Effect of severe hyperemesis gravidarum on maternal vascular endothelial health: evaluation of soluble adhesion molecules.

Purpose: This study aimed to clarify the effect of severe hyperemesis gravidarum (sHG) on maternal vascular endothelial health with evaluation of soluble adhesion molecules.Method: The study population consisted of two groups of pregnant participants between 18 and 35 years of age who were between 5 and 13 weeks of gestation: sHG group and a healthy control group. A group of 26 participants whose pregnancies were complicated by sHG was compared with 26 healthy participants regarding serum levels of the soluble adhesion molecules such as E-selectin, soluble intracellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule one (sVCAM-1), as well as other biochemical markers. The two groups had similar baseline characteristics.Results: Maternal baseline characteristics were similar in both groups. Serum levels of E-selectin (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were higher in the sHG group compared with the control group. Higher blood urea nitrogen, creatinine, and sodium levels, serum osmolarity, and urine density (p < .001, < .001, .006, .041, and .001, respectively) were also observed in the sHG group compared with the control group.Conclusions: The findings of this study indicated that sHG could impact endothelial cell function and these changes represented hypovolemia and dehydration caused by severe vomiting. Large-scale studies are required to understand the clinical importance of this finding regarding the long-term consequences and underlying mechanisms of elevated sICAM-1, sVCAM-1, and sE-selectin synthesis.

Maternal type 1collagen N-terminal telopeptide levels in severe hyperemesis gravidarum.

BACKGROUND: Nausea and vomiting occur 50-90% during the first trimester of pregnancy. However, patients with hyperemesis gravidarum (HG) may be hospitalized at an incidence rate of 0.8-2% before the 20th week of gestational age. The symptoms generally start during the 5-6th gestational weeks, reaching the highest degree during the 9th week, and decline after the 16-20th weeks of gestation. Clinical findings are proportional to the severity of the disease and severe HG is characterized with dehydration, electrolyte imbalance, and nutritional deficiency as a result of vomiting. METHODS: The study population consisted of two groups of pregnant volunteers at 5-12 weeks of gestation: a severe HG group and a control group. The HG severity was scored using the Pregnancy-Unique Quantification of Emesis (and nausea) (PUQE).The serum levels of the maternal Ca, parathyroid hormone (PTH), Na, K, blood urea nitrogen(BUN), creatinine, vitamin D(25OHD3), and the maternal urine NTx levels were compared between the groups. RESULTS: In total, 40 volunteers were enrolled in this study: 20 healthy pregnant volunteers and 20 with severe HG. There were no statistically significant differences between the maternal characteristics. The first trimester weight loss of ≥5 kg was significantly higher in the severe HG group (p < 0.001), while the control group had a significantly higher sunlight exposure ratio than the severe HG group (p = 0.021). The urine NTx levels were significantly higher in the severe HG group (39.22 ± 11.68NTx/Cre) than in the control group(32.89 ± 8.33NTx/Cre) (p = 0.028).The serum Ca, PTH, Na, K, BUN, and creatinine levels were similar between the groups (p = 0.738, p = 0.886, p = 0.841, p = 0.957, p = 0.892, and p = 0.824, respectively). In the severe HG group, the serum 25OHD3 levels were significantly lower than in the control group (p < 0.001). CONCLUSIONS: The data from this study indicated that severe HG is associated with increased urine NTx levels. However, large-scale studies are required to understand the clinical significance of this finding, as well as the long-term consequences of elevated urine NTx levels and the underlying mechanisms. TRIAL REGISTRATION: NCT02862496 Date of registration: 21/07/2016.

Efficacy of omega-3 in the treatment of polycystic ovary syndrome.

