Biomedical subjects

Daniel B Williams

Publications and source records attributed to Daniel B Williams.

11 recordsLinked to original sources

PubMed2006

Trizygotic quintuplet pregnancy following simultaneous embryo splitting in an oocyte donatin cycle.

PURPOSE: To report a trizygotic quintuplet pregnancy following simultaneous embryo splitting in an oocyte donation cycle after transfer of 3 embryos. METHODS: A 40-year-old Caucasian female G3P1 with two previous spontaneous abortions and diminished ovarian reserve presented for IVF. The patient underwent an oocyte donation cycle secondary to diminished ovarian reserve. Three embryos were transferred per patient request. RESULTS: The three embryo transfer resulted in a trizygotic quintuplet pregnancy. Selective embryo reduction was performed at 11 weeks leaving a dizygotic twin gestation. The patient underwent SVD, or spontaneous vaginal delivery at 36 weeks gestation with respective weights and apgars of 2673 g (apgars 7(1), 9(5)) and 2722 g (apgars 7(1), 9(5)). The twins are presently doing well without complications. CONCLUSIONS: Although rare, the possibility of simultaneous embryo splitting must be factored into determining number of embryos for fresh transfer.

Adult↗

PubMed2006

Embryo morphology score on day 3 is predictive of implantation and live birth rates.

PURPOSE: To determine if embryo cleavage state or morphology on day 3 correlates with implantation or live birth rates. A retrospective cohort study of all fresh embryo transfers over 2 years. METHODS: Patients were grouped by the average cleavage state and morphology. Cleavage state groups were: <6, > or =6, <8, and > or =8 cells. Morphology groups by average grade were: group 1 (best) = 1, group 2 = >1< or =2, group 3 = >2< or =3, and group 4 (worst) = >3< or =4. RESULTS: The overall implantation rate for 158 cycles was 28.1% with a live birth rate of 37.3%. Morphologic state was highly predictive of both implantation rate and live birth rate. Implantation rates by group were 54.8% (group 1), 30.4% (group 2), 23.8% (group 3), and 11.1% (group 4). Likewise, live birth rates among groups were 61.5, 39, 20, and 21%, respectively. Cleavage state was not predictive of outcome. CONCLUSIONS: Embryo grade is highly predictive of implantation and live birth rate and can be used to determine the number of embryos to transfer. Cleavage state is not predictive of outcome.

Adult↗

PubMed2005

The effect of multiple cycles in oocyte donors.

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.

Adult↗

PubMed2005

Stabilization and regression of a recurrent desmoid tumor with the antiestrogen toremifene.

OBJECTIVE: To report a case of a pelvic desmoid tumor that was treated with the antiestrogen toremifene after a failed attempt at surgical excision. DESIGN: Case report. SETTING: University reproductive endocrine practice. PATIENT(S): A reproductive-aged woman with a recurrent desmoid tumor. INTERVENTION(S): After surgical excision of a desmoid tumor that presented during childbirth, subsequent recurrence resulted in the use of toremifene for tumor stabilization. MAIN OUTCOME MEASURE(S): Magnetic resonance imaging was used to monitor desmoid tumor size. RESULT(S): One year after postsurgical recurrence of the desmoid tumor, the patient began treatment with the antiestrogen toremifene. Tumor stabilization and regression with symptomatic relief was observed. Nine years of antiestrogen use revealed no progression in tumor size or patient symptoms. After the patient demonstrated perimenopausal symptoms, toremifene administration was discontinued without a return of symptoms or tumor growth after 3 years. CONCLUSION(S): Our case demonstrates that toremifene is a safe and effective therapy that can be used for the stabilization and regression of desmoid tumors. An antiestrogen should be considered as adjuvant therapy after surgery and as a first-line treatment with disease recurrence. Discontinuation of antiestrogen therapy was shown to be done safely after the patient started to show signs of decreased endogenous estrogen production.

Adult↗

PubMed2005

A comparison of three downregulation approaches for poor responders undergoing in vitro fertilization.

OBJECTIVE: To assess the efficacy of three different GnRH agonist (GnRH-a) stimulation regimens to improve ovarian response in poor responders undergoing IVF. DESIGN: Retrospective cohort study. SETTING: Center for Reproductive Health at the University of Cincinnati Medical Center. PATIENT(S): Women diagnosed as poor responders who presented consecutively from January 1999 to January 2004. INTERVENTION(S): Patients underwent three different stimulation regimens during IVF cycles: [1] stop protocol: GnRH-a 500 microg/d administered from the midluteal phase to the start of menses, then gonadotropins from day 2 of cycle, [2] microdose flare: GnRH-a 20 microg administered twice daily with gonadotropins from day 2 to the day of hCG administration, or [3] regular dose flare: gonadotropins beginning with GnRH-a on day 2 at 1 mg/d for 3 days, followed by 250 microg/d until the day of hCG administration. MAIN OUTCOME MEASURE(S): Ovarian response, implantation rates, clinical pregnancy and delivery rates. RESULT(S): Sixty-one IVF cycles were included in the study. None of the comparisons reached statistical significance; however, the microdose group demonstrated a trend toward a higher completed pregnancy rate. CONCLUSION(S): The microdose flare protocol for poor responders demonstrated a trend toward higher delivery rates. A larger prospective study would need to be performed to determine whether this trend leads to a significant finding in this patient population.

