Biomedical subjects

E Weisberg

Publications and source records attributed to E Weisberg.

At least 19 recordsLinked to original sources

PubMed2001

ARG tyrosine kinase activity is inhibited by STI571.

The tyrosine kinase inhibitor STI571 inhibits BCR/ABL and induces hematologic remission in most patients with chronic myeloid leukemia. In addition to BCR/ABL, STI571 also inhibits v-Abl, TEL/ABL, the native platelet-derived growth factor (PDGF)beta receptor, and c-KIT, but it does not inhibit SRC family kinases, c-FMS, FLT3, the epidermal growth factor receptor, or multiple other tyrosine kinases. ARG is a widely expressed tyrosine kinase that shares substantial sequence identity with c-ABL in the kinase domain and cooperates with ABL to regulate neurulation in the developing mouse embryo. As described here, ARG has recently been implicated in the pathogenesis of leukemia as a fusion partner of TEL. A TEL/ARG fusion was constructed to determine whether ARG can be inhibited by STI571. When expressed in the factor-dependent murine hematopoietic cell line Ba/F3, the TEL/ARG protein was heavily phosphorylated on tyrosine, increased tyrosine phosphorylation of multiple cellular proteins, and induced factor-independent proliferation. The effects of STI571 on Ba/F3 cells transformed with BCR/ABL, TEL/ABL, TEL/PDGFbetaR, or TEL/ARG were then compared. STI571 inhibited tyrosine phosphorylation and cell growth of Ba/F3 cells expressing BCR/ABL, TEL/ABL, TEL/PDGFbetaR, and TEL/ARG with an IC(50) of approximately 0.5 microM in each case, but it had no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by TEL/JAK2. Culture of TEL/ARG-transfected Ba/F3 cells with IL-3 completely prevented STI571-induced apoptosis in these cells, similar to what has been observed with BCR/ABL- or TEL/ABL-transformed cells. These results indicate that ARG is a target of the small molecule, tyrosine kinase inhibitor STI571.

Adenosine Triphosphate↗

PubMed2001

Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients.

The tyrosine kinase inhibitor imatinib (STI571, Glivec) blocks the activity of the BCR/ABL oncogene and induces hematologic remissions in the majority of patients with chronic myeloid leukemia (CML). Glivec is an aminopyrimidine derivative that interacts with the ATP-binding site within the kinase domain of ABL and several other tyrosine kinases, including c-KIT, PDGF beta receptor, and ARG. The compound is currently in phase III clinical trials. Although patients with chronic phase CML have been found to develop drug resistance only rarely so far, patients in more advanced phases of the leukemia develop resistance frequently. The available information on Glivec resistance will be reviewed.

Animals↗

PubMed2001

A randomised controlled trial comparing a dilating vaginal speculum with a conventional bivalve speculum.

Cervical smears are traditionally taken with the aid of a metal or disposable plastic bivalve speculum. Many women complain of discomfort with these specula. This study compares the efficacy and women's experiences of a new 'dilating speculum' called the Veda-scope, with a conventional metal bivalve speculum (Pederson). The aims of this study were: to determine whether the Veda-scope provides adequate visualisation of the cervix and vaginal walls and an adequate cervical cytology specimen; and to compare user acceptability and women's levels of comfort between the Veda-scope and the bivalve speculum. Sixty-four women were randomised to be examined with the Veda-scope and 60 with the bivalve speculum, by one of two operators. Each woman completed a questionnaire that included subjective views of their previous cervical smear experiences, and acceptability of the examination at the study consultation. Cytologists were blinded as to which speculum was used for cervical sampling. Of women examined, 7-83% of women found Veda-scope examinations comfortable, compared to 38-62% of women who found examinations with the bivalve comfortable; 94% of the women preferred the 'comfort' of the Veda-scope. The Veda-scope was as good as the bivalve speculum in providing samples for cytological analysis following the initial learning curve, and also provided markedly superior magnified views of the cervix and vaginal fornices.

Adult↗

PubMed2000

Serotonin-dependent collagenase transcription in myometrial cells requires extended AP-1 site.

