Acute resistance exercise increases skeletal muscle angiogenic growth factor expression.

AIMS: Both aerobic and resistance exercise training promote skeletal muscle angiogenesis. Acute aerobic exercise increases several pro-angiogenic pathways, the best characterized being increases in vascular endothelial growth factor (VEGF). We hypothesized that acute resistance exercise also increases skeletal muscle angiogenic growth factor [VEGF and angiopoietin (Ang)] expression. METHODS: Seven young, sedentary individuals had vastus lateralis muscle biopsies and blood drawn prior to and at 0, 2 and 4 h post-resistance exercise for the measurement of VEGF; VEGF receptor [KDR, Flt-1 and neuropilin 1 (Nrp1)]; Ang1 and Ang2; and the angiopoietin receptor--Tie2 expression. Resistance exercise consisted of progressive knee extensor (KE) exercise to determine one repetition maximum (1-RM) followed by three sets of 10 repetitions (3 x 10) of KE exercise at 60-80% of 1-RM. RESULTS: Resistance exercise significantly increased skeletal muscle VEGF mRNA and protein and plasma VEGF protein at 2 and 4 h. Resistance exercise increased KDR mRNA and Tie2 mRNA at 4 h and Nrp1 mRNA at 2 and 4 h. Skeletal muscle Flt-1, Ang1, Ang2 and Ang2/Ang1 ratio mRNA were not altered by resistance exercise. CONCLUSIONS: These findings suggest that acute resistance exercise increases skeletal muscle VEGF, VEGF receptor and angiopoietin receptor expression. The increases in muscle angiogenic growth factor expression in response to acute resistance exercise are similar in timing and magnitude with responses to acute aerobic exercise and are consistent with resistance exercise promoting muscle angiogenesis.

Physiological range of human chorionic gonadotropin for support of early human pregnancy.

OBJECTIVE: To determine the physiological range of hCG in early pregnancy. DESIGN: Retrospective study of patient charts. SETTING: Magee-Women's Hospital IVF clinic, Monroeville, Pennsylvania. PATIENT(S): Sixty patients with successful, singleton birth outcomes. INTERVENTION(S): Serum hCG measurements on days 12-16 post-oocyte retrieval (OR). MAIN OUTCOME MEASURE(S): Lowest values, highest values, mean values, quartile mean values, and 48-hour doubling times for days 12-16 post-OR. RESULT(S): The average production of hCG in successful pregnancies is roughly 4-fold greater than the lowest amount observed in successful pregnancies, suggesting that a considerable excess of hCG is normally produced. Additionally, the average doubling time is almost 2-fold greater than the slowest doubling rate. CONCLUSION(S): The data from this study provide a set of values for the minimum and maximum threshold of hCG for days 12-16 post-OR that may be physiologically required, although not entirely predictive, for a successful IVF pregnancy outcome.

A novel X chromosome-linked genetic cause of recurrent spontaneous abortion.

OBJECTIVE: Unexplained recurrent spontaneous abortion is a common women's health problem that affects approximately 1 of every 200 women who wish to have children. It has long been assumed that a large proportion of recurrent spontaneous abortion results from genetic problems, but no causative genes have been identified to date. Here, we tested the hypothesis that a subset of women with recurrent spontaneous abortion are carriers of X-linked recessive disorders that result in the loss of male pregnancies. STUDY DESIGN: X chromosome inactivation patterns, an assay used to detect women who are likely to be carriers of X-linked recessive cell-lethal traits, were compared between 105 female patients with idiopathic recurrent pregnancy loss and 101 women (control subjects) with a single successful pregnancy and no history of pregnancy loss. Inheritance patterns and gender of offspring were studied in relevant subsets of participants. RESULTS: Female patients showed a highly statistically significant increase in the frequency of skewed X chromosome inactivation (90%; P < .0005). Female patients with highly skewed X chromosome inactivation showed a significant decrease in male children. Four of 6 families that were studied showed maternal inheritance of the skewed inactivation trait. CONCLUSION: We found the 14% of women with unexplained recurrent pregnancy loss show highly skewed X inactivation, which suggests that they are carriers of X-linked recessive lethal traits. Furthermore, the observed gender bias among women with highly skewed X inactivation suggests selective loss of male conceptions, which is consistent with an X chromosome-linked genetic defect that leads to cell death or growth disadvantage. Identification of such female carriers is important for the reproductive counseling and treatment of these women.

