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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cardiovascular risks: perception versus reality.

The high estrogen doses in the original oral contraceptive (OC) formulations were associated with an increased risk of cardiovascular events. Since then the steroid doses in OC have been reduced steadily, so that current low-estrogen-dose (< or = 35 micrograms) combination OC are associated with a lower risk of arterial and venous events than occurs with higher-estrogen-dose formulations. Based on the currently available epidemiologic evidence, the following conclusions can be made regarding the cardiovascular disease risks associated with use of low-dose OC by healthy, nonsmoking women: there is no increased risk of myocardial infarction (MI) or hemorrhagic or ischemic stroke; and there is a three- to fourfold increased risk of venous thrombosis and embolism (VTE). This risk is about half that associated with pregnancy. Smoking is the most important independent risk factor for MI, and is synergistic with OC use. Women smokers should be advised strongly to stop smoking, but those aged < 35 years may use any OC containing < or = 35 micrograms of estrogen. Women smokers aged > or = 35 years should be advised to use a nonestrogen or nonhormonal contraceptive method.

Adolescent↗
PubMed1999

Effect of oral contraceptives containing 20 and 35 micrograms ethinyl estradiol on urinary prostacyclin and thromboxane metabolite levels in smokers and nonsmokers.

The interaction between smoking and oral contraceptive (OC) use with respect to thrombogenesis was investigated by studying the effects of OC and smoking on urinary prostacyclin (PGI2) and thromboxane A2 (TxA2) metabolite levels in smokers and nonsmokers. Sixty healthy women, aged 19-32 years, who were not taking any hormonal treatment for at least 3 months before initiating the study, were divided into three equal groups: OC users who smoked (N = 20), OC users who did not smoke (N = 20), and a control group of 10 smokers and 10 nonsmokers. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE2) (35 micrograms) (N = 10) or NET acetate (1 mg)/EE2 (20 micrograms) (N = 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at the end of the 3-month study. Serum levels of NET and EE2, as well as urinary levels of cotinine and the stable metabolites of PGI2 and TxA2, namely 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (TxB2), respectively, were measured by specific immunoassays. Analysis of pre- to posttreatment changes in mean urinary 6-keto-PGF1 alpha and TxB2 levels for each subgroup, as determined by smoking status and EE2 dose, showed no statistically significant differences. Also, no significant differences were found in each subgroup with respect to changes in the 6-keto-PGF1 alpha/TxB2 ratios. Large intersubject variability in urinary 6-keto-PGF1 alpha and TxB2 levels were observed in all subgroups. The results of this study indicate that both low-estrogen-dose compounds, when used by smokers or nonsmokers, did not significantly alter the ratio of PGI2 to TXA2 metabolites, compared with pretreatment. However, the small number of subjects and the large intersubject variability in this study make it difficult to determine if there is a significant difference between the 20- and 30-microgram EE2 doses.

6-Ketoprostaglandin F1 alpha↗
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

A comparison of tamoxifen and misoprostol to misoprostol alone for early pregnancy termination.

A study was undertaken to determine whether the combination of oral tamoxifen and moistened misoprostol administered vaginally was superior to that of placebo and moistened misoprostol administered vaginally for elective termination of early pregnancies.A clinical trial was conducted with a study group of 150 healthy women with pregnancies of </=56 days gestational age who desired pregnancy termination. Subjects were randomized to ingest either 20 mg of tamoxifen (group 1) or placebo (group 2) twice daily for 1 day, followed 48 h later by vaginal administration of 800 micrograms of saline-moistened misoprostol. This dose of misoprostol was repeated 24 h later and 8 days later if an abortion had not occurred. The main outcome measures were incidence of complete abortion, hemoglobin levels, duration of vaginal bleeding, and incidence of side effects. Complete abortion occurred in 709 (93.3%) in group 1 and 68 (90.7%) in group 2. There were no differences in either group between earlier (</=49 days) and later (50-56 days) gestations. The mean duration of uterine bleeding was 7.9 days and 8.2 days in group 1 and group 2, respectively. In group 1, 94.3% who aborted bled for <14 days, and in group 2, 95.6%. No subject required a blood transfusion. There were no significant differences in side effects between the two groups. These data suggest that pretreatment with tamoxifen is not necessary when using moistened vaginal misoprostol for abortion of pregnancies of </=56 days of gestation.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

A comparison of two dosing regimens of intravaginal misoprostol for second-trimester pregnancy termination.