Adult↗

PubMed2003

The role of phosphorylation in D1 dopamine receptor desensitization: evidence for a novel mechanism of arrestin association.

Homologous desensitization of D(1) dopamine receptors is thought to occur through their phosphorylation leading to arrestin association which interdicts G protein coupling. In order to identify the relevant domains of receptor phosphorylation, and to determine how this leads to arrestin association, we created a series of mutated D(1) receptor constructs. In one mutant, all of the serine/threonine residues within the 3rd cytoplasmic domain were altered (3rdTOT). A second construct was created in which only three of these serines (serines 256, 258, and 259) were mutated (3rd234). We also created four truncation mutants of the carboxyl terminus (T347, T369, T394, and T404). All of these constructs were comparable with the wild-type receptor with respect to expression and adenylyl cyclase activation. In contrast, both of the 3rd loop mutants exhibited attenuated agonist-induced receptor phosphorylation that was correlated with an impaired desensitization response. Sequential truncation of the carboxyl terminus of the receptor resulted in a sequential loss of agonist-induced phosphorylation. No phosphorylation was observed with the most severely truncated T347 mutant. Surprisingly, all of the truncated receptors exhibited normal desensitization. The ability of the receptor constructs to promote arrestin association was evaluated using arrestin-green fluorescent protein translocation assays and confocal fluorescence microscopy. The 3rd234 mutant receptor was impaired in its ability to induce arrrestin translocation, whereas the T347 mutant was comparable with wild type. Our data suggest a model in which arrestin directly associates with the activated 3rd cytoplasmic domain in an agonist-dependent fashion; however, under basal conditions, this is sterically prevented by the carboxyl terminus of the receptor. Receptor activation promotes the sequential phosphorylation of residues, first within the carboxyl terminus and then the 3rd cytoplasmic loop, thereby dissociating these domains and allowing arrestin to bind to the activated 3rd loop. Thus, the role of receptor phosphorylation is to allow access of arrestin to its receptor binding domain rather than to create an arrestin binding site per se.

Amino Acid Sequence↗

PubMed2003

Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women.

OBJECTIVES: To determine whether exercise training added to ongoing hormone replacement therapy (HRT) increases bone mineral density (BMD) in physically frail elderly women. DESIGN: Prospective controlled trial. SETTING: University-based research center. PARTICIPANTS: Twenty-eight women on HRT, aged 75 and older with physical frailty. INTERVENTIONS: Participants were assigned to 9 months of supervised (EXER) or home (HOME) exercise. The EXER program started with physical therapy and gradually incorporated resistance and endurance training. The HOME program consisted of flexibility exercises. MEASUREMENTS: Changes in BMD and body composition. RESULTS: There were larger increases in lumbar spine BMD in response to EXER than with HOME (3.5% vs 1.5%, P =.048), with a trend for larger increases in total body BMD (1.5% vs 0.2%, P =.058). There were no significant between-group differences in hip BMD. The EXER group had decreases in weight (-2.2 +/- 0.3 kg, P =.010) and fat mass (-2.7 +/- 0.4 kg, P =.018) and increases in muscle strength (9-30%, P <.05). CONCLUSION: In physically frail elderly women on HRT, relatively vigorous exercise training significantly increased lumbar spine BMD. The improved BMD and strength in response to exercise could reduce fracture risk in frail women already on HRT.

Aged↗

PubMed2003

Effects of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy: a pilot study.

OBJECTIVE: The purpose of this study was to determine the effect of trimonthly progestin administration on the endometrium in elderly postmenopausal women who receive hormone replacement therapy. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study at a university teaching program. Twenty-five postmenopausal women who were >or=75 years old with an intact uterus were assigned randomly to receive conjugated equine estrogens (0.625 mg/d plus medroxyprogesterone acetate 5 mg/d for 13 days every 3 months (n = 13) or placebo (n = 12) for 9 months). At the end of the 9 months, patients in the hormone replacement therapy arm continued therapy for an additional 9 months. Statistical analysis was performed with the Student t test, the chi(2) test, and the Fisher exact test. RESULTS: Transvaginal sonography was performed at baseline and at 9 and 18 months. Endometrial biopsy was performed if the endometrial thickness was >4 mm or as clinically indicated at 18 months. Patients in the hormone replacement therapy group demonstrated a significant increase in endometrial thickness between baseline (3.9 + 0.8 mm) and 9 months (8.0 + 4.8 mm). There were no cases of endometrial hyperplasia at the 18-month endometrial biopsy. CONCLUSION: Trimonthly progestin administration in elderly postmenopausal women who receive hormone replacement therapy may be a reasonable alternative to the monthly administration of progestin in hormone replacement therapy.