Primary cultures of uterine smooth muscle cells from post-partum rats express interstitial collagenase in response to serotonin and the serotonin-dependent production of interleukin-1 (IL-1) [Wilcox, B.D., Dumin, J.A. and Jeffrey, J.J. Serotonin regulation of interleukin-1 messenger RNA in rat uterine smooth muscle cells. Relationship to the production of interstitial collagenase J. Biol. Chem., 269, (1994a), 29658]. Transient transfections of these cells indicate that rat collagenase transcription is regulated via a proximal consensus AP-1 site within an extended palindrome. Mutation of either the AP-1 site or extended palindrome (EP) decreases promoter activity to approximately 30% of the wild-type. Electrophoretic mobility shift assays reveal the binding of smooth muscle cell nuclear proteins to the AP-1 EP. This binding is barely detectable after mutation of the EP and is completely eliminated by mutation of the AP-1 heptamer. Competition experiments demonstrate that binding to the AP-1 EP is specific and of higher affinity than binding to oligonucleotides containing a mutated EP. Binding to the AP-1 EP is higher when smooth muscle cells are cultured in the presence of serotonin than in its absence. Although IL-1 is required for collagenase transcription, binding to the AP-1 EP appears to be IL-1-independent. FosB, Fra-2, c-Jun, JunB and, most abundantly, JunD bind the AP-1 EP in the absence and presence of serotonin. In contrast, Fra-1 expression and binding are serotonin-dependent suggesting that the activation of Fra-1 may be a key component of collagenase transcriptional activation.

Animals↗

PubMed2000

Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines.

The tyrosine kinase activity of the Bcr/Abl oncogene is required for transformation of hematopoietic cells. The tyrosine kinase inhibitor STI571 (formerly called CGP57148B, Novartis Pharmaceuticals) inhibits BCR/ABL, TEL/ABL, and v-ABL kinase activity and inhibits growth and viability of cells transformed by any of these ABL oncogenes. Here we report the generation of 2 BCR/ABL-positive cell lines that have developed partial resistance to STI571. BCR/ABL-transformed Ba/F3 hematopoietic cells and Philadelphia-positive human K562 cells were cultured in gradually increasing concentrations of STI571 over a period of several months to generate resistant lines. Resistant Ba/F3.p210 cells were found to have an increase in Bcr/Abl messenger RNA, amplification of the Bcr/Abl transgene, and a greater than tenfold increase in the level of BCR/ABL protein. In contrast to Ba/F3.p210 cells, drug-resistant K562 cells did not undergo detectable amplification of the BCR/ABL gene, although they displayed a 2-fold to 3-fold increase in p210BCR/ABL protein. The addition of STI571 to both resistant Ba/F3. p210 and K562 cells resulted in a rapid reduction of tyrosine phosphorylation of cellular proteins, similar to that observed for nonresistant cells. However, the inhibition of kinase activity was transient and partial and was not accompanied by apoptosis. The results suggest that resistance to STI571 may be multifactorial. Increased expression of the target protein BCR/ABL was observed in both lines, and resulted from oncogene amplification in one line. However, altered drug metabolism, transport, or other related mechanisms may also contribute to drug resistance.

Animals↗

PubMed2000

Vaginal epithelial surface appearances in women using vaginal rings for contraception.

Vaginal inspections using colposcopy before insertion of contraceptive vaginal rings and at 2-month intervals during ring use were conducted on 169 users of four different formulations. The rings studied released Nestorone alone (50, 75, 100 g daily over 6 months); ethinyl estradiol: Nestorone (30:100 and 15:150 g daily over 6 months); ethinylestradiol:norethindrone acetate (20:1000 and 15:1000 g daily over 4 months); and ethinyl estradiol:norethindrone acetate (20:1000 g daily over 12 months). A total of 88 altered or atypical conditions of the vaginal surface appearance were recorded in 507 inspections (17.4% of inspections). Many of these atypical appearances were quite subtle. The incidence was significantly higher (p <0.01) than in the single pretreatment examinations (11 in 158 inspections; 7.0%), but closely matched that of a "control group" of sexually active women who were the subject of an earlier study by the same investigators. In that study, the incidence was 18% (57 atypical conditions in 317 inspections). In all, 83% of atypical conditions identified in the vagina during ring use had disappeared by the next scheduled colposcopy despite continued ring use. Findings of potential significance were conservatively defined as all ulcerations, those abrasions and ecchymoses that were >0.5 cm in any direction, and fields of five or more petechiae. Findings fitting those criteria comprised 30% of atypical conditions in ring users, 33% in the control group, and 27% pretreatment. The corresponding incidence as a percentage of inspections were 5.3%, 6. 0%, and 2.5% in the ring users, control groups, and pretreatment groups, respectively. These differences were not statistically significant. The findings suggest that the vaginal rings included in the studies contributed little, if at all, to clinically significant lesions or to total lesion incidence. Further definition would require a larger and longer-term study with matched controls.