OBJECTIVE: To compare the effectiveness of misoprostol administered intravaginally every 6 versus every 12 hours for termination of second-trimester pregnancies. METHODS: One hundred pregnant women at 12-22 weeks' gestation were randomized to receive 200 microg of misoprostol intravaginally either every 6 or every 12 hours for up to 48 hours. RESULTS: The incidences of abortion within 48 hours after initial drug administration were 87.2 and 89.2%, the complete abortion rates 43.9 and 33.3%, and the mean abortion intervals 13.8 and 14.0 hours in the 6- and 12-hour groups, respectively. Side effects were similar between groups. CONCLUSION: Misoprostol administered vaginally is effective for terminating second-trimester pregnancies. Shortening the dosing interval from 12 to 6 hours produced no significant benefit.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

A breast clinic in a department of obstetrics and gynecology.

In 1988, the Department of Obstetrics and Gynecology of the University of Southern California School of Medicine; created its own Breast Diagnostic Center for training resident physicians and providing breast care for outpatients and inpatients of Women's and Children's Hospital, Los Angeles, California. The structure and function of the Breast Diagnostic Center allow residents to be directly involved in and responsible for evaluation and care of benign breast problems and allow comprehensive breast-care education and integration of referral breast services for residents and patients. Direct faculty supervision, uniform history and physical records on printed forms, fine-needle aspirations and breast biopsies, and staff assistance with follow-up and patient tracking maximize resident physician education and experience. This departmental approach to resident physician training in breast care can be adapted to the resources and logistics of any department of obstetrics and gynecology.

Breast Diseases↗
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↗
PubMed1998

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

Contraceptive Agents, Female↗
PubMed1998

A medical method of early pregnancy termination using tamoxifen and misoprostol.

A study was undertaken to determine whether ingestion of the selective estrogen receptor modulator tamoxifen followed by vaginal administration of the prostaglandin misoprostol would be an effective medical method of elective termination of early pregnancy. A clinical trial was conducted with a study group of 100 healthy women with pregnancies of 56 days gestational age or less who desired elective pregnancy termination. Each subject ingested 20 mg of tamoxifen once daily for 4 days followed 4 days later by intravaginal placement of four 200 micrograms tablets of misoprostol. If abortion did not occur within the next 24 h a second dose of 800 micrograms of misoprostol was given. The main outcome measures were incidence of complete abortion, hemoglobin levels, duration of vaginal bleeding, and incidence of side effects. Complete abortion occurred in 92 (92%, 95% CI 86.7, 97.3%) of 100 subjects. Of these 92 women, four aborted after ingesting tamoxifen without use of misoprostol, 84 within 24 h after receiving a single dose of misoprostol, one 21 days following a single dose of misoprostol, and three after a second dose of misoprostol was administered. There were six (6.0%) complete treatment failures and two (2%) incomplete abortions that required a dilatation and curettage. The mean duration of uterine bleeding was 8.1 days (range 1-34 days) and there was a median decrease in hemoglobin level of 0.50 g/dL (+2.2 to -4.7 g/dL). Vomiting occurred in 28% of subjects and diarrhea in 8%. These initial data suggest that ingestion of tamoxifen followed by intravaginal misoprostol may be an effective, easily administered, and inexpensive method to electively induce complete abortion in pregnancies of 56 days gestational age or less. Additional studies are necessary to determine whether the addition of tamoxifen increases the success rate compared with that obtained with the use of vaginally administered misoprostol by itself.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Contraception with two levonorgestrel rod implants. A 5-year study in the United States and Dominican Republic.

A 5-year trial of a two-rod contraceptive implant, which releases the progestin levonorgestrel (LNG rod), was conducted at four clinics with 594 women. Mean age and weight at admission were 25.5 years and 62.4 kg, respectively. Consent to continue through 5 years was sought and obtained when the 3-year cumulative pregnancy rate proved to be 0.8 per 100. No pregnancies occurred in the fourth or fifth years. The 5-year cumulative pregnancy rate was, therefore, 0.8 per 100 with an annual average pregnancy rate below 2 per 1000 women. Prolonged bleeding/spotting (8.2% of subjects) and irregular bleeding (5.6%) were the most frequently cited medical reasons for removal. Removals for headache (4.7%) and weight change (4.0%) were the next most frequent medical reasons. Between 1% and 2% of subjects during the 5-year trial sought removals for each of the following conditions: mood changes, lower abdominal pain, depression, or pain at the implant site. The mean annual continuation rate during the study was 77 per 100. Use per woman averaged 2.96 years. Mean removal time was 5.9 +/- 0.6 min. These data indicate that, for a 5-year period, the two LNG rod implants are equivalent to the six Norplant capsule implants with respect to safety and efficacy parameters, but permit easier and more rapid implant removal.

Adolescent↗
PubMed1998

Levonorgestrel capsule implants in the United States: a 5-year study.

