IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia.

OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and non-cachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50‒80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the inflammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 non-cachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT- PCR analysis. RESULTS: Our findings demonstrated that IL-6 mRNA levels considerably increased 19.89±8.25, 5.18±2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21±11.72 and 8.85±3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p<0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

Investigation of the association between the outcomes of sperm chromatin condensation and decondensation tests, and assisted reproduction techniques.

The main purpose of this prospective study is to examine possible influences of abnormalities of sperm nuclear condensation and chromatin decondensation with sodium dodecyl sulphate (SDS)-EDTA on outcomes of intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI) cycles. Semen samples from 122 IUI and 236 ICSI cycles were evaluated. Before semen preparation for IUI or ICSI, basic semen analysis was performed and a small portion from each sample was spared for fixation. The condensation of sperm nuclear chromatin was evaluated with acidic aniline blue, followed by sperm chromatin decondensation by SDS-EDTA and evaluation under light microscope. Ongoing pregnancy rate was 24% and 26.2% in the IUI and ICSI groups respectively. The chromatin condensation rate was significantly higher in the ongoing pregnancy-positive group compared to the negative group, both in IUI (P = 0.042) and ICSI groups (P = 0.027), and it was positively correlated with ongoing pregnancy rate in both IUI and ICSI groups (P = 0.015, r = 0.214 and P = 0.014, r = 0.312 respectively). Chromatin decondensation rates were not significantly different in neither of the groups. These results indicate that IUI and ICSI outcome is influenced by the rate of spermatozoa with abnormal chromatin condensation. Sperm chromatin condensation with aniline blue is useful for selecting assisted reproduction techniques (ART) patients.

Sperm selection based on motility in polyvinylpyrrolidone is associated with successful pregnancy and embryo development.

The aim of this study was to investigate whether spermatozoon motility in polyvinylpyrrolidone (PVP) is associated with better embryo development and pregnancy rates in ICSI cycles. A total of 123 primary ICSI treatment cycles were included in this study. Semen samples were tested for motility before ICSI procedure in PVP. Within 3 min, the presence or absence of motility was recorded. Sperm functions were examined by the aniline blue (AB) chromatin condensation test and the hypoosmotic swelling test, and the chromatin stability was evaluated by inducing its decondensation with sodium dodecyl sulphate and ethylenediaminetetraacetic acid (EDTA). Fertilisation and embryo scoring were evaluated. Fifty (64%) of 78 women conceived in the PVP (+) group; and 12 (26%) of 45 women conceived in the PVP (-) group; the pregnancy rate was significantly higher in the PVP (+) group (P = 0.003). Semen parameters were observed to be similar in both groups. The mean number of total embryos obtained in ICSI procedure and transferred grade 1 embryos were significantly higher in PVP (+) group (P = 0.01 and P = 0.003 respectively). The presence of sperm motility in PVP is associated with increased pregnancy rate, higher percentage of good quality embryos, sperm chromatin condensation and decondensation.

Melatonin levels and enzymatic antioxidant defense system decrease in blood of patients with bronchial asthma.

The etiology of bronchial asthma (BA) is not clearly understood. In recent years, a few studies have investigated the possible role of reactive oxygen species (ROS) in the etiology of BA. There are some defense mechanisms in the organism to avoid the harmful effects of ROS. Melatonin (MEL) is synthesized by the pineal gland at night and exhibits antioxidant properties. The aim of this study was to investigate serum MEL levels, erythrocyte antioxidant enzyme activities, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the association of the respiratory function tests, namely dynamic lung volumes; the forced vital capacity (FVC/L, FVC%), the forced expiratory volume in 1 s (FEV(1)/L, FEV(1)%), and peak expiratory flow (PEF/L/s, PEF%) in 30 patients with BA and 30 age-matched healthy controls. The levels of serum MEL, the activities of erythrocyte SOD, and the values of FVC/L, FVC%, FEV(1)/L, and FEV(1)% were significantly lower in the patients with BA than in control group. The positive correlations were observed between FVC% with erythrocyte SOD and GSH-Px, FEV(1)/L as well as FEV(1)% with erythrocyte SOD, whereas negative correlation was observed between PEF/L/s with levels of serum MEL. In conclusion, these results provide some evidence for a potential role of decreased antioxidant enzymes, MEL, and respiratory function test values in BA.