Stimulation of uterine cell cytokine production by ovarian hormones.

PROBLEM: Although leukocytes do not possess significant numbers of ovarian steroid hormone receptors, their numbers in the endometrium vary consistently, relative to the menstrual cycle. The possibility that cell types within the endometrium express leukocyte-attracting genes in response to ovarian hormones was investigated. METHOD OF STUDY: Endometrial biopsies were collected 10 days post-leutinizing hormone surge; the cell types were separated and cultured individually for 5 days in the presence of increasing amounts of estrogen or progesterone. Following culture, RNA was collected from cells and reverse-transcription-polymerase chain reaction was used to determine relative levels of gene expression of monocyte chemotactic proteins (MCP)-1, -2, and -3, and interleukin (IL)-12 p35 and p40. RESULTS: Although both endometrial stroma and glands were able to make MCP mRNA, steady-state levels of gene expression did not vary significantly relative to hormone treatment. The same was found for the p35 molecule of the IL-12 gene; however, differences were observed for the p40 subunit. CONCLUSIONS: Within the human endometrium, chemokines other than MCP and IL-12 are most likely responsible for cycle-related leukocyte recruitment.

Topical pharyngeal anesthesia does not improve upper gastrointestinal endoscopy in conscious sedated patients.

OBJECTIVE: We undertook this study to determine whether topical pharyngeal anesthesia with conscious sedation is superior to conscious sedation alone, with respect to procedure performance or tolerance in patients undergoing diagnostic upper gastrointestinal endoscopy. METHODS: Ninety-five patients undergoing diagnostic upper endoscopy with conscious sedation were randomized to receive either topical pharyngeal anesthesia with 2% tetracaine/14% benzocaine spray or no pharyngeal anesthesia. Conscious sedation was achieved in all patients using intravenous midazolam and meperidine. Patients were asked to rate their pretest anxiety, comfort during endoscopy, recollection of the procedure, and willingness to undergo subsequent examinations using a 100-mm visual analog scale. Additionally, they were asked to estimate procedure duration and rate their tolerance for topical pharyngeal anesthesia. All examinations were performed by two endoscopists who were blinded to whether or not patients had received pharyngeal anesthesia. Endoscopists were asked to determine whether they believed that patients had received topical pharyngeal anesthesia and to estimate ease of esophageal intubation and procedure performance using a 100-mm visual analog scale. Procedure duration and doses of midazolam and meperidine were measured. RESULTS: The two groups did not differ with respect to age, gender, and previous endoscopic history. There were no significant differences between the two groups with respect to pretest anxiety, procedural comfort, and willingness to undergo subsequent examinations. Patients receiving topical pharyngeal anesthesia rated it as moderately unpleasant. Endoscopists were able to discriminate patients who received pharyngeal anesthesia from those who did not with a sensitivity of 0.73 and a specificity of 0.59. There were no significant differences between the two groups with respect to ease of intubation, procedure performance, procedure duration, and dosing of midazolam or meperidine. CONCLUSIONS: In patients undergoing diagnostic upper endoscopy using intravenous midazolam and meperidine, the use of topical pharyngeal anesthesia does not improve patient tolerance or procedure performance. Elimination of this agent in the performance of diagnostic upper endoscopy will save time and money without adversely affecting patient care or outcomes.

Endometriosis impairs the efficacy of gamete intrafallopian transfer: results of a case-control study.

