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Biomedical subjects

E Weisberg

Publications and source records attributed to E Weisberg.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

Smad4 and FAST-1 in the assembly of activin-responsive factor.

Members of the TGF-beta superfamily of signalling molecules work by activating transmembrane receptors with phosphorylating activity (serine-threonine kinase receptors); these in turn phosphorylate and activate SMADs, a class of signal transducers. Activins are growth factors that act primarily through Smad2, possibly in partnership with Smad4, which forms heteromeric complexes with different ligand-specific SMADs after activation. In frog embryos, Smad2 participates in an activin-responsive factor (ARF), which then binds to a promoter element of the Mix.2 gene. The principal DNA-binding component of ARF is FAST-1, a transcription factor with a novel winged-helix structure. We now report that Smad4 is present in ARF, and that FAST-1, Smad4 and Smad2 co-immunoprecipitate in a ligand-regulated fashion. We have mapped the site of interaction between FAST-1 and Smad2/Smad4 to a novel carboxy-terminal domain of FAST-1, and find that overexpression of this domain specifically inhibits activin signalling. In a yeast two-hybrid assay, the FAST-1 carboxy terminus interacts with Smad2 but not Smad4. Deletion mutants of the FAST-1 carboxy terminus that still participate in ligand-regulated Smad2 binding no longer associated with Smad4 or ARF. These results indicate that Smad4 stabilizes a ligand-stimulated Smad2-FAST-1 complex as an active DNA-binding factor.

Activins↗

Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring.

The study population included 159 women aged 18 to 37 years requiring contraception (60 in Sydney, 99 in Los Angeles). The design consisted of a 6 month study of a contraceptive vaginal ring (CVR) releasing 20 micrograms ethinyl estradiol and 1 mg of norethindrone acetate daily over two successive cycles with a new ring on each of three different insertion regimens. A total of 831 woman-months of exposure were recorded, and 129 women completed the study. The overall incidence of side effects was similar in the two centers and differences between the insertion regimens were not observed. Transient nausea following insertion of a new ring (mainly lasting 0.5 to 48 h) was the most prominent side effect, with no significant difference between the insertion regimens (although the incidence tended to be highest with bedtime insertion [34%] and lowest with early evening insertion and temporary removal during the first night [27%]). Transient vomiting occurred in about 10% of women in the first 24 h after first insertion of a new ring. The incidence and severity of nausea was greatly reduced in cycle 2 with each regimen (6% to 9% of women). Nausea could be prevented by overnight soaking of the ring in water before use. Other side effects such as headache, dizziness, uterine cramps, breakthrough bleeding, weight gain, and ring expulsion occurred with similarly low frequency in all three insertion groups. One pregnancy occurred with probable ovulation between cycles 5 and 6, the only pregnancy recorded to date in studies with this ring. The study demonstrated that this effective and generally well tolerated CVR causes a relatively high incidence of transient nausea after insertion of a new ring, which is probably due to accumulation of ethinyl estradiol on the ring surface during storage. Acceptability is still high, and this particular CVR merits further development.

Adult↗

Progression and regression of low-grade epithelial abnormalities of the cervix.

The records of 738 women with low-grade cervical epithelial abnormalities were examined for changes in degree of cervical disease and lesion size, as well as sociodemographic and behavioural factors which influence the development of invasive cancer of the cervix. Survival analysis was used to determine the predictors and rates of progression and regression. The results suggest that about 80% of the low-grade epithelial abnormalities of the cervix will not progress within 2 years. The only predictors of progression were a biopsy diagnosis of CIN 1 and the size of the lesion. Predictors of regression were older age, older age at first intercourse, greater parity, fewer sexual partners, and absence of a past history of genital herpes. Although progression rates of low-grade abnormalities of the cervix were very low, CIN 1 lesions were 2.4 times (95% CI: 1.6 to 3.7) more likely to progress than lower-grade lesions and large lesions (> 1/2 ectocervix) were 2.0 times (95% CI: 1.2 to 3.3) more likely to progress than small ones (< 1/4 ectocervix).