Occupational asthma, eosinophil and skin prick tests and serum total IgE values of the workers in a plant manufacturing rose oil.

This study was aimed to determine the rate of occupational asthma (OA) in workers at a rose extracting plant. Specific clinical tests of 52 workers, randomly chosen from four local rose extracting plants, were statistically compared with the test results of 30 local control subjects of similar age and sex as the plant workers, but who had never worked in such a plant. There were no significant differences in pulmonary function tests (FVC, FEV1, FEV1/FVC, PEFR) between the control and test groups. Significantly higher serum total IgE values (p < 0.0001) were observed for the test subjects (239.08+/-240 IU/ml) compared to the control subjects (81.33+/-61.45 IU/ml). There were also significant differences (p < 0.0001) in the number of eosinophils between the control and test groups, with corresponding mean values of 2.28+/-2.75% and 0.73+/-1.72%, respectively. A specifically prepared skin prick test using a rose allergen (Rosa domescena) was positive for 53.84% in the test subjects whereas only 5.33% positive test results were seen in the control group. We have demonstrated the involvement of Rosa domescena pollen in occupational allergy, through IgE-mediated hypersensitivity. It was concluded that the workers of a rose oil extracting plant are more susceptible to the rose pollens.

Is serum leptin level regulated by thyroid functions, lipid metabolism and insulin resistance in polycystic ovary syndrome?

Our aim was to determine whether serum leptin level is regulated by thyroid hormones, lipid metabolic products and insulin resistance status in women with polycystic ovary syndrome (PCOS). A prospective case-controlled study was carried out in Istanbul University, Cerrahpasa School of Medicine in 25 lean PCOS (L-PCOS) women, 19 obese PCOS (O-PCOS) women and 28 normal women. The diagnosis of PCOS was established according to the clinical, hormonal (elevated luteinizing hormone and serum androgens) and ultrasonographic findings. Fasting serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), fasting glucose, insulin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and leptin were measured and compared in the three groups and the correlations between serum levels of leptin and other parameters were evaluated. Serum leptin levels were higher in the O-PCOS group, while its level was comparable between the L-PCOS and control groups. Serum levels of FT4 were significantly lower in both L-PCOS and O-PCOS groups than the control group. Women in both L-PCOS and O-PCOS groups were found to be significantly hyperinsulinemic and insulin resistant. Serum levels of TC, VLDL-C and TG were significantly higher in the O-PCOS group, while serum HDL-C level was lower. There was a poor correlation between serum leptin, and FT4, TC, TG, HDL-C and VLDL-C levels. A significant correlation was observed between serum leptin levels and both BMI and insulin resistance status in PCOS. We believe that, although thyroid hormones and lipid metabolic products do not seem to participate in the regulation of serum leptin levels, BMI and insulin resistance status may have a key role in women with PCOS.

Hematological abnormalities in adolescent menorrhagia.

BACKGROUND: The purpose of this study is to determine the frequency of underlying hematological disorders as the cause of acute adolescent menorrhagia. METHODS: The records of 25 patients that were hospitalized with acute adolescent menorrhagia in the Obstetrics and Gynecology Department of Cerrahpasa Medical School of Istanbul University between 1988 and 1995 were analyzed. RESULTS: The mean age of the patients was 13.9 +/- 1.6 (SD) years. A hematological abnormality that caused bleeding diathesis and acute menorrhagia was diagnosed in 7 of the 25 patients (28%). There were four cases of immune thrombocytopenic purpura, two cases of Van Willebrand disease and one case of acute promyelocytic leukemia. All seven patients with a coagulation disorder required blood transfusions and the mean hemoglobin level at presentation was 6.2 g/dl.

A huge abdominal mass mimicking ovarian cancer: p53-negative but aneuploid myxoid leiomyosarcoma of the uterus.