OBJECTIVE: To measure effectiveness, adverse event experience, and acceptability of the Food and Drug Administration-approved variant of levonorgestrel capsule implants in the United States through 5 years and to examine determinants of these outcomes. METHODS: In a prospective, multicenter study, 511 sexually active women selecting contraceptive implants were monitored four times in the 1st year, then semiannually through 5 years. Adverse events were elicited by query and physical examination, and their incidence was measured. Lifetable analyses computed pregnancy and other discontinuation rates. Cox regression models examined effects of age, parity, and preadmission desire for more children on continuation. Removal times were analyzed by analysis of variance. RESULTS: Three pregnancies occurred, yielding a 5-year cumulative rate of 1.3+/-0.8 per 100 users, an average annual rate of three per 1000 women, and an ectopic pregnancy rate of 0.6 per 1000 woman years. No pregnancies occurred to women weighing less than 79 kg. Prolonged or irregular menstrual bleeding, followed distantly by headache, weight gain, and mood changes, was the most frequent medical conditions leading to removal. Weight gain averaged 1 kg per year. Each annual continuation rate was above 80 per 100, for a cumulative 5-year rate of 39 per 100. Continuation was age-dependent, with younger women (younger than 25 years at entry) having lower 5-year continuation rates than older subjects (P < .01). Tissue trauma from deeply placed or poorly aligned implants or severe reactions to local anesthetic affected subjects in 3.1% of removals (nine cases). CONCLUSION: As measured by annual continuation rates of 80 per 100 or higher and annual pregnancy rates below one per 100, implant contraception in the United States was found to be highly acceptable and effective, year after year, regardless of the woman's age or family formation status. The cumulative 5-year pregnancy rate, 1.3 per 100, is comparable to that of tubal ligation.

Adult↗
PubMed1998

Devices for endometrial sampling. A comparison.

OBJECTIVE: To compare the clinical performance of two endometrial sampling devices, the GynoSampler and Pipelle. STUDY DESIGN: During a single office visit, gynecology patients at Women's Hospital, Los Angeles, and the teaching clinic of the University of Florida Health Science Center, Jacksonville, underwent two endometrial biopsies, one with each device. The specimen adequacy, pain associated with the sampling procedure and ease of use of the two devices were compared. RESULTS: One hundred women, 50 at each clinical center, were evaluated. No significant differences in specimen adequacy were noted, with at least 90% of specimens retrieved with each device sufficient for diagnosis. Patient discomfort ratings were similar for the two devices. However, physicians performing the biopsies noted that the GynoSampler device was easier to use than the Pipelle based on three parameters (P < .05). CONCLUSION: Although the GynoSampler and Pipelle appear comparable from the perspectives of diagnostic performance and patient discomfort, the GynoSampler was easier to use.

Adult↗
PubMed1997

Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes. Results of a multicentered randomized clinical trial. The Vitrectomy for Treatment of Macular Hole Study Group.

OBJECTIVE: To prospectively assess the risks and benefits of vitrectomy surgery for eyes with stage 3 or 4 macular holes. DESIGN: A multicentered, controlled, randomized clinical trial. SETTING: Community- and university-based ophthalmology clinics. PATIENTS: One hundred twenty patients (129 eyes) with stage 3 or 4 macular holes. INTERVENTIONS: Standardized macular hole surgery vs observation alone. MAIN OUTCOME MEASURES: Four measures of best-corrected visual function, standardized photographic evaluation of the extent of hole closure, evaluation of lens opacification, and determination of adverse events. Outcomes were determined at 6 months after randomization. RESULTS: Compared with observation alone, a significant benefit due to surgery was found in the rate of hole closure (4% vs 69%, P < .001). After adjusting for baseline visual acuity, hole duration, and maximum hole diameter, a significant benefit due to surgery was found in visual acuity for the Bailey-Lovie Word Reading (P = .02) and the Potential Acuity Meter (P < .01) tests; a marginally significant benefit due to surgery was found in visual acuity for the Early Treatment Diabetic Retinopathy Study chart (P = .05). Although the proportion of eyes achieving a change in visual acuity of 2 or more lines on the Early Treatment Diabetic Retinopathy Study chart was significantly greater for the surgery group vs the observed group (11 [19%] of 59 eyes vs 3 [5%] of 58 eyes, adjusted P = .05), 20 (34%) of 59 eyes randomized to surgery had a loss in visual acuity of 1 or more lines. Compared with the observation group, eyes randomized to surgery had higher nuclear sclerosis scores (2.4 vs 1.3, P < .001). Fourteen adverse events were noted in the surgery group; none were noted in the observed group. CONCLUSIONS: Some visual benefit of vitrectomy surgery for macular holes exists, despite a notable incidence of adverse events. The large variability in visual acuity outcome in the surgical group may be because of complications or progressive cataract. A study of the long-term outcome after macular hole surgery is needed.

Aged↗