The purpose of this study was to evaluate the efficacy and safety of omega-3 in the treatment of polycystic ovary syndrome and to compare the clinical, hormonal, TNF-α and resistin levels in the patients treated with omega-3. A total of 45 non-obese PCOS women were studied. Women were treated with daily oral 1,500 mg of omega-3 for 6 months. Body mass index (BMI), hirsutism score, fasting glucose and insulin levels were noted for each case. Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Hormonal, TNF-α and resistin levels at 6 months of therapy were compared with baseline values. BMI, F-G scoring, insulin and HOMA levels decreased significantly during treatment, but glucose levels did not change. In the hormonal profile, serum LH and testosterone levels decreased and sex hormone-binding globulin levels increased significantly after the 6 months of therapy. On the other hand, TNF-α levels showed a significant increase, whereas resistin levels showed no change. Omega-3 may be also effective in improving hirsutism and insulin resistance in patients with PCOS.

The effect of sorafenib in postoperative adhesion formation in a rat uterine horn model.

OBJECTIVE: Postoperative adhesions are a serious problem. In this study, we aimed to observe the effects of sorafenib in postoperative adhesions and, to examine the effects of sorafenib on tissue levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). MATERIAL AND METHODS: Twenty female Wistar albino rats were randomized into two equal groups; sorafenib group (sorafenib treated) and control group; then all rats underwent laparotomy. Adhesions were developed by scalping on the anti-mesenteric surfaces of the right uterine horns. After 14 days, adhesions were investigated by using macroscopic, histopathological and immunohistochemical (for VEGF and PDGF) methods. RESULTS: The sorafenib group had lower scores of total adhesions [1 (0-2.5) vs 1.5 (1-4); p: 0.037], staining of VEGF [1 (0-1) vs 1 (1-3); p: 0.029] and PDGF [1 (0-2) vs 2 (1-3); p: 0.006], and vascular proliferation [1 (0-2) vs 2 (1-3); p: 0.038] than the control group. CONCLUSION: The findings of the present study show that sorafenib, a tyrosine kinase inhibitor, significantly reduced postoperative adhesion formation. This effect may be explained by inhibition of VEGF, PDGF, and thus vascular proliferation.

Effect of fibrin glue and comparison with suture on experimental induction of endometriosis in a rat endometrial autograft model.

OBJECTIVE: The effects of fibrin glue (FG) and suture were investigated and compared with experimental induction in an endometriosis model. MATERIAL AND METHODS: A randomized, controlled, and double-blind study was performed with 25 adult female Wistar Albino rats. Two autologous endometrial grafts were obtained from each of the rats. The endometrial grafts were transplanted by gluing with FG on the right abdominal wall and suturing with only 5/0 prolene on the left in ten rats. Gluing+suturing and after suturing over the covering with FG of the endometrial graft were performed, respectively, on the right and left in another ten rats. Covering with FG glue of the endometrial graft was performed in another five rats. The endometriosis-like lesions and intraperitoneal adhesions were evaluated macroscopically and histopathologically. RESULTS: The mean volume (31.4 +/- 17.3), adhesion (0.8 +/- 0.7) and inflammatory reaction (1.2 +/- 0.7) score of the implants in the group using only FG were significantly lower than in the group using suture [respectively, (49.2 +/- 20.6), (2.4 +/- 0.8), (2.2 +/- 0.8)] (p < 0.05). CONCLUSIONS: Our results demonstrate the general feasibility of reproducible and reliable endometrial graft fixation with FG onto the inner abdominal surface in rats. Furthermore, several advantageous characteristics could be demonstrated such as less inflammation and fewer adhesions.

Newborn hearing screening programme outcomes in a research hospital from Turkey.