OBJECTIVE: Less than 20 myxoid leiomyosarcoma cases were reported in literature. Since, these tumors are very rare and may exhibit highly malignant behavior despite their low mitotic index, clinical course and optimum type of therapy of myxoid variant of leiomyosarcoma were not well understood. The goal of this report is to contribute the better understanding of this rare type of tumor. METHODS: A 39-year-old woman presented with a huge abdominal cystic mass. Laparotomy was performed and frozen section diagnosis was low-grade uterine leiomyosarcoma. TAH-BSO, omentectomy, pelvic lymph node and peritoneal samplings were carried out. No chemotherapy was performed after surgical therapy. RESULTS: Final histopathological diagnosis was uterine myxoid leiomyosarcoma. The tumor was p53-negative and had aneuploid DNA content. The patient tolerated well the operation and she is alive and free of disease after 24 months of primary surgical treatment. CONCLUSION: Uterine myxoid leiomyosarcoma may present a huge abdominal cystic mass and can be treated successfully with surgery alone.

Apoptosis in the placenta of pregnancies complicated with IUGR.

OBJECTIVE: In this study we have investigated the presence of apoptosis in the placental tissue of pregnancies complicated with intra-uterine growth restriction (IUGR). METHOD: Placental samples were obtained from 22 normal third trimester pregnancies and 20 pregnancies complicated with IUGR. The criteria for fetal growth impairment were clinical evidence of sub-optimal growth, ultrasonographic demonstration of deviation from normal percentiles of growth and birth weight under 10th percentile. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) staining was used to demonstrate the apoptotic cells in all samples. Student-t, Mann-Withney U-test, Fisher exact test and Spearman correlation were used for statistical analysis. RESULTS: We detected apoptosis in 10 placentas in the study group vs. none in the control group. Placentas from pregnancies complicated with IUGR demonstrated 0.12% (0.1%-0.4%) apoptotic cells. The rate of apoptotic cells in the placenta was significantly higher in pregnancies complicated with IUGR than normal uncomplicated pregnancy (P=0.0019). Apoptosis were more abundant in the trophoblasts, especially cytotrophoblasts, in the placenta. We could not find a correlation between the apoptosis in the placenta of pregnancies complicated with IUGR and birth weight, multi-parity, gestational age, birth weight percentile and mode of delivery (C/S vs. vaginal delivery). CONCLUSION: We believe that the increased number of apoptosis in the placenta of pregnancies complicated with IUGR may have an important compensatory role to transmit nutrition and gas exchange easily to the fetus.

Symptomatic treatment of premenstrual mastalgia in premenopausal women with lisuride maleate: a double-blind placebo-controlled randomized study.

OBJECTIVE: To determine the therapeutic effect of lisuride maleate on premenstrual mastalgia in premenopausal women. DESIGN: Double-blind randomized prospective study. SETTING: Department of obstetrics and gynecology at a university hospital. PATIENT(S): Sixty women with premenstrual mastalgia were included in the study. Study and control groups consisted of 30 women each. INTERVENTION(S): Women enrolled in the study and control group were given one tablet daily (0.2 mg) of lisuride maleate or placebo orally for 2 months. Severity of mastalgia was evaluated using the visual analog scale. MAIN OUTCOME MEASURE(S): Severity of mastalgia and side effects of the drug administered. RESULT(S): Mastalgia subsided significantly in women receiving lisuride maleate compared with controls. There were no significant side effects from lisuride maleate. Prolactin levels decreased significantly in the group receiving lisuride, which correlated well with pain resolution. CONCLUSION(S): Lisuride maleate may be useful for the symptomatic treatment of premenstrual mastalgia.

Perinatal and maternal outcomes of fetal macrosomia.