Adolescent↗

Role of focal adhesion proteins in signal transduction and oncogenesis.

The focal adhesion is a structure that is formed when a cell comes into contact with the extracellular matrix. Originally, the focal adhesion was thought to only provide structural support for the actin-based cytoskeleton of the cell. However, the last decade has yielded considerable information linking various protein components of the focal adhesion to signal transduction pathways. Examples of focal adhesion proteins include the catalytically active p125FAK, SH2-containing tensin, and the multifunctional LIM domain-containing paxillin. The interactions of focal adhesion proteins may be altered after cellular transformation. This review details how certain focal adhesion proteins are associated in cellular signaling as well as transformation. The importance of various GTP-binding proteins in interacting with and forming the focal adhesion, and the influence they have on neoplastic transformation, are discussed. A key feature of this review is how oncogenes and their respective oncoproteins affect the focal adhesion. Classically, v-src transformation of adherent cells has been studied to characterize focal adhesions, namely, because of the distinct morphological changes that occur in the focal adhesion concomitantly with src transformation. Similarly, the BCR/ABL oncogene, which causes chronic myelogenous leukemia, leads to adhesion defects and can alter the properties of focal adhesion proteins. Thus, we describe some of the relevant interactions between the focal adhesion and the Src and BCR/ABL oncoproteins, respectively.

Animals↗

Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077.

We investigated the mitochondrial toxicity of the lipophilic cation, MKT-077, and the role of mitochondria in selective malignant cell killing by this compound by examining the effect of MKT-077 on mitochondrial structure and function in treated cells and in isolated organelles. Results of this study demonstrate changes in mitochondrial ultrastructure that are induced by MKT-077 treatment in carcinoma cells but not in similarly treated normal epithelial cells. In addition, MKT-077 was found to inhibit respiratory activity in isolated intact mitochondria and electron transport activity in freeze-thawed mitochondrial membrane fragments in a dose-dependent manner. The concentration of MKT-077 necessary to obtain half-maximal inhibition of ADP-stimulated respiration was approximately 4-fold greater in mitochondria isolated from cells of the normal epithelial cell line, CV-1 (15 micrograms MKT-077/mg protein), as compared to the human colon carcinoma cell line, CX-1 (4 micrograms MKT-077/mg protein). Further, the data show a selective loss of mitochondrial DNA in CX-1 and CRL1420 cells (carcinoma) but not CV-1 cells (normal epithelial) treated with 3 microgram/ml MKT-077 for up to 3 days. Under the same conditions, nuclear DNA was unaffected in all three cell lines. The sensitivity of the cell lines tested to mitochondrial damage by MKT-077 correlates well with their sensitivity to cytotoxicity by MKT-077. These results demonstrate selective mitochondrial damage by MKT-077 at the cellular, biochemical, and molecular levels and suggest that selective effects on mitochondrial structure and function may provide a basis for the selective malignant cell killing exhibited by this compound.

Animals↗

Usefulness of the protection motivation theory in explaining hearing protection device use among male industrial workers.

The present study examined the usefulness of personal variables: noise annoyance, and components of the protection motivation theory (R. W. Rogers, 1983) along with social-organizational factors in explaining hearing protection device (HPD) use among Israeli manufacturing workers. Participants were 281 men exposed to harmful noise levels for which routine HPD use is required by regulation. In practice, 3 HPD user groups were identified: nonusers (n = 38), occasional users (n = 125), and regular users (n = 118). HPD use was objectively verified. HPD use was primarily related to the personal variables but not to management pressure, coworker pressure, or family support. The most powerful predictors of HPD use were perceived self-efficacy (for long-term HPD use), perceived susceptibility (to hearing loss), and noise annoyance, together explaining 48% of the outcome variance. These findings have implications for interventions aimed at motivating workers to use HPDs regularly.