BACKGROUND: Universal neonatal hearing screening programmes are encouraged to define and manage hearing loss in early ages of life. The aim of this study is to introduce our 14-month three-step hearing screening programme results with 16 975 births in Turkey. METHODS: In healthy neonates, Transient Evoked Otoacoustic Emission (TEOAE) is served as the initial screening in the first day of life. In newborns that did not meet pass criteria TEOAE was repeated in 10-day period. If the second test was 'refer' again, the screening was completed with auditory brainstem response (ABR). Additionally, ABR was performed for the neonates with neonatal intensive care unit (NICU) requirement and at high audiologic risk. Neonates who failed the screening test with ABR were referred for further evaluation. RESULTS: A total of 15 323 newborns and 1652 NICU infants were tested. The screening coverage was 94.4%; 14 521 neonates (94.7%) passed the first screening step (TEOAE), while 802 (5.2%) neonate failed. In total, 322 (40.1%) of the neonates out of 802 was subjected to the second TEOAE after 10 days have failed and ABR was applied. From the neonates participated the third step (ABR) totalling 1974, 43 (2.17%) of neonates obtained a 'refer' response. Out of these 43 neonates, 17 neonates were (39.5%) NICU infants. From the 43 neonates, 38 cases (88.4%) were found to have hearing impairment. The false-positive rate for first step screening with TEOAE was 4.9%; second step with TEOAE was 1.85% and for ABR was 0.25%. CONCLUSIONS: It is apparent that three step national hearing screening programme which has been applied for the latest years in Turkey is an accurate and non-invasive method to determine the congenital hearing loss. In the future, screening programmes could be rearranged with two steps as initial with TEOAE and retest with ABR and the coverage of the screening programme can be extended.

New alternative treatment in hirsutism: bicalutamide 25 mg/day.

The efficacy of low-dose bicalutamide (25 mg/day) in the treatment of hirsutism was investigated in this study. Hirsutism score was determined, according to a modified Ferriman-Gallwey scoring system, in 42 women with hirsutism. Each patient received 25 mg/day bicalutamide. Before therapy, multiscreen blood chemistry, hormonal analysis, and complete blood counts were performed. These parameters and hirsutism scores were repeated at 3 and 6 months during therapy. The paired Student's t-test was used to compare repeated values. Clinical improvement in the degree of hirsutism was observed in all patients by the same author. The modified Ferriman-Gallwey scores decreased from a mean of 22.0 +/- 5.1 to 8.6 +/- 3.5 (p < 0.0001). The reduction in hirsutism scores was 41.2 +/- 11.4% at 3 months and 61.6 +/- 11.1% at 6 months. In conclusion, bicalutamide at 25 mg/day is an effective drug in the treatment of patients with hirsutism.

Treatment of hirsutism with lowest-dose flutamide (62.5 mg/day).

Flutamide has been used successfully in the treatment of hirsutism. However, flutamide may cause important side-effects. The aim of this study was to evaluate the clinical and hormonal effects of lowest-dose flutamide therapy. Sixty-one women with hirsutism aged 18-37 years (mean +/- SD 23.4 +/- 5.9 years) were included in the study. Patients received 62.5 mg flutamide once per day for a period of 12 months. A hirsutism score was determined according to a modified Ferriman-Gallwey scoring system. Before therapy, multiscreen blood chemistry, hormonal analysis and complete blood counts were performed. These parameters and hirsutism scores were repeated at 3, 6, 9 and 12 months during therapy. The modified Ferriman-Gallwey scores significantly decreased from 19.1 +/- 4.9 to 5.8 +/- 3.3 during the study (p < 0.0001). The percentage reductions in hirsutism scores (mean +/- SD) were 60.3 +/- 14.4% at 6 months, and 70.3 +/- 13.2% at 12 months. No significant side-effects or modifications in the menstrual cycles were observed. There were no significant differences in any of the hormone levels during therapy. In conclusion, the lowest dose of flutamide, 62.5 mg/day, is a well-tolerated therapeutic agent and can be used in the treatment of hirsutism.

A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride (5 mg/d) in the treatment of hirsutism.