OBJECTIVE: To determine whether pelvic endometriosis impairs the efficacy of GIFT. DESIGN: Matched follow-up study. SETTING: University-based assisted reproduction program. PARTICIPANTS: Patients undergoing GIFT between 1987 and 1991. Cases had a primary diagnosis of endometriosis. Controls had no endometriosis and were matched with cases according to age, number of mature eggs transferred, and sperm grade. INTERVENTION: Gamete intrafallopian transfer was performed in all patients in an identical manner independent of their underlying diagnosis. MAIN OUTCOME MEASURES: Pregnancy and delivery rates. RESULTS: Of 114 laparoscopic egg retrievals performed in the endometriosis group, there were 37 pregnancies (32.5%) and 27 deliveries (23.7%). Of the 214 retrievals in the control group, there were 101 pregnancies (47.2%) and 76 deliveries (35.5%). Mantel-Haenszel estimates of relative risk indicated that endometriosis significantly impaired pregnancy and delivery rates. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. CONCLUSIONS: Our finding that GIFT pregnancy rates were lower in women with a primary diagnosis of endometriosis than in matched controls suggests that endometriosis is associated with reduced efficacy of GIFT.

A prospective evaluation of successful terminal ileum intubation during routine colonoscopy.

This study prospectively evaluated a dedicated effort to intubate the terminal ileum in an unselected population of patients undergoing colonoscopy in conjunction with our training program. The influence of the visual appearance of the terminal ileal mucosa on patient management was assessed subjectively. The cecum was reached in 270/295 (91%) patients, with successful terminal ileal intubation being accomplished in 213/270 (79%) examinations. The time required to intubate the terminal ileum (x = 3.4 minutes; range, 30 seconds to 10 minutes) was not significantly different (p < 0.05) between the several levels of training in our fellowship program. The terminal ileum was considered to be visually abnormal in 4 cases, but only 1 of these was abnormal on histologic examination. In this unselected population, routine ileoscopy was unrewarding for finding an incidental positive diagnosis; however, brief attempts at terminal ileal intubation may be useful to improve or maintain endoscopic skills, especially in a training setting.

Establishment of pregnancies in humans after transcervical transfer of gametes immediately after oocyte retrieval.

This study, like that of Veersema et al. demonstrates the feasibility of direct intrauterine transfer of gametes in initiating pregnancy. Whether the success of this procedure can be further improved with modification (preincubation, in vitro insemination) remains the subject of continued investigation. Notwithstanding this uncertainty, we feel that transcervical transfer of gametes may be an alternative to IVF for patients with ethical concerns regarding IVF.

Randomized, prospective trial of leuprolide acetate and conventional superovulation in first cycles of in vitro fertilization and gamete intrafallopian transfer.

Ovarian stimulation after pituitary suppression with gonadotropin-releasing hormone agonists (GnRH-a) has been effective in women who have exhibited a poor response to conventional superovulation strategies. Their effectiveness in unselected women undergoing their first cycle of in vitro fertilization or gamete intrafallopian transfer, however, remains to be established. To address this question, we randomized 114 women to one of two treatment protocols. Protocol 1 consisted of 100 mg of clomiphene citrate on days 5 to 9, followed by 150 IU human menopausal gonadotropin (hMG) beginning on day 9. Protocol 2 consisted of daily GnRH-a beginning in the midluteal phase. Stimulation with 150 IU hMG commenced after pituitary down regulation and ovarian suppression were achieved. Human menopausal gonadotropin was continued in both protocols until adequate follicular development and serum estradiol concentrations were obtained. Protocol 2 patients reached egg retrieval significantly more often (87%) than Protocol 1 patients (61%), but the mean number of mature eggs retrieved and the pregnancy rate per retrieval were not significantly different between the two groups.

Estrogen induces premature luteal regression in rhesus monkeys during spontaneous menstrual cycles, but not in cycles driven by exogenous gonadotropin-releasing hormone.