Adolescent↗

PubMed2000

A detailed analysis of menstrual blood loss in women using Norplant and Nestorone progestogen-only contraceptive implants or vaginal rings.

Changes to the pattern of menstrual bleeding are almost universal in women using progestogen-only methods of contraception, and are an important cause of discontinuation of these methods. The present study was designed to explore the changes in menstrual bleeding patterns and objectively measure menstrual blood loss (MBL) in 110 women before and during one year of use of 4 different progestogen-only contraceptives: Norplant subdermal levonorgestrel implants; Nestorone progestogen 4-cm or 6-cm implants nominally delivering 100 microg or 150 microg daily; or a vaginal ring (CVR) delivering 100 microg of Nestorone (NES) daily (CVR users were limited to only 6 months of use). Groups could not be directly compared because of the differences in numbers of subjects and durations of treatment. The total MBL during each of the three 8-week collection periods during treatment decreased significantly in each group compared to the total blood loss in the two control cycles (greater than 50% decrease in all groups during the first 6 months), although the differences between individual women at the extremes remained considerable. The highest blood loss measured on any single day during the treatment collection periods was significantly reduced (p <0.001) in users of all four devices in all three collection periods compared to the control period (CVR users did not have a 3rd collection period). The Nestorone-releasing CVR was associated with an 88% reduction in mean MBL and a high incidence of amenorrhea at 6 months. There was considerable variation in percentage reduction in total blood loss at 6 and 12 months between individual women ranging from 100% (women with amenorrhea) to a small minority experiencing an increase compared with control cycles. The increases in measured blood loss during treatment were almost entirely in women with light bleeding in the control period and were related to prolonged episodes of light bleeding rather than heavy bleeding. Women contemplating use of a progestogen-only contraceptive method need to be counseled about alterations to the menstrual cycle but can be reassured that total blood loss will usually be much less than with normal cycles.

Administration, Intravaginal↗

PubMed2000

A randomized comparison of the effects on vaginal and cervical epithelium of a placebo vaginal ring with non-use of a ring.

Little is known about the effects of contraceptive vaginal rings on the vaginal surface epithelium, although most studies have not demonstrated any significant deleterious effect. However, one study found that some medium-to-long-term levonorgestrel-releasing ring users developed chronic erythematous and ulcerative lesions in the posterior vaginal fornix. Subsequently, this ring was completely redesigned (IVR-2) with different dimensions and much greater flexibility. The first version of IVR-2 was designed as a placebo ring to explore effects on the vagina and cervix without addition of a progestogen. One-hundred-sixty-six healthy sexually active women volunteers were recruited in four centers and randomly assigned for 6 months to either placebo ring use or control (non-use) using a predetermined randomization code generated by WHO in a 2:1 ratio. Careful inspections of the vaginal and cervical epithelium were performed with a colposcope at admission and at 2-month intervals. No clinically significant lesions were detected in any center either among ring users or controls. However, a number of minor changes in appearance of the vaginal and cervical epithelium (erythema, petechiae, ecchymosis, and minor aceto-white changes) were described from the Sydney Center, some of which were present on admission and some of which were found on subsequent examination. Ten of eleven "red" changes on the cervix and vagina were noted in IVR-2 users, and only one in the controls, suggesting a contribution by the IVR-2 to minor epithelial surface changes. Five of ten resolved completely with continued ring use. There was no correlation in this study between epithelial changes and cigarette smoking or frequency of intercourse in the 14 days prior to colposcopic examination but a significant relationship between tampon use in the last 7 days and all epithelial changes (p = 0.05) and especially red changes (p = 0. 027) was noted. Red changes were significantly less likely to be found among condom users (p = 0.007). The IVR-2 placebo ring did not produce clinically significant changes in the vaginal epithelium and cervical mucosa and a carefully controlled and randomized study should be considered to compare the epithelial appearances in women using a placebo IVR-2 and one releasing 20 microg levonorgestrel.

