Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels.

Maternal cardiovascular changes and neonatal acid-base status, including lactate levels, were assessed in 30 healthy women undergoing elective caesarean section under spinal anaesthesia. Patients were allocated randomly to receive IV ephedrine infusion (n = 15) (5 mg.min(-1) immediately after the spinal injection or bolus administration of IV ephedrine (n = 15) (10 mg) in case of development of hypotension. Maternal and neonatal blood pressure, heart rate and acid-base status including lactate levels were compared between the groups. Systolic blood pressure in the bolus group was significantly lower when compared to the infusion group. Nausea was observed in one patient (6%) in the infusion group and nausea and vomiting were observed in 10 patients (66%) in the bolus group. Although umbilical arterial pH values were significantly lower in the bolus group, lactate levels were similar In conclusion, ephedrine infusion prevented maternal hypotension, reduced the incidence of nausea and vomiting and led to improved umbilical blood pH during spinal anaesthesia for caesarean section.

GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in leiomyoma.

UNLABELLED: OBJECTIVES To define the effect of GnRH agonist (GnRHa) treatment on endothelial nitric oxide synthase (eNOS) expression in leiomyoma. As eNOS expression is more pronounced in leiomyoma compared to parental myometrium, we hypothesized that the mechanism(s) of tumor shrinkage by GnRHa may be due to decreased nitric oxide (NO) production in leiomyoma. METHODS: Eleven patients with leiomyoma were operated for myoma enucleation by laparatomy. Six of them were treated with GnRHa every 28 days, three times before the operation. The remaining five patients who had no treatment prior to operation formed the control group. Blood was drawn from the patients before treatment and on the day of operation for the assay of serum estradiol (E(2)). Immunohistochemical localization of eNOS expression in leiomyoma and myometrium in treated patients, and in leiomyoma in the control group, was performed using monoclonal antibodies specific to eNOS. RESULTS: All treated subjects showed a significant reduction of fibroid volume at the end of therapy. eNOS-positive cells were localized primarily within the vascular endothelium and smooth muscle cells, but had weak expression in fibroid and myometrial muscle cells in the treated group. The immunoreactivity was similar for both the leiomyoma and myometrium (P > 0.05). In contrast to this, the control group had shown strong expression in leiomyoma muscle cells (P < 0.005) in addition to the vascular endothelium and smooth muscle cells. CONCLUSION: GnRHa-induced tumor shrinkage should be due to diminished eNOS expression, most probably by lowering estrogen secretion.

Role of endometrial suppression on the frequency of intrauterine adhesions after resectoscopic surgery.

STUDY OBJECTIVES: To evaluate long-term effects of operative hysteroscopy on the development of intrauterine adhesions (IUA), and to determine whether hypoestrogenism has a modulatory role in preventing IUA. DESIGN: Prospective, randomized study (Canadian Task Force classification I). SETTING: Tertiary-care teaching hospital. PATIENTS: Ninety-five women requiring resectoscopic surgery. Intervention. Hysteroscopic surgery using the resectoscope and 1.5% glycine for uterine distention. MEASUREMENTS AND MAIN RESULTS: Indications for hysteroscopy were polyps (28 patients), solitary myoma (32), multiple myomata (20), and uterine septa (15). Patients in each group were randomized to endometrial suppression with danazol or placebo. Second-look office hysteroscopy with CO2 for uterine distention was performed after the first menses after surgery to assess the frequency, extent, and severity of IUA. The likelihood and severity of IUA depended on the pathology treated at initial surgery. Of women treated for polyps and uterine septa, in only one with septa (placebo group) developed IUA. Mild IUA formation was present in 10 patients (31.3%) with solitary fibroids and 9 (45.5%) with multiple myomata. The frequency was similar in placebo- and danazol-treated groups with both solitary and multiple myomas (50% and 44.4% vs 50% and 55.6%). All IUA were lysed during second-look surgery, except in one woman with multiple myomata who required repeat resectoscopy. CONCLUSION: Intrauterine adhesions are the major long-term complication of operative hysteroscopy, with frequency dependent on the pathology initially treated. Second-look office hysteroscopy is a cost-effective method of diagnosing and lysing IUA after resectoscopy.

Effect of stimulatory and inhibitory drugs on uterine electrical activity measured noninvasively from the abdominal surface of pregnant rats.

OBJECTIVE: Our purposes were (1) to identify and analyze parameters of uterine electrical activity that change during active term and preterm labor in response to stimulatory (oxytocin) or inhibitory (terbutaline) agents and (2) to correlate the information obtained from abdominal surface measurement of electrical activity with intrauterine pressure and with the electrical activity measured directly from the uterine surface in vivo. STUDY DESIGN: Electromyographic activity was acquired simultaneously from the uterine wall and the abdominal surface by means of unipolar electrodes. Electromyographic activity was recorded in the 0.3 to 50-Hz range and digitized at 200 samples per second. Intrauterine pressure was measured via an intrauterine catheter. The effect of cumulative doses of oxytocin and terbutaline on power density spectrum, amplitude, number and duration of electromyographic bursts, and intrauterine pressure was recorded in anesthetized rats during spontaneous active term labor (n = 7) and induced preterm labor (n = 6). RESULTS: Bursts of electromyographic activity recorded from the abdominal surface mirrored those from the uterine wall, albeit at a lower amplitude. During active term labor, lower concentrations of oxytocin did not significantly affect power-density-spectrum energy, amplitude, or number of bursts per unit time. The duration of electromyographic bursts increased dose dependently. Myometrial contractions were phasic, with return to the baseline between phases. As the concentration of oxytocin increased, the energy, amplitude, and number of bursts per unit time declined while the intrauterine pressure continued to rise until the contraction became tetanic, without return to the baseline. In rats with induced preterm labor, terbutaline inhibited uterine contractility by decreasing the intrauterine pressure. This was accompanied by a progressive decrease in the power density spectrum, amplitude, number, and duration of the uterine wall and abdominal surface electrical bursts. CONCLUSIONS: First, uterine electromyographic activity measured noninvasively from the abdominal surface reflects changes in uterine electrical activity and intrauterine pressure measured directly and invasively in term and preterm labor, as well as during treatments to stimulate or inhibit labor. Second, this noninvasive method may be useful in monitoring uterine activity in vivo. Third, clinical studies to evaluate this technology in human subjects are warranted.

Increased nitric oxide production in the spermatic vein of patients with varicocele.

OBJECTIVE: To define the level of nitric oxide (NO) in the spermatic vein of patients with varicocele and its relation with male infertility. MATERIALS AND METHODS: Following physical and color Doppler ultrasonographic examination, whole blood samples were drawn from a peripheral vein and a dilated varicocele vein from fourteen patients with clinically palpable varicocele (G2-3) before ligation. NO levels in the serum were determined as total nitrite by Greiss reaction and results were compared with Mann-Whitney U test. RESULTS: NO levels in the internal spermatic vein were 36.05 +/- 8. 92 micromol/l, compared to 19.41 +/- 4.12 micromol/l in the peripheral vein and the difference was statistically significant (p < 0.01). CONCLUSION: In view of our results, increased NO levels in the dilated varicocele vein might be responsible for spermatozoa dysfunction.

Endothelial nitric oxide synthase expression in leiomyoma and parental myometrium.

The aim of this study was to determine the expression of endothelial nitric oxide synthase (eNOS) in leiomyomatous tissue as a possible mediator of the growth process. Nine patients had myoma enucleation during the follicular phase. The myomata and adjacent myometrial tissues were fixed in formol until study. Immunohistochemical localization of leiomyomatous and myometrial tissue eNOS expression was performed using specific monoclonal antibodies to eNOS. Statistical comparisons were made using the Mann-Whitney Wilcoxon rank-sum test for the expression of eNOS. The test was considered significant when p values were <0.05. Immunostaining for eNOS was seen in the cytoplasm of myometrial endothelial and smooth muscle cells in both tissue sections. eNOS expression was significantly higher in the smooth muscle cells of leiomyomata, compared to parental myometrium (p < 0.0005). The expression of eNOS in vascular endothelial cells was not different in the leiomyoma and myometrium (p > 0.05). To our knowledge, this is the first study to document marked expression of eNOS in leiomyomatous tissue, compared to parental myometrium. We also conclude that the mechanism(s) of the growth-promoting effect of estrogen on leiomyomata is mediated by more synthesis of NO.

Laparoscopic management of selected adnexal masses.

STUDY OBJECTIVE: To investigate the significance, safety, and intraoperative and immediate postoperative outcomes of laparoscopic management of adnexal masses thought to be at low risk for malignancy. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary-care teaching hospital. PATIENTS: Two hundred twenty women undergoing laparoscopic surgery for adnexal masses. INTERVENTIONS: Laparoscopic treatment including cystectomy, oophorectomy, adnexectomy, and peritoneal cytology, and, if necessary, frozen sections. A histologic diagnosis was obtained in every patient. MEASUREMENTS AND MAIN RESULTS: Only one ovarian cancer and one borderline ovarian tumor were diagnosed by histologic examination, and both were managed by laparotomy. The remaining 218 patients had laparoscopy for benign adnexal masses. CONCLUSION: Operative laparoscopy with the finding of incidental ovarian malignancy is rare, as shown by pathologic examination. With appropriate preoperative evaluation, laparoscopic surgery is technically feasible, safe, and advantageous, with minimal morbidity, and should replace laparotomy in the management of most adnexal masses. (J Am Assoc Gynecol Laparosc 6(3):313-316, 1999)

The effect of chronic nitric oxide synthase inhibition on blood pressure and heart rate in unrestrained pregnant rats as recorded by radiotelemetry.

OBJECTIVES: The objective of this study was to determine the effect of chronic nitric oxide synthase inhibition on heart rate and intravascular blood pressure in unrestrained pregnant rats as recorded by radiotelemetry. STUDY DESIGN: Heart rate and systolic and diastolic blood pressures were monitored beginning with day 6 of pregnancy and until 1 week post partum with a radiotelemetric device. On day 10 of pregnancy osmotic minipumps were implanted subcutaneously and loaded to continuously deliver N(G)-nitro-L -arginine methyl ester (50 mg/d per rat, n = 6 animals) or vehicle (control group, n = 6 animals). RESULTS: Blood pressure in the animals treated with N(G)-nitro-L -arginine methyl ester significantly increased compared with that in the control group and heart rate significantly decreased immediately after nitric oxide synthase blockade. Blood pressure then trended downward as gestation progressed, until the difference between the control group and the group treated with N(G)-nitro-L -arginine methyl ester became nonsignificant after day 17. Refractoriness to nitric oxide synthase blockade was especially evident in the diastolic pressure. Systolic, diastolic, and mean blood pressures in the rats treated with N(G)-nitro-L -arginine methyl ester were again significantly higher than those in the control group immediately after delivery and remained so despite a lower heart rate until the experiment was ended on postpartum day 6. CONCLUSIONS: Radiotelemetry can be used to monitor heart rate and intra-arterial blood pressure in unstressed, unrestrained animals. Chronic inhibition of nitric oxide does not cause sustained hypertension throughout pregnancy. Nitric oxide does not appear to be the only factor responsible for the vascular changes in pregnancy. The factors responsible for the refractoriness to nitric oxide synthase blockade are specific to pregnancy and disappear immediately after delivery.

Adhesion formation after microlaparoscopic and laparoscopic ovarian coagulation for polycystic ovary disease.

STUDY OBJECTIVE: To compare the effects of microlaparoscopy and decreased CO2 exposure on peritoneal microcirculation and potential adhesion formation after ovarian surgery with those of conventional operative laparoscopy. DESIGN: Prospective, randomized study (Canadian Task Force classification I). SETTING: Teaching hospital. PATIENTS: Eighteen women with polycystic ovary disease. INTERVENTIONS: Microlaparoscopic or laparoscopic ovarian coagulation of the ovaries. MEASUREMENTS AND MAIN RESULTS: Approximately 10 to 12 coagulation points were applied to each ovary. Two to 3 weeks after the initial surgery second-look microlaparoscopy was performed to determine the extent of adhesions in both groups. The frequency of adhesion formation and changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues obtained during surgery in each group. RESULTS: Clinical profiles were similar between groups. Mean exposure, amount, and pressure of CO2 were significantly less in the microlaparoscopy group (p <0.05). The laparoscopy group had significantly more adhesions than the microlaproscopy group (24% vs 48%, p <0.05). The GSH-Px, SOD, CAT, and GSH levels were significantly lower in the laparoscopy group (0. 425 micromol, 1.2 ng, 37.55 micromol, and 0.9 nmol vs 0.755 micromol, 2.l ng, 625 micromol, and 2.6 nmol, respectively). CONCLUSION: Reduced exposure to and amount of CO2 during microlaparoscopy may result in decreased adhesion formation compared with conventional laparoscopy. This effect may possibly be due to lack of or minimal adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms for adhesion formation and closely related to peritoneal injury. In addition, microlaparoscopy may be a cost-effective alternative to conventional laparoscopy. (J Am Assoc Gynecol Laparosc 6(2):159-163, 1999)

Normal pregnancy outcome after inadvertent exposure to long-acting gonadotrophin-releasing hormone agonist in early pregnancy.