OBJECTIVE: To compare the long-term (1 year) effects of flutamide (250 mg/d) and finasteride (5 mg/d) for the treatment of hirsutism in women. DESIGN: Randomized, prospective clinical study. SETTING: Departments of Gynecology and Obstetrics and Endocrinology at Erciyes University Medical Faculty, Kayseri, Turkey. PATIENT(S): Seventy patients with hirsutism were studied. INTERVENTION(S): Thirty-five patients were treated with flutamide (250 mg/d) and 35 patients with finasteride (5 mg/d) for 12 months. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals. MAIN OUTCOME MEASURE(S): Reduction in hair growth. RESULT(S): The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SD of 17. 8 +/- 5.8 to 6.0 +/- 3.4 and 17.8 +/- 5.8 to 4.8 +/- 3.2, respectively, in group 1; and from 19.1 +/- 6.1 to 14.2 +/- 4.9 and 19.1 +/- 6.1 to 11.3 +/- 5.0 in group 2, respectively. There were no statistically significant differences in any of the hormonal indices in group 1, but in group 2, E(2) and sex hormone-binding globulin increased significantly while DHEAS decreased significantly at 12 months of therapy. CONCLUSION(S): This study shows that flutamide (250 mg/d) is more effective than finasteride (5 mg/d) in reducing hair growth. We conclude that flutamide (250 mg/d) may represent a more effective and well tolerated treatment for patients.

Finasteride treatment for one year in 35 hirsute patients.

This study was performed to confirm the favourable therapeutic effects of finasteride in hirsute women as described by previous publications of different research groups. Our study was a non-randomized, prospective clinical trial. Thirty five patients with hirsutism were included in the study. The patients received 5 mg finasteride orally once per day over a period of 12 months. Hirsutism score, FSH, LH, E2, total T, free T, androstenedione (A), DHEAS, 17-hydroxyprogesterone (17-OHP) and sex hormone-binding globulin (SHBG) levels were determined in all the patients before treatment and every 6 months during treatment. The modified Ferriman-Gallwey score decreased from a mean of 19.06 +/- 6.12 to 11.31 +/- 4.93 during the study. Clinical improvement in the degree of hirsutism was observed in 26 of 35 patients. The percent reductions in hirsutism scores (mean% +/- SD) at 6 and at 12 months were 25.8 +/- 11.3 and 41.3 +/- 18.5, respectively. During the finasteride therapy E2 and SHBG were increased significantly while DHEAS was decreased significantly at 12 months. There were no significant changes in the values of the other hormones and no serious side effects were observed in the study. In conclusion, finasteride is a well tolerated therapeutic agent without significant side pathological laboratory findings and can be used in the treatment of hirsutism.

Clinical efficacy of lower dose flutamide 125 mg/day in the treatment of hirsutism.

Thirty-four patients with moderate-severe hirsutism were enrolled in this study. The patients received 125 mg/day flutamide for a period of 6 months. Hirsutism score and hormone parameters including FSH, LH, T, free T, androstenedione (A), DHEAS, PRL and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and repeated at every three-monthly intervals. Hirsutism greatly improved during flutamide therapy, and the hirsutism score significantly decreased at month 3 and 6 from a mean (+/-SD) of 17.19+/-4.55 to 10.75+/-3.84 (p<0.001) and 17.19+/-4.55 to 5.91+/-2.53 (p<0.001), respectively. A significant reduction in hirsutism score (mean%+/-SD) as compared to baseline was observed at 3 months (37.78+/-13.30, p<0.001) and at 6 months (65.47+/-13.49, p<0.001). No significant changes in the levels of hormone and no serious side effects were observed in the patients. The lower dose flutamide, 125 mg/day, is a safe and cost-effective drug in the treatment of hirsutism. Lower dose flutamide may be used in place of high dose flutamide, 250 to 750 mg/day.

A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism.