Administration of exogenous estradiol during the mid- to late luteal phase of the menstrual cycle results in premature regression of the corpus luteum. The present study was initiated to identify the site of action of estrogen as well as to determine why administration of estrogen during the early luteal phase of the menstrual cycle does not result in luteolysis. Based upon extant literature, we hypothesized that estrogen and progesterone synergize to promote premature luteal regression. We tested this hypothesis in intact, spontaneously cycling rhesus monkeys by inserting estradiol, progesterone, or estrogen plus progesterone capsules on days 2 through 6 of the luteal phase. Insertion of estrogen or progesterone capsules alone did not advance luteolysis compared with the effect of control empty implants (n = 3). In contrast, insertion of estrogen plus progesterone implants on days 2 through 6 of the luteal phase resulted in a significant lowering of serum progesterone concentrations, and menses was advanced 5-6 days compared with control cycles. On the basis of these findings in spontaneously cycling monkeys, we speculated that estrogen treatment causes luteal regression only in the presence of a progesterone-mediated decrease in LH pulse frequency. To test this hypothesis, we used rhesus monkeys whose endogenous gonadotropin secretion was abolished by either placement of radiofrequency lesions in the mediobasal hypothalamus or transection of the hypothalamic-pituitary stalk. Ovulatory menstrual cycles were restored by pulsatile administration of exogenous synthetic GnRH. Insertion of estradiol capsules during the luteal phase into animals whose gonadotropin pulse frequency was set at either one pulse per h or one pulse per 8 h failed to cause premature luteal regression (n = 4). These findings indicate that whereas estrogen promotes luteal regression in intact, spontaneous cycling rhesus monkeys, it does not do so in animals whose gonadotropin secretion is controlled by exogenous GnRH. On the basis of these observations, we conclude that the hypothalamus is a major site of action of estrogen in the initiation of luteal regression in macaques.

Effect of exogenous luteinizing hormone-releasing hormone on hypothalamic pituitary function in women with ovarian failure.

Pituitary luteinizing hormone (LH) pulse frequency and amplitude were assessed as an indirect indicator of hypothalamic luteinizing hormone-releasing hormone (LH-RH) release in women with evidence of ovarian failure. Exogenous LH-RH (20 micrograms) was administered intravenously every 2 hours for 48 hours to determine the effect on pituitary LH release and the hypothalamic pulse generator for LH-RH secretion. This study design was used to investigate the possibility of an ultrashort negative feedback of LH-RH upon the synthesis and release of endogenous LH-RH. A wide range of LH pulse frequencies (8 to 28 pulses/24 hours) was present in these women. There was no discernible inhibition of hypothalamic LH-RH pulse frequency during or following exogenous LH-RH administration. Mean peripheral LH levels were significantly increased during exogenous LH-RH administration (P = 0.0038), reflecting both an increased baseline and an augmented pituitary LH response to the exogenous LH-RH. There were no differences found in LH pulse amplitude before and after LH-RH treatment. These data indicate that pituitary LH secretion in women with ovarian failure can be further stimulated by exogenous LH-RH. However, there was no evidence for inhibition of either pituitary LH secretion or hypothalamic LH-RH release using this administration schedule of exogenous LH-RH.

Ureteral obstruction as a complication of the Burch colposuspension procedure: case report.

Major complications of the Burch procedure for stress urinary incontinence are rare. Inadvertent kinking of the ureter during this procedure has been described only once previously in the literature. We present a second such case, hoping to draw attention to this rare but significant complication.

Ovarian responses in macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH.

This study investigated the relationship between plasma gonadotropin concentrations and the initiation and maintenance of preovulatory follicular growth in macaques. Eight adult cynomolgus monkeys were treated with a GnRH antagonist [AcD2Nal1-4ClDPhe2, DTrp3, DArg6, DAla10]GnRH X HOAc to block endogenous gonadotropin secretion. In four animals, a pulsatile infusion of human FSH and human LH (hLH) (one 3-min pulse/h) was initiated, and the amount of hFSH delivered per pulse was increased every 3-4 days until serum estradiol concentrations rose. Thereafter, the amount of FSH delivered per pulse was reduced by 12.5%/day for 5 days, whereas the amount of LH delivered per pulse was not altered. Results indicated that plasma FSH concentrations in the range of 15-20 mIU/ml were associated with the initiation of estrogen production; in addition, a progressive reduction in plasma FSH concentration to 8-10 mI/ml over the subsequent 5 days was accompanied by continued rises in estradiol concentrations and preovulatory follicular growth. In contrast, in four control animals, maintenance of plasma FSH concentrations at 8-10 mIU/ml for 13 days did not result in elevation in serum estradiol concentrations or antral follicular growth. These observations demonstrate that after stimulation by elevated FSH concentration, follicles can continue to mature in the presence of FSH concentrations which are unable to support the growth of less mature follicles. Thus, this may account for the mechanisms by which the maturing follicle continues to develop during the mid-through late follicular phase of the menstrual cycle, whereas other less mature follicles undergo atresia.