OBJECTIVE: To determine the perinatal and maternal outcome of the macrosomic infants. STUDY DESIGN: A case-control, retrospective study is performed in the Department of Gynecology and Obstetrics, Istanbul University Cerrahpasa Medical Faculty, between 1988-1992. The maternal and neonatal records of infants with birthweight of at least 4000g (n=1000) were reviewed. Another 1000 cases amongst the newborns delivered in the same period between 2500 and 3999g formed the control group. The obstetrical outcome variables of the groups including mode of delivery and the incidence of maternal and perinatal complications were compared. RESULTS: A total of 16,112 deliveries occurred during the study period. The rate of macrosomic deliveries was 6.21% and the rate of the deliveries (4500g or heavier) was 1.04%. The mean birthweight of the study group was 4272+/-239 and 3277+/-316g of the control group (P<0.001). While the cesarean section rate was 28.8% for the study group and it was 16.6% for the control group (P<0.001). In the study group, 17 cases of brachial plexus palsy (2.4%), 16 cases of clavicular fracture (2.3%) and one case of humeral fracture were observed (P<0.001). The rate of perinatal mortality was 0.8% in the study group. No perinatal mortality was recorded in the control group. There were 14 cases (1.4%)of asphyxia related to delivery in the study group (P<0.01). The rate of maternal complications, were significantly higher in the study group (P<0.01). CONCLUSION: The macrosomic infants are in increased risk for birth trauma and asphyxia. The risk of birth trauma for the infants weighing 4500g or more is even greater.

Does leukocytospermia associate with poor semen parameters and sperm functions in male infertility? The role of different seminal leukocyte concentrations.

To investigate the effect of leukocytospermia on standard semen analysis and sperm function tests such as acrosome reaction, hypoosmotic swelling, antisperm antibody binding and cervical mucus penetration, a prospective clinical study was performed. Two hundred and nineteen male infertility patients undergoing investigation and treatment were included in the study. There was a significant association between acrosome reaction positivity and leukocytospermia according to WHO (World Health Organization) criteria. Increased hypoosmotic swelling test score, higher sperm concentration and enhanced acrosome reaction were closely related to leukocytospermia. When the patients were divided into subgroups according to seminal leukocyte concentrations, acrosome reaction and hypoosmotic swelling were observed to be higher in semen samples with higher leukocyte concentrations compared to those with low seminal leukocyte concentration. In addition, higher sperm concentrations were observed in semen samples with increased leukocyte levels compared to semen samples with low leukocyte levels. These results suggest that leukocytospermia may have a favorable effect on some sperm functions at seminal leukocyte concentrations between 1 and 3x10(6)/ml.

Effect of different types of intrauterine devices on intrauterine activity.

OBJECTIVE: To compare the effects of various IUDs on intrauterine activity. PATIENTS AND METHODS: 57 women volunteers aged 18 to 25 in the outpatient clinic of the Department of Obstetrics and Gynecology at Cerrahpasa Medical Faculty of Istanbul University were included in the study. All were in good health and menstruating normally. The subjects were introduced to different types of IUDs on the fifth to eighth days of their menstrual cycle. Intrauterine activities with and without naproxen were recorded, for at least 20 minutes each time, with a micro-tip transducer before insertion, just after insertion, and 1 month later. RESULTS: Intrauterine activity increased just after insertion of both IUDs and disappeared 1 month later in copper-T wearing women, but persisted in multiload wearers. Naproxen seemed to be useful in preventing intrauterine activity caused by the IUD. CONCLUSIONS: The IUD itself causes an increase in intrauterine activity which is preventable by naproxen, suggesting the possible role of prostaglandins. Persistence of intrauterine activity depends upon the type of device. Optimal designing of IUDs is required to decrease side effects and make them more acceptable.

Fetal weight estimation and prediction of fetal macrosomia in non-diabetic pregnant women.

In the present study we investigated the accuracy of Shepard's formula in the sonographic diagnosis of macrosomic fetus of non-diabetic pregnant women. Three hundred and eighty-one macrosomic and 450 appropriate for gestational age (AGA) fetuses born to non-diabetic mothers between 37-42 weeks of gestation were included in the study. Ultrasonographic fetal weight estimation within two days of delivery was made using Shepard's formula in all patients. The estimated fetal weights were compared with the actual birth weights of the same subjects. We did not observe any macrosomic newborn birth in pregnant women with 3200 g or less fetal weight estimation. However, in patients with 3400-3499 g fetal weight estimation, a statistically significant increase in macrosomic newborn birth was observed. Only 3.2% of newborns having actual birth weights greater than or equal to 4000 g had sonographic birth weight estimation less than 4000 g. Accuracy of weight estimations using the Shepard's formula was found to be low in macrosomic fetus. On the other hand, increased incidence of macrosomic newborn birth was observed in subjects with ultrasonographic fetal weight estimations above 3400 g and this level may be useful as a cut-off value for prediction of macrosomic fetus in non-diabetic pregnant women.

