PubMed Health⌕ Search

Biomedical subjects

A J Friedman

Publications and source records attributed to A J Friedman.

At least 19 recordsLinked to original sources
PubMed2006

The ORTHO BC-SAT--a satisfaction questionnaire for women using hormonal contraceptives.

OBJECTIVE: To assess the reliability and validity of the ORTHO Birth Control Satisfaction Assessment Tool (ORTHO BC-SAT). DESIGN: 339 women using 1 of 4 hormonal birth control methods (oral contraceptives, transdermal patch, vaginal ring, injections), completed the questionnaire 1-2 times. MATERIALS AND METHODS: The questionnaire was developed based on findings from the literature, focus groups, and interviews. Internal consistency reliability, test-retest reliability, construct validity, and known groups validity were evaluated. RESULTS: Based on variable clustering, 8 domains were identified (Ease of Use/Convenience, Compliance, Lifestyle Impact, Symptom/Side Effect Bother, Menstrual Impact, Future Fertility Concerns, Assurance/Confidence, Overall Satisfaction). Internal consistency reliability was demonstrated with Cronbach's alpha values ranging from 0.70 to 0.89. All multi-item scales reported acceptable test-retest reliability (0.79-0.87). Construct validity was demonstrated by support of a hypothesized pattern of correlations. Known groups validity was confirmed by examining scale scores of women categorized by levels of symptom bother. As expected, women with the least amount of bother reported higher scores on all satisfaction scales than those with higher bother (p < 0.0001), except on Future Fertility Concerns (p = 0.27). CONCLUSION: Our results support the reliability and validity of the ORTHO BC-SAT. It may be used in future studies to evaluate satisfaction among hormonal contraceptive users.

Adult↗
PubMed2005

Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study.

OBJECTIVE: The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. METHODS: After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. RESULTS: For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. CONCLUSIONS: Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

Absorptiometry, Photon↗
PubMed2003

Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea.

This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.

Adolescent↗
PubMed2001

Beta 93 modified hemoglobin: kinetic and conformational consequences.

The reactive sulfhydryl on Cys beta93 in human adult hemoglobin (HbA) has been the focus of much attention. It has purported functional roles such as a transporter of nitric oxide and a detoxifier of super oxide. In addition, it has a proposed role in the allosteric mechanism. The present study addresses the functional and conformational consequences of modifying the beta93 sulfhydryl using either maleimide or disulfide-based reactions. The geminate and bimolecular recombination of CO derivatives of several different beta93-modified Hbs in both solution and sol-gel matrixes provide a window into functional modifications associated with both the R and T states of these proteins. Nanosecond time-resolved visible resonance Raman spectroscopy is used to probe conformational consequences associated with the proximal heme environment. The results show functional and conformational consequences that depend on the specific chemistry used to modify beta93. Maleimide-based modification show the most significant alterations of R-state properties including a consistent pattern of a reduced geminate yield and a loss of the favorable heme-proximal histidine interaction normally seen for liganded R-state HbA. A mechanism based on a displacement of the side chain of Tyr beta145 is explored as a basis for this effect as well as other situations where there is loss of the quaternary enhancement effect. The quaternary enhancement effect refers to the enhancement of ligand binding properties of the alphabeta dimers when they are associated into the R-state tetramer.

Carboxyhemoglobin↗
PubMed2000

Sol-gel trapping of functional intermediates of hemoglobin: geminate and bimolecular recombination studies.

The encapsulation of proteins in porous sol-gels is a promising technique for generating, trapping, and probing functionally significant nonequilibrium protein species. An essential step needed in the pursuit of that goal is establishing the degree to which the sol-gel limits conformational change upon adding or removing substrates. In the present study, geminate recombination and solvent phase bimolecular recombination of CO to human adult hemoglobin (HbA) are used as sensitive probes of the degree of conformational constraint within the sol-gel. Two forms of CO saturated encapsulated HbA are generated. In one case, designated [COHbA], the equilibrium form of COHbA is directly encapsulated. In the second case, designated as [deoxyHbA] + CO, the equilibrium form of deoxyHbA is encapsulated and only after the sample has aged is CO introduced to the HbA through the porous sol-gel matrix. Three different preparative protocols are used to generate the sol-gels for each of the two forms of encapsulated COHbA. The kinetic traces obtained from these encapsulated samples allow for an easy evaluation of the extent to which the sol-gel is locking in the initial tertiary/quaternary structure. The results show that the sol-gel encapsulated samples can be used with pulsed laser sources and that one of the tested encapsulation protocols is far superior with respect to conformational locking. This protocol is used to trap and probe nonequilibrium forms such as the liganded T state of HbA, a species whose properties are needed to fully explore allostery in HbA.