Adolescent↗

Hostility and hearing protection behavior: the mediating role of personal beliefs and low frustration tolerance.

The authors examined whether hostility would negatively be associated with occupational health behavior, namely, the use of hearing protection devices (HPDs). Also examined as possible mediators were the protection motivation theory (PMT) components and low frustration tolerance (LFT). Participants were 226 male industrial workers, all exposed to potentially hearing-damaging noise. Hostility was negatively related to HPD use. It moderately correlated with the PMT components: negatively with perceived susceptibility, severity, effectiveness, and self-efficacy and positively with perceived barriers. Hostility correlated highly with LFT. Regression analyses confirmed the mediating role of perceived barriers, low self-efficacy, and LFT in the negative relationship between hostility and the use of HPDs. Thus, intrapsychic characteristics of hostile people may be significant for hearing protection behavior.

Adolescent↗

A graduate course in work site health promotion for occupational health practitioners.

This paper describes the rationale, teaching strategies, outcomes, and a 6-month follow-up of an academic course in work site health promotion, in which 35 occupational health practitioners participated. The one-semester course was part of the Masters in Science program in occupational health at the Tel-Aviv University Medical School. The primary goals of the study were to teach the theoretical bases of work site health promotion and their application to specific health needs, and to train better role models for employees. The primary teaching strategies were: (1) facilitation of experiential learning, by encouraging students to undergo health screening and then engage in a personal health promotion plan; (2) use of health promotion experts as guest teachers; and (3) an increase in formal knowledge through formal lectures and background reading. At the time of follow-up, most of the students were still adhering to their plans and maintaining much of their health promotion achievements. Additional outcomes included increased awareness of health risks and health promotion issues, and positions as role models in the private and professional domains. The primary barrier to adherence was low frustration tolerance, which can be regarded as the major challenge to health promotion programs and courses. It is suggested that the course format is an effective means of educating health promoters.

Adult↗

Termination of pregnancy in New South Wales, 1990.

This article reports on terminations of pregnancy done in New South Wales (NSW) for NSW residents, using routinely collected data from the Health Insurance Commission (HIC) and the NSW Inpatient Statistics Collection (ISC). The HIC and ISC recorded 29,348 terminations for NSW residents in 1990, representing a termination rate of 21.6 per 1000 women aged 15 to 44. Terminations were frequent at all ages, but the highest termination rate was in the 20 to 24 age range (36.8 per 1000). About one-quarter of all known pregnancies were terminated (excluding spontaneous abortions). The majority of terminations were done in private clinics; only 10 per cent of women having terminations were public patients in public hospitals. Outside the Sydney metropolitan area, termination rates were lower than in Sydney, and the procedures were more likely to be done in public hospitals. Large numbers of terminations are done in NSW, but the rate appears to have been constant since the early 1980s.

Abortion, Induced↗

A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy.

OBJECTIVE: To compare the safety, efficacy and acceptability of a continuous low dose oestradiol releasing vaginal ring with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. DESIGN: An open, parallel, comparative multicentre trial. SETTING: Sydney and Melbourne, Australia. PARTICIPANTS AND INTERVENTIONS: One hundred and ninety-four postmenopausal women with symptoms and signs of urogenital atrophy were randomised on a 2:1 basis to 12 weeks of treatment with an oestrogen vaginal ring versus an oestrogen cream. MAIN OUTCOME MEASURES AND RESULTS: Equivalence (95% CI) was demonstrated between the two treatments for relief of vaginal dryness and dyspareunia, resolution of atrophic signs, improvement in vaginal mucosal maturation indices and reduction in vaginal pH. No significant difference was demonstrated in endometrial response to a progestogen challenge test and equivalence was demonstrated in the incidence of intercurrent bleeding episodes. The vaginal ring was significantly more acceptable than the cream P < 0.0001), and was preferred to the cream (P < 0.001). CONCLUSION: With equivalent efficacy and safety and superior acceptability to vaginal cream, the low dose oestradiol vaginal ring is an advance in vaginal delivery systems for the treatment of urogenital atrophy.

