg/kg groups had incomplete closure of the interventricular septum. Therefore, maternal and fetal no-effect levels were not obtained in this study of raloxifene.

Administration, Oral↗

Treatment with cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord--II--Recovery of function.

Previous reports have suggested a correlation between autoimmunity and abortive axonal regeneration in mammalian CNS. In this study we investigated the effects of immunosuppressive treatment with Cyclosporine A (CyA) (2.5-5 mg/kg/day) on axonal regeneration after complete spinal transection in rats. Partial recovery of function was observed 30 days after surgery in rats treated with CyA, with the presence of incomplete spontaneous locomotion and a positive contact placing reaction. Restoration of somatosensory evoked potentials and positive retrograde fluorescent tracing were also observed. CyA reduced the autoimmune reaction which targeted components of the axons. These results provide further evidence of the role played by autoimmunity in blocking regeneration of fibre tracts in mammalian CNS.

Animals↗

Equine herpes myeloencephalopathy.

The neurologic form of EHV-1 infection appears to be the result of central nervous system infarction caused by vasculitis, which is initiated in endothelial cells of small blood vessels. The etiologic agent is equine herpesvirus-1, subtype 1. There is some evidence to suggest that the neurologic form of the disease actually results from reactivation of a previous infection. Whether the vasculitis that causes the central nervous system injury is the direct result of the infection or an immune response to the infection has not been determined. The clinical signs are rapid in onset, nonprogressive, and many horses may improve. The diagnosis must often remain tentative, particularly in horses that recover, because there is no single reliable confirmatory test. The prognosis is generally good, although recovery may be slow and incomplete. Supportive therapy is essential, and administration of corticosteroids may be useful. There is no specific therapy for the virus or for the vasculitis. Currently no vaccine can be claimed to protect against the central nervous system form of the disease. Vaccination is recommended, however, to reduce the incidence of respiratory disease, abortion, and neonatal death on the farm. Repeated vaccination is necessary to maintain presumably protective antibody concentrations. Vaccination every 3 to 4 months may decrease the incidence of EHV-1 infection on the farm and therefore may indirectly prevent the occurrence of the neurologic form of the disease.

Animals↗

Risk factors among young women with endometrial cancer: a Danish case-control study.

OBJECTIVE: This study was undertaken to identify and quantify risk factors for endometrial cancer among young women. STUDY DESIGN: This case-control study included all Danish women <50 years old who had endometrial cancer diagnosed during the period 1987 to 1994. A total of 237 case patients and 538 population control subjects matched with the case patients for age and residence were included in the analysis. RESULTS: Women with a family history of endometrial cancer had an odds ratio for endometrial cancer of 2.1 (95% confidence interval, 1.1-3.8)). Completion of 1 term pregnancy implied an odds ratio of 0.6 (95% confidence interval, 0.3-1.1). The risk of endometrial cancer decreased significantly with increasing age at first birth and with the number of induced abortions. Use of oral contraceptives for 1 to 5 years decreased the risk of endometrial cancer (odds ratio, 0.2; 95% confidence interval, 0.1-0.3). The odds ratio for endometrial cancer among women who received hormone replacement therapy for 1 to 5 years was 3.1 (95% confidence interval, 1.4-7.0). Body mass index was not demonstrated to be an independent risk factor in this study. The protective impacts of the different exposures (risk factors) can be expressed as etiologic fractions, which indicate how much each exposure reduces the occurrence of endometrial cancer compared with a situation without the existence of that particular exposure. These fractions were as follows: oral contraceptive use for > or =1 year, -45%; 2 term pregnancies, -88%; age > or =30 y when giving birth for the first time, -38%; and a history of incomplete pregnancy, -16%. CONCLUSION: A number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women: family history, reproductive history, hormone replacement therapy, and the use of oral contraceptives. Among young women reproductive variables imply the greatest prophylactic potential.

Abortion, Induced↗

The management of first trimester miscarriage by general practitioners in Ireland.

A single shot questionnaire was sent to 500 general practitioners, with 39 per cent valid response, to audit first trimester miscarriage management. With threatened miscarriage 60 per cent were cared for at home (10 per cent of these had ultrasound) and 40 per cent were transferred to hospital. The miscarriage rate was 14 per cent-61.7 per cent had no symptoms (of these 42.2 per cent had a positive pregnancy test), 24.4 per cent had threatened miscarriage with 11.6 per cent incomplete and 2.3 per cent complete. The general practitioner is ideally placed to develop initial clinical management strategies and direct access to ultrasound would be helpful.

Abortion, Spontaneous↗