Buffers↗
PubMed1996

A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗
PubMed1995

Fertility therapy in the setting of a history of invasive epithelial ovarian cancer.

A link between fertility drugs and epithelial ovarian cancer has been suggested by at least one case-control study, and by multiple case reports of such tumors developing following fertility drug therapy. We report the case of a woman with stage IC grade 1 mucinous epithelial ovarian cancer who died of recurrent disease shortly after receiving gonadotropin therapy for ovulation induction. The patient was initially treated with a staging procedure, unilateral salpingo-oophorectomy, and 3 courses of cytoxan and carboplatinum. Over the next 3 years she underwent 2 cycles of ovulation induction with exogenous gonadotropins. Five months after the second cycle, the patient presented with a bowel obstruction and extensive recurrence of disease. Two months later she died despite extensive surgical debulking, and cis-platinum and Taxol chemotherapy. Although a causal relationship between fertility therapy and ovarian cancer has not been established, this case report suggests ovulation induction may be inadvisable in a woman with a prior diagnosis of invasive epithelial ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed1995

Evaluation of hormonal testing in the screening for in vitro fertilization (IVF) of women with tubal factor infertility.

PURPOSE: To evaluate the frequency of abnormal prolactin and thyroid stimulating hormone (TSH) test results in ovulatory women with tubal factor infertility who were screened for in vitro fertilization (IVF). METHODS: Charts were identified from 112 ovulatory women with follicle stimulating hormone (FSH) < 20 mIU/ml who were diagnosed with tubal factor infertility and were screened for IVF with thyroid stimulating hormone (TSH) and prolactin levels. Women previously diagnosed with thyroid disease were subsequently excluded and 98 subjects remained. All subjects were determined to be ovulatory by biphasic basal body temperature (BBT) charts, luteal phase progesterone > 4 ng/ml, or endometrial biopsy revealing secretory endometrium. Results of cycle day 3 serum TSH and prolactin concentrations were recorded. The normal range for each test reflects the geometric mean +/- 2 standard deviations (i.e., 95% interval), as obtained from the reference laboratory. Under this construct, hypothesis tests were performed to determine whether or not our study population was consistent with the reference range of normal hormone levels. Under the null hypothesis (normal levels), we expected 5% of the TSH tests to be abnormal (i.e., high or low levels), and 2.5% of the prolactin tests to be abnormal (i.e., high levels). Exact bionomial confidence intervals and P-values were calculated. We also tested for age trend in the proportion of abnormal results. RESULTS: Study subjects had an age range of 25-43. In the study group, 4 (0.041) out of the 98 women screened had abnormal TSH levels. Of these four abnormal TSH results, three were elevated (i.e., TSH > 4.6 microIU/ml) and one was low (i.e., TSH < 0.6 microIU/ml). The frequency of an abnormal TSH value was not significantly different from that expected from the reference laboratory normal values (95% CI 0.011, 0.101). Of the 98 subjects, 7 (0.071) had abnormal prolactin levels, which was significantly different from that expected from the reference laboratory normal values (95% CI 0.029, 0.142; P = 0.023). When stratified by age, there was no observed trend of abnormalities for TSH or prolactin levels with increasing age. CONCLUSIONS: In ovulatory women presenting for IVF with tubal factor infertility, our results show that routine screening with a TSH test does not yield a significantly higher proportion of abnormal results than that expected from the reference laboratory normal values. However, prolactin level screening was found to yield a higher incidence of abnormal tests than expected from the reference laboratory normal values.

Adult↗
PubMed1995

Progesterone: a critical role in the pathogenesis of uterine myomas.

Uterine leiomyomas are monoclonal tumors. However, the factors involved in their initiation and growth remain poorly understood. The neoplastic transformation of myometrium to leiomyoma likely involves somatic mutations of normal myometrium and the complex interactions of sex steroids and local growth factors. Traditionally, estrogen has been considered the major promoter of myoma growth. The purpose of this review is to highlight the biochemical, histologic, and clinical evidence that supports an equally important role for progesterone in the growth of uterine myomas. Biochemical studies suggest that progesterone, progestins, and the progesterone receptor modulate myoma mitotic activity. Several clinical trials demonstrate that progestins inhibit and/or reverse the ability of hypoestrogenism induced by a gonadotropin-releasing hormone agonist to shrink uterine myomas, suggesting a critical role for progesterone in growth of myomas. A new hypothesis to explain the pathogenesis of myomas is presented.

Female↗
PubMed1995

The reproducibility of the postcoital test: a prospective study.