Aged↗

PubMed2002

Structural evidence that propofol stabilizes different GABA(A) receptor states at potentiating and activating concentrations.

The GABA(A) receptor is a target of many general anesthetics, such as propofol. General anesthetic binding sites are distinct from the GABA binding sites. At low concentrations, the anesthetics potentiate the currents induced by submaximal GABA concentrations. At higher concentrations the anesthetics directly activate GABA(A) receptors. In contrast, benzodiazepines, such as diazepam, only potentiate currents induced by submaximal GABA concentrations. Channel kinetic studies suggest that these drugs stabilize different receptor states. We previously showed that the accessibility of the anionic sulfhydryl reagent p-chloromercuribenzenesulfonate (pCMBS(-)) applied extracellularly to cysteines substituted for residues in the GABA(A) alpha1 subunit M3 membrane-spanning segment was state-dependent. The subset of pCMBS(-)-accessible, M3 segment cysteine mutants acts as a reporter for receptor conformation. Here we show that pCMBS(-), applied in the presence of a potentiating concentration of propofol, reacts with a subset of alpha1 subunit, M3 segment, cysteine-substitution mutants (Y294C, V297C, I302C, F304C). In the presence of a directly activating concentration of propofol pCMBS(-) reacts with a different subset of the M3 cysteine-substitution mutants (Y294C, S299C, I302C, E303C, A305C). These subsets are distinct from the subsets of M3 cysteine-substitution mutants that are reactive with pCMBS(-) in the absence and presence of GABA and in the presence of diazepam. We hypothesize that distinct subsets of reactive residues represent distinct conformations or ensembles of conformations of the receptor. These results provide structural evidence for at least five distinct receptor states, three nonconducting states, resting, diazepam-bound and potentiating propofol-bound, and two conducting-desensitized states, the activating propofol-bound and GABA-bound states.

4-Chloromercuribenzenesulfonate↗

PubMedDate not supplied

Intranasal hormone replacement therapy.

Although the optimal route of delivery for hormone replacement therapy has not yet been determined, desirable qualities would include good efficacy, easy administration, minimal side effects, and optimal therapeutic profile. This would potentially serve to improve patient compliance and satisfaction. The intranasal route has been evaluated for the administration of menopausal hormones and seems to fulfill these requirements. The intranasal route would also seem to be a viable alternative for drugs that are poorly absorbed after ingestion by avoiding hepatic first-pass elimination. The intranasal route is, therefore, innovative for the delivery of natural sex steroids in postmenopausal women receiving hormone replacement therapy. Early studies demonstrate that it is safe, effective, and acceptable to postmenopausal women. In addition, the nasal administration of a combination of estradiol and progesterone would seem to be an attractive way to deliver hormones to nonhysterectomized postmenopausal women. Providing alternative routes of administration may also enhance compliance.

Administration, Intranasal↗

PubMedDate not supplied

The motility of epididymal or testicular spermatozoa does not directly affect IVF/ICSI pregnancy outcomes.

Our objective was to determine whether the presence of motility in surgically obtained sperm samples improves fertilization and pregnancy rates for patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This was a retrospective study in a hospital-based infertility center. Sixty-seven couples with a diagnosis of azoospermia or severe oligozoospermia who had undergone a sperm retrieval procedure in conjunction with 100 IVF/ICSI cycles from 1995 to 2004 were evaluated. The impact of sperm motility on fertilization and clinical pregnancy rates was determined. The motile and nonmotile sperm groups differed in the number of mature oocytes retrieved (10.7 +/- 5.8 vs 13.4 +/- 6.0), but fertilization (56.7% vs 59.1%) and embryo cryopreservation rates (35.9% vs 39.3%) were statistically similar. Clinical pregnancy rates did not differ between the motile (38.5%) and nonmotile (31.2%) groups, nor did they differ between obstructive and nonobstructive patients (35.3% vs 26.7%). There was also no statistical difference in pregnancy rates between testicular and epididymal aspiration (35.3% vs 26.7%), although epididymal sperm were significantly more likely to be motile than testicular sperm (100% vs 39.3%, P < .0001). Epididymal aspiration is more likely to produce motile sperm than testicular sperm retrieval. The use of motile sperm from epididymal or testicular samples, however, does not appear to enhance fertilization or clinical pregnancy rates.

Adult↗