Ali Buhur

The effects of duration of CO2 insufflation and irrigation on peritoneal microcirculation assessed by free radical scavengers and total glutathion levels during operative laparoscopy.

STUDY OBJECTIVE To investigate the effects of peritoneal exposure to carbon dioxide (CO2) on peritoneal microcirculation and free radical scavenger (FRS) metabolism, and its role in potential adhesion formation after operative laparoscopy. DESIGN Randomized, controlled study (Canadian Task Force classification I). SETTING University-affiliated hospital. PATIENTS Twenty-eight women undergoing operative laparoscopy for adnexal masses. INTERVENTION For each patient, a 1 x 1-cm sidewall peritoneal flap was excised at the end of laparoscopy and numbered randomly. Similar flaps obtained from 24 women immediately after entering the abdomen during laparotomy served as controls. MEASUREMENTS AND MAIN RESULTS Changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues. The duration of CO2 exposure and amount of CO2 used were correlated with levels of free radical scavengers and compared with controls. Mean CO2 exposure, amount of CO2 used, and CO2 pressure (15 mm Hg) was similar between low irrigation and irrigated laparoscopy (118.3 +/- 25 and 39.2 +/- 8.81 min and 125 +/- 20 and 44.5 +/- 6.81 min, respectively). The change in FRS levels was significantly correlated with duration and amount of CO2 exposure (r = -0.92). Levels of GSH-Px, SOD, CAT, and GSH were significantly lower in the CO2 exposure group than in controls (0.57 micro mol, 1.8 ng, 48.5 micro mol, 1.5 nmol vs 0.8 micro mol, 2.6 +/- 0.4 ng, 79 micro mol, 3.6 nmol, respectively). CONCLUSION Exposure to CO2 has adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms in adhesion formation. Avoiding long CO2 exposure and copiously irrigating the abdominal cavity throughout surgery may lessen these effects. The potential role of the peritoneal FRS system on postoperative adhesion formation and its relation to estrogen status mandates further studies.

Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin treatment in patients with endometriosis.

OBJECTIVE To investigate the efficacy and safety of tibolone on hypoestrogenic vasomotor symptoms and bone parameters in patients treated with goserelin acetate. DESIGN Prospective, randomized placebo controlled double-blind study. SETTING Human volunteers in a university-based fertility clinic. PATIENT(S) Twenty-nine women of mean age 29.2 +/- 4.8 years with mild to severe endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in an SC depot formulation were studied. INTERVENTION(S) The patients were allocated randomly to either 2.5 mg/d tibolone (n = 15) or an iron pill (n = 14) in a double-blinded fashion beginning in the third cycle. MAIN OUTCOME MEASURE(S) Frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were assessed by the patients using 0 to 6 point scoring system and compared. Samples of urine were obtained for calcium and creatinine (Ca:Cr) ratios at the start of treatment and monthly there after. The vasomotor scoring for each symptom and Ca:Cr ratios before the treatment and at the end of 6th month were analyzed by parametric and nonparametric tests. RESULT(S) The mean age, weight, vasomotor scores, pelvic scores, and urine Ca:Cr ratios were similar in both placebo and tibolone group (28.7 +/- 4.8 versus 27.6 +/- 6.3 years, 50.9 +/- 5.3 versus 53.1 +/- 7.1 kg, 4.7 +/- 1.1 versus 4.2 +/- 0.8, and 0.056 +/- 0.008 versus 0.059 +/- 0.006, respectively). The decreases in vasomotor scoring as regards to hot flushing, sweating, and other associated symptoms were statistically significant in tibolone group compared with placebo (10.4 +/- 1.6 versus 24.6 +/- 4.9). During the study significant reductions in urine Ca:Cr ratio was obtained in the tibolone patients compared with placebo (0.031 +/- 0.006 versus 0.0055 +/- 0.007). The incidence of side effects (weight change, vaginal bleeding) was low and did not differ from the placebo group. CONCLUSION(S) Considering the beneficial effects of tibolone on vasomotor symptoms and bone loss, our data suggest that this synthetic steroid is an effective and safe option in relieving symptoms induced by GnRH-analogue.

