Sex differences in quadriceps strength in OA.

The purposes of this study were to determine 1) whether sex differences in quadriceps torque and isotonic power persist when controlling for muscle volume (i. e., torque/muscle volume and power/muscle volume) in participants with knee osteoarthritis (OA) and 2) the factors responsible for potential sex differences. Isometric torque, isotonic power (the product of torque and velocity, measured at 10, 20, 30, 40 and 50% maximal voluntary contraction; MVC) and maximal unloaded velocity were assessed in men (n=16, mean age=62.1 ± 7.2) and women (n=17, mean age=60.4 ± 4.3) with knee OA. Torque and power were normalized to muscle volume. The interpolated twitch technique was used to measure voluntary activation (VA) and evoked twitch and torque-frequency characteristics were measured to obtain information about muscle fibre distribution. Torque and power at all loads were significantly lower in women (p<0.05). Sex differences in power were reduced by 50% when controlling for muscle volume but were still significant at 10-40% MVC (p<0.05). No differences in VA, torque-frequency properties or time-to-peak tension of the evoked twitch were observed (p>0.05). These results suggest that only minor sex differences in torque and power persist when controlling for muscle volume. As VA and contractile property differences were not observed, other factors seem to be responsible.

Quadriceps neuromuscular function and self-reported functional ability in knee osteoarthritis.

The purposes of this study were to determine 1) the relationships of self-reported function scores in patients with knee osteoarthritis (OA) to both maximal isometric torque and to isotonic power at a variety of loads, and 2) the degree to which muscle volume (MV) or voluntary activation (VA) are associated with torque and power measures in this population. Isometric maximal voluntary contraction (MVC) torque and isotonic power [performed at loads corresponding to 10, 20, 30, 40, and 50% MVC, and a minimal load ("Zero Load")] were measured in 40 participants with knee OA. Functional ability was measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) function subscale. MV was determined with magnetic resonance imaging, and VA was measured with the interpolated twitch technique. In general, power measured at lower loads (Zero Load and 10-30% MVC, r(2) = 0.21-0.28, P < 0.05) predicted a greater proportion of the variance in function than MVC torque (r(2) = 0.18, P < 0.05), with power measured at Zero Load showing the strongest association (r(2) = 0. 28, P < 0.05). MV was the strongest predictor of MVC torque and power measures in multiple regression models (r(2) = 0.42-0.72). VA explained only 6% of the variance in MVC torque and was not significantly associated with power at any load (P > 0.05). Quadriceps MVC torque and power are associated with self-reported function in knee OA, but muscle power at lower loads is more predictive of function than MVC torque. The variance in MVC torque and power between participants is due predominantly to differences in MV and has little to do with deficits in VA.

Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells.

BACKGROUND: Umbilical cord blood (UCB) has been examined for the presence of stem cells capable of differentiating into cell types of all three embryonic layers (i.e. endo-, ecto- and mesoderm). The few groups reporting success have typically confirmed endodermal potential using hepatic differentiation. We report differentiation of human UCB-derived multipotent stem cells, termed multilineage progenitor cells (MLPC), into respiratory epithelial cells (i.e. type II alveolar cells). METHODS: Using a cell separation medium (PrepaCyte-MLPC; BioE Inc.) and plastic adherence, MLPC were isolated from four of 16 UCB units (American Red Cross) and expanded. Cultures were grown to 80% confluence in mesenchymal stromal cell growth medium (MSCGM; Cambrex BioScience) prior to addition of small airway growth medium (SAGM; Cambrex BioScience), an airway maintenance medium. Following a 3-8-day culture, cells were characterized by light microscopy, transmission electron microscopy, immunofluorescence and reverse transcriptase (RT)-PCR. RESULTS: MLPC were successfully differentiated into type II alveolar cells (four of four mixed lines; two of two clonal lines). Differentiated cells were characterized by epithelioid morphology with lamellar bodies. Both immunofluorescence and RT-PCR confirmed the presence of surfactant protein C, a protein highly specific for type II cells. DISCUSSION: MLPC were isolated, expanded and then differentiated into respiratory epithelial cells using an off-the-shelf medium designed for maintenance of fully differentiated respiratory epithelial cells. To the best of our knowledge, this is the first time human non-embryonic multipotent stem cells have been differentiated into type II alveolar cells. Further studies to evaluate the possibilities for both research and therapeutic applications are necessary.