OBJECTIVE: To determine the reproducibility of the postcoital test among trained observers. METHODS: Twenty-eight infertile patients presenting to the Brigham and Women's Hospital over a 1-year period were recruited for the study. After a standardized collection of specimens for the postcoital test, four fellowship-trained reproductive endocrinologists evaluated six postcoital test characteristics and gave their overall impression of the test. Each observer was blinded to the patients' identities and clinical histories as well as to the ratings of the other observers. The six characteristics included an assessment of the cervical mucus by ferning, cellularity, spinnbarkeit, and consistency, and of sperm by total count per high power field and percent motility. Scoring was adapted from World Health Organization (WHO) criteria for semen-cervical mucus interaction. Statistical analysis included the kappa statistic to determine agreement among observers for postcoital test characteristics and the Mantel-Haenszel test to determine the association between overall impression and the other test characteristics. RESULTS: Agreement among the four observers was best for sperm number and motility (39% of cases) and worst for cellularity, spinnbarkeit, and overall test impression (11, 14, and 14% of cases, respectively). The kappa statistic ranged from a low of 0.13 for cellularity, demonstrating poor reliability (95% confidence interval [CI] 0.03-0.23), to a high of 0.51 for sperm number, demonstrating fair reliability (95% CI 0.41-0.60). Only sperm number and percent motility were significantly associated with the overall impression (P < .001). CONCLUSIONS: In a blinded study, the characteristics of the postcoital test were found to have poor to fair reproducibility among trained observers using a standardized WHO scoring system. The observers' overall impressions of test quality correlated with sperm number and motility only. We question the validity of the postcoital test as a diagnostic tool in the evaluation of infertility.

Adult↗
PubMed1995

Does low-dose combination oral contraceptive use affect uterine size or menstrual flow in premenopausal women with leiomyomas?

OBJECTIVE: To assess whether low-dose oral contraceptive (OC) use affects uterine size or menstrual flow in women with leiomyomas. METHODS: Eighty-seven premenopausal women with leiomyomas were enrolled in a 1-year study. Fifty-five women took low-dose monophasic OCs, and 32 took no OCs or other hormonally active medications. Uterine size was assessed by bimanual and sonographic examinations before and after the study. Duration of menstrual flow and hematocrit were also assessed. RESULTS: Fifty (91%) of 55 women completed 1 year of OC use. There was no significant difference in mean uterine size determined by bimanual examination or in uterine volume measured by sonography after 12 months of OC use. Likewise, there were no significant changes in these indices among the 32 women who did not take OCs. The mean duration of menstrual flow decreased significantly, from 5.8 to 4.4 days (P < .01), in the group of women taking OCs. The mean hematocrit increased significantly, from 35.8 to 37.8% (P = .014), in this group. In contrast, the women who did not take OCs had no significant changes in these indices. CONCLUSION: In most women with leiomyomas, low-dose OC use provides the noncontraceptive benefit of a reduction in the duration of menstrual flow, with resultant improvement in hematocrit, without increasing uterine size.

Adult↗
PubMed1995

The predictive value of discriminatory human chorionic gonadotropin levels in the diagnosis of implantation outcome in in vitro fertilization cycles.

OBJECTIVE: To determine if early serum hCG levels are predictive of implantation outcome in patients undergoing IVF-ET. DESIGN: Retrospective study of IVF cycles using receiver operator characteristic curve (ROC) analysis. SETTING: Tertiary-care, university hospital-affiliated IVF program. PATIENTS: Three hundred fifty-one conception cycles were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Implantation failure, defined as chemical pregnancies, ectopic gestations, and first trimester abortions, or implantation success, defined as delivered singleton and multiple pregnancies, and second trimester abortions. RESULTS: For each post-ET day 14 to 20, mean hCG levels of the implantation success group were significantly greater than implantation failure outcomes (P < 0.0001). Using ROC curve analysis, hCG cutoff values for each post-ET day were calculated for optimal discrimination of implantation failure from implantation success cycles. A patient with an hCG measurement greater than the calculated cutoff value had a > or = 90% chance of having an implantation success after IVF-ET. CONCLUSION: Discriminatory hCG cutoff values may be useful in predicting implantation outcome in IVF-ET cycles and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population. This information also may be useful in providing counseling to IVF patients regarding pregnancy prognosis and result in cost savings.

Chorionic Gonadotropin↗
PubMed1995

The myometrium of postmenopausal women produces prolactin in response to human chorionic gonadotropin and alpha-subunit in vitro.