Endometrial Na+, K+-ATPase pump function and vasopressin levels during hysteroscopic surgery in patients pretreated with GnRH agonist *

STUDY OBJECTIVE To investigate the effects of gonadotropin-releasing hormone (GnRH) analog pretreatment on endometrial Na+, K+-adenosine triphosphatase (ATPase) pump function and peripheral blood vasopressin levels, and their role in fluid absorption and mechanisms of hyponatremia in patients undergoing hysteroscopic endometrial ablation. DESIGN Prospective, randomized, placebo-controlled study (Canadian Task Force classification I). SETTING University-affiliated hospital. PATIENTS Seventeen women with dysfunctional uterine bleeding. INTERVENTION Nine women received a GnRH analog and eight received saline approximately 6 to 8 weeks before hysteroscopic ablation by electrosurgery. MEASUREMENTS AND MAIN RESULTS Both before randomization and immediately before surgery, endometrial biopsy samples were obtained and numbered consecutively without patient identification. Operative hysteroscopy was performed with glycine 1.5% mixed with 2% alcohol. The amount of irrigant and irrigant deficit; blood levels of albumin and ethanol; hematocrit and hemoglobin; changes in sodium levels; and central venous pressure were compared. The Na+, K+-ATPase pump activity was significantly increased in the GnRH analog group compared with the saline group and correlated with decreased estradiol levels (0.4 +/- 0.08 vs 0.26 +/- 0.06 micro mol/min/ml). Vasopressin levels were significantly lower in the GnRH group (3.2 +/- 0.9 vs 7.6 +/- 1.7 micro mol/L). Mean volume of irrigant used and operating time were similar in both groups. Volume deficit, decrease in protein, and hematocrit were less in GnRH than in the saline group. Blood ethanol levels, decrease in sodium, and irrigant deficit were significantly lower in GnRH group. CONCLUSION Pretreatment with GnRH analogs may prevent the adverse effects of estradiol on endometrial Na+, K+-ATPase and creates a protective mechanism against iatrogenic hyponatremia, which is more critical in women than men in case of absorption of irrigating fluid. Moreover, created hypoestrogenism may enhance Na+, K+-ATPase activity in brain as well as endometrium, thus decreasing womens susceptibility to hyponatremic complications and brain damage. Suppressed vasopressin levels may be protective against fluid absorption in GnRH analog-treated patients.

O-130 The effects of twisted ischemic adnexa managed by detorsion on ovarian viability and histology: An ischemia-reperfusion rodent model

This prospective controlled follow-up study was designed to examine the effects of adnexal torsion on long-term ovarian histology and radical scavenger (FRS) activity, and subsequent viability following the detorsion of twisted ischaemic adnexa, in a primate centre of a university clinic. Adnexal torsion/occlusion was created by twisting the adnexa three times and fixing on to the side wall or by applying vascular clips in cycling female rats at 70 days of age. Following an ischaemic period of 4 to 36 h, the twisted adnexas were surgically removed and fixed. In the second group of rats, following the above ischaemic periods, the torsion/occlusion were relieved by detwisting or removing the vascular clips. Then the animals were reperfused for a week and adnexas were extirpated. After both ischaemia and reperfusion, the removed adnexas were examined histologically and tissue concentrations of glutathione peroxidase, superoxide dismutase, catalase and glutathione were determined. Regardless of the ischaemia time, all the twisted adnexas were black-bluish in appearance. Despite the gross ischaemic-haemorrhagic features, histological sections revealed negligible changes, with intact ovarian structure similar to controls in 4-24 h groups. Though decreased compared with controls, the change in tissue concentrations of FRS was not significant in 4-24 h groups. Only the 36 h group showed prominent congestion on all sections and a significant decrease in all radical scavenger concentrations studied. While no long-term reperfusion injury was observed histologically in 4-24 h groups, the 36 h group ended with adnexal necrosis. Our findings support the importance of early diagnosis and conservative surgical management (detorsion) in adnexal torsion. Lack of histological changes and unimpaired FRS metabolism are consistent with the recent data that vascular compromise is caused by venous or lymphatic stasis in early torsion and that adnexal integrity is not correlated with gross ischaemic appearance, thus providing evidence of adnexal resistance against ischaemia.

The effects of daflon on pelvic pain in women with Taylor syndrome

The syndrome of chronic pelvic pain without an obvious pathology has been described as pelvic congestion (Taylor) syndrome. It is frequently associated with continuous bilateral lower abdominal pain and dyspareunia. Pelvic examination reveals tenderness without induration or masses. Although their importance in the pathophysiology of pain is uncertain, prominent enlarged broad ligament veins are observed at laparoscopy. We evaluated the effects of daflon, a venomimetic agent that regulates the circulatory tonus of the venous system, on pelvic pain and investigated the role of enlarged veins in the pathophysiology of Taylor syndrome. Ten women (age 28-35 yrs) with chronic pelvic pain were diagnosed with the syndrome at laparoscopy. They all had prominent broad ligament and ovarian veins without other pathologies such as endometriosis to explain the etiology of pelvic pain. Five women were randomized in a double-blind fashion to receive daflon 500 mg twice/day for 4 months, and five a vitamin pill placebo; they were crossed over for another 4 months. They scored the frequency and severity of lower abdominal pain and dyspareunia on a scale from 0 to 6, and the results were compared with pretreatment values. At the end of the fourth month the frequency and severity of pelvic symptoms began to decrease with daflon compared with pretreatment and placebo. The mean scores were significantly less at the end of 4 months (9.3 ± 1.1 vs 4.2 ± 1.4, respectively, p <0.05). Based on our preliminary results, we conclude that venous dysfunction and stasis may be pathophysiologic components of pelvic pain in women with Taylor syndrome. Pharmacologic enhancement of venous tonus may restore pelvic circulation and relieve pelvic symptomatology.