OBJECTIVE: To compare the effects of flutamide at 250 mg/d and 500 mg/d in the treatment of hirsutism. DESIGN: Randomized, prospective clinical study. PATIENT(S): Sixty-five patients with moderate to severe hirsutism. INTERVENTION(S): Group I (n = 35) patients were treated with flutamide, 250 mg/d, and group II (n = 30) patients were treated with flutamide, 500 mg/d, for 12 months. Baseline hormone levels, body mass index, and hirsutism scores were similar between the groups. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals for 12 months. RESULT(S): The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SEM of 17.8 +/- 0.9 to 6.0 +/- 0.6 (P < 0.001) and 17.8 +/- 0.9 to 4.8 +/- 0.7 (P < 0.001) in group I and from 17.0 +/- 0.9 to 6.6 +/- 0.7 and 17.0 +/- 0.9 to 5.2 +/- 0.7 (P < 0.001) in group II, respectively. The reductions in hirsutism scores (mean +/- SEM) were similar in group I at 6 months (64.6% +/- 2.5%) and at 12 months (71.2% +/- 2.2%) and in group II at 6 months (62.1% +/- 3.0%) and at 12 months (70.3% +/- 3.0%). The percent reductions in hirsutiam scores at 6 and at 12 months were similar within group I (64.6% +/- 2.5% and 71.2% +/- 2.2%) and group II (62.1% +/- 3.0% and 70.3% +/- 3.0%), respectively. The decreases in hirsutism scores in the first 6 months were more significant than in the last 6 months of treatment in both groups. There were no significant differences in any of the hormone levels during therapy in either group. One patient in group II was excluded from the study because of liver dysfunction. CONCLUSION(S): This study shows that two different doses of flutamide (250 mg/d and 500 mg/d) are similarly effective in reducing hair growth. Flutamide at a dose of either 250 mg/d or 500 mg/d has no further effect after 6 months. We conclude that if flutamide is administered at a dose of 250 mg/d it may represent an effective and well tolerated treatment with reduced cost for the patient.

Effects of angiotensin converting enzyme inhibitor cilazapril and angiotensin II antagonist saralasin in ovarian hyperstimulation syndrome in the rabbit.

We investigated the possible effects of the angiotensin converting enzyme (ACE) inhibitor cilazapril and angiotensin II antagonist saralasin on ovulation, ovarian steroidogenesis and ascites formation in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model. OHSS was induced in rabbits by human menopausal gonadotropin (hMG) and intermittent human chorionic gonadotropin (hCG). In the cilazapril group (n = 10), animals also received cilazapril 2 mg/kg intraperitoneally daily for 7 days. In the saralasin group (n = 8), animals received saralasin intraperitoneally 1 h before or 1 h after hCG administration. Control animals (n = 8), received intraperitoneal saline solution. Serial blood samples were drawn on days 1, 5, 7 and 9 to measure serum estradiol and progesterone levels. On day 9, all rabbits underwent surgical exploration. Peritoneal and pleural fluid formation, ovarian weights and number of ovulations were determined. The volume of the ascitic and pleural fluids after hyperstimulation were not statistically different between the control, cilazapril and saralasin groups. The weight gains and ovarian weights of animals were similar between treatment and control groups. Saralasin significantly (p < 0.05) inhibited ovulation, but cilazapril did not. Cilazapril and saralasin did not affect progesterone production. Only cilazapril significantly decreased estradiol production (p < 0.05). In conclusion, the ACE inhibitor cilazapril and angiotensin II antagonist saralasin did not prevent ascites formation in OHSS. The ovarian renin-angiotensin system may not be the only factor acting in ascites formation in the OHSS.

The efficacy of 250 mg/day flutamide in the treatment of patients with hirsutism.

OBJECTIVE: To investigate the effects of low dose flutamide (250 mg/d) on hirsutism score and hormone levels in women with hirsutism. DESIGN: Nonrandomized, prospective clinical trial. PATIENTS: Forty-one patients with moderate-severe hirsutism were included in the study. INTERVENTION: Hirsute patients received 250 mg/d flutamide for a period of 6 months. MAIN OUTCOME MEASURES: Hirsutism score, FSH, LH, E2, total T, free T, androstenedione, DHEAS, PRL, 17-hydroxyprogesterone, and sex hormone-binding globulin levels were detected in all the patients before treatment and every 3 months during treatment. RESULTS: Treatment with the antiandrogen flutamide resulted in a particularly rapid and marked decrease in the hirsutism score, which decreased from 17.48 +/- 5.35 to 5.07 +/- 2.89 after 6 months. No significant changes in the levels of hormone and no serious side effects were observed in the study. CONCLUSION: The low-dose flutamide, 250 mg/d, is a cost-effective drug in the treatment of hirsutism. Low-dose flutamide may be used in place of high-dose flutamide, 500 to 750 mg/d.