Five infertile women exposed to long-acting gonadotrophin-releasing hormone agonist (GnRHa) during early pregnancy were studied to assess the risks of embryotoxicity on the outcome of their pregnancies. All the patients were diagnosed as stage 3-4 endometriosis following laparoscopy. Long-acting GnRHa (3.75 mg) was given in the first 3 days of their preceding menstrual period. Four of the five patients had two GnRHa injections and the last patient had three GnRHa injections. All patients were advised to use a barrier contraception (condoms) throughout the treatment period. Since all complained of no bleeding following the initial injections, human chorionic gonadotrophin (beta-HCG) concentrations were tested in order to rule out any pregnancy. Ultrasonographic examinations were commenced routinely and all patients had amniocentesis at 16-18 weeks gestational age. Genetic analysis revealed a normal karyotype in all fetuses. All five pregnancies progressed to term without complication, and normal healthy infants were delivered. Although there are still no clear answers concerning teratogenic and hormonal effects of GnRHa exposure in pregnancy, our data may suggest that luteal function, genetic structure and pregnancy outcome are not adversely affected by GnRHa. Since possible subtle effects on fetal endocrine organs cannot be disregarded, close monitoring is still needed in GnRHa-exposed pregnancies.

The effects of hormone replacement therapy on echocardiographic basic cardiac functions in postmenopausal women.

This prospective study was designed to investigate the effects of hormone replacement therapy (HRT) on systolic and diastolic functions. Twenty-eight non-smoking, healthy postmenopausal women who had not received any kind of HRT for at least three years within the onset of menopause were included in the study. All patients received 0.625 mg conjugated oestrogens and 2.5 mg medroxyprogesterone acetate as daily HRT regimen. Their basic systolic and diastolic functions were investigated echocardiographically using standard positions and windows before and 6 months after initiation of HRT. The means of age, weight and length of postmenopausal period were 49.3 +/- 5.8 years, 63.5 +/- 8.7 kg and 46.3 +/- 7.1 months, respectively. Heart rate and systolic and diastolic pressures were similar during the pre- and post-treatment periods. After 6 months of HRT, the mean left ventricular end-systolic and end-diastolic volumes were decreased significantly (71.3 +/- 16.4 versus 56.3 +/- 22.8 ml, 144.5 +/- 26.1 versus 111.7 +/- 24.0 ml, respectively, P < 0.05). Left ventricular ejection fraction was increased (45.1 +/- 6.2% versus 54.8 +/- 4.1%, P < 0.05). Improvement in diastolic function was significant compared with the pretreatment period (E/A 0.90 +/- 0.2 versus 1.10 +/- 0.4, deceleration time 238 +/- 36.8 versus 201 +/- 24.2 ms, respectively, P < 0.05). Based on our preliminary results, we conclude that besides the known favourable effects on women's lives, HRT may also improve cardiac performance and age-related dysfunctions. The present results further suggest that oestrogens exert many direct effects on the cardiovascular system, other than the metabolic changes related to lipoproteins.

Placebo-controlled cross-over study of effects of tibolone on premenstrual symptoms and peripheral beta-endorphin concentrations in premenstrual syndrome.

Central nervous system hormones have been linked to premenstrual syndrome (PMS) and beta-endorphin (beta-EP) is thought to be involved in the pathophysiology. We have tested the efficacy of the synthetic steroid Org OD 14 (tibolone) in the treatment of PMS. This prospective, randomized, placebo-controlled, double-blind cross-over study included 18 ovulatory women with PMS as ascertained by a visual linear analogue scale (VLAS). The women in each group received either 2.5 mg per day Org OD 14 (n = 9) or a multi-vitamin pill as placebo (n = 9) for 3 months. Treatments were then crossed over to a placebo for a further 3 months. VLAS ratings were evaluated at the end of each menstrual cycle throughout the study. Peripheral beta-EP concentrations were determined by radioimmunoassay on days 7 and 25 of each menstrual cycle. Changes in VLAS score and beta-EP concentrations from baseline were calculated and analysed by Student's paired t-test. Improvements in VLAS scores and beta-EP concentrations were evident during the second and third months of tibolone treatment. At the end of the third month, there was a significant improvement in VLAS scores of all symptom categories compared with pretreatment and placebo during treatment with tibolone (P < 0.05). Similar results were obtained in the first placebo group when switched to tibolone. Beta-EP concentrations were not significantly different between the study groups at the initial cycle (15.9 +/- 3.6 versus 17.2 +/- 2.3 pg/ml). The increase in beta-EP concentration was significantly greater on day 25 of the menstrual cycle in women treated with tibolone compared with baseline and placebo group (22.5 +/- 4.4 versus 15.9 +/- 3.6 and 17.2 +/- 2.3 pg/ml respectively, P < 0.05). Our data confirm the clinical efficacy of tibolone in PMS-related symptoms, as well as its effects on serum beta-EP concentrations in patients with PMS.