OBJECTIVES: To examine the effect of equimolar concentrations of hCG and dissociated alpha-subunit on PRL production by leiomyoma and myometrial tissue obtained from different hormonal states and to examine changes in PRL messenger RNA levels as PRL protein levels increased. DESIGN: Explant cultures of leiomyomas and myometrium were established and cultured for 96 hours. Tissue was studied from normal cycling women, postmenopausal women, pregnant women, and women undergoing GnRH agonist (GnRH-a) therapy. Cultured medium was collected at 24, 48, and 96 hours and assayed for PRL. In selected experiments, tissue was processed at 0 and 96 hours to analyze messenger RNA (mRNA) levels. RESULTS: Human chorionic gonadotropin and alpha-subunit stimulated PRL secretion in [1] explant cultures of leiomyoma and myometrium from premenopausal women, [2] cultures of tissue treated in vivo with leuprolide acetate for both leiomyoma and myometrium, and [3] myometrium obtained from postmenopausal women. Postmenopausal myometrium was significantly more responsive to stimulation. Prolactin mRNA levels were documented to increase after hormone treatment in postmenopausal myometrium. CONCLUSION: Myometrium from postmenopausal women is very responsive to hCG and alpha-subunit. There is a difference in response between tissue obtained from menopausal women and that from women undergoing GnRH-a therapy to achieve a "medical menopause" and reproductive age women. The level of endogenous gonadotropins as well as the steroid milieu may modulate myometrial PRL secretion.

Antineoplastic Agents, Hormonal↗
PubMed1995

Capnocytophaga ochracea chronic blepharoconjunctivitis.

A 70-year-old woman presented with a 10-month history of chronic blepharoconjunctivitis that had been unresponsive to multiple methods of treatment. The patient was not immunocompromised and had no history of corneal disease, ocular trauma, or lacrimal duct obstruction. Gram and Giemsa staining of conjunctival smears resulted in visualization of slender, fusiform bacilli. Culture of conjunctival scrapings led to the recovery of a fastidious isolate identified as Capnocytophaga ochracea. The same microorganism was also recovered from cultures of the patient's gingiva. The blepharoconjunctivitis responded well to treatment with fortified cefazolin eye drops. Awareness of this easily overlooked bacterial species should prompt the use of smear and cultural techniques.

Aged↗
PubMed1994

Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata.

Uterine leiomyomata are thought to be monoclonal neoplasms. Accordingly, investigations of clonality with G6PD isoforms used as a marker for X chromosome inactivation have suggested independent origins for multiple tumors within individual uteri. However, results from a recent study assessing methylation differences between DNA of active and inactive X chromosomes have been interpreted to suggest that multiple tumors may arise from a common precursor. We have examined the clonality of 36 leiomyomata from 16 patients by analyzing X chromosome inactivation as indicated by the methylation status of the X-linked androgen receptor gene. As shown by this assay, all informative leiomyomata were monoclonal in origin. In patients with multiple leiomyomata, a random distribution of inactivation between the X homologs was noted, consistent with an independent origin of each tumor. Cytogenetic analysis was also performed on short-term cell cultures of 27 of the 36 tumors. In each of two tumors that had both cells with a clonal karyotypic abnormality and karyotypically normal cells, DNA prepared from short-term cultures showed a monoclonal pattern of X inactivation identical to that of the leiomyoma from which they were derived. These data suggest that karyotypically normal cells present in short-term cultures of uterine leiomyomata are part of the tumor clone, and that clonal expansion of tumor cells precedes the development of cytogenetic aberrations.

Alleles↗
PubMed1994

Glycoprotein hormones and their common alpha-subunit stimulate prolactin production by explant cultures of human leiomyoma and myometrium.

OBJECTIVE: The purpose of this study was to examine the effect of the gonadotropins luteinizing hormone, follicle-stimulating hormone, and human chorionic gonadotropin on prolactin production by human leiomyomas and myometrium. A secondary goal was to explore the effect of thyroid-stimulating hormone and the alpha-subunit common to all these glycoproteins in the same system. STUDY DESIGN: Explant cultures were established, and harvested medium was assayed for total protein and prolactin. Dose-response studies were performed with follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. A second set of studies was conducted with a single dose of human chorionic gonadotropin, thyroid-stimulating hormone, and alpha-subunit. RESULTS: Gonadotropins, thyroid-stimulating hormone, and alpha-subunit all stimulated prolactin production in both leiomyoma and myometrium. Prolactin production was significantly higher in leiomyoma than in myometrium. A positive effect of time, dose, and gonadotropin treatment on prolactin production was seen in each tissue. There was no treatment effect on total protein secretion. CONCLUSIONS: All four glycoprotein hormones and their common alpha-subunit stimulate prolactin production. This appears to be a specific effect.

Cells, Cultured↗