Biopsy↗

PubMed2000

Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide.

OBJECTIVE: We sought to determine the safety and acceptability of vaginal gel formulation PC-503 among low risk, abstinent women. The active ingredient was 2% pharmaceutical grade lambda carrageenan, a sulphated polymer that is generally recognised as safe by the US Food and Drug Administration. METHODS: 35 women in five sites applied 5 ml of the PC-503 gel vaginally once a day for 7 days while abstaining from sexual intercourse. Visual vaginal examinations were performed on days 1, 4, and 8. STI testing and vaginal pool Gram stain preparations were done on days 1 and 8. Participants were asked about product acceptability. RESULTS: 34 of the 35 women enrolled completed 7 days' use. Following product use, five reported mild symptoms including "bladder fullness," "genital warmth," or discomfort, and lower abdominal pain, and one had moderate pale yellow cervical discharge. Using the Nugent criteria, three women had bacterial vaginosis (BV) before and after use; three had BV before but not after, and two had BV after but not before. Most of the women found PC-503 to be pleasant or neutral in feel and smell and considered extra lubrication to be an advantage; however, one third found it to be messy. CONCLUSIONS: Vaginal use of PC-503 gel did not cause significant adverse effects in a small number of low risk, sexually abstinent women. Further testing in larger numbers of sexually active women is planned. A smaller volume of gel may be more acceptable to some women.

Anti-Infective Agents, Local↗

PubMed2000

A comparison of cycle control and effect on well-being of monophasic gestodene-, triphasic gestodene- and monophasic desogestrel-containing oral contraceptives. Gestodene Study Group.

This was an open-label multicenter study to compare the cycle control and effect on well-being of two oral contraceptives containing gestodene and one containing desogestrel. A total of 2419 healthy women < or = 41 years of age were randomized to receive oral contraceptives containing monophasic gestodene (Minulet; n = 806, mean age 24.5 years), triphasic gestodene (Tri-Minulet; n = 808, mean age 24.6 years) or monophasic desogestrel (Mercilon; n = 805, mean age 24.6 years). Subjects were to participate in the study for up to 13 treatment cycles. A modified Moos Menstrual Distress Questionnaire was used to evaluate menstrual symptoms and to assess overall well-being. A total of 698 women were withdrawn from the study, 154 due to adverse events. Cycle control with gestodene was superior to that with desogestrel at almost all time points, particularly for breakthrough bleeding and/or spotting, which occurred significantly less frequently with gestodene than with desogestrel at cycles 1-7 and 9-11 (p < 0.05). Generally, the proportion of subjects with breakthrough bleeding and/or spotting was almost twice as great with desogestrel as with gestodene. The duration of bleeding was not consistently different between the gestodene and desogestrel groups; however, the intensity of bleeding was greater with gestodene at all time points (p < 0.05). The latent period before withdrawal bleeding was significantly longer for monophasic gestodene at cycles 1-5 and 8-10 (p < 0.05). Treatment significantly improved overall well-being at cycles 6 and 9 with triphasic gestodene and at cycle 13 with desogestrel; however, no statistically significant differences among treatment groups in overall well-being scores or individual factors of well-being could be identified. All three treatments were well tolerated. The most common drug-related adverse events were headache (14.2%), breast pain (6.2%), nausea (4.1%), metrorrhagia (3.9%) and abdominal pain (3.5%). The incidence of adverse events in all treatment groups was similar, with the exception of metrorrhagia, which occurred in more patients in the desogestrel group than in the gestodene treatment groups (p < 0.05).

Adolescent↗

PubMed2000

A multifaceted mental health training program in reducing burnout among occupational social workers.

This article looks at ways of reducing stress through a multifaceted training program involving the acquisition of mental health knowledge and skills and experiential training in a group of occupational social workers. The training group of 13 occupational workers was compared to a group of occupational social workers not attending the program. Post-training revealed statistically significant increases in professional self-efficacy associated with awareness of psychological and psychopathological issues and professional social support. Reduction in cognitive weariness and listlessness associated with burnout was also found. Gaining competence in mental health issues relating to the occupational setting coupled with emotional sharing helped to reduce professional burnout.