Administration, Intravaginal↗

A survey of women seeking termination of pregnancy in New South Wales.

OBJECTIVES: To identify characteristics of women seeking termination of pregnancy, their reasons for having a termination, and whether they intended to submit a Medicare claim for the procedure. DESIGN: Survey by self-administered questionnaire. SUBJECTS AND SETTING: All women who attended 11 private clinics in New South Wales (NSW) over a six-week period in 1992. RESULTS: 2249 completed questionnaires were received (94% response rate). Terminations were frequent at all ages, but women in their 20s accounted for more than half the terminations (54%) and teenagers accounted for only 17%. Respondents were generally well educated and from various ethnic and religious backgrounds; 56% were single and 41% had had one or more previous terminations. Fifteen per cent of respondents could not or did not intend to make a Medicare claim. The most frequently cited factors contributing to the decision to seek a termination were concerns about finances, change in lifestyle, single parenthood and being too young. CONCLUSIONS: Private clinics, where most terminations are performed, clearly meet a major demand, but it is likely that terminations in NSW as recorded by Health Insurance Commission claims are under-reported by at least 15%.

Abortion, Induced↗

Emergency contraception. General practitioner knowledge, attitudes and practices in New South Wales.

OBJECTIVES: To assess the knowledge, attitudes and practices of general practitioners in New South Wales regarding the provision of emergency contraception. DESIGN: Randomised group comparison of 100 rural and 100 urban general practitioners (GPs) by questionnaire. RESULTS: Eighty-four rural and 76 urban GPs responded. More rural GPs were knowledgeable about emergency contraception than urban GPs (95% v. 78%), and more women knew about it than men. More urban GPs frequently prescribed emergency contraception than rural GPs (26% v. 6%) and female GPs prescribed it more readily than male GPs (22% v. 12%). There was great variation in the regimens prescribed, especially among rural GPs. Twenty-five per cent of urban GPs and 31% of rural GPs did not offer women information about emergency contraception, while 16% of both groups included such information in any discussion about contraceptive options, and 18% gave information only if requested by the woman. More than 60% of the GPs would provide information about emergency contraception as a back-up to use of barrier methods. CONCLUSIONS: The sex, attitude and knowledge of the GPs influence the likelihood of women being made aware of or being given emergency contraception in NSW. There is a need to further educate both the public and practitioners about emergency contraception.

Attitude of Health Personnel↗

The acceptability of a combined oestrogen/progestogen contraceptive vaginal ring.

The acceptability of a vaginal ring releasing ethinyl oestradiol 20 mcg per day and norethindrone acetate 1 mg per day was assessed during a six-month phase II trial comparing three different regimens, which was carried out simultaneously in Los Angeles and Sydney. Sixty women were enrolled in Sydney and 90 in Los Angeles. On admission into the study, the women were asked to complete a questionnaire which gave details of age, last contraceptive method used, contraceptive methods used in the past and their reason for liking or disliking previous contraceptive methods, as well as their reason for stopping the last method. On completion of the study or leaving the study for any reason, each woman was asked to complete an acceptability questionnaire which included her experiences with the ring and the rating of the method. The responses to these two questionnaires form the basis of this report. The overall rating of the ring was similar in both the Sydney and Los Angeles groups. Sixty-nine percent of women rated the method as very good. Seventy-two percent of women in Los Angeles and 62% of women in Sydney liked the ring much more than their most liked previous method. In both groups the method they liked best apart from the ring was the pill (62% in Sydney and 53% in Los Angeles). The major reasons for liking the ring were convenience of use, effectiveness and no requirements for taking medication daily. Most women in both studies would recommend the ring to others (92% in Sydney and 89% in Los Angeles).

Adolescent↗