Ovarian stromal hypertrophy in polycystic ovary syndrome.

OBJECTIVE: To investigate the relationship between the ovarian stromal area and clinical hormonal characteristics in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Twenty-eight women with PCOS (group 1) and 26 healthy women (group 2) participated in this study. For measuring the ovarian stromal area, transvaginal ultrasonography was performed on all women during the early follicular phase of the menstrual cycle. Venous blood was sampled from the women to determine serum follicle stimulating hormone, luteinizing hormone (LH), estradiol, androstenedione, free testosterone (FT), total testosterone (TT), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate, and fasting insulin and glucose levels. Two-tailed t and Pearson correlation tests were used for statistical analysis. RESULTS: Women with PCOS were heavier, and their serum FT, TT and LH levels were significantly higher than in the normals (P < .001, P < .012 and P < .001, respectively). The ovarian stromal area measured by transvaginal ultrasonography was also significantly larger than in the normals (P < .001). Only basal serum insulin levels seemed to correlate positively with the ovarian stromal area in women with PCOS (r = .43 P = .09). CONCLUSION: Although transvaginal ultrasonography has played an important role in the evaluation of women with PCOS, we could not demonstrate a relationship between the ovarian stromal area and hormonal characteristics of PCOS. Therefore, transvaginal ultrasonography and hormonal parameters must be used as complementary diagnostic methods in women with PCOS.

A strong prognostic variable in endometrial carcinoma: flow cytometric S-phase fraction.

BACKGROUND: The purpose of this study was to determine the role of flow cytometric S-phase fraction as a prognostic factor in patients with endometrial adenocarcinoma. METHODS: The study included 80 patients with endometrial adenocarcinoma of endometrioid type who were followed regularly between 1984-1995 in the Department of Obstetrics and Gynecology at Cerrahpasa Faculty of Medicine in Istanbul, Turkey. The method employed for the flow cytometric analysis was modified from Hedley et al. RESULTS: The S-phase fraction was identified as the most significant variable associated with death from endometrial carcinoma of endometrioid type by the Cox proportional hazards model. The risk of death was significantly higher in patients with S-phase values greater than 20%. Aneuploidy and DNA indexes were also significant prognostic variables. CONCLUSIONS: The S-phase fraction is considered to be a significant prognostic variable in identifying those patients with endometrial carcinoma who have a poor prognosis. The authors believe that S-phase fraction distinguishes those patients who may benefit from additional treatment approaches.

DNA ploidy of ectopic pregnancy and first trimester spontaneous abortion investigated by flow cytometry.

BACKGROUND: To compare the success rate of DNA flow cytometry in determining the DNA ploidy status in ectopic pregnancy and first trimester spontaneous abortion. METHODS: Thirteen women with ectopic pregnancy (Group I) and 17 women with first trimester spontaneous abortion (Group II) were included into this study. DNA flow cytometric analysis was performed on all specimens. Aneuploidy was classified according to DNA index. The first trimester spontaneous abortions were also karyotyped after long-term culture of chronic villi. Student-t test and Fisher's exact test were used in statistical comparisons. RESULTS: DNA aneuploidy was found in five women with ectopic pregnancy (38.5%) versus in 12 women with first trimester spontaneous abortion (70.6%), and it was comparable. A triploidy and a tetraploidy were detected in group I. Six tubal ectopic pregnancies were unruptured at laparatomy and four of them had aneuploid DNA content. CONCLUSIONS: We believed that DNA flow cytometry was successful in determining the ploidy status of ectopic pregnancy and first trimester spontaneous abortion. In addition, it was interesting that ectopic pregnancies with aneuploid DNA content tended to be unruptured. However, this suggestion needs to be confirmed by further studies with larger numbers of cases.

Appendectomy in the surgical staging of ovarian carcinoma.

OBJECTIVES: Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. METHODS: The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. RESULTS: Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. CONCLUSION: Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.