Adaptation, Psychological↗

PubMed1999

HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

Animals↗

PubMed1999

Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring.

A combined contraceptive vaginal ring designed to last 12 months was tested at three clinic sites. This ring released approximately 1 mg of norethindrone acetate (NET-Ac) and 20 micrograms of ethinyl estradiol (EE) daily. A total of 60 women were enrolled to use the ring in a schedule of 3 weeks in/1 week out. Serum norethindrone (NET) and ethinyl estradiol (EE) levels were assayed twice weekly in cycles 6, 9, and 13. Mean NET concentrations between cycles 6 and 9 were relatively stable between 13 and 19 nmol/L but showed a 10%-21% decrease in all centers between cycles 9 and 13. Mean EE concentrations ranged from 75 to 103 pmol/L, but did not have the same decrease as NET between cycles 9 and 13. Cycles with progesterone peaks (> 9.6 nmol/L) compatible with some luteal activity occurred in 4% of cycles sampled in Sydney, 3% in Santo Domingo, and 26% in Los Angeles. Half of these cycles exhibited at least one progesterone value > 32 nmol/L with three of 18 occurring in noncompliant cycles. Heavier body weight was associated with increased probability of luteal activity. Based on serum estradiol peaks > 400 pmol/L, eight of 81 cycles appeared to have marked follicular activity with no luteal activity. No pregnancies occurred. Nausea was reported by about half the subjects in approximately 10% of the visits (mainly in the first 1-2 days in the first cycle immediately after ring insertion). Vomiting was reported by 20% of subjects early in the first cycle only. Headache was reported on occasion by nearly 50% of the women, but the relationship to ring use was uncertain. Vaginal discharge was reported by 17 women (82% of these were from one clinic). Of 60 women, 14 discontinued before completing the study, but only two discontinuations were for medical reasons. Small but statistically significant changes occurred in lipid levels in two of the three centers. All changes remained within normal limits and were similar to those seen with many oral contraceptives. It appears that this ring may perform slightly differently in different populations, but is a highly satisfactory method of contraception for many women. Minor modifications in design could provide higher levels of steroid release and in the later months of the ring life span would assure continuing high levels of contraceptive protection for heavier women.

Adolescent↗

PubMed1999

A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.

Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation (serum progesterone > 32 nmol/L) occurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was significantly more luteal activity in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only three cycles with a marked degree of luteal activity (progesterone > 10 nmol/L) occurred among compliant women. Serum levels of NET and EE were consistently elevated during use of both rings. There was no significant difference between serum levels with the two rings because of wide interindividual variations, although both NET and EE levels tended to be higher with the 1/20 ring. However, there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly changed during treatment. Triglycerides increased but remained within the normal range. Overall cycle control was good with both formulations, but there was slightly more cycle disturbance with the lower dose ring. There was no change in mean body weight during the study, and individual weight changes appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women complained of vaginal discharge, one with accompanying itch and one with a vaginal Candida infection in cycle 1. Overall, both of these EE/NET-Ac rings performed well, with only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, and progesterone levels and lipids, and on vaginal bleeding patterns.

Adolescent↗

PubMed1999

Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities.

A double-blind, placebo-controlled, randomized, factorial study using a daily oral administration of 30 mg beta-carotene and/or 500 mg vitamin C was conducted in 141 women with colposcopically and histologically confirmed minor squamous atypia or cervical intra-epithelial neoplasia (CIN) I. Over approximately 2 years of follow-up, 43 lesions regressed to normal and 13 progressed to CIN II. The regression rate was slightly higher, but not significantly so, in those randomized to beta-carotene compared to no beta-carotene (hazard ratio = 1.58, 95% CI: 0.86-2.93, P = 0.14) and slightly lower, but not statistically significant, for those randomized to vitamin C compared to no vitamin C (hazard ratio = 0.65, 95% CI: 0.35-1.21, P = 0.17). In a model with no interaction, the progression rate was slightly higher in those randomized to beta-carotene (hazard ratio = 1.75, 95% CI: 0.57-5.36, P = 0.32) and also in those randomized to vitamin C (hazard ratio = 2.40, 95% CI: 0.74-7.80, P = 0.13). Neither of these were statistically significant. However, there was some evidence of an interaction effect of the two compounds on the progression rate (P = 0.052), with seven of the progressed lesions occurring in those randomized to both vitamins compared to a total of six in the three other groups. The currently available evidence from this and other trials suggests that high doses of these compounds are unlikely to increase the regression or decrease the progression of minor atypia and CIN I.