Effectiveness and long-term safety of prolonged gosereline and tibolone in women with endometriosis

Gonadotropin-releasing hormone (GnRH) agonists are widely administered to treat endometriosis, but generally are not prescribed for more than 6 months since they are associated with vasomotor symptoms and bone loss. A GnRH agonist and steroid add-back therapy can be given for longer times without flare-up or significant hypoestrogenic symptoms. We examined the efficacy and safety of a weak estrogenic steroid, OD14, with prolonged goserelin treatment in seven regularly menstruating women (age 26-33 yrs) with laparoscopically diagnosed, symptomatic endometriosis. The women received goserelin 3.65 mg subcutaneously/month and 2.5 mg OD14 2.5 mg/day beginning in the fourth cycle for 18 to 20 months. The frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were scored by the women on a scale of 0 to 6 and compared. Samples of blood and urine were obtained to measure serum estradiol (E2) levels, lipids, and urinary calcium:creatinine (Ca:Cr) ratios at the start of treatment and monthly thereafter. The vasomotor scores, serum E2 levels, and urine Ca:Cr ratios were consistent with the hypoestrogenism induced by goserelin (24.2 ± 3.1, 18.5 ± 7.2 pg/ml, and 0.063 ± 0.008, respectively). The decreases in vasomotor scoring with regard to hot flushing, sweating, and urinary Ca:Cr ratios were significant after adding OD14 (14.8 ± 2.2, 0.031 ± 0.005, p <0.05), whereas E2 levels remained below 40 pg/ml (23.1 ± 8.2 pg/ml, p >0.05) throughout therapy. The increased low-density:high-density lipoprotein ratio with goserelin improved with OD14, remaining at the lower limit of normal. Thus, OD14 add-back to GnRH agonist therapy enabled us to extend medical therapy of endometriosis longer than 6 months, preventing hypoestrogenic side effects, and with adequate suppression endometriosis symptoms.

O-020 Comparison of the effects of tibolone and hormone replacement therapy on echocardiographic basic cardiac functions in postmenopausal women: A randomized placebo controlled study

Objectives: This study is designed to investigate and compare the effects of synthetic steroid tibolone and HRT on systolic and diastolic heart functions in post-menopausal women. Methods: This prospective, randomized placebo controlled double blind study was conducted in a university clinic. Fifty-eight non-smoking, otherwise healthy post-menopausal women who did not receive any kind of HRT at least for 3 years within the onset of menopause were included in the study. The patients were randomly allocated to either 2.5 mg per day tibolone (OD, n = 18), daily combined 0.625 mg of conjugated estrogens 2.5 mg −1 of medroxy progesterone acetate pill (EP, n = 20) or a vitamin pill (n = 20) in a double blinded fashion. Their basic systolic and diastolic functions were investigated with HP Sonos-1000 echocardiography using standard positions and windows before and 6 months after the initiation of HRT. Results: Mean age, weight, length of post-menopausal period, heart rate, systolic and diastolic pressures were similar between the groups. At the initiation of the study all groups had similar echocardiographic measurements. However, at the end of 6 months, left ventricular end-systolic and -diastolic volumes were decreased significantly compared to pretreatment and placebo in both EP and OD treated groups. (55 .5 ± 18.4 and 53.7 ± 19.1.8 ml; 109.9 ± 19.9 and 110.7 ± 20.8 ml versus 74.5 ± 14.9 and 142.7 ± 19.1 ml, respectively; P< 0.05). Improvement in diastolic functions was significant in EP/OD groups compared to pre-treatment period and the placebo groups (E/A 1.34 ± 0.1 and 1.38 ± 0.1 versus 1.18 ± 0.09, deceleration time 204 ± 11.1 and 202.8 ± 27.1 ms versus 237.6 ± 26.9 ms, respectively). Besides increase in left ventricular mass adjusted for height, decrease in left ventricular relative wall thickness, and systemic vascular resistance were significant in EP and OD treated groups than placebo and the pre-treatment measurements. Although improved in both OD and EP groups, the changes in systolic and diastolic functions were significantly higher in the OD treated group. Based on our preliminary results, we may conclude that both EP and OD regimens may improve cardiac performance and age related dysfunctions. Conclusion: The present results may further support that both OD and EP exert