Mifepristona 5 mg frente a 10 mg diarios en el tratamiento del leiomioma. Ensayo clínico aleatorizado

Objective

To estimate the efficacy and safety of 5 mg or 10 mg mifepristone daily in the treatment of leiomyoma.

Material and methods

Ninety women with symptomatic uterine myomas were randomised to receive 5 mg or 10 mg of mifepristone (45 per group). Leiomyomata and uterine volumes were evaluated by ultrasonography. Efficacy was estimated by the reduction of the leiomyomata and uterine volumes and the prevalence of symptoms.

Results

After treatment, in the 5 mg group there was a 60.8%, (P < .001), reduction in the fibroid volume and it was 59.4%, (P < .001), in the 10 mg group. The prevalence of symptoms decreased significantly. After treatment, 93.8% subjects from the 10 mg mifepristone group and 86.4% subjects from the 5 mg group were amenorrheic, respectively.

Conclusions

Both treatments were effective for treating uterine fibroids.     

Presurgical short term treatment of uterine fibroids with different doses of cetrorelix acetate: a double-blind, placebo-controlled multicenter study

Objective

To assess the efficacy and safety of different dosing schedules of cetrorelix acetate as a short term treatment for 4 weeks prior to surgery in patients with uterine fibroids.

Study design

Randomized, double-blind, placebo-controlled study. Patients were 109 premenopausal women, with at least one uterine fibroid, more than 4 cm in diameter. Groups 1–3 received placebo, 5 and 10 mg of cetrorelix on days 1, 8, 15 and 22, respectively group 4 received 10 mg of cetrorelix on days 1 and 15. MRI scan was performed at screening and on day 29. The main outcome measure was the reduction of uterine volume on day 29 and response, defined as >30% size reduction.

Results

Mean (±S.D.) reduction of uterine volume on day 29 (MRI scan) was 5.1 ± 32.1% with placebo, 15.6 ± 20.2% with 4 × 5 mg, 15.4 ± 34.6% with 4 × 10 mg and 0.6 ± 30.6% with 2 × 10 mg cetrorelix. Significant response versus placebo (p < 0.05) occurred in the 4 × 10 mg group (42.3% versus 11.1%)

Conclusions

Best objective response after 4 weeks of treatment was achieved after therapy with 4 × 10 mg of cetrorelix acetate. Short term presurgical treatment with the LHRH-antagonist cetrorelix is a flexible treatment protocol without any major side effects.     

Laparoscopic myomectomy in peri- and post-menopausal women is safe, efficacious and associated with long-term patient satisfaction

Objective

Women in the peri- and post-menopause may ask for uterus-preserving therapy options when presenting with benign uterine disorders such as symptomatic fibroids. Laparoscopic myomectomy (LM) for patients in the peri- and post-menopause as a surgical alternative to hysterectomy is widely considered to be non-standard treatment. The aim of this study was to analyze safety and outcome of LM beyond the reproductive period.

Study design

We evaluated the surgical outcome and patient satisfaction for a total of 451 patients: 85 peri- or post-menopausal women as group A and, for reference, 366 premenopausal women in group B, who received LM from 1998 to 2008 in our department. We analyzed data from our medical records and applied a patient questionnaire in September 2009.

Results

The average number of fibroids removed and size of the leading fibroid were similar in both groups. Time of surgery was different in group A, at 102.8 min, compared to group B, 128.6 min (p < 0.01). Rates of intra- (2.21% overall) and post-operative complications (6.22% overall) were comparable for both groups. Post-surgical hospitalization was shorter in group B (4.4 days) compared to group A (5.0 days) (p < 0.01). Evaluation of the questionnaire showed high satisfaction with the results of LM in both subgroups with a significantly lower number of relapses in group A (3.5%) compared to group B (11.2%).

Conclusion

Laparoscopic myomectomy as a surgical treatment option in the peri- and post-menopause was characterized by a low rate of complications and relapses as well as a high degree of patient satisfaction in our analysis.     