Adult↗

PubMed1999

Variations in vaginal epithelial surface appearance determined by colposcopic inspection in healthy, sexually active women.

A total of 107 sexually active women, aged 18-35 years, was recruited through family planning clinics in four centres in different countries. Each woman underwent two or three gentle but thorough and systematic vaginal inspections using a consistent technique with colposcopic magnification over a 4-6 month period to look for changes in vaginal and cervical appearance which might be related to sexual intercourse, tampon use, contraceptive method used, cigarette smoking or other environmental factors. Obvious changes in appearance were photographed at x10 magnification. These 'appearances' or 'conditions' were classified according to a modification of the recommendations of a workshop sponsored by the World Health Organization, the Population Council and the Conrad Program. Most of these alterations in the appearance of the vaginal epithelium were judged to be of such minor clinical importance that they have been termed 'conditions' or 'changes in appearance' rather than 'lesions'. In all, 56 'conditions' or 'appearances' were noted in 314 inspections, the commonest being petechiae (53.6%). Potentially significant conditions justifying the term 'lesions' (three microulcerations, two ecchymoses, five abrasions and one mucosal tear; 3.5% of inspections) usually healed spontaneously and disappeared rapidly. The incidence of these conditions was highest when the inspections followed intercourse in the previous 24 h (25.2 versus 14.2%; P < 0.0008), or tampon use (32.4 versus 15.9%; P < 0. 0001). These processes may be regarded as a reflection of regular minor trauma to the vaginal epithelium.

Adolescent↗

PubMed1999

Interactions between oral contraceptives and antifungals/antibacterials. Is contraceptive failure the result?

The effectiveness of oral contraceptives may be impaired by concomitant treatment with antimicrobials. This may occur because of reductions in plasma concentrations of ethinylestradiol by the induction of hepatic metabolism, as for rifampicin (rifampin) and possibly griseofulvin, or in a small percentage of women because of interference with enterohepatic recirculation. There are no scientific data to support the anecdotal evidence that the concomitant use of combined oral contraceptives and antimicrobials reduces contraceptive efficacy in the majority of women. It has been postulated that there is a subset of women in whom the enterohepatic recirculation of ethinylestradiol plays an important role. In these women the action of an antimicrobial may reduce the efficacy of oral contraceptives by interfering with this mechanism. Studies that have quantitatively examined these effects may have failed to include women from this subset because of the small numbers involved in the studies. On the other hand, there are no good prospective studies comparing contraceptive failure rates between compliant women who use combined oral contraceptives with and without antimicrobials. All women using combined oral contraceptives should be informed of the very low level of risk of interactions with antimicrobials (probably about 1%) and that it is not possible to identify who may be at risk. Women concerned about this low level of risk should be given information about the use of barrier methods or avoidance of intercourse during the first 7 days of concomitant antimicrobial therapy and for 7 subsequent days. Women who have had previous contraceptive failures or developed breakthrough bleeding during concomitant antimicrobial use should be strongly advised to follow these precautions, as they may be part of the subset of women at higher risk of contraceptive failure.

Animals↗

PubMed1998

A mouse homologue of FAST-1 transduces TGF beta superfamily signals and is expressed during early embryogenesis.

The transcription factor FAST-1 has recently been shown to play a key role in the specification of mesoderm by TGF beta superfamily signals in the early Xenopus embryo. We have cloned Fast1, a mouse homologue of Xenopus FAST-1, and characterized its expression during embryogenesis and function in activin/TGF beta signal transduction. In vitro, Fast1 associates with Smads in response to an activin/TGF beta signal to form a complex that recognizes the Xenopus activin responsive element (ARE) targeted by Xenopus FAST-1. In intact cells, introduction of Fast1 confers activin/TGF beta regulation of an ARE-luciferase reporter. In embryos, Fast1 is expressed predominantly throughout the epiblast before gastrulation and declines as development progresses. We propose that mouse Fast1, like Xenopus FAST-1, mediates TGF beta superfamily signals specifying developmental fate during early embryogenesis.

Animals↗