Multivariate analysis of factors predictive of successful live births in in vitro fertilization (IVF) suggests strategies to improve IVF outcome.

PURPOSE: Our purpose was (1) to identify characteristics correlated with pregnancy outcome, (2) to use these characteristics to predict in vitro fertilization (IVF) outcome, and (3) to develop strategies that might improve IVF success. METHODS: Maternal age, cause for IVF, donor insemination, rank of attempt, serum estradiol and luteinizing hormone levels on the day of human chorionic gonadotropin administration, flexible vs rigid catheter, number of embryos transferred of each morphologic type, and cell number were analyzed by logistic regression. RESULTS: Variables positively correlated with success are as follows: (1) for pregnancy, endometriosis and 2-, 3-, and 4-cell good and 4-cell excellent embryos; (2) for live births, 2-, 3-, and 4-cell good and 4-cell excellent embryos and donor insemination; and (3) for multiple births, 2- and 4-cell good and 4-cell excellent embryos. Maternal age was negatively correlated with live births. CONCLUSIONS: Embryos derived from IVF have different potentials for implantation, live births, and multiple births. Transferring one additional good-quality embryo for each 5 years of incremental increase in maternal age is predicated to improve live birth rates without increasing multiple births.

Cost of assisted reproductive technologies for a health maintenance organization.

OBJECTIVE: To calculate the cost of assisted reproductive technologies (ART) for a health maintenance organization (HMO), assess factors that contribute to the cost per delivery and to analyze how utilization rates can be controlled by the use of clinical criteria. STUDY DESIGN: Pregnancy outcome and a cost analysis of all ART cycles at an HMO in a state with mandated coverage for these procedures was performed. All patients (n = 148) undergoing ART cycles insured by the HMO performed at one in vitro fertilization (IVF) center during 1990-1995 were studied. RESULTS: ART cycle outcomes and a cost analysis, including global cycle and cancellation charges, medication costs, obstetric costs and neonatal care costs, were assessed. ART cycles (n = 375) included IVF (n = 278), gamete intrafallopian transfer (n = 46), cryopreserved embryo transfer (ET) (n = 42), zygote intrafallopian transfer/tubal embryo transfer (n = 7) and donor oocyte (n = 2). Pregnancy outcome with IVF was 18.3% deliveries per retrieval, for gamete intrafallopian transfer 27.8% deliveries per retrieval and for frozen ET 19% per procedure. Overall, 62/148 (41.9%) of the patients delivered. There were 35 singletons, 22 twin sets and 5 triplet sets. This resulted in an average cycle cost per delivery of $36,417. The mean obstetric and neonatal charges were $9,329 for a singleton delivery, $20,318 for twins and $153,335 for triplets. If these charges are expressed in terms of the number of infants born, a twin pregnancy would cost $10,159 per infant and a triplet pregnancy, $51,112. The ART cycle cost per HMO plan member was $2.49 per annum. Our IVF utilization was 295 cycles per million population. CONCLUSION: An HMO can control the cost of ART services by establishing preauthorization clinical criteria. Our utilization rates might be used as a benchmark for other insurers considering ART coverage. The cost of ART ($2.49 per annum) would be only a small fraction of the typical annual insurance premium.

Safety of a freestanding surgical unit for the assisted reproductive technologies.

OBJECTIVE: To determine the safety of a freestanding surgical unit for assisted reproductive technology (ART), using the rate of unplanned admissions to a hospital within 24 hours of surgery. DESIGN: Prospective. SETTING: A freestanding surgical unit within a medical office building. PATIENTS: A mixture of private and university-referred patients undergoing 6,776 ART surgical procedures. MAIN OUTCOME MEASURES: Patients admitted during the first 24 hours of surgery were recorded and hospital progress was monitored for invasive procedures, treatments, time of discharge, and residual complications. Variables tabulated included age, fertility diagnosis, ART procedure, E2 level, number of follicles by ultrasound, previous surgery, and type of anesthesia. RESULTS: There were 11 hospital admissions (0.16%). Four patients required surgery: one laparoscopy and three laparotomies. Admissions after vaginal oocyte retrieval were no different from those after GIFT via laparoscopy, 0.16% versus 0.18%, respectively. The number of admissions after monitored anesthesia care was higher than expected compared with general anesthesia. Profiles of hospitalized patients showed no apparent differences from the nonhospitalized patients. CONCLUSIONS: Surgical procedures for ART performed in a freestanding surgical unit can be performed safely with a low hospitalization rate and minimal morbidity.

On naevi and melanomas in dysplastic naevus syndrome patients.

Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size > or = 2 mm or > or = 5 mm on the back than women (P = 0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma.

Effect of sequential and daily continuous hormone replacement therapy on indexes of mineral metabolism.

BACKGROUND: Continuous regimens of estrogen-progesterone have recently been favored over sequential regimens because of a lower incidence of withdrawal bleeding. To determine whether the beneficial effects of sequential hormonal therapy on bone metabolism are preserved with the newer continuous regimens, we studied indexes of skeletal metabolism and changes in bone mineral density during a 1-year prospective trial. METHODS: Our subjects were randomized to one of three treatment groups: those in group C-2.5 were treated with 0.625 mg of conjugated estrogen with 2.5 mg of micronized medroxyprogesterone acetate daily continuously; group C-5 received 0.625 mg of conjugated estrogen and 5.0 mg of micronized medroxyprogesterone acetate daily continuously; and group S-5 received 0.625 mg of conjugated estrogen on days 1 through 25 and 5 mg of micronized medroxyprogesterone acetate on days 14 through 25. RESULTS: At 1 year, all groups demonstrated a significant decrease in indexes of bone formation turnover, including decrements in alkaline phosphatase levels of 11% to 30% and in osteocalcin levels of 45% to 60%. Intact parathyroid hormone levels rose 10% to 20%, with a concomitant near-significant decrement in ionized calcium levels at 12 months. In addition, there were significant decrements in the 24-hour urinary calcium-creatinine ratios and hydroxyproline-creatinine ratios of 13% to 28%, measures of bone resorption. Linear regression analyses showed that the subjects with the high bone resorption achieved the greatest increment in bone mineral density in response to hormone therapy. CONCLUSION: The daily continuous estrogen-progesterone regimens are as efficacious as sequential hormonal therapy in decreasing indexes of bone turnover and stabilizing bone mineral density of the spine and proximal femur.

Microscopic epididymal sperm aspiration (MESA): a new option for treatment of the obstructive azoospermia associated with cystic fibrosis.

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.

Comparison of unilateral and bilateral tubal transfer in gamete intrafallopian transfer (GIFT).

Gamete intrafallopian transfer (GIFT) is traditionally performed by delivering gametes into the ampullary region of either one or two fallopian tubes. The choice is made by the surgeon at the time of laparoscopy based upon the patient's anatomy, the number of oocytes available, and clinical judgment. In this nonrandomized, retrospective review, 399 tubal gamete transfers were performed over a period of 18 months, 133 to a single tube and 266 to both tubes. A clinical pregnancy rate of approximately 24% was observed in each modality. The multiple pregnancy rate of 31.3% for one tube was not significantly different from the 25% seen for two tubes. Unilateral tubal transfer offers the distinct advantages of less gamete and tissue handling. This, along with the apparent same outcome parameters, makes unilateral tubal transfer the preferred method of returning gametes at GIFT.

Gamete intrafallopian transfer: assessment of the optimal number of oocytes to transfer.

The optimum number of oocytes that should be transferred at the time of gamete intrafallopian transfer (GIFT) is important information. Nonessential oocytes can be inseminated and frozen for later use or the extra oocytes can be donated to another women. In this preliminary study, the results of 399 consecutive GIFT procedures were evaluated retrospectively as a function of the number of oocytes transferred. Women who received four or more oocytes were three times more likely to achieve a clinical pregnancy than those who received three or less. There was no statistically significant difference in pregnancy rates between patients who received five, six, seven, or eight oocytes. Oocytes in excess of five may be more effectively used if they are fertilized and frozen as embryos for later transfer rather than replacing them all at the time of GIFT.

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.

Phenotypic differences in upper genital tract abnormalities and reproductive history in dizygotic twins exposed to diethylstilbestrol in utero. A case report.

Major phenotypic variations in reproductive function and upper genital tract abnormalities were found between 30-year-old dizygotic twins exposed in utero to diethylstilbestrol (DES). The women were exposed to maternal DES doses of 12.5-50.0 mg daily starting from the 12th gestational week as documented in the original antepartum obstetric office records. Twin A had primary involuntary infertility of over four years' duration associated with a severe DES uterine deformity on hysterosalpingography (HSG). A complete evaluation demonstrated all other infertility investigations to be normal. Twin B had two term pregnancies but a significant history of reproductive loss, including three miscarriages and one ectopic pregnancy. HSG demonstrated mild DES-induced changes. Cervical adenosis was observed only in the more severely affected twin.

Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report.

In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility. Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility. We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.

Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study.

We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis.

The association between smoking and female infertility as influenced by cause of the infertility.

Smoking histories were compared in 901 women with infertility of different types and 1264 women admitted for delivery at seven collaborating hospitals. The relative risk for infertility associated with cigarette smoking prior to the infertility diagnosis for nulliparous cases or first live birth for controls was calculated using a multivariate logistic-regression model to control for potential confounding factors, including center, age, religion, education, number of sexual partners, and contraceptive use. The adjusted risk for infertility attributed primarily to cervical factor (n = 96) was 1.7 (P = 0.04), to tubal disease unrelated to endometriosis (n = 225) was 1.6 (P = 0.009), to ovulatory factor (n = 389) was 1.0 (not significant [NS]), and to endometriosis (n = 191) was 0.9 (NS). The authors conclude that cigarette smoking is significantly associated only with certain types of primary female infertility.

Comparison of intermediate-dose purified urinary follicle-stimulating hormone with and without human chorionic gonadotropin for ovulation induction in polycystic ovarian disease.

Urinary FSH is capable of inducing ovulation in PCOD. The duration of treatment can be reduced by administering an intermediate dose. However, it appears that prospective monitoring with E2 assays and ultrasound, combined with hCG, is required to optimize outcome and minimize complications. Studies comparing urinary FSH with similar doses of hMG with and without hCG are needed to determine the most effective form of gonadotropin therapy in PCOD.

Danazol therapy for proximal obstruction of the oviduct.

Danazol therapy for proximal tubal obstruction and associated endometriosis has been suggested to be highly effective. Of 12 women treated with danazol for two to nine months, 5 had resolution of their proximal tubal obstruction after three to eight months of therapy. Two of the five had no associated pelvic endometriosis, and one of them became pregnant. Due to the heterogeneity of the patient population studied, it is difficult to make a definitive statement about the efficacy of danazol in patients with proximal tubal obstruction. However, the data suggest that danazol is effective in the treatment of some patients with proximal tubal obstruction and should be considered prior to surgery.

Lymphocyte dysfunction in autoimmune oophoritis. Resumption of menses with corticosteroids.

In a 32-year-old woman with secondary amenorrhea and biopsy-proven oophoritis, the circulating T lymphocytes were examined utilizing monoclonal antibody L243 to the nonpolymorphic region of the Ia antigen. The percentage of peripheral T cells expressing the Ia "immune-associated' antigen was 5.6 percent (normal 3 percent or less). With corticosteroid therapy, the percentage decreased to 2 percent and menses resumed after secondary amenorrhea of two years' duration. Following cessation of steroid administration, the percentage of Ia-positive T cells rose to 7.0 percent and secondary amenorrhea redeveloped in the patient. After corticosteroid therapy was reinstituted, menses resumed and the percentage of Ia-positive T cells fell to normal. This report represents additional new evidence of immune dysfunction in patients with "autoimmune" oophoritis.