Evolución del leiomioma uterino después del tratamiento con mifepristona. Ensayo clínico aleatorizado

Objectives

To evaluate the extent in time of the reduction of uterine and fibroids size in women treated with mifepristone.

Patients and methods

One-hundred women who received mifepristone 10 or 5 mg for three months were followed-up for six months after treatment termination.

Results

Six months after treatment the fibroids mean sizes were 19% and 23% lower than baseline values in 10 and 5 mg mifepristone groups, respectively, and mean uterine volumes were 8% and 17% lesser than before treatment in 10 and 5 mg groups, respectively. Prevalence of symptoms was still significantly lower than before treatment.

Conclusions

Six months after treatment termination the sizes of fibroids and uteri were near to the initial values but a clinical improvement was maintained.     

Decreasing margins to the uterine serosa as a method for increasing the volume of fibroids ablated with magnetic resonance-guided focused ultrasound surgery

Objective

To demonstrate the safety of magnetic resonance-guided focused ultrasound surgery (MRgFUS) treatments regardless of the distance between the treatment region and the uterine serosa.

Study design

83 pre-menopausal women with symptomatic uterine fibroids were treated with MRgFUS in 88 treatments. Treatment data was analyzed, measuring the distance between the treatment spots (sonications) and the serosa. Patients were followed up for 1 year and adverse events were collected.

Results

79% and 37% of the sonications were less than 15 mm and 10 mm from the serosa, respectively. Treatment was always confined to the fibroid capsule. There were no unexpected or serious adverse events.

Conclusion

Reducing the margin between the fibroid treatment area and the uterine serosa, when possible, enables MRgFUS treatment of greater fibroid volume, while maintaining a high safety profile. Special attention should be paid when the uterus lies adjacent to other sensitive organs to avoid unintentional heating of these organs, using the planning and real-time MR images.     

The effect of mifepristone on apoptosis and caspase-3 activation in human ovarian luteinized granulosa cells

Objective

To investigate the effect of mifepristone, an oral contraceptive, on apoptosis in human ovarian luteinized granulosa cells.

Study design

Human ovarian luteinized granulosa cells were treated in vitro with 1.25, 2.5, 5.0, 10.0, or 20.0 μM of mifepristone. Nuclear morphology, apoptosis ratio, and level of caspase-3 expression were determined with immunofluorescence microscopy, the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay, and flow cytometry.

Results

We found that mifepristone-treated cells contained single condensed chromatin with multiple nuclear fragments, which is morphologic evidence of apoptosis. A significant difference was observed in the TUNEL assay between mifepristone-treated cells and control cells (P < 0.05). Consistent with the results of the TUNEL assay, the fluorescence intensity of caspase-3 in drug-treated cells was also significantly different (P < 0.05) from control cells; specifically, the difference between cells treated with different doses of drugs was much smaller and negligible.

Conclusion

From these results, we propose that mifepristone induces human ovarian luteinized granulosa cells to undergo apoptosis by activating caspase-3.     

Tratamiento de la endometriosis con 5 mg o 25 mg diarios de mifepristona durante 6 meses. Ensayo clínico aleatorizado,doble ciego

Objectives

To evaluate the safety and efficacy of 5 mg and 25 mg doses of mifepristone for the treatment of endometriosis.

Design

Randomized double-blind study.

Setting

Eusebio Hernández Hospital, Havana, Cuba.

Subjects

Twenty-six women laparoscopically diagnosed with endometriosis were included.

Treatment

Group I received one tablet of 25 mg mifepristone daily and group II received one tablet of 5 mg mifepristone daily for 6 months. Laparoscopy and endometrial biopsy were performed before and after treatment.

Variable to evaluate efficacy

Reduction in the intensity of dysmenorrhea measured by a visual analogue scale.

Results

In both groups reductions in the intensity of dysmenorrhea and dyspareunia were highly significant compared with initial values (P <.001). All the women were amenorrheic after 45 days of treatment.

Conclusions

At doses of 5 mg or 25 mg, mifepristone could be an alternative for the treatment of endometriosis.     

The effect of edaravone on ischemia-reperfusion injury in rat ovary

Objective

The aim of this study was to investigate the effect of edaravone on experimentally induced ovarian torsion/detorsion ischemia/reperfusion (I/R) injury.

Study design

: Forty-six female adult Wistar-Albino rats were utilized to create five groups: In group 1, only 5 mg/kg edaravone was given and ovary torsion was not performed. In group 2, torsion was not performed and no drug was given. In group 3, vehicle was given and torsion/detorsion was performed. In group 4, 1 mg/kg edaravone was given and torsion/detorsion was performed. In group 5, edaravone; 5 mg/kg drug was administered and torsion/detorsion was performed. Right ovarian torsion was simulated for a 3-h period of ischemia and a 1-h reperfusion period. Right ovaries were then surgically extirpated in all groups. In ovarian tissue samples malondialdehyde (MDA) levels and activity of superoxide dismutase were studied. Microscopic ovarian tissue damage was scored by histologic and electron microscopic findings.

Results

The MDA level in the group 5 was significantly lower than group 3 (p < 0.001). Superoxide dismutase activity in the group 5 was significantly higher than group 3 (p < 0.001). Histopathological ovarian tissue damage in the group 5 were significantly lower than group 3 (p < 0.001).

Conclusion

These results indicate that edaravone could be an effective agent in the short-term treatment and prevention of ovarian ischemia and reperfusion damage.     

Susceptibility of red blood cell lipids to in vitro oxidation and antioxidant status in preeclampsia

Objective

To investigate susceptibility of red blood cell (RBC) lipids to oxidation and antioxidant status in preeclampsia.

Study design

Twenty-one women with mild preeclampsia, 21 women with severe preeclampsia, and 20 healthy pregnant women were included in this cross-sectional study. Susceptibility of RBC to oxidative stress was determined by measuring RBC-malondialdehyde levels after incubation with hydrogen peroxide. Vitamins E and C, total carotenoids and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) activities and serum total antioxidant capacity (TAC) were determined spectrophotometrically. One-way analysis of variance and correlation analysis were used for statistical analyses.

Results

Compared with the normal pregnant women, susceptibility of RBC to oxidation was enhanced in the mild (p < 0.05) and severe (p < 0.01) preeclampsia groups, TAC was lower in the mild (p < 0.01) and severe (p < 0.001) preeclampsia groups. Vitamin C level was decreased in severe preeclampsia and total carotene level was decreased in mild and severe preeclampsia groups (p < 0.05). GPx activity was also decreased in the mild (p < 0.01) and severe (p < 0.05) preeclampsia groups.

Conclusion

The results of the present study supported the oxidative stress hypothesis of preeclampsia and it is possible that RBC play a role in the pathophysiology of the disease.     

Improved quality of life is partly explained by fewer symptoms after treatment of fibroids with mifepristone

Objective

To examine mediators of mifepristone treatment on improvements in health-related quality of life (HRQOL) among women with symptomatic fibroids.

Methods

The study sample included women with symptomatic uterine fibroids who were treated with 5 mg or 2.5 mg of mifepristone or placebo. Assessments of uterine size (ultrasound), pain (McGill pain questionnaire), bleeding (diary), anemia (gm/dL), and HRQOL measured using the uterine fibroid symptom quality of life scale were done at baseline, 3 months, and 6 months. The improvements in HRQOL that could be explained by changes in these clinical factors were assessed.

Results

The final sample included 62 women. Treatment with mifepristone was associated with significant improvement in HRQOL, which was explained in part by reduction in pain (28%, P < 0.001) and bleeding (18%, P < 0.001). Reduction in uterine volume was of marginal significance (P = 0.05) and was associated with a decrease in HRQOL (7%). Much of the impact of treatment on HRQOL (61%) remained unexplained in this model.

Conclusions

Improvements in HRQOL after treatment with mifepristone are partly explained by improvements in pain and bleeding, but not uterine size. However, most of the improvement in HRQOL is not explained by improvements in these clinical parameters.     

Hysteroscopic myomectomy for menorrhagia using Versascope™ bipolar system: Efficacy and prognostic factors at a minimum of one year follow up

Objective

To evaluate the effectiveness of hysteroscopic submucous myomectomy for women with heavy menstrual bleeding (HMB) over a minimum 1-year period and assess prognostic factors associated with treatment success.

Study design

Prospective observational study set in a university teaching hospital in UK involving 92 women symptomatic of HMB with submucous myomas consecutively recruited between June 2003 and November 2006. Hysteroscopic myomectomy was performed under outpatient local anaesthetic (n = 35, 38%) or daycase general anaesthesia (n = 57, 62%) using Gynecare Versascope™ bipolar system. The main outcome measures were: the need for secondary surgical or medical re-intervention, menstrual improvement and patient satisfaction. Other outcome measures include: successful completion of primary resection, type of secondary treatment.

Result

Mean follow up was 2.6 years (95% CI 2.3–2.9). Complete fibroid excision was achieved in 66%. Secondary surgical re-intervention was required in 27 (29%) of which 11 (12%) were repeat hysteroscopic myomectomy and 10 (11%) were hysterectomy procedures. Multiple uterine fibroids and adenomyosis were identified in 80% of hysterectomies. At follow up, improved menstrual symptoms and patient satisfaction were reported by 91% and 86%, respectively. Irregular cycle HMB and incomplete fibroid excision were associated with secondary retreatment. Size of the submucous fibroid resected, presence of intramural and subserosal fibroids, or LA vs. GA setting were unrelated to treatment success.

Conclusion

HMB with submucous myomas may be successfully treated by completely removing the intracavity myoma component, irrespective of co-existent intramural or subserosal fibroids or size of fibroid resected. This effect remains sustained over at least a 1–2 year period.     

Intravaginally applied metronidazole is as effective as orally applied in the treatment of bacterial vaginosis, but exhibits significantly less side effects

Objective

Metronidazole is the drug of choice for the treatment of bacterial vaginosis (BV). However, so far the oral administration has not been clinically compared to the intravaginal application regarding efficacy, side effects and patient satisfaction in a scientific sound fashion.

Study design

Therefore, this randomized, double-blind, placebo-controlled clinical trial was designed to demonstrate non-inferiority of short-term intravaginal (i.vag.) application of metronidazole (2× 1000 mg pessaries 24 h apart) vs. a single oral dose (p.o.) of metronidazole (1 × 2000 mg tablets) in 263 patients with BV (double-dummy design). The follow-up period was 12 weeks. In addition, the number and the type of adverse events induced by the two regimens were compared, assuming better tolerability of the intravaginal application.

Results

Following the diagnosis of BV a total of 129 women (mean age 36.2 years) was orally treated with a single dose of 2 g metronidazole whereas a total of 134 patients (mean age 35.5 years) was treated intravaginally with 1 g metronidazole each day on two consecutive days and included in the per-protocol analysis. Non-inferiority of i.vag. application compared to p.o. administration was statistically significant regarding efficacy: Following intravaginal application the cure rate, assessed on day 8 after starting of the treatment, was 92.5% as compared to 89.9% after oral administration. Nausea was the most common adverse event reported in 10.2% i.vag. vs. 30.4% p.o. of all cases (p < 0.001), abdominal pain in 16.8% i.vag. vs. 31.9% p.o. (p < 0.01), a “metallic taste” in 8.8% i.vag. vs. 17.9% p.o. (p < 0.05). Women treated i.vag. were highly satisfied with the treatment and more content as compared to the women treated p.o. with metronidazole (p < 0.05, intent-to-treat analysis).

Conclusion

In this clinical trial the intravaginal application was as effective as the oral administration of metronidazole in treating BV. However, significantly less adverse events were reported after short-term intravaginal as compared to oral application (p = 0.023) and probably led to a better patient compliance.     

Serum C-reactive protein in the differential diagnosis of ovarian masses

Objective

A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer.

Study design

In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n = 44, epithelial ovarian cancer [EOC]: n = 198) ovarian masses. Results were correlated to clinical data.

Results

Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6) mg/dL, 0.5 (0.5, 0.9) mg/dL, and 1.36 (0.5, 4.9) mg/dL, respectively (p < 0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p < 0.001), residual tumor mass (p < 0.001), and patients’ age (p = 0.04), but not with tumor grade (p = 0.2) and histologic type (p = 0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients’ age, serum CRP independently predicted the presence of malignant ovarian masses (p < 0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8–7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively.

Conclusion

Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients’ age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.     

Comparative evaluation of the Joel-Cohen cesarean section versus the transrectal incision

Objective

The aim of this study was to compare the Joel-Cohen method for cesarean section to the traditional transrectal incision.

Method

Fifty-two patients requiring a caesarean section were enrolled in this prospective study. Overall morbidity and post-operative pain was assessed. Four surgeons participated to this study, each included 13 patients. The main judgement criterion was post-operative pain on the first day.

Results

Post-operative pain on the first day was less important (50 vs 23% p = 0.04) in Joel-Cohen's. This method was shorter compared to the transrectal incision (33,6 + 6,4 min vs 51,2 + 8 min p < 0.0001). There was no difference in overall morbidity between the two groups.

Conclusion

Joel-Cohen's method decrease post-operative pain and is a shorter procedure compared to the transrectal incision.     

Laparoscopic treatment of endometrial cancer: feasibility and results

Objective

The aim of this study was to compare laparoscopic and abdominal approach in the treatment of endometrial cancer in our department.

Study design

From January 1999 to November 2002, 77 patients underwent surgery for stages I–III endometrial cancer. The first group of 36 patients had abdominal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. The remaining 41 patients received laparoscopic assisted vaginal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy.In this retrospective study, we have compared the surgical results, the short- and long-term morbidity and the outcome of the two patient groups.

Results

Body mass index (BMI) was significantly higher in the laparoscopic group (27.3 versus 24.6; p = 0.009). The average time for surgery was significantly longer for the laparoscopic group (143.6 min versus 109.7 min; p = 0.0001), but lymphadenectomy was performed in more patients (63.4% versus 25%; p = 0.001).Postoperative hospital stay was significantly longer in patients undergoing the abdominal approach (4.59 days versus 3.18 days; p < 0.0001). No blood transfusions were performed and the rates of complications were similar in the two groups. No differences were found in recurrence and survival rate.

Conclusions

In our experience, laparoscopic and abdominal surgery can achieve similar results in the treatment of endometrial cancer. In our series, even with the BMI and the number of lymphadenectomies being higher in the laparoscopic group, the rates of complications were similar in the two groups.     

High expression of cyclooxygenase-2 in uterine fibroids and its correlation with cell proliferation

Objective

To investigate the expression of cyclooxygenase-2 (COX-2) in uterine fibroids and healthy uterine smooth muscle as well as its role in the pathogenesis of uterine fibroids.

Methods

We collected uterine fibroid tissues and their paired adjacent healthy uterine smooth muscle tissues from 30 cases of uterine fibroids. We used immunohistochemistry and quantitative real-time PCR, as well as western blot to detect COX-2 expression. Using the COX-2 inhibitors NS-398 and celecoxib, we observed the response to the inhibitors in the healthy and fibroid smooth muscle cell pairs.

Results

COX-2 was detected by immunohistochemistry in both uterine fibroids and uterine smooth muscle, with higher immunoreactivity in uterine fibroids; the positive index of the smooth muscle cells was 11.90 and the positive index of uterine fibroids cells was 46.50 (P < 0.05). The expression of COX-2 mRNA in uterine fibroids was higher (0.122 ± 0.062) than in normal smooth muscle tissue (0.025 ± 0.009; P < 0.05). Also, the western blot results showed that COX-2 expression was significantly higher in uterine fibroid cases, as compared to the expression in uterine smooth muscle. Immunofluorescence showed that the occurrence of COX-2 was obviously higher in smooth muscle cells of uterine fibroids than in the healthy smooth muscle cells. NS-398 or celecoxib significantly inhibited the proliferation of smooth muscle cells of uterine fibroids, but did not inhibit the proliferation of healthy smooth muscle cells. Accordingly, NS-398 or celecoxib significantly reduced the expression of the downstream metabolite of COX-2, PGE2, in the smooth muscle cells of uterine fibroids, but not in healthy smooth muscle cells.

Conclusion

COX-2 expression in uterine fibroids was significantly higher than in healthy uterine smooth muscles. The inhibition of COX-2 activity significantly reduced the proliferation of smooth muscle cells of the uterine fibroids, suggesting that COX-2 plays an important role in the pathogenesis of uterine fibroids.     

Does 45,X/46,XX mosaicism with 6–28% of aneuploidy affect the outcomes of IVF or ICSI?

Objective

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI.

Study design

Forty-six women with a 45,X/46,XX karyotype with 6–28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype.

Results

No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p = 0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p = 0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p = 0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p = 0.51).

Conclusion

45,X/46,XX mosaicism with 6–28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies.     

Effectiveness of local anaesthetics with and without vasoconstrictors for perineal repair during spontaneous delivery: double-blind randomised controlled trial

Objective

to investigate the use of local anaesthetics, in the presence or absence of vasoconstrictors, for perineal repair during spontaneous delivery.

Design

double-blind, randomised-controlled trial.

Setting

a birth centre, in the city of Sao Paulo, Brazil.

Participants

from June to December 2004, a total of 96 women were allocated into three groups (first-degree perineal lacerations, second-degree perineal lacerations or episiotomy), and treated with local anaesthesia (1% lidocaine or 1% lidocaine with epinephrine) (n=16 per treatment per group).

Interventions

an initial local infiltration of the anaesthetic solution was given so that episiotomy could be carried out (5 ml) and to suture spontaneous lacerations (1 ml), followed by repeated doses (1 ml) until pain was completely inhibited.

Measurements and findings

the main outcome measurement was the volume of anaesthetic used during episiotomy and perineal suture. Our data suggest that the concomitant use of the vasoconstrictor resulted in a significantly lower average volume used in the treatment of first-degree (1 ml, 95% confidence interval (CI) 0.4–1.6) and second-degree (3.7 ml, 95% CI 1.6–5.8) lacerations (p=0.002 and 0.001, respectively). A 0.3 ml (95% CI 1.5–2.1) average decrease in anaesthetic volume was observed with episiotomy (p=0.724). The maximum volume of anaesthetic used with and without vasoconstrictor was 1–2 ml in 95% and 3–4 ml in 50% of first-degree lacerations, respectively, and 1–6 ml in 88% and 7–15 ml in 81% of second-degree lacerations, respectively. For episiotomy, the maximum dose was 15 ml, regardless of anaesthetic solution used.

Key conclusions

our data confirm the hypothesis that the use of anaesthetics in conjunction with vasoconstrictors is more effective than anaesthetics alone in the repair of perineal lacerations, but not for episiotomy.     

L-arginine pathway in neonates with meconium-stained amniotic fluid

Objective

To study the arginase, nitric oxide synthase and nitric oxide pathways associated with passage of meconium.

Study design

Cord blood samples were collected from 20 newborns with meconium-stained amniotic fluid (MSAF) and from 23 newborns with clear amniotic fluid. Cord blood pH, arginase, nitric oxide synthase and nitric oxide levels were compared between the groups.

Result

The differences between the arginase and nitric oxide measurements of the newborns with MSAF and those with clear amniotic fluid were significant. In the MSAF group arginase levels were significantly lower (p = 0.007) and nitric oxide levels were significantly higher (p = 0.032) than the clear amniotic fluid group.

Conclusion

Hypoxia may be involved in the pathogenesis of meconium passage due to decreased arginase and increased nitric oxide levels.     

First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia

Objective

To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive.

Study design

A retrospective case–control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11–14 weeks and stored at −70 °C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls.

Results

Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p < 0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 13.5 pg/mL, p < 0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p < 0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p < 0.001, p < 0.001 and p < 0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia.

